Gregory W. Albers, MD

All Publications

• CT perfusion derived relative cerebral blood volume < 42 % is negatively associated with poor functional outcomes at discharge in anterior circulation large vessel occlusion stroke. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Lakhani, D. A., Balar, A. B., Vagal, V., Salim, H., Mei, J., Koneru, M., Wen, S., Berksu Ozkara, B., Lu, H., Wang, R., Xu, R., Nabi, M., Mazumdar, I., Cho, A., Chen, K., Sepehri, S., Deng, F., Hyson, N., Urrutia, V., Luna, L. P., Sriwastwa, A., Hillis, A. E., Heit, J. J., Albers, G. W., Rai, A. T., Dmytriw, A. A., Faizy, T. D., Wintermark, M., Nael, K., Yedavalli, V. S. 2024; 130: 110907

  Abstract

  Recent studies have shown that the CT Perfusion (CTP) parameter of rCBV < 42 % lesion volume can predict 90-day functional outcomes in stroke patients. However, its correlation with discharge outcomes, including functional dependence, has not been investigated. Our study aims to evaluate the relationship between rCBV < 42 % and poor functional outcomes at discharge, defined as a modified Rankin score (mRS) of 3 or higher.This retrospective study analyzed patients with confirmed occlusion on CT angiography, who also received CT perfusion between 9/1/2017 and 10/01/2023. Statistical tests (Student's T, Mann-Whitney U, and Chi-Square) were used to assess differences. Univariable and multivariable logistic regression analyses were performed to evaluate the associations of rCBV < 42 % with discharge mRS. A p-value ≤ 0.05 was considered significant.A total of 268 patients [median age: 68 years (IQR: 59-77), 56.3 % female] met the inclusion criteria. Among them, 85 patients (31.7 %) received intravenous thrombolysis (IVT), and 221 patients (82.5 %) underwent mechanical thrombectomy (MT). After adjusting for various variables, logistic regression analysis indicated that rCBV < 42 % lesion volume was associated with poor functional outcomes at discharge (aOR = 0.97, p < 0.05). T.The rCBV < 42 % could be a valuable tool in prognosticating AIS-LVO patients.

  View details for DOI 10.1016/j.jocn.2024.110907

  View details for PubMedID 39536379

• Prolonged venous transit is associated with worse neurological recovery in successfully reperfused large vessel strokes. Annals of clinical and translational neurology Mei, J., Salim, H. A., Lakhani, D. A., Luna, L., Balar, A., Shahriari, M., Hyson, N. Z., Deng, F., Dmytriw, A. A., Guenego, A., Vagal, V., Urrutia, V. C., Marsh, E. B., Lu, H., Xu, R., Leigh, R., Wolman, D., Shah, G., Pulli, B., Nael, K., Albers, G. W., Wintermark, M., Heit, J. J., Faizy, T. D., Hillis, A. E., Llinas, R., Yedavalli, V. 2024

  Abstract

  Venous outflow (VO) impairment predicts unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Prolonged venous transit (PVT), a visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps, has been associated with unfavorable 90-day functional outcomes despite successful reperfusion. This study investigates the association between PVT and percent change on the National Institutes of Health Stroke Scale (NIHSS) among AIS-LVO patients who have undergone successful reperfusion.We performed a retrospective analysis of prospectively collected data from consecutive adult AIS-LVO patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s in the superior sagittal sinus, torcula, or both. The primary outcome was continuous NIHSS percent change and dichotomous NIHSS percent change ≥70%. Regression analyses were performed to assess the effect of PVT on NIHSS percent change.In 119 patients of median (IQR) age 71 (63-81) years, the admission and discharge NIHSS scores were significantly higher in PVT+ patients compared to PVT- patients (17 [14-23.5] vs. 13 [9.5-19], p = 0.011, and 7.5 [4-12] vs. 3 [1-7], p < 0.001, respectively). After adjusting for age, sex, hypertension, diabetes, atrial fibrillation, administration of intravenous thrombolysis (IVT), Alberta Stroke Program Early CT Scores (ASPECTS), mTICI 2c and/or 3, Tmax >6 s volume, and hemorrhagic transformation, PVT+ was significantly associated with lower NIHSS percent change (B = -0.163, 95%CI -0.326 to -0.001, p = 0.049) and was less likely to achieve higher than 70% NIHSS improvement (OR = 0.331, 95% CI 0.127-0.863, p = 0.024).PVT+ was significantly associated with reduced neurological improvement despite successful reperfusion in AIS-LVO patients, highlighting the critical role of VO impairment in short-term functional outcomes. These findings further validate PVT as a valuable adjunct imaging biomarker derived from CTP for assessing VO profiles in AIS-LVO.

  View details for DOI 10.1002/acn3.52243

  View details for PubMedID 39529443

• Interfacility Transfer for Thrombectomy: A Promising Therapeutic Window. Stroke Seners, P., Baron, J., Wouters, A., Desilles, J., Pico, F., Macrez, R., Olivot, J., Lemmens, R., Albers, G. W., Lansberg, M. G. 2024

  Abstract

  Currently, most acute ischemic stroke patients presenting with a large vessel occlusion are first evaluated at a nonthrombectomy-capable center before transfer to a comprehensive stroke center that performs thrombectomy. Interfacility transfer is a complex process that requires extensive coordination between the referring, transporting, and receiving facilities. As a result, long delays are common, contributing to poor clinical outcomes. In this review, we summarize the accumulating literature about the clinical as well as radiological-infarct growth, collateral change, arterial recanalization, and hemorrhagic transformation-changes during interfacility transfer for thrombectomy. Recent evidence shows that clinical/radiological changes during transfer are heterogeneous across patients and impact long-term functional outcomes, highlighting the urgent need to optimize care during this time window. We review some of the most promising therapeutic strategies-for example, penumbral protection to reduce infarct growth-that may improve clinical outcome in patients being transferred to thrombectomy-capable centers. Finally, we discuss key methodological considerations for designing clinical trials aimed at reducing infarct growth during transfer.

  View details for DOI 10.1161/STROKEAHA.124.049167

  View details for PubMedID 39502034

• Role of Hypoperfusion Intensity Ratio in Vessel Occlusions: A Review on Safety and Clinical Outcomes. AJNR. American journal of neuroradiology Rehman, S., Nadeem, A., Kasi, A. B., Husnain, A., Waseem, S., Kumar, S., Owais, S. M., Banu, N., Lakhani, D. A., Salim, H. A., Xu, R., Vagal, V. S., Aziz, Y. N., Hillis, A. E., Urrutia, V. C., Llinas, R. H., Marsh, E. B., Leigh, R., Lu, H., Dmytriw, A. A., Guenego, A., Albers, G. W., Heit, J. J., Faizy, T. D., Yedavalli, V. S. 2024

  Abstract

  The hypoperfusion intensity ratio (HIR) is a quantitative metric used in vascular occlusion imaging to evaluate the extent of brain tissue at risk due to hypoperfusion. Defined as the ratio of tissue volume with a time-to-maximum (Tmax) of >10 seconds to that of >6 seconds, HIR assists in differentiating between the salvageable penumbra and the irreversibly injured core infarct. This review explores the role of HIR in assessing clinical outcomes and guiding treatment strategies, including mechanical thrombectomy and thrombolytic therapy, for patients with large vessel occlusions (LVOs). Evidence suggests that higher HIR values are associated with worse clinical outcomes, indicating more severe tissue damage and reduced potential for salvage through reperfusion. Additionally, HIR demonstrates predictive accuracy regarding infarct growth, collateral flow, and the risk of reperfusion hemorrhage. It has shown superiority over traditional metrics, such as core infarct volume, in predicting functional outcomes. HIR offers valuable insights for risk stratification and treatment planning in patients with LVOs and distal medium vessel occlusions (DMVOs). Incorporating HIR into clinical practice enhances patient care by improving decision-making processes, promoting timely interventions, and optimizing post-intervention management to minimize complications and improve recovery outcomes.

  View details for DOI 10.3174/ajnr.A8557

  View details for PubMedID 39477546

• Blood-brain barrier profile pretreatment is associated with hemorrhagic transformation after endovascular reperfusion. Annals of clinical and translational neurology Leigh, R., Seners, P., Rousseau, V., Christensen, S., Albucher, J. F., Drif, A., Cognard, C., Guenego, A., Viguier, A., Sommet, A., Raposo, N., Calviere, L., Januel, A. C., Mlynash, M., Bonneville, F., Gaudilliere, B., Thalamas, C., Sibon, I., Tourdias, T., Mazighi, M., Heit, J. J., Maier, B., Albers, G. W., Olivot, J. M. 2024

  Abstract

  While advances in endovascular thrombectomy (EVT) have led to high reperfusion rates, most patients treated with EVT do not avoid disability. Post-reperfusion hemorrhagic transformation (HT) is a potential target for improving outcomes. This study examined pretreatment blood-brain barrier (BBB) disruption in tissue that would subsequently become part of the final infarct to evaluate its role in post-EVT HT.This post hoc analysis of the FRAME study, which enrolled patients with anterior large vessel occlusion who received EVT within 6 hours of onset, included patients if they had successful pretreatment MRI perfusion weighted imaging (PWI) and underwent successful EVT. BBB disruption was measured as the percent signal change due to gadolinium leakage on the PWI source images prior to thrombectomy. Mean permeability derangement (MPD) was defined as the average of all voxels in the stroke core that are two standard deviations above normal. The primary outcome was hemorrhagic transformation with parenchymal hematoma (PH).In total, 164 patients were included; mean age was 71 and 48% were female. PH occurred in 57 patients. Median MPD was 13.5% for patients with PH versus 3.6% for patients without (p < 0.0001). Elevated MPD was independently associated with PH with a 20% increased risk of PH for each 5% increase in MPD (OR 1.206; 95% CI 1.037:1.405; p = 0.0147, adjusted for NIHSS and procedure duration).Even in patients who are successfully recanalized in an early time window, pretreatment BBB disruption in regions that go on to infarct is associated with an increased risk of post-EVT HT.

  View details for DOI 10.1002/acn3.52236

  View details for PubMedID 39462241

• Efficacy and Safety of Intravenous Tenecteplase Before Endovascular Thrombectomy for Acute Ischemic Stroke: The Multicenter, Randomized, BRIDGE-TNK Trial Protocol. Journal of the American Heart Association Qiu, Z., Li, F., Xie, D., Yuan, G., Nguyen, T. N., Zhou, K., Nogueira, R. G., Saver, J. L., Campbell, B. C., Albers, G. W., Sang, H., Li, L., Tian, Y., Meng, Z., Wang, D., Zi, W., Yang, Q., BRIDGE‐TNK investigators 2024: e036765

  Abstract

  BACKGROUND: Six randomized trials have not detected a difference between intravenous alteplase plus endovascular thrombectomy and endovascular thrombectomy alone in stroke. Tenecteplase, a recombinant human tenecteplase tissue-type plasminogen activator, is a genetically modified variant of alteplase. It is unclear whether the outcomes are different if alteplase is replaced with tenecteplase. This trial aims to determine whether intravenous tenecteplase within 4.5 hours of time last known well confers benefit in patients with acute ischemic stroke with large-vessel occlusion who undergo endovascular thrombectomy.METHODS: BRIDGE-TNK (Thrombectomy With Versus Without rhTNK-tPA in Stroke) is an investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded end point evaluation conducted at 40 thrombectomy-capable centers in China. This trial will randomize 544 patients with intravenous thrombolysis-eligible stroke (272 in each arm) with large-vessel occlusion within 4.5 hours of last known well to receive bridging intravenous tenecteplase with endovascular thrombectomy (tenecteplase-plus-thrombectomy group) or endovascular thrombectomy alone (thrombectomy-alone group). The primary outcome is the proportion of patients achieving functional independence, defined as a score of 0 to 2 on the modified Rankin Scale, at 90days. Safety will be assessed via symptomatic intracranial hemorrhage at 48 hours and death at 90days.CONCLUSIONS: BRIDGE-TNK will provide important data on the role of intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke with large-vessel occlusion who can be treated within 4.5 hours of last known well.REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT04733742.

  View details for DOI 10.1161/JAHA.124.036765

  View details for PubMedID 39435713

• Poor venous outflow is associated with hyperintense acute reperfusion marker on follow-up MRI in patients with acute ischemic stroke with a large vessel occlusion. Journal of neurointerventional surgery Zamarud, A., Yuen, N., Wouters, A., Mlynash, M., Hugdal, S. M., Seners, P., Kesten, J., Yedavalli, V., Faizy, T. D., Albers, G. W., Lansberg, M. G., Heit, J. J. 2024

  Abstract

  Hyperintense acute reperfusion marker (HARM) refers to delayed enhancement in the subarachnoid or subpial space on post-contrast fluid attenuated inversion recovery (FLAIR) images. HARM is a measure of blood-brain barrier breakdown, which has been correlated with poor outcomes in patients with acute ischemic stroke with large vessel occlusion (AIS-LVO). We hypothesized that unfavorable venous outflow (VO) would be correlated with HARM after thrombectomy treatment of AIS-LVO.To determine whether poor VO is associated with HARM on follow-up MRI after stroke in patients with AIS-LVO.Patients with AIS-LVO from the prospective CRISP2 and DEFUSE2 studies with a baseline CT angiography (CTA) scan and a follow-up MRI with FLAIR sequence were screened for enrollment. VO was measured on the baseline CTA scan using the cortical venous opacification score (COVES). HARM was determined on FLAIR sequences at the follow-up MRI. The primary outcome was the occurrence of HARM between those with good VO (VO+; COVES 3-6) and bad VO (VO-; COVES 0-2).121 patients were included; 60.3% (n=73) had VO+ and 39.7% (n=48) had VO-. Patients with VO- had higher presentation National Institutes of Health Stroke Scale scores (18 (IQR 12-20) vs 12 (IQR 8-16) in VO+; P<0.001). Middle cerebral artery M1 segment occlusions were more common in VO- patients (65% vs 43% VO+; P=0.028). VO- patients also had a larger pre-treatment ischemic core (23 (4-44) mL vs 12 (3-22) mL in VO+; P=0.049) and Tmax >6 s volumes (105 (72-142) mL vs 66 (35-95) mL in VO+; P<0.001). VO- patients were more likely to develop HARM after thrombectomy (31% vs 10% in VO+; P=0.003). On multivariable regression analysis, VO- (OR=3.6 (95% CI 1.2 to 10.6); P=0.02) and the presence of any ICH (OR=3.6 (95% CI 1.2 to 10.5); P=0.02) were independently associated with the occurrence of HARM.In patients with AIS-LVO, VO- correlated with HARM on post-thrombectomy MRI.

  View details for DOI 10.1136/jnis-2024-022064

  View details for PubMedID 39393917

• Utility of automated CT perfusion software in acute ischemic stroke with large and medium vessel occlusion. Annals of clinical and translational neurology Ashayeri Ahmadabad, R., Tran, K. H., Zhang, Y., Kate, M. P., Mishra, S., Buck, B. H., Khan, K. A., Rempel, J., Albers, G. W., Shuaib, A. 2024

  Abstract

  Early diagnosis of large vessel occlusion (LVO) in acute stroke often requires CT angiography (CTA). Automated CT perfusion (CTP) software, which identifies blood flow abnormalities, enhances LVO diagnosis and patient selection for endovascular thrombectomy (EVT). This study evaluates the sensitivity of automated CTP images in detecting perfusion abnormalities in patients with acute ischemic stroke (AIS) and LVO or medium vessel occlusion (MeVO), compared to CTA.We screened acute ischemic stroke patients presenting within 24 h who underwent CT, CTA, and CTP as per institutional protocol. RAPID AI software processed CTP images, while neuroradiologists reviewed CTA for intracranial arterial occlusions. Sensitivity, specificity, and accuracy of automated CTP maps in detecting occlusions were assessed.Of 790 screened patients, 31 were excluded due to lack of RAPID CTP data or poor-quality scans, leaving 759 for analysis. The median age was 71 years (IQR: 61-81), with 47% female. Among them, 678 had AIS, and 81 had AIS ruled out. CTA identified arterial occlusion in 562 patients (74%), with corresponding CTP abnormalities in 537 patients (Tmax > 6 sec). In the 197 without occlusion, CTP was negative in 161. Automated CTP maps had a sensitivity of 95.55% (CI 95: 93.50-97.10%), specificity of 81.73% (CI 95: 75.61-86.86%), negative predictive value of 98.22% (CI 95: 97.39-98.79%), positive predictive value of 63.54% (CI 95: 56.46-70.09%), and overall accuracy of 85.18% (CI 95: 82.45-87.64%).Automated CTP maps demonstrated high sensitivity and negative predictive value for LVOs and MeVOs, suggesting their usefulness as a rapid diagnostic tool, especially in settings without expert neuroradiologists.

  View details for DOI 10.1002/acn3.52207

  View details for PubMedID 39375881

• High Hypoperfusion Intensity Ratio Is Independently Associated with Very Poor Outcomes in Large Ischemic Core Stroke. Clinical neuroradiology Yedavalli, V., Adel Salim, H., Lakhani, D. A., Balar, A., Mei, J., Luna, L., Deng, F., Hyson, N. Z., Fiehler, J., Stracke, P., Broocks, G., Heitkamp, C., Albers, G. W., Wintermark, M., Faizy, T. D., Heit, J. J. 2024

  Abstract

  BACKGROUND: Recent advances have highlighted the efficacy of endovascular thrombectomy (EVT) in patients with large ischemic core stroke, yet asignificant portion still experience very poor outcomes, defined as a90-day modified Rankin Score (mRS) of 5-6. This study aims to investigate the hypoperfusion intensity ratio (HIR) as aprognostic imaging parameter for these outcomes.METHODS: In amulticenter retrospective cohort study, data from consecutive patients undergoing EVT for acute ischemic stroke with large vessel occlusion (AIS-LVO) at two comprehensive stroke centers were analyzed. The study included patients with an Alberta Stroke Program Early CT Score (ASPECTS) of5 or less and utilized pretreatment perfusion imaging to calculate HIR. The primary outcome was very poor outcomes (90days mRS 5-6).RESULTS: Among 102 patients included, 59 (57.8%) had very poor outcome (90days mRS 5-6). Multivariable logistic regression analysis adjusting for multiple covariates including admission National Institutes of Health Stroke Scale (NIHSS) and EVT revealed that higher admission NIHSS (adjusted odds ratio [aOR] 1.224, 95% CI 1.089-1.374, p =0.001) and HIR (aOR per 0.1 incremental change, 1.34, 95% CI 1.02-1.82, P =0.042) were independently associated with very poor outcomes.CONCLUSION: This study demonstrates that admission NIHSS and HIR are independently associated with very poor outcome (90days mRS 5-6) in patients with large ischemic core strokes. These findings highlight the importance of collateral status and perfusion imaging in predicting outcomes in this patient population, suggesting apotential role for HIR in the triage and management of large core stroke patients.

  View details for DOI 10.1007/s00062-024-01463-7

  View details for PubMedID 39373942

• Prediction of Ischemic Stroke Functional Outcomes from Acute-Phase Noncontrast CT and Clinical Information. Radiology Liu, Y., Yu, Y., Ouyang, J., Jiang, B., Ostmeier, S., Wang, J., Lu-Liang, S., Yang, Y., Yang, G., Michel, P., Liebeskind, D. S., Lansberg, M., Moseley, M. E., Heit, J. J., Wintermark, M., Albers, G., Zaharchuk, G. 2024; 313 (1): e240137

  Abstract

  Background Clinical outcome prediction based on acute-phase ischemic stroke data is valuable for planning health care resources, designing clinical trials, and setting patient expectations. Existing methods require individualized features and often involve manually engineered, time-consuming postprocessing activities. Purpose To predict the 90-day modified Rankin Scale (mRS) score with a deep learning (DL) model fusing noncontrast-enhanced CT (NCCT) and clinical information from the acute phase of stroke. Materials and Methods This retrospective study included data from six patient datasets from four multicenter trials and two registries. The DL-based imaging and clinical model was trained by using NCCT data obtained 1-7 days after baseline imaging and clinical data (age; sex; baseline and 24-hour National Institutes of Health Stroke Scale scores; and history of hypertension, diabetes, and atrial fibrillation). This model was compared with models based on either NCCT or clinical information alone. Model-specific mRS score prediction accuracy, mRS score accuracy within 1 point of the actual mRS score, mean absolute error (MAE), and performance in identifying unfavorable outcomes (mRS score, >2) were evaluated. Results A total of 1335 patients (median age, 71 years; IQR, 60-80 years; 674 female patients) were included for model development and testing through sixfold cross validation, with distributions of 979, 133, and 223 patients across training, validation, and test sets in each of the six cross-validation folds, respectively. The fused model achieved an MAE of 0.94 (95% CI: 0.89, 0.98) for predicting the specific mRS score, outperforming the imaging-only (MAE, 1.10; 95% CI: 1.05, 1.16; P < .001) and the clinical information-only (MAE, 1.00; 95% CI: 0.94, 1.05; P = .04) models. The fused model achieved an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.89, 0.92) for predicting unfavorable outcomes, outperforming the clinical information-only model (AUC, 0.88; 95% CI: 0.87, 0.90; P < .001) and the imaging-only model (AUC, 0.85; 95% CI: 0.84, 0.87; P < .001). Conclusion A fused DL-based NCCT and clinical model outperformed an imaging-only model and a clinical-information-only model in predicting 90-day mRS scores. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Lee in this issue.

  View details for DOI 10.1148/radiol.240137

  View details for PubMedID 39404632

• Early penumbral FLAIR changes predict tissue fate in patients with large vessel occlusions. International journal of stroke : official journal of the International Stroke Society Scheldeman, L., Seners, P., Wouters, A., Dupont, P., Christensen, S., Mlynash, M., Arquizan, C., Ter Schiphorst, A., Costalat, V., Henon, H., Bretzner, M., Albucher, J. F., Cognard, C., Olivot, J. M., Heit, J. J., Albers, G. W., Lansberg, M. G., Lemmens, R. 2024: 17474930241289235

  Abstract

  In patients with an acute ischemic stroke, the penumbra is defined as ischemic tissue that remains salvageable when reperfusion occurs. However, the expected clinical recovery congruent with penumbral salvage, is not always observed.We aimed to determine if the Magnetic Resonance Imaging (MRI) defined penumbra includes irreversible neuronal loss that impedes expected clinical recovery after reperfusion.In the prospective French Acute Multimodal Imaging Study to Select Patients for Mechanical Thrombectomy (FRAME) and an observational cohort of patients with large vessel occlusions undergoing endovascular treatment, we quantified penumbral integrity by FLAIR changes. We studied the influence of recanalization status on the evolution of penumbral FLAIR changes and studied penumbral FLAIR changes as predictor of tissue fate and functional outcome on the 90 days modified Rankin Scale (mRS).Recanalization status did not modify the evolution of rFLAIR signal intensity (SI) over time in the total cohort, but was associated with lower SI in the FRAME subset (b=-0.06, p for interaction=0.04). Median rFLAIR SI was higher at baseline in the subsequently infarcted penumbra compared to the salvaged (ratio=1.07, standard deviation [SD] 0.07 vs 1.03, SD 0.06 p<0.0001, n=150). The severity and extent of rFLAIR SI changes did not predict 90 day functional outcome in univariate (p=0.09) and multivariate logistic regression (p=0.4).Recanalization status did not influence the evolution of penumbral FLAIR changes. FLAIR SI changes in the baseline penumbra were associated with tissue fate, but not functional outcome.The data supporting the study are available upon reasonable request; following a signed data access agreement.

  View details for DOI 10.1177/17474930241289235

  View details for PubMedID 39315649

• Clinical and Imaging Features Associated With Fast Infarct Growth During Interhospital Transfers of Patients With Large Vessel Occlusions. Neurology Wouters, A., Seners, P., Yuen, N., Mlynash, M., Heit, J. J., Kemp, S., Demeestere, J., Christensen, S., Albers, G. W., Lemmens, R., Lansberg, M. G. 2024; 103 (6): e209814

  Abstract

  BACKGROUND AND OBJECTIVES: Acute ischemic stroke patients with a large vessel occlusion (LVO) who present to a primary stroke center (PSC) often require transfer to a comprehensive stroke center (CSC) for thrombectomy. Not much is known about specific characteristics at the PSC that are associated with infarct growth during transfer. Gaining more insight into these features could aid future trials with cytoprotective agents targeted at slowing infarct growth. We aimed to identify baseline clinical and imaging characteristics that are associated with fast infarct growth rate (IGR) during interhospital transfer.METHODS: We included patients from the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project, a prospective multicenter study. Patients with an anterior circulation LVO who were transferred from a PSC to a CSC for consideration of thrombectomy were eligible if imaging criteria were fulfilled. A CT perfusion (CTP) needed to be obtained at the PSC followed by an MRI at the CSC, before consideration of thrombectomy. The interhospital IGR was defined as the difference between the infarct volumes on MRI and CTP, divided by the time between the scans. Multivariable logistic regression was used to determine characteristics associated with fast IGR (≥5 mL/h).RESULTS: A total of 183 patients with a median age of 74 years (interquartile range 61-82), of whom 99 (54%) were male and 82 (45%) were fast progressors, were included. At baseline, fast progressors had a higher NIH Stroke Scale score (median 16 vs 13), lower cerebral blood volume index (median 0.80 vs 0.89), more commonly poor collaterals on CT angiography (35% vs 13%), higher hypoperfusion intensity ratios (HIRs) (median 0.51 vs 0.34), and larger core volumes (median 11.80 mL vs 0.00 mL). In multivariable analysis, higher HIR (adjusted odds ratio [aOR] for every 0.10 increase 1.32 [95% CI 1.10-1.59]) and larger core volume (aOR for every 10 mL increase 1.54 [95% CI 1.20-2.11]) remained independently associated with fast IGR.DISCUSSION: Fast infarct growth during interhospital transfer of acute stroke patients is associated with imaging markers of poor collaterals on baseline imaging. These markers are promising targets for patient selection in cytoprotective trials aimed at reducing interhospital infarct growth.

  View details for DOI 10.1212/WNL.0000000000209814

  View details for PubMedID 39173104

• Clinical and Perfusion Imaging Characteristics of Acute Large Vessel Occlusion in Intracranial Atherosclerosis: Clinical and Perfusion Imaging in ICAD-LVO. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Liu, H. Y., Heit, J. J., Yuen, N., Yang, C. H., Mlynash, M., Zamarud, A., Lun, R., Lansberg, M. G., Albers, G. W. 2024: 108024

  Abstract

  This study aimed to compare clinical and perfusion imaging profiles in acute ischemic stroke with large vessel occlusion (AIS-LVO) between patients with intracranial atherosclerotic disease (ICAD) and non-ICAD who underwent endovascular treatment (EVT).Data from AIS-LVO patients over the anterior circulation undergoing EVT across two stroke centers were retrospectively analyzed. Clinical profiles and perfusion parameters from automated processing of perfusion imaging were compared between ICAD and non-ICAD groups. Ischemic core was defined as relative cerebral blood flow < 30% on CT perfusion or apparent diffusion coefficient ≤ 620  ×  10-6 mm2/s on MR diffusion weighted imaging.A total of 111 patients were included (46 ICAD, 65 non-ICAD). The ICAD group exhibited a higher male proportion (60.9% vs. 35.4%), more M1 segment occlusions (78.3% vs. 56.9%), lower atrial fibrillation rates (17.4% vs. 63.1%), and lower baseline NIH Stroke Scale (NIHSS) scores (median [IQR]: 13 [8.75-18] vs. 15 [10-21]) at presentation compared to non-ICAD (all p< 0.05). However, there was no difference in NIHSS scores at discharge or in good functional outcomes (modified Rankin Scale 0-2) at 3 months between the two groups. ICAD patients also had smaller median ischemic core volumes (0 [IQR 0-9.7] vs. 4.4 [0-21.6] ml, p=0.038), smaller median Tmax >6s tissue volulmes (89.3 [IQR 51.1-147.1] vs. 124.4 [80.5-178.6] ml, p=0.017) and lower median HIR (hypoperfusion intensity ratio defined as Tmax >10s divided by Tmax >6s; 0.28 [IQR 0.09-0.42] vs. 0.44 [0.24-0.60], p=0.003). Higher baseline NIHSS scores correlated with larger Tmax >6s lesion volumes as well as higher HIR value in non-ICAD patients, but not in ICAD patients.In anterior circulation of AIS-LVO, ICAD patients exhibited distinct clinical presentations and perfusion imaging characteristics when compared to non-ICAD patients. Perfusion imaging profiles may serve as indicators for identifying ICAD patients before EVT.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2024.108024

  View details for PubMedID 39303867

• The single-phase CTA Clot Burden Score is independently associated with DSA ASITN collateral score. The British journal of radiology Lakhani, D. A., Balar, A. B., Koneru, M., Wen, S., Ozkara, B., Wang, R., Hoseinyazdi, M., Nabi, M., Mazumdar, I., Cho, A., Chen, K., Sepehri, S., Xu, R., Urrutia, V., Albers, G. W., Rai, A. T., Yedavalli, V. S. 2024

  Abstract

  The variation in quality and quantity of collateral status (CS) is in part responsible for a wide variability in extent of neural damage following acute ischemic stroke from large vessel occlusion (AIS-LVO). Single-phase CTA based Clot Burden Score (CBS) is a promising marker in estimating CS. The aim of this study is to assess the relationship of pretreatment CTA based CBS with the reference standard DSA based American Society of Interventional and Therapeutic Neuroradiology (ASITN) CS.In this retrospective study, inclusion criteria were as follows: a) Anterior circulation LVO confirmed on CTA from 9/1/2017 to 10/01/2023; b) diagnostic CTA; and c) underwent MT with documented DSA CS. Spearman's rank correlation analysis, multivariate logistic regression and ROC analysis was performed to assess the correlation of CTA CBS with DSA CS. p ≤ 0.05 was considered significant.292 consecutive patients (median age = 68 years; 56.2% female) met our inclusion criteria. CTA CBS and DSA CS showed significant positive correlation (ρ = 0.51, p < 0.001). On multivariate logistic regression analysis CBS was found to be independently associated with DSA CS (adjusted OR = 1.83, p < 0.001, 95% CI: 1.54-2.19), after adjusting for age, sex, race, hyperlipidemia, hypertension, diabetes, prior stroke or TIA, atrial fibrillation, premorbid mRS, admission NIH stroke scale, and ASPECTS. ROC analysis of CBS in predicting good DSA CS showed AUC of 0.76 (p < 0.001; 95%CI: 0.68-0.82). CBS threshold of > 6 has 84.6% sensitivity and 42.3% specificity in predicting good DSA CS.CTA CBS is independently associated with DSA CS and serves as a valuable supplementary tool for collateral status estimation. Further research is necessary to enhance our understanding of the role of CTA CBS in clinical decision-making for patients with AIS-LVO.CBS by indirectly estimating CS has shown to predict outcomes in AIS-LVO patients. No studies report association of CBS with reference standard DSA. In this study we further establish CBS as an independent marker of CS.

  View details for DOI 10.1093/bjr/tqae181

  View details for PubMedID 39235927

• Perfusion imaging for delayed cerebral ischemia detection in patients following ruptured aneurysmal subarachnoid hemorrhage: Interrater reliability assessment. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Bombardieri, A. M., Wouters, A., Seners, P., Zamarud, A., Mlynash, M., Yuen, N., Albers, G. W., Sussman, E. S., Pulli, B., Lansberg, M. G., Steinberg, G. K., Heit, J. J. 2024: 15910199241277953

  Abstract

  Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is associated with adverse neurological outcomes. Early and accurate diagnosis of DCI is crucial to prevent cerebral infarction. This study aimed to assess the diagnostic accuracy and interrater agreement of the visual assessment of neuroimaging perfusion maps to detect DCI in patients suspected of vasospasm after aSAH.In this case-control study, cases were adult aSAH patients with DCI who underwent magnetic resonance perfusion or computed tomography perfusion (CTP) imaging in the 24 h prior to digital subtraction angiography for vasospasm diagnosis. Controls were patients with dizziness and no aSAH on CTP imaging. Three independent raters, blinded to patients' clinical information, other neuroimaging studies, and angiographic results, visually assessed anonymized perfusion color maps to classify patients as either having DCI or not. Tmax delay was classified by symmetry into no delay, unilateral, or bilateral.Perfusion imaging of 54 patients with aSAH and 119 control patients without aSAH was assessed. Sensitivities for DCI diagnosis ranged from 0.65 to 0.78, and specificities ranged from 0.70 to 0.87, with interrater agreement ranging from 0.60 (moderate) to 0.68 (substantial).Visual assessment of perfusion color maps demonstrated moderate to substantial accuracy in diagnosing DCI in aSAH patients.

  View details for DOI 10.1177/15910199241277953

  View details for PubMedID 39219541

• Prolonged Venous Transit Is Associated With Lower Likelihood of Favorable Clinical Recovery in Reperfused Anterior Circulation Large-Vessel Occlusion Stroke STROKE-VASCULAR AND INTERVENTIONAL NEUROLOGY Yedavalli, V. S., Koneru, M., Balar, A. B., Lakhani, D. A., Cho, A., Wen, S., Mei, Y., Hoseinyazdi, M., Greene, C., Xu, R., Luna, L. P., Caplan, J. M., Dmytriw, A. A., Guenego, A., Heit, J. J., Albers, G. W., Wintermark, M., Gonzalez, L., Urrutia, V. C., Huang, J., Nael, K., Faizy, T. D., Leigh, R., Marsh, E. B., Hillis, A. E., Llinas, R. H. 2024; 4 (5)

  View details for DOI 10.1161/SVIN.124.001412

  View details for Web of Science ID 001304321900020

• Deep venous outflow as a surrogate for collaterals in late-window patients with successful revascularization from the DEFUSE 3 cohort. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Adusumilli, G., Faizy, T. D., Christensen, S., Mlynash, M., Loh, Y., Albers, G. W., Lansberg, M. G., Fiehler, J., Heit, J. J. 2024: 15910199241276905

  Abstract

  Deep venous outflow (VO) may be an important surrogate marker of collateral blood flow in acute ischemic stroke patients with a large vessel occlusion (AIS-LVO). Researchers have yet to determine the relationship between deep VO status in late-window patients and imaging measures of collaterals, which are key in preserving tissue.We performed a multicenter retrospective cohort study on a subset of DEFUSE 3 patients recruited across 38 centers between May 2016 and May 2017 who underwent successful thrombectomy revascularization. Internal cerebral vein opacification was scored on a scale of 0-2. This metric was added to the cortical vein opacification score to derive the comprehensive VO (CVO) score from 0 to 8. Patients were stratified by favorable (ICV+) and unfavorable (ICV-) ICV scores, and similarly CVO+ and CVO-. Analyses comparing outcomes were primarily conducted by Mann-Whitney U and χ2 tests.Forty-five patients from DEFUSE 3 were scored and dichotomized into CVO+, CVO-, ICV+, and ICV- categories, with comparable demographics. Hypoperfusion intensity ratio, a marker of tissue level collaterals, was significantly worse in the ICV- and CVO- groups (p = 0.005). ICV- alone was also associated with a larger perfusion lesion (138 ml vs 87 ml; p = 0.023). No significant differences were noted in functional and safety outcomes.Impaired deep venous drainage alone may be a marker of poor tissue level collaterals and a greater degree of affected tissue in AIS-LVO patients presenting in the late-window who subsequently undergo successful revascularization.

  View details for DOI 10.1177/15910199241276905

  View details for PubMedID 39194997

• Author Response: Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion NEUROLOGY Seners, P., Lansberg, M. G., Albers, G. W. 2024; 103 (4): e209507

  View details for DOI 10.1212/WNL.0000000000209507

  View details for Web of Science ID 001276786000001

  View details for PubMedID 39052966

• Decreased Quantitative Cerebral Blood Volume Is Associated With Poor Outcomes in Large Core Patients. Stroke Yedavalli, V., Salim, H. A., Mei, J., Lakhani, D. A., Balar, A., Musmar, B., Adeeb, N., Hoseinyazdi, M., Luna, L., Deng, F., Hyson, N. Z., Dmytriw, A. A., Guenego, A., Faizy, T. D., Heit, J. J., Albers, G. W., Lu, H., Urrutia, V. C., Nael, K., Marsh, E. B., Hillis, A. E., Llinas, R. 2024

  Abstract

  BACKGROUND: Recent large core trials have highlighted the effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke with large vessel occlusion. Variable perfusion-imaging thresholds and poor Alberta Stroke Program Early Computed Tomography Score reliability underline the need for more standardized, quantitative ischemia measures for MT patient selection. We aimed to identify the computed tomography perfusion parameter most strongly associated with poor outcomes in patients with acute ischemic stroke-large vessel occlusion with significant ischemic cores.METHODS: In this study from 2 comprehensive stroke centers from 2 comprehensive stroke centers within the Johns Hopkins Medical Enterprise (Johns Hopkins Hospita-East Baltimore and Bayview Medical Campus) from July 29, 2019 to January 29, 2023 in a continuously maintained database, we included patients with acute ischemic stroke-large vessel occlusion with ischemic core volumes defined as relative cerebral blood flow <30% and ≥50 mL on computed tomography perfusion or Alberta Stroke Program Early Computed Tomography Score <6. We used receiver operating characteristics to find the optimal cutoff for parameters like cerebral blood volume (CBV) <34%, 38%, 42%, and relative cerebral blood flow >20%, 30%, 34%, 38%, and time-to-maximum >4, 6, 8, and 10 seconds. The primary outcome was unfavorable outcomes (90-day modified Rankin Scale score 4-6). Multivariable models were adjusted for age, sex, diabetes, baseline National Institutes of Health Stroke Scale, intravenous thrombolysis, and MT.RESULTS: We identified 59 patients with large ischemic cores. A receiver operating characteristic curve analysis showed that CBV<42% ≥68 mL is associated with unfavorable outcomes (90-day modified Rankin Scale score 4-6) with an area under the curve of 0.90 (95% CI, 0.82-0.99) in the total and MT-only cohorts. Dichotomizing at this CBV threshold, patients in the ≥68 mL group exhibited significantly higher relative cerebral blood flow, time-to-maximum >8 and 10 seconds volumes, higher CBV volumes, higher HIR, and lower CBV index. The multivariable model incorporating CBV<42% ≥68 mL predicted poor outcomes robustly in both cohorts (area under the curve for MT-only subgroup was 0.87 [95% CI, 0.75-1.00]).CONCLUSIONS: CBV<42% ≥68 mL most effectively forecasts poor outcomes in patients with large-core stroke, confirming its value alongside other parameters like time-to-maximum in managing acute ischemic stroke-large vessel occlusion.

  View details for DOI 10.1161/STROKEAHA.124.047483

  View details for PubMedID 39185560

• Ischemic Core Volumes and Collateral Status have Diurnal Fluctuations - A Retrospective Cohort Study of 18,137 Patients. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lun, R., Sreekrishnan, A., Liu, H., Albers, G. W. 2024: 107965

  Abstract

  INTRODUCTION: Recent observations suggest that circadian rhythms are implicated in the timing of stroke onset and the speed of infarct progression. We aimed to replicate these observations in a large, multi-center, automated imaging database.METHODS: The RAPID Insights database was queried from 02/01/2016 to 01/31/2022 for patients with perfusion imaging and automated detection of an ischemic stroke due to a presumed large vessel occlusion. Exclusion criteria included: patient age ≤25, mismatch volume of <0 cc, and failure to register a positive value on either relative cerebral blood flow (rCBF) reduction of 38% less than normal or total mismatch volume. Imaging time was subdivided into three epochs: Night: 23:00h-06:59h and Day: 07:00h-14:59h, and Evening: 15:00h-22:59h. Perfusion parameters were defined using standard conventions for core volume, penumbra, and collateral circulation (measured via the Hypoperfusion Intensity Ratio, HIR). Statistical significance was tested using a sinusoidal regression analysis.RESULTS: A total of 18,137 cases were analyzed. The peak incidence of stroke imaging of patients with LVOs occurred around noon. A sinusoidal pattern was present, with larger ischemic core volumes and higher HIR during the night compared to the day: peak ischemic core volume of 23.4 cc occurred with imaging performed at 3:56 AM (p<0.001) and peak HIR of 0.35 at 3:40 AM (p<0.001).CONCLUSION: We found that ischemic core volumes were larger and collateral status worse at nighttime compared to daytime in this large national database. These findings support prior data suggesting that poor collateral recruitment with subsequent larger ischemic stroke volumes may occur at night.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2024.107965

  View details for PubMedID 39187216

• Simplifying venous outflow: Prolonged venous transit as a novel qualitative marker correlating with acute stroke outcomes. The neuroradiology journal Yedavalli, V. S., Lakhani, D. A., Koneru, M., Balar, A. B., Greene, C., Hoseinyazdi, M., Nabi, M., Lu, H., Xu, R., Luna, L., Caplan, J., Dmytriw, A. A., Guenego, A., Heit, J. J., Albers, G. W., Wintermark, M., Urrutia, V., Huang, J., Nael, K., Leigh, R., Marsh, E. B., Hillis, A. E., Llinas, R. H. 2024: 19714009241269475

  Abstract

  BACKGROUND: Prolonged venous transit (PVT), defined as presence of time-to-maximum ≥ 10 s within the superior sagittal sinus (SSS) and/or torcula, is a novel, qualitatively assessed computed tomography perfusion surrogate parameter of venous outflow with potential utility in pretreatment acute ischemic stroke imaging for neuroprognostication. We aim to characterize the correlation between PVT and neurological functional outcomes in thrombectomy-treated patients.METHODS: A prospectively-collected database of large vessel occlusion acute ischemic stroke patients treated with thrombectomy was retrospectively analyzed. Spearman's rank correlation coefficient and point-biserial correlations were performed between PVT status (i.e., no region, either SSS or torcula, or both), 90-day modified Rankin score (mRS), mortality (mRS 6), and poor functional outcome (mRS 4-6 vs 0-3).RESULTS: Of 128 patients, correlation between PVT and 90-day mRS (rho = 0.35, p < 0.0001), mortality (r = 0.26, p = 0.002), and poor functional outcome (r = 0.27, p = 0.002) were significant.CONCLUSION: There is a modest, significant correlation between PVT and severity of neurological functional outcome. Consequently, PVT is an easily-ascertained, qualitative metric that may be useful as an adjunct for anticipating a patient's clinical course. Future analyses will determine the significance of incorporating PVT in clinical decision-making.

  View details for DOI 10.1177/19714009241269475

  View details for PubMedID 39067016

• Neurological outcomes for patients meeting radiographic criteria for DEFUSE 3 and SELECT2. Journal of neurointerventional surgery Karamchandani, R. R., Satyanarayana, S., Yang, H., Strong, D., Rhoten, J., Clemente, J., Defilipp, G., Patel, N. M., Bernard, J., Stetler, W., Parish, J. M., Albers, G. W., Heit, J. J., Guzik, A. K., Wolfe, S. Q., Hines, A., Patel, H. N., Helms, A. M., Macko, L., Williams, L., Retelski, J., Asimos, A. W. 2024

  Abstract

  The DEFUSE 3 and SELECT2 thrombectomy trials included some patients with similar radiographic profiles, although the rates of good functional outcomes differed widely between the studies.To report neurological outcomes for patients who meet CT and CT perfusion (CTP) inclusion criteria common to both DEFUSE 3 and SELECT2.Retrospective study of thrombectomy patients, presenting between November 2016 and December 2023 to a large health system, with Alberta Stroke Program Early CT score ≥6, core infarction 50-69 mL, mismatch ratio ≥1.8, and mismatch volume ≥15 mL. The primary outcome was 90-day modified Rankin Scale score 0-2. A logistic regression analysis was performed to identify independent predictors of the primary outcome.85 patients, with mean age 64.6 (16.6) years and median National Institutes of Health Stroke Scale score 18 (15-23), were included. Thirty-eight of 85 patients (44.7%) were functionally independent at 90 days. Predictors of functional independence included age (OR=0.943, 95% CI 0.908 to 0.980; P=0.003), initial glucose (OR=0.989, 95% CI 0.978 to 1.000; P=0.044), and time last known well to skin puncture (OR=0.997, 95% CI 0.994 to 1.000; P=0.028). The area under the curve for the multivariable model predicting the primary outcome was 0.82 (95% CI 0.73 to 0.92).Nearly half of patients meeting radiographic criteria common to DEFUSE 3 and SELECT2 are functionally independent at 90 days, similar to rates reported for the treated DEFUSE 3 cohort. This might be due to their moderate core volumes and large ischemic penumbra.

  View details for DOI 10.1136/jnis-2024-021976

  View details for PubMedID 38969496

• Assessment of smoking care by stroke specialists in patients with recent TIA and minor stroke: an international prospective registry-based cohort study. BMJ open Lavallee, P., Charles, H., Labreuche, J., Albers, G. W., Caplan, L., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Molina, C. A., Rothwell, P., Steg, G., Touboul, P. J., Uchiyama, S., Vicaut, E., Wong, L. K., Amarenco, P. 2024; 14 (7): e078632

  Abstract

  The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA).The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study.From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort).Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model.Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080).In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.

  View details for DOI 10.1136/bmjopen-2023-078632

  View details for PubMedID 38960468

• Overestimation of the Ischemic Core Is Associated With Higher Core Lesion Volume and Degree of Reperfusion After Thrombectomy. Radiology Broocks, G., Meyer, L., Winkelmeier, L., Kniep, H., Heitkamp, C., Christensen, S., Lansberg, M. G., Thaler, C., Kemmling, A., Schön, G., Zeleňák, K., Stracke, P. C., Albers, G., Fiehler, J., Wintermark, M., Heit, J. J., Faizy, T. D. 2024; 312 (1): e231750

  Abstract

  Background CT perfusion (CTP)-derived baseline ischemic core volume (ICV) can overestimate the true extent of infarction, which may result in exclusion of patients with ischemic stroke from endovascular treatment (EVT). Purpose To determine whether ischemic core overestimation is associated with larger ICV and degree of recanalization. Materials and Methods This retrospective multicenter cohort study included patients with acute ischemic stroke triaged at multimodal CT who underwent EVT between January 2015 and January 2022. The primary outcome was ischemic core overestimation, which was assumed when baseline CTP-derived ICV was larger than the final infarct volume at follow-up imaging. The secondary outcome was functional independence defined as modified Rankin Scale scores of 0-2 90 days after EVT. Successful vessel recanalization was defined as extended Thrombolysis in Cerebral Infarction score of 2b or higher. Categorical variables were compared between patients with ICV of 50 mL or less versus large ICV greater than 50 mL with use of the χ2 test. Adjusted multivariable logistic regression analyses were used to assess the primary and secondary outcomes. Results In total, 721 patients (median age, 76 years [IQR, 64-83 years]; 371 female) were included, of which 162 (22%) demonstrated ischemic core overestimation. Core overestimation occurred more often in patients with ICV greater than 50 mL versus 50 mL or less (48% vs 16%; P < .001) and those with successful versus unsuccessful vessel recanalization (26% vs 13%; P < .001). In an adjusted model, successful recanalization after EVT (odds ratio [OR], 3.14 [95% CI: 1.65, 5.95]; P < .001) and larger ICV (OR, 1.03 [95% CI: 1.02, 1.04]; P < .001) were independently associated with core overestimation, while the time from symptom onset to imaging showed no association (OR, 0.99; P = .96). Core overestimation was independently associated with functional independence (adjusted OR, 2.83 [95% CI: 1.66, 4.81]; P < .001) after successful recanalization. Conclusion Ischemic core overestimation occurred more frequently in patients presenting with large CTP-derived ICV and successful vessel recanalization compared with those with unsuccessful recanalization. © RSNA, 2024 Supplemental material is available for this article.

  View details for DOI 10.1148/radiol.231750

  View details for PubMedID 39078297

• Acute myocardial infarction and ischaemic stroke: differences and similarities in reperfusion therapies-a review. European heart journal Scheldeman, L., Sinnaeve, P., Albers, G. W., Lemmens, R., Van de Werf, F. 2024

  Abstract

  Acute ST-elevation myocardial infarction (STEMI) and acute ischaemic stroke (AIS) share a number of similarities. However, important differences in pathophysiology demand a disease-tailored approach. In both conditions, fast treatment plays a crucial role as ischaemia and eventually infarction develop rapidly. Furthermore, in both fields, the introduction of fibrinolytic treatments historically preceded the implementation of endovascular techniques. However, in contrast to STEMI, only a minority of AIS patients will eventually be considered eligible for reperfusion treatment. Non-invasive cerebral imaging always precedes cerebral angiography and thrombectomy, whereas coronary angiography is not routinely preceded by non-invasive cardiac imaging in patients with STEMI. In the late or unknown time window, the presence of specific patterns on brain imaging may help identify AIS patients who benefit most from reperfusion treatment. For STEMI, a uniform time window for reperfusion up to 12 h after symptom onset, based on old placebo-controlled trials, is still recommended in guidelines and generally applied. Bridging fibrinolysis preceding endovascular treatment still remains the mainstay of reperfusion treatment in AIS, while primary percutaneous coronary intervention is the strategy of choice in STEMI. Shortening ischaemic times by fine-tuning collaboration networks between ambulances, community hospitals, and tertiary care hospitals, optimizing bridging fibrinolysis, and reducing ischaemia-reperfusion injury are important topics for further research. The aim of this review is to provide insights into the common as well as diverging pathophysiology behind current reperfusion strategies and to explore new ways to enhance their clinical benefit.

  View details for DOI 10.1093/eurheartj/ehae371

  View details for PubMedID 38941344

• Projections of Endovascular Therapy-Eligible Patients With Stroke for the US Population. Stroke Mistry, E. A., Khoury, J. C., Kleindorfer, D. O., Kissela, B. M., Alwell, K. S., Jasne, A. S., Ferioli, S., De Los Rios La Rosa, F., Coleman, E., Demel, S. L., Walsh, K. B., Slavin, S. J., Star, M., Haverbusch, M., Mackey, J., Woo, D., Aziz, Y. N., Heldner, M. R., Fischer, U., Jadhav, A. P., Jovin, T. G., Albers, G. W., Nogueira, R. G., Khatri, P. 2024

  Abstract

  As stroke endovascular thrombectomy (EVT) treatment indications expand, understanding population-based EVT eligibility becomes critical for resource planning. We aimed to project current and future population-based EVT eligibility in the United States.We conducted a post hoc analysis of the physician-adjudicated GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study; 2015 epoch), a population-based, cross sectional, observational study of stroke incidence, treatment, and outcomes across a 5-county region. All hospitalized patients ≥18 years of age with acute ischemic stroke were ascertained using the International Classification of Diseases, Ninth Revision codes 430-436 and Tenth Revision codes I60-I67 and G45-G46 and extrapolated to the US adult census 2020. We determined the rate of EVT eligibility within the GCNKSS population using time from last known well to presentation (0-5 versus 5-23 hours), presenting National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale. Both conservative and liberal estimates of prevalence of large vessel occlusion and large core were then applied based on literature review (unavailable within the 2015 GCNKSS). This eligibility was then extrapolated to the 2020 US population.Of the 1 057 183 adults within GCNKSS in 2015, 2741 had an ischemic stroke and 2176 had data available for analysis. We calculated that 8659 to 17 219 patients (conservative to liberal) meet the current guideline-recommended EVT criteria (nonlarge core, no prestroke disability, and National Institutes of Health Stroke Scale score ≥6) in the United States. Estimates (conservative to liberal) for expanded EVT eligibility subpopulations include (1) 5316 to 10 635 by large core; (2) 10 635 to 21 270 by mild presenting deficits with low National Institutes of Health Stroke Scale score; (3) 13 572 to 27 089 by higher prestroke disability; and (4) 7039 to 14 180 by >1 criteria. These expanded eligibility subpopulations amount to 36 562 to 73 174 patients.An estimated 8659 to 17 219 adult patients in the United States met strict EVT eligibility criteria in 2020. A 4-fold increase in population-based EVT eligibility can be anticipated with incremental adoption of recent or future positive trials. US stroke systems need to be rapidly optimized to handle all EVT-eligible patients with stroke.

  View details for DOI 10.1161/STROKEAHA.123.045766

  View details for PubMedID 38934124

• Advancing diagnostic precision of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: The potential for a vasospasm index score on perfusion imaging to detect vasospasm. European journal of radiology Maria Bombardieri, A., Seners, P., Wouters, A., Zamarud, A., Mlynash, M., Yuen, N., Albers, G. W., Sussman, E. S., Pulli, B., Lansberg, M. G., Steinberg, G. K., Heit, J. J. 2024; 178: 111578

  Abstract

  The occurrence of delayed cerebral ischemia and vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in high morbidity and mortality, but the diagnosis remains challenging. This study aimed to identify neuroimaging perfusion parameters indicative of delayed cerebral ischemia in patients with suspected vasospasm.This is a case-control study. Cases were adult aSAH patients who underwent magnetic resonance perfusion or computed tomography perfusion (CTP) imaging ≤ 24 h before digital subtraction angiography performed for vasospasm diagnosis and treatment. Controls were patients without aSAH who underwent CTP. Quantitative perfusion parameters at different thresholds, including Tmax 4-6-8-10 s delay, cerebral blood flow and cerebral blood volume were measured and compared between cases and controls. The Vasospasm Index Score was calculated as the ratio of brain volume with time-to-max (Tmax) delay > 6 s over volume with Tmax > 4 s.54 patients with aSAH and 119 controls without aSAH were included. Perfusion parameters with the strongest prediction of vasospasm on cerebral angiography were the combination of the Vasospasm Index Score (Tmax6/Tmax4) + CBV ≤ 48 % (area under the curve value of 0.85 [95 % CI 0.78-0.91]) with a sensitivity of 63 % and specificity of 95 %.The Vasospasm Index Score in combination with CBV ≤ 48 % on cerebral perfusion imaging reliably identified vasospasm as the cause of DCI on perfusion imaging.

  View details for DOI 10.1016/j.ejrad.2024.111578

  View details for PubMedID 38981177

• Predictors of Futile Recanalization in Ischemic Stroke Patients with low baseline NIHSS. International journal of stroke : official journal of the International Stroke Society Heitkamp, C., Heitkamp, A., Winkelmeier, L., Thaler, C., Flottmann, F., Schell, M., Kniep, H., Broocks, G., Heit, J. J., Albers, G. W., Thomalla, G., Fiehler, J., Faizy, T. D. 2024: 17474930241264737

  Abstract

  There is yet no randomized controlled evidence that mechanical thrombectomy (MT) is superior to best medical treatment in patients with large vessel occlusion but minor stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] <6). Prior studies of patients with admission NIHSS scores >6 observed unfavorable functional outcomes despite successful recanalization, commonly termed as futile recanalization (FR), in up to 50% of cases.The aim of this study is to determine the prevalence of FR in patients with minor stroke and identify associated patient-specific risk factors.Our multicenter cohort study screened all patients prospectively enrolled in the German Stroke Registry Endovascular Treatment from 2015 to 2021 (n=13082). Included were patients who underwent MT for anterior circulation vessel occlusion with a baseline NIHSS score of <6 and successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3). FR was defined by a modified Rankin Scale (mRS) score of 2-6 at 90 days. Multivariable logistic regression analysis was conducted to explore factors associated with FR.A total of 674 patients met the inclusion criteria. FR occurred in 268 (40%) patients. Multivariable logistic regression analysis indicates that higher age (adjusted odds ratio: 1.04 [95% confidence interval: 1.02-1.06]), pre-stroke mRS 1 (aOR: 2.70 [1.51-4.84]), transfer from admission hospital to comprehensive stroke center (aOR: 1.67 [1.08-2.56]), longer time from symptom onset/last seen well to admission (aOR: 1.02 [1.00-1.04]), MT under general anesthesia (aOR: 1.78 [1.13-2.82]), higher NIHSS after 24 hours (aOR: 1.09 [1.05-1.14]), and symptomatic intracranial hemorrhage (aOR: 16.88 [2.03-140.14]) increased the odds of FR. There was no significant difference in primary outcome between achieving mTICI 2b or 3.Unfavorable functional outcomes despite successful vessel recanalization were frequent in acute ischemic stroke patients with low NIHSS scores on admission. We provide patient-specific risk factors that indicate an increased risk of FR and should be considered when treating patients with minor stroke.The data that support the findings of our study are available on reasonable request after approval of the GSR steering committee.

  View details for DOI 10.1177/17474930241264737

  View details for PubMedID 38888031

• Exploring the Limits of Endovascular Therapy for Large Core Patients: Where Do We Need More Data? Stroke Albers, G. W., Heit, J. J., Lansberg, M. G., Inoue, M., Huo, X., Yedavalli, V. S., Seners, P., McCullough-Hicks, M., Cereda, C. W., Tsai, J. P., Mistry, E. A., Chatterjee, A. R., Derdeyn, C. P., Khatri, P., Olivot, J. M., Hill, M. D., Saver, J. L., Fisher, M. 2024

  View details for DOI 10.1161/STROKEAHA.124.047228

  View details for PubMedID 38836345

• Lower admission stroke severity is associated with good collateral status in distal medium vessel occlusion stroke. Journal of neuroimaging : official journal of the American Society of Neuroimaging Mei, J., Salim, H. A., Lakhani, D. A., Balar, A., Musmar, B., Adeeb, N., Hoseinyazdi, M., Luna, L., Deng, F., Hyson, N. Z., Dmytriw, A. A., Guenego, A., Faizy, T. D., Heit, J. J., Albers, G. W., Urrutia, V. C., Llinas, R., Marsh, E. B., Hillis, A. E., Nael, K., Yedavalli, V. S. 2024

  Abstract

  BACKGROUND AND PURPOSE: Distal medium vessel occlusions (DMVOs) are a significant contributor to acute ischemic stroke (AIS), with collateral status (CS) playing a pivotal role in modulating ischemic damage progression. We aimed to explore baseline characteristics associated with CS in AIS-DMVO.METHODS: This retrospective analysis of a prospectively collected database enrolled 130 AIS-DMVO patients from two comprehensive stroke centers. Baseline characteristics, including patient demographics, admission National Institutes of Health Stroke Scale (NIHSS) score, admission Los Angeles Motor Scale (LAMS) score, and co-morbidities, including hypertension, hyperlipidemia, diabetes, coronary artery disease, atrial fibrillation, and history of transient ischemic attack or stroke, were collected. The analysis was dichotomized to good CS, reflected by hypoperfusion index ratio (HIR) <.3, versus poor CS, reflected by HIR ≥.3.RESULTS: Good CS was observed in 34% of the patients. As to the occluded location, 43.8% occurred in proximal M2, 16.9% in mid M2, 35.4% in more distal middle cerebral artery, and 3.8% in distal anterior cerebral artery. In multivariate logistic analysis, a lower NIHSS score and a lower LAMS score were both independently associated with a good CS (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.82-0.95, p<.001 and OR: 0.77, 95% CI: 0.62-0.96, p=.018, respectively). Patients with poor CS were more likely to manifest as moderate to severe stroke (29.1% vs. 4.5%, p<.001), while patients with good CS had a significantly higher chance of having a minor stroke clinically (40.9% vs. 12.8%, p<.001).CONCLUSIONS: CS remains an important determinant in the severity of AIS-DMVO. Collateral enhancement strategies may be a worthwhile pursuit in AIS-DMVO patients with more severe initial stroke presentation, which can be swiftly identified by the concise LAMS and serves as a proxy for underlying poor CS.

  View details for DOI 10.1111/jon.13208

  View details for PubMedID 38797931

• Arterial Recanalization During Interhospital Transfer for Thrombectomy. Stroke Seners, P., Wouters, A., Ter Schiphorst, A., Yuen, N., Mlynash, M., Arquizan, C., Heit, J. J., Kemp, S., Christensen, S., Sablot, D., Wacongne, A., Lalu, T., Costalat, V., Lansberg, M. G., Albers, G. W. 2024

  Abstract

  Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes.We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis.Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; Ptrend<0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; Ptrend<0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization.Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes.

  View details for DOI 10.1161/STROKEAHA.124.046694

  View details for PubMedID 38752736

• The Los Angeles motor scale (LAMS) is independently associated with CT perfusion collateral status markers. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Lakhani, D. A., Mehta, T. R., Balar, A. B., Koneru, M., Wen, S., Ozkara, B. B., Caplan, J., Dmytriw, A. A., Wang, R., Lu, H., Hoseinyazdi, M., Nabi, M., Mazumdar, I., Cho, A., Chen, K., Sepehri, S., Hyson, N., Xu, R., Urrutia, V., Luna, L., Hillis, A. H., Heit, J. J., Albers, G. W., Rai, A. T., Faizy, T. D., Wintermark, M., Nael, K., Yedavalli, V. S. 2024; 125: 32-37

  Abstract

  The Los Angeles Motor Scale (LAMS) is an objective tool that has been used to rapidly assess and predict the presence of large vessel occlusion (LVO) in the pre-hospital setting successfully in several studies. However, studies assessing the relationship between LAMS score and CT perfusion collateral status (CS) markers such as cerebral blood volume (CBV) index, and hypoperfusion intensity ratio (HIR) are sparse. Our study therefore aims to assess the association of admission LAMS score with established CTP CS markers CBV Index and HIR in AIS-LVO cases.In this prospectively collected, retrospectively reviewed analysis, inclusion criteria were as follows: a) CT angiography (CTA) confirmed anterior circulation LVO from 9/1/2017 to 10/01/2023, and b) diagnostic CT perfusion (CTP). Logistic regression analysis was performed to assess the relationship between admission LAMS with CTP CS markers HIR and CBV Index. p ≤ 0.05 was considered significant.In total, 285 consecutive patients (median age = 69 years; 56 % female) met our inclusion criteria. Multivariable logistic regression analysis adjusting for sex, age, ASPECTS, tPA, premorbid mRS, admission NIH stroke scale, prior history of TIA, stroke, atrial fibrillation, diabetes mellitus, hyperlipidemia, coronary artery disease and hypertension, admission LAMS was found to be independently associated with CBV Index (adjusted OR:0.82, p < 0.01), and HIR (adjusted OR:0.59, p < 0.05).LAMS is independently associated with CTP CS markers, CBV index and HIR. This finding suggests that LAMS may also provide an indirect estimate of CS.

  View details for DOI 10.1016/j.jocn.2024.05.005

  View details for PubMedID 38735251

• Tenecteplase for Stroke at 4.5 to 24 Hours. Reply. The New England journal of medicine Albers, G. W., Purdon, B., Campbell, B. C. 2024; 390 (18): 1729

  View details for DOI 10.1056/NEJMc2403602

  View details for PubMedID 38718370

• Low Cerebral Blood Volume Index, Thrombectomy, and Prior Stroke Are Independently Associated With Hemorrhagic Transformation in Medium-Vessel Occlusion Ischemic Stroke STROKE-VASCULAR AND INTERVENTIONAL NEUROLOGY Yedavalli, V. S., Koneru, M., Hoseinyazdi, M., Marsh, E. B., Llinas, R. H., Urrutia, V., Leigh, R., Gonzalez, L., Xu, R., Caplan, J., Huang, J., Lu, H., Wintermark, M., Dmytriw, A. A., Guenego, A., Albers, G. W., Luna, L., Heit, J. J., Nael, K., Hillis, A. E. 2024; 4 (3)

  View details for DOI 10.1161/SVIN.123.001250

  View details for Web of Science ID 001215306400021

• CT Perfusion Derived rCBV < 42% Lesion Volume Is Independently Associated with Followup FLAIR Infarct Volume in Anterior Circulation Large Vessel Occlusion. Diagnostics (Basel, Switzerland) Lakhani, D. A., Balar, A. B., Salim, H., Koneru, M., Wen, S., Ozkara, B., Lu, H., Wang, R., Hoseinyazdi, M., Xu, R., Nabi, M., Mazumdar, I., Cho, A., Chen, K., Sepehri, S., Hyson, N., Urrutia, V., Luna, L., Hillis, A. E., Heit, J. J., Albers, G. W., Rai, A. T., Dmytriw, A. A., Faizy, T. D., Wintermark, M., Nael, K., Yedavalli, V. S. 2024; 14 (8)

  Abstract

  Pretreatment CT Perfusion (CTP) parameter rCBV < 42% lesion volume has recently been shown to predict 90-day mRS. In this study, we aim to assess the relationship between rCBV < 42% and a radiographic follow-up infarct volume delineated on FLAIR images. In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 9 January 2017 and 10 January 2023. Follow-up FLAIR imaging was used to determine the final infarct volume. Student t, Mann-Whitney-U, and Chi-Square tests were used to assess differences. Spearman's rank correlation and linear regression analysis were used to assess associations between rCBV < 42% and follow-up infarct volume on FLAIR. In total, 158 patients (median age: 68 years, 52.5% female) met our inclusion criteria. rCBV < 42% (ρ = 0.56, p < 0.001) significantly correlated with follow-up-FLAIR infarct volume. On multivariable linear regression analysis, rCBV < 42% lesion volume (beta = 0.60, p < 0.001), ASPECTS (beta = -0.214, p < 0.01), mTICI (beta = -0.277, p < 0.001), and diabetes (beta = 0.16, p < 0.05) were independently associated with follow-up infarct volume. The rCBV < 42% lesion volume is independently associated with FLAIR follow-up infarct volume.

  View details for DOI 10.3390/diagnostics14080845

  View details for PubMedID 38667490

• Clinical Change During Inter-Hospital Transfer For Thrombectomy: Incidence, Associated Factors and Relationship With Outcome. International journal of stroke : official journal of the International Stroke Society Seners, P., Ter Schiphorst, A., Wouters, A., Yuen, N., Mlynash, M., Arquizan, C., Heit, J. J., Kemp, S., Christensen, S., Sablot, D., Wacongne, A., Lalu, T., Costalat, V., Albers, G. W., Lansberg, M. G. 2024: 17474930241246952

  Abstract

  Patients with acute ischemic stroke with a large vessel occlusion (LVO) admitted to non endovascular-capable centers often require inter-hospital transfer for thrombectomy. We aimed to describe the incidence of substantial clinical change during transfer, the factors associated with clinical change, and its relationship with 3-month outcome.We analyzed data from two cohorts of acute stroke patients transferred for thrombectomy to a comprehensive center (Stanford, USA, Nov 2019 to Jan 2023; Montpellier, France, Jan 2015 to Jan 2017), regardless of whether thrombectomy was eventually attempted. Patients were included if they had evidence of an LVO at the referring hospital and had an NIHSS score documented before and immediately after transfer. Inter-hospital clinical change was categorized as improvement (>=4 points and >=25% decrease between the NIHSS score in the referring hospital and upon comprehensive center arrival), deterioration (>=4 points and >=25% increase), or stability (neither improvement nor deterioration). The stable group was considered as the reference, and was compared to the improvement or deterioration groups separately.A total of 504 patients were included, of whom 22% experienced inter-hospital improvement, 14% deterioration, and 64% were stable. Pre-transfer variables independently associated with clinical improvement were intravenous thrombolysis use, more distal occlusions, and lower serum glucose; variables associated with deterioration included more proximal occlusions and higher serum glucose. On post-transfer imaging, clinical improvement was associated with arterial recanalization and smaller infarct growth; and deterioration with larger infarct growth. As compared to stable patients, those with clinical improvement had better 3-month functional outcome (adjusted cOR=2.43; 95%CI 1.59-3.71; P<0.001), while those with deterioration had worse outcome (adjusted cOR=0.60; 95%CI 0.37-0.98; P=0.044).Substantial inter-hospital clinical changes are frequently observed in LVO-related ischemic strokes, with significant impact on functional outcome. There is a need to develop treatments that improves the clinical status during transfer.

  View details for DOI 10.1177/17474930241246952

  View details for PubMedID 38576067

• CT perfusion based rCBF <38% volume is independently and negatively associated with digital subtraction angiography collateral score in anterior circulation large vessel occlusions. The neuroradiology journal Lakhani, D. A., Balar, A. B., Koneru, M., Wen, S., Ozkara, B. B., Wang, R., Hoseinyazdi, M., Nabi, M., Mazumdar, I., Cho, A., Chen, K., Sepehri, S., Hyson, N., Xu, R., Urrutia, V., Luna, L., Hillis, A. E., Heit, J. J., Albers, G. W., Rai, A. T., Yedavalli, V. S. 2024: 19714009241242639

  Abstract

  BACKGROUND: Collateral status (CS) is an important biomarker of functional outcomes in patients with acute ischemic stroke secondary to large vessel occlusion (AIS-LVO). Pretreatment CT perfusion (CTP) parameters serve as reliable surrogates of collateral status (CS). In this study, we aim to assess the relationship between the relative cerebral blood flow less than 38% (rCBF <38%), with the reference standard American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score (CS) on DSA.METHODS: In this prospectively collected, retrospectively reviewed analysis, inclusion criteria were as follows: (a) CT angiography (CTA) confirmed anterior circulation large vessel occlusion from 9/1/2017 to 10/01/2023; (b) diagnostic CT perfusion; and (c) underwent mechanical thrombectomy with documented ASITN CS. The ratios of the CTP-derived CBF values were calculated by dividing the values of the ischemic lesion by the corresponding values of the contralateral normal region (which were defined as rCBF). Spearman's rank correlation and logistic regression analysis were performed to determine the relationship of rCBF <38% lesion volume with DSA ASITN CS. p ≤ .05 was considered significant.RESULTS: In total, 223 patients [mean age: 67.77 ± 15.76 years, 56.1% (n = 125) female] met our inclusion criteria. Significant negative correlation was noted between rCBF <38% volume and DSA CS (rho = -0.37, p < .001). On multivariate logistic regression analysis, rCBF <38% volume was found to be independently associated with worse ASITN CS (unadjusted OR: 3.03, 95% CI: 1.60-5.69, p < .001, and adjusted OR: 2.73, 95% CI: 1.34-5.50, p < .01).CONCLUSION: Greater volume of tissue with rCBF <38% is independently associated with better DSA CS. rCBF <38% is a useful adjunct tool in collateralization-based prognostication. Future studies are needed to expand our understanding of the role of rCBF <38% within the decision-making in patients with AIS-LVO.

  View details for DOI 10.1177/19714009241242639

  View details for PubMedID 38528780

• Follow-up infarct volume on fluid attenuated inversion recovery (FLAIR)imaging in distal medium vessel occlusions: the role of cerebral blood volume index. Journal of neurology Salim, H., Lakhani, D. A., Balar, A., Musmar, B., Adeeb, N., Hoseinyazdi, M., Luna, L., Deng, F., Hyson, N. Z., Mei, J., Dmytriw, A. A., Guenego, A., Faizy, T. D., Heit, J. J., Albers, G. W., Urrutia, V. C., Llinas, R., Marsh, E. B., Hillis, A. E., Nael, K., Yedavalli, V. 2024

  Abstract

  BACKGROUND: Distal medium vessel occlusions (DMVOs) contribute substantially to the incidence of acute ischemic strokes (AIS) and pose distinct challenges in clinical management and prognosis. Neuroimaging techniques, such as Fluid Attenuation Inversion Recovery (FLAIR) imaging and cerebral blood volume (CBV) index derived from perfusion imaging, have significantly improved our ability to assess the impact of strokes and predict their outcomes. The primary objective of this study was to investigate relationship between follow-up infarct volume (FIV) as assessed by FLAIR imaging in patients with DMVOs.METHODS: This prospectively collected, retrospective reviewed cohort study included patients from two comprehensive stroke centers within the Johns Hopkins Medical Enterprise, spanning August 2018-October 2022. The cohort consisted of adults with AIS attributable to DMVO. Detailed imaging analyses were conducted, encompassing non-contrast CT, CT angiography (CTA), CT perfusion (CTP), and FLAIR imaging. Univariable and multivariable linear regression models were employed to assess the association between different factors and FIV.RESULTS: The study included 79 patients with DMVO stroke with a median age of 69years (IQR, 62-77years), and 57% (n=45) were female. There was a negative correlation between the CBV index and FIV in a univariable linear regression analysis (Beta=-16; 95% CI, -23 to -8.3; p<0.001) and a multivariable linear regression model (Beta=-9.1 per 0.1 change; 95% CI, -15 to -2.7; p=0.006). Diabetes was independently associated with larger FIV (Beta=46; 95% CI, 16 to 75; p=0.003). Additionally, a higher baseline ASPECTS was associated with lower FIV (Beta=-30; 95% CI, -41 to -20; p<0.001).CONCLUSION: Our findings underscore the CBV index as an independent association with FIV in DMVOs, which highlights the critical role of collateral circulation in determining stroke outcomes in this patient population. In addition, our study confirms a negative association of ASPECTS with FLAIR FIV and identifies diabetes as independent factor associated with larger FIV. These insights pave the way for further large-scale, prospective studies to corroborate these findings, thereby refining the strategies for stroke prognostication and management.

  View details for DOI 10.1007/s00415-024-12279-3

  View details for PubMedID 38507075

• Stroke in the Time of Circadian Medicine. Circulation research Mergenthaler, P., Balami, J. S., Neuhaus, A. A., Mottahedin, A., Albers, G. W., Rothwell, P. M., Saver, J. L., Young, M. E., Buchan, A. M. 2024; 134 (6): 770-790

  Abstract

  Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying stroke onset or tolerance as well as in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, and inflammation/immunity. Furthermore, we present clinical evidence supporting the link between disrupted circadian rhythms and increased susceptibility to stroke and dementia. We propose that circadian regulation of biochemical and physiological pathways in the brain increase susceptibility to damage after stroke in sleep and attenuate treatment effectiveness during the active phase. This review underscores the importance of considering circadian biology for understanding the pathology and treatment choice for stroke and vascular dementia and speculates that considering a patient's chronotype may be an important factor in developing precision treatment following stroke.

  View details for DOI 10.1161/CIRCRESAHA.124.323508

  View details for PubMedID 38484031

• Prolonged venous transit on perfusion imaging is associated with higher odds of mortality in successfully reperfused patients with large vessel occlusion stroke. Journal of neurointerventional surgery Yedavalli, V. S., Koneru, M., Hoseinyazdi, M., Greene, C., Lakhani, D. A., Xu, R., Luna, L. P., Caplan, J. M., Dmytriw, A. A., Guenego, A., Heit, J. J., Albers, G. W., Wintermark, M., Gonzalez, L. F., Urrutia, V. C., Huang, J., Nael, K., Leigh, R., Marsh, E. B., Hillis, A. E., Llinas, R. H. 2024

  Abstract

  Poor venous outflow (VO) profiles are associated with unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO), despite achieving successful reperfusion. The objective of this study is to assess the association between mortality and prolonged venous transit (PVT), a novel visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps.We performed a retrospective analysis of prospectively collected data from consecutive adult patients with AIS-LVO with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s timing on CTP Tmax maps in at least one of the following: superior sagittal sinus (proximal venous drainage) and/or torcula (deep venous drainage). PVT- was defined as lacking this in both regions. The primary outcome was mortality at 90 days. In a 1:1 propensity score-matched cohort, regressions were performed to determine the effect of PVT on 90-day mortality.In 127 patients of median (IQR) age 71 (64-81) years, mortality occurred in a significantly greater proportion of PVT+ patients than PVT- patients (32.5% vs 12.6%, P=0.01). This significant difference persisted after matching (P=0.03). PVT+ was associated with a significantly increased likelihood of 90-day mortality (OR 1.22 (95% CI 1.02 to 1.46), P=0.03) in the matched cohort.PVT+ was significantly associated with 90-day mortality despite successful reperfusion therapy in patients with AIS-LVO. PVT is a simple VO profile marker with potential as an adjunctive metric during acute evaluation of AIS-LVO patients. Future studies will expand our understanding of using PVT in the evaluation of patients with AIS-LVO.

  View details for DOI 10.1136/jnis-2024-021488

  View details for PubMedID 38471762

• Clinical relevance of intracranial hemorrhage after thrombectomy versus medical management for large core infarct: a secondary analysis of the SELECT2 randomized trial. Journal of neurointerventional surgery Chen, M., Joshi, K. C., Kolb, B., Sitton, C. W., Pujara, D. K., Abraham, M. G., Ortega-Gutierrez, S., Kasner, S. E., Hussain, S. M., Churilov, L., Blackburn, S., Sundararajan, S., Hu, Y. C., Herial, N., Arenillas, J. F., Tsai, J. P., Budzik, R. F., Hicks, W., Kozak, O., Yan, B., Cordato, D., Manning, N. W., Parsons, M., Hanel, R. A., Aghaebrahim, A., Wu, T., Cardona Portela, P., Gandhi, C. D., Al-Mufti, F., Perez de la Ossa, N., Schaafsma, J., Blasco, J., Sangha, N., Warach, S., Kleinig, T. J., Johns, H., Shaker, F., Abdulrazzak, M. A., Ray, A., Sunshine, J., Opaskar, A., Duncan, K. R., Xiong, W., Al-Shaibi, F. K., Samaniego, E. A., Nguyen, T. N., Fifi, J. T., Tjoumakaris, S. I., Jabbour, P., Mendes Pereira, V., Lansberg, M. G., Sila, C., Bambakidis, N. C., Davis, S., Wechsler, L., Albers, G. W., Grotta, J. C., Ribo, M., Hassan, A. E., Campbell, B., Hill, M. D., Sarraj, A. 2024

  Abstract

  The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized.SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined.Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3-6) vs 4 (3-6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (Pinteraction=0.77).ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

  View details for DOI 10.1136/jnis-2023-021219

  View details for PubMedID 38471760

• The Relative Cerebral Blood Volume (rCBV) < 42% Is Independently Associated with Collateral Status in Anterior Circulation Large Vessel Occlusion. Journal of clinical medicine Lakhani, D. A., Balar, A. B., Koneru, M., Wen, S., Ozkara, B. B., Lu, H., Wang, R., Hoseinyazdi, M., Mei, J., Xu, R., Nabi, M., Mazumdar, I., Cho, A., Chen, K., Sepehri, S., Hyson, N., Urrutia, V., Luna, L., Hillis, A. E., Heit, J. J., Albers, G. W., Rai, A. T., Dmytriw, A. A., Faizy, T., Wintermark, M., Nael, K., Yedavalli, V. S. 2024; 13 (6)

  Abstract

  Background: The pretreatment CT perfusion (CTP) marker the relative cerebral blood volume (rCBV) < 42% lesion volume has recently been shown to predict 90-day functional outcomes; however, studies assessing correlations of the rCBV < 42% lesion volume with other outcomes remain sparse. Here, we aim to assess the relationship between the rCBV < 42% lesion volume and the reference standard digital subtraction angiography (DSA)-derived American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) collateral score, hereby referred as the DSA CS. Methods: In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 1 September 2017 and 1 October 2023. Group differences were assessed using the Student's t test, Mann-Whitney U test and Chi-Square test. Spearman's rank correlation and logistic regression analyses were used to assess associations between rCBV < 42% and DSA CS. Results: In total, 222 patients (median age: 69 years, 56.3% female) met our inclusion criteria. In the multivariable logistic regression analysis, taking into account age, sex, race, hypertension, hyperlipidemia, diabetes, atrial fibrillation, prior stroke or transient ischemic attack, the admission National Institute of Health stroke scale, the premorbid modified Rankin score, the Alberta stroke program early CT score (ASPECTS), and segment occlusion, the rCBV < 42% lesion volume (adjusted OR: 0.98, p < 0.05) was independently associated with the DSA CS. Conclusion: The rCBV < 42% lesion volume is independently associated with the DSA CS.

  View details for DOI 10.3390/jcm13061588

  View details for PubMedID 38541813

• Stroke and High-risk TIAs Outcomes with Reduction of Treatment duration when treatment initiated in Emergency Rooms. (SHORTER-Study). International journal of stroke : official journal of the International Stroke Society Alhazzani, A., AlAjlan, F., Alkhathaami, A., Al-Senani, F. M., Muayqil, T., Alghamdi, S., AlKawi, A., AlZahrani, S., Bakheet, M., Aljohani, M., Taher, N., Almutairi, A., AlQarni, M., Alsalman, S., Alqahtani, S., Almansour, N., Abukhamsin, L., Mouminah, A., AlModarra, N. B., Mohamed, G., Almodhy, M., Albogumi, E. A., AlZawahmah, M., AlReshaid, A., Akhtar, N., Hussain, M. S., Albers, G. W., Shuaib, A. 2024: 17474930241237120

  Abstract

  Following TIA and minor stroke, the risk of recurrent stroke can be significantly reduced with short duration dual antiplatelet therapy (DAPT). We wish to investigate if 10 days of DAPT is as effective as 21 days treatment.This is an open-label, randomized, parallel-group study comparing whether 10 days of DAPT treatment (ASA+Clopidogrel) is non-inferior to 21-day of DAPT. in patients with minor ischemic stroke (AIS) or high-risk transient ischemic attack (TIA). In both groups DAPT is started within 24 hours of symptom onset.This study is being conducted in approximately 15 study sites in the Kingdom of Saudi Arabia. The planned sample size if 1932.Noninferiority of 10 days compared to 21 days of DAPT in the prevention of the composite endpoint of stroke and death at 90 days in AIS/TIA patients. The primary safety outcome is major intracranial and systemic hemorrhage.Enrolment started in the second quarter of 2023, and the completion of the study is expected in the fourth quarter of 2025.The trial is expected to show that 10 days of DAPT is non-inferior for the prevention of early recurrence of vascular events in patients with high-risk TIAs and minor strokes.

  View details for DOI 10.1177/17474930241237120

  View details for PubMedID 38395748

• A Clinical and Imaging Fused Deep Learning Model Matches Expert Clinician Prediction of 90-Day Stroke Outcomes. AJNR. American journal of neuroradiology Liu, Y., Shah, P., Yu, Y., Horsey, J., Ouyang, J., Jiang, B., Yang, G., Heit, J. J., McCullough-Hicks, M. E., Hugdal, S. M., Wintermark, M., Michel, P., Liebeskind, D. S., Lansberg, M. G., Albers, G. W., Zaharchuk, G. 2024

  Abstract

  Predicting long-term clinical outcome in acute ischemic stroke is beneficial for prognosis, clinical trial design, resource management, and patient expectations. This study used a deep learning-based predictive model (DLPD) to predict 90-day mRS outcomes and compared its predictions with those made by physicians.A previously developed DLPD that incorporated DWI and clinical data from the acute period was used to predict 90-day mRS outcomes in 80 consecutive patients with acute ischemic stroke from a single-center registry. We assessed the predictions of the model alongside those of 5 physicians (2 stroke neurologists and 3 neuroradiologists provided with the same imaging and clinical information). The primary analysis was the agreement between the ordinal mRS predictions of the model or physician and the ground truth using the Gwet Agreement Coefficient. We also evaluated the ability to identify unfavorable outcomes (mRS >2) using the area under the curve, sensitivity, and specificity. Noninferiority analyses were undertaken using limits of 0.1 for the Gwet Agreement Coefficient and 0.05 for the area under the curve analysis. The accuracy of prediction was also assessed using the mean absolute error for prediction, percentage of predictions ±1 categories away from the ground truth (±1 accuracy [ACC]), and percentage of exact predictions (ACC).To predict the specific mRS score, the DLPD yielded a Gwet Agreement Coefficient score of 0.79 (95% CI, 0.71-0.86), surpassing the physicians' score of 0.76 (95% CI, 0.67-0.84), and was noninferior to the readers (P < .001). For identifying unfavorable outcome, the model achieved an area under the curve of 0.81 (95% CI, 0.72-0.89), again noninferior to the readers' area under the curve of 0.79 (95% CI, 0.69-0.87) (P < .005). The mean absolute error, ±1ACC, and ACC were 0.89, 81%, and 36% for the DLPD.A deep learning method using acute clinical and imaging data for long-term functional outcome prediction in patients with acute ischemic stroke, the DLPD, was noninferior to that of clinical readers.

  View details for DOI 10.3174/ajnr.A8140

  View details for PubMedID 38331959

• Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial. JAMA neurology Sarraj, A., Hill, M. D., Hussain, M. S., Abraham, M. G., Ortega-Gutierrez, S., Chen, M., Kasner, S. E., Churilov, L., Pujara, D. K., Johns, H., Blackburn, S., Sundararajan, S., Hu, Y. C., Herial, N. A., Budzik, R. F., Hicks, W. J., Arenillas, J. F., Tsai, J. P., Kozak, O., Cordato, D. J., Hanel, R. A., Wu, T. Y., Portela, P. C., Gandhi, C. D., Al-Mufti, F., Maali, L., Gibson, D., Pérez de la Ossa, N., Schaafsma, J. D., Blasco, J., Sangha, N., Warach, S., Kleinig, T. J., Shaker, F., Sitton, C. W., Nguyen, T., Fifi, J. T., Jabbour, P., Furlan, A., Lansberg, M. G., Tsivgoulis, G., Sila, C., Bambakidis, N., Davis, S., Wechsler, L., Albers, G. W., Grotta, J. C., Ribo, M., Campbell, B. C., Hassan, A. E., Vora, N., Manning, N. W., Cheung, A., Aghaebrahim, A. N., Paipa Merchán, A. J., Sahlein, D., Requena Ruiz, M., Elijovich, L., Arthur, A., Al-Shaibi, F., Samaniego, E. A., Duncan, K. R., Opaskar, A., Ray, A., Xiong, W., Sunshine, J., DeGeorgia, M., Tjoumakaris, S., Mendes Pereira, V. 2024

  Abstract

  Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT).To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes.This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024.EVT vs MM.Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication.A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80).Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport.ClinicalTrials.gov Identifier: NCT03876457.

  View details for DOI 10.1001/jamaneurol.2024.0206

  View details for PubMedID 38363872

• Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial. Lancet (London, England) Sarraj, A., Abraham, M. G., Hassan, A. E., Blackburn, S., Kasner, S. E., Ortega-Gutierrez, S., Hussain, M. S., Chen, M., Johns, H., Churilov, L., Pujara, D. K., Shaker, F., Maali, L., Cardona Portela, P., Herial, N. A., Gibson, D., Kozak, O., Arenillas, J. F., Yan, B., Pérez de la Ossa, N., Sundararajan, S., Hu, Y. C., Cordato, D. J., Manning, N. W., Hanel, R. A., Aghaebrahim, A. N., Budzik, R. F., Hicks, W. J., Blasco, J., Wu, T. Y., Tsai, J. P., Schaafsma, J. D., Gandhi, C. D., Al-Mufti, F., Sangha, N., Warach, S., Kleinig, T. J., Yogendrakumar, V., Ng, F., Samaniego, E. A., Abdulrazzak, M. A., Parsons, M. W., Rahbar, M. H., Nguyen, T. N., Fifi, J. T., Mendes Pereira, V., Lansberg, M. G., Albers, G. W., Furlan, A. J., Jabbour, P., Sitton, C. W., Sila, C., Bambakidis, N., Davis, S. M., Wechsler, L., Hill, M. D., Grotta, J. C., Ribo, M., Campbell, B. C. 2024

  Abstract

  Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients.SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed.The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]).In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up.Stryker Neurovascular.

  View details for DOI 10.1016/S0140-6736(24)00050-3

  View details for PubMedID 38346442

• Association between occlusion location, net water uptake and ischemic lesion growth in large vessel anterior circulation strokes. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Winkelmeier, L., Heit, J. J., Broocks, G., Prüter, J., Heitkamp, C., Schell, M., Albers, G. W., Lansberg, M. G., Wintermark, M., Kemmling, A., Stracke, C. P., Guenego, A., Paech, D., Fiehler, J., Faizy, T. D. 2024: 271678X241232193

  Abstract

  Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging (β estimate, 5.50, 95% CI, 3.81-7.19, P < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location.

  View details for DOI 10.1177/0271678X241232193

  View details for PubMedID 38329032

• Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection. The New England journal of medicine Albers, G. W., Jumaa, M., Purdon, B., Zaidi, S. F., Streib, C., Shuaib, A., Sangha, N., Kim, M., Froehler, M. T., Schwartz, N. E., Clark, W. M., Kircher, C. E., Yang, M., Massaro, L., Lu, X. Y., Rippon, G. A., Broderick, J. P., Butcher, K., Lansberg, M. G., Liebeskind, D. S., Nouh, A., Schwamm, L. H., Campbell, B. C. 2024

  Abstract

  Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited.We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage.The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively.Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

  View details for DOI 10.1056/NEJMoa2310392

  View details for PubMedID 38329148

• Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles. JAMA Sarraj, A., Hassan, A. E., Abraham, M. G., Ortega-Gutierrez, S., Kasner, S. E., Hussain, M. S., Chen, M., Churilov, L., Johns, H., Sitton, C. W., Yogendrakumar, V., Ng, F. C., Pujara, D. K., Blackburn, S., Sundararajan, S., Hu, Y. C., Herial, N. A., Arenillas, J. F., Tsai, J. P., Budzik, R. F., Hicks, W. J., Kozak, O., Yan, B., Cordato, D. J., Manning, N. W., Parsons, M. W., Cheung, A., Hanel, R. A., Aghaebrahim, A. N., Wu, T. Y., Portela, P. C., Gandhi, C. D., Al-Mufti, F., Pérez de la Ossa, N., Schaafsma, J. D., Blasco, J., Sangha, N., Warach, S., Kleinig, T. J., Shaker, F., Al Shaibi, F., Toth, G., Abdulrazzak, M. A., Sharma, G., Ray, A., Sunshine, J., Opaskar, A., Duncan, K. R., Xiong, W., Samaniego, E. A., Maali, L., Lechtenberg, C. G., Renú, A., Vora, N., Nguyen, T., Fifi, J. T., Tjoumakaris, S. I., Jabbour, P., Tsivgoulis, G., Pereira, V. M., Lansberg, M. G., DeGeorgia, M., Sila, C. A., Bambakidis, N., Hill, M. D., Davis, S. M., Wechsler, L., Grotta, J. C., Ribo, M., Albers, G. W., Campbell, B. C. 2024

  Abstract

  Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain.To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect.An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022.EVT vs MM.Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI.Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled.In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased.ClinicalTrials.gov Identifier: NCT03876457.

  View details for DOI 10.1001/jama.2024.0572

  View details for PubMedID 38324414

• Random expert sampling for deep learning segmentation of acute ischemic stroke on non-contrast CT. Journal of neurointerventional surgery Ostmeier, S., Axelrod, B., Liu, Y., Yu, Y., Jiang, B., Yuen, N., Pulli, B., Verhaaren, B. F., Kaka, H., Wintermark, M., Michel, P., Mahammedi, A., Federau, C., Lansberg, M. G., Albers, G. W., Moseley, M. E., Zaharchuk, G., Heit, J. J. 2024

  Abstract

  Outlining acutely infarcted tissue on non-contrast CT is a challenging task for which human inter-reader agreement is limited. We explored two different methods for training a supervised deep learning algorithm: one that used a segmentation defined by majority vote among experts and another that trained randomly on separate individual expert segmentations.The data set consisted of 260 non-contrast CT studies in 233 patients with acute ischemic stroke recruited from the multicenter DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trial. Additional external validation was performed using 33 patients with matched stroke onset times from the University Hospital Lausanne. A benchmark U-Net was trained on the reference annotations of three experienced neuroradiologists to segment ischemic brain tissue using majority vote and random expert sampling training schemes. The median of volume, overlap, and distance segmentation metrics were determined for agreement in lesion segmentations between (1) three experts, (2) the majority model and each expert, and (3) the random model and each expert. The two sided Wilcoxon signed rank test was used to compare performances (1) to 2) and (1) to (3). We further compared volumes with the 24 hour follow-up diffusion weighted imaging (DWI, final infarct core) and correlations with clinical outcome (modified Rankin Scale (mRS) at 90 days) with the Spearman method.The random model outperformed the inter-expert agreement ((1) to (2)) and the majority model ((1) to (3)) (dice 0.51±0.04 vs 0.36±0.05 (P<0.0001) vs 0.45±0.05 (P<0.0001)). The random model predicted volume correlated with clinical outcome (0.19, P<0.05), whereas the median expert volume and majority model volume did not. There was no significant difference when comparing the volume correlations between random model, median expert volume, and majority model to 24 hour follow-up DWI volume (P>0.05, n=51).The random model for ischemic injury delineation on non-contrast CT surpassed the inter-expert agreement ((1) to (2)) and the performance of the majority model ((1) to (3)). We showed that the random model volumetric measures of the model were consistent with 24 hour follow-up DWI.

  View details for DOI 10.1136/jnis-2023-021283

  View details for PubMedID 38302420

• Perfusion Profiles May Differ Between Asymptomatic Versus Symptomatic Internal Carotid Artery Occlusion. Journal of stroke Chang, T. Y., Christensen, S., Mlynash, M., Heit, J. J., Marks, M. P., Lee, S., McCullough-Hicks, M. E., Ostojic, L. V., Kemp, S., Albers, G. W., Srivatsan, A., Lee, T. H., Lansberg, M. G. 2024; 26 (1): 108-111

  View details for DOI 10.5853/jos.2023.02768

  View details for PubMedID 38326709

• Robust Collaterals Are Independently Associated With Excellent Recanalization in Patients With Large Vessel Occlusion Causing Acute Ischemic Stroke STROKE-VASCULAR AND INTERVENTIONAL NEUROLOGY Yedavalli, V., Koneru, M., Hoseinyazdi, M., Greene, C., Copeland, K., Xu, R., Luna, L., Caplan, J., Dmytriw, A., Guenego, A., Heit, J., Albers, G., Wintermark, M., Gonzalez, L., Urrutia, V., Huang, J., Leigh, R., Marsh, E., Llinas, R., Hillis, A., Nael, K. 2024; 4 (1)

  View details for DOI 10.1161/SVIN.123.001141

  View details for Web of Science ID 001160115800013

• Pretreatment CTP Collateral Parameters Predict Good Outcomes in Successfully Recanalized Middle Cerebral Artery Distal Medium Vessel Occlusions. Clinical neuroradiology Yedavalli, V., Koneru, M., Hamam, O., Hoseinyazdi, M., Marsh, E. B., Llinas, R., Urrutia, V., Leigh, R., Gonzalez, F., Xu, R., Caplan, J., Huang, J., Lu, H., Wintermark, M., Heit, J., Guenego, A., Albers, G., Nael, K., Hillis, A. 2023

  Abstract

  Distal medium vessel occlusions (DMVOs) account for a large percentage of vessel occlusions resulting in acute ischemic stroke (AIS) with disabling symptoms. We aim to assess whether pretreatment quantitative CTP collateral status (CS) parameters can serve as imaging biomarkers for good clinical outcomes prediction in successfully recanalized middle cerebral artery (MCA) DMVOs.We performed a retrospective analysis of consecutive patients with AIS secondary to primary MCA-DMVOs who were successfully recanalized by mechanical thrombectomy (MT) defined as modified thrombolysis in cerebral infarction (mTICI) 2b, 2c, or 3. We evaluated the association between the CBV index and HIR independently with good clinical outcomes (modified Rankin score 0-2) using Spearman rank correlation, logistic regression, and ROC analyses.From 22 August 2018 to 18 October 2022 8/22/2018 to 10/18/2022, 60 consecutive patients met our inclusion criteria (mean age 71.2 ± 13.9 years old [mean ± SD], 35 female). The CBV index (r = -0.693, p < 0.001) and HIR (0.687, p < 0.001) strongly correlated with 90-day mRS. A CBV index ≥ 0.7 (odds ratio, OR, 2.27, range 6.94-21.23 [OR] 2.27 [6.94-21.23], p = 0.001)) and lower likelihood of prior stroke (0.13 [0.33-0.86]), p = 0.024)) were independently associated with good outcomes. The ROC analysis demonstrated good performance of the CBV index in predicting good 90-day mRS (AUC 0.73, p = 0.003) with a threshold of 0.7 for optimal sensitivity (71% [52.0-85.8%]) and specificity (76% [54.9-90.6%]). The HIR also demonstrated adequate performance in predicting good 90-day mRS (AUC 0.77, p = 0.001) with a threshold of 0.3 for optimal sensitivity (64.5% [45.4-80.8%]) and specificity (76.0% [54.9-90.6%]).A CBV index ≥ 0.7 may be independently associated with good clinical outcomes in our cohort of AIS caused by MCA-DMVOs that were successfully treated with MT. Furthermore, a HIR < 0.3 is also associated with good clinical outcomes. This is the first study of which we are aware to identify a CBV index threshold for MCA-DMVOs.

  View details for DOI 10.1007/s00062-023-01371-2

  View details for PubMedID 38155255

  View details for PubMedCentralID 7668337

• Redefining CT perfusion-based ischemic core estimates for the ghost core in early time window stroke. Journal of neuroimaging : official journal of the American Society of Neuroimaging Koneru, M., Hoseinyazdi, M., Lakhani, D. A., Greene, C., Copeland, K., Wang, R., Xu, R., Luna, L., Caplan, J. M., Dmytriw, A. A., Guenego, A., Heit, J. J., Albers, G. W., Wintermark, M., Gonzalez, L. F., Urrutia, V. C., Huang, J., Nael, K., Leigh, R., Marsh, E. B., Hillis, A. E., Llinas, R. H., Yedavalli, V. S. 2023

  Abstract

  In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients.Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short-term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long-term outcome was 90-day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p-value⩽.05.Among 73 patients, median age was 66 (interquartile range 54-76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes.Our multisite analysis shows that favorable short-term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger-scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients.

  View details for DOI 10.1111/jon.13180

  View details for PubMedID 38146065

• Nationwide diurnal pattern among intracerebral hemorrhage incidence and volume. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Sreekrishnan, A., Lun, R., Albers, G. W. 2023; 33 (2): 107521

  Abstract

  INTRODUCTION: Intracerebral hemorrhage (ICH) incidence follows both seasonal and diurnal patterns with greater severity reported in nighttime hemorrhages. These differences have been attributed to variations in the coagulation cascade, blood pressure, and sleep-wake cycle that all have their own rhythmicity. The purpose of this analysis was to validate these trends in a large nationwide database of automated ICH detection scans and evaluate for differences in hematoma volume by image acquisition time.METHODS: Serial non-contrast head CT (NCHCT) data, processed with an automated imaging software (iSchemaView), was acquired from U.S. hospitals between 1/1/2020 and 12/31/2021. Final exclusion criteria included: (1) patient age ≤ 25, (2) hematoma volume ≥ 100 ml, (3) hematoma volume ≤ 0.4 ml. Imaging time was subdivided into three epochs: (1) Night: 23:00h-06:59h, (2) Day: 07:00h-14:59h, and (3) Evening: 15:00h-22:59h.RESULTS: A total of 19,397 scans were included in the final analysis with a median ICH volume of 2.9 ml and mean volume of 13.23 mL; 15.6% of scans had volumes above 30 ml. Peak imaging occurred around noon. Hematoma volume was significantly different across timepoints (p=0.003), with ICHs presenting at night (average volume 14.2 ml) larger than those presenting during the day (12.9 ml, p=0.002) or evening (13.0 ml, p=0.012).CONCLUSION: In this real world, multi-site data set, we show similar diurnal trends in ICH incidence as previously reported and detected subtle differences in volume based on time of imaging. Further research is required to elucidate the potential underlying mechanisms for these differences.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2023.107521

  View details for PubMedID 38134549

• Pretreatment parameters associated with hemorrhagic transformation among successfully recanalized medium vessel occlusions. Journal of neurology Koneru, M., Hoseinyazdi, M., Wang, R., Ozkara, B. B., Hyson, N. Z., Marsh, E. B., Llinas, R. H., Urrutia, V. C., Leigh, R., Gonzalez, L. F., Xu, R., Caplan, J. M., Huang, J., Lu, H., Luna, L., Wintermark, M., Dmytriw, A. A., Guenego, A., Albers, G. W., Heit, J. J., Nael, K., Hillis, A. E., Yedavalli, V. S. 2023

  Abstract

  Although pretreatment radiographic biomarkers are well established for hemorrhagic transformation (HT) following successful mechanical thrombectomy (MT) in large vessel occlusion (LVO) strokes, they are yet to be explored for medium vessel occlusion (MeVO) acute ischemic strokes. We aim to investigate pretreatment imaging biomarkers representative of collateral status, namely the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index, and their association with HT in successfully recanalized MeVOs. A prospectively collected registry of acute ischemic stroke patients with MeVOs successfully recanalized with MT between 2019 and 2023 was retrospectively reviewed. A multivariate logistic regression for HT of any subtype was derived by combining significant univariate predictors into a forward stepwise regression with minimization of Akaike information criterion. Of 60 MeVO patients successfully recanalized with MT, HT occurred in 28.3% of patients. Independent factors for HT included: diabetes mellitus history (p=0.0005), CBV index (p=0.0071), and proximal versus distal occlusion location (p=0.0062). A multivariate model with these factors had strong diagnostic performance for predicting HT (area under curve [AUC] 0.93, p<0.001). Lower CBV indexes, distal occlusion location, and diabetes history are significantly associated with HT in MeVOs successfully recanalized with MT. Of note, HIR was not found to be significantly associated with HT.

  View details for DOI 10.1007/s00415-023-12149-4

  View details for PubMedID 38099953

• Early neurological deterioration in patients with acute ischemic stroke is linked to unfavorable cerebral venous outflow. European stroke journal Heitkamp, C., Winkelmeier, L., Heit, J. J., Albers, G. W., Lansberg, M. G., Kniep, H., Broocks, G., Stracke, C. P., Schell, M., Guenego, A., Paech, D., Wintermark, M., Fiehler, J., Faizy, T. D. 2023: 23969873231208277

  Abstract

  Early neurological deterioration (END) is associated with poor outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Causes of END after mechanical thrombectomy (MT) include unsuccessful recanalization and reperfusion hemorrhages. However, little is known about END excluding the aforementioned causes. We aimed to investigate factors associated with unexplained END (ENDunexplained) with regard to the cerebral collateral status.Multicenter retrospective study of AIS-LVO patients with successful MT (mTICI 2b-3). On admission CT angiography (CTA), pial arterial collaterals and venous outflow (VO) were assessed using the modified Tan-Scale and the Cortical Vein Opacification Score (COVES), respectively. ENDunexplained was defined as an increase in NIHSS score of ⩾ 4 within the first 24 hours after MT without parenchymal hemorrhage on follow-up imaging. Multivariable regression analyses were performed to examine factors of ENDunexplained and unfavorable functional outcome (modified Rankin Scale score 3-6).A total of 620 patients met the inclusion criteria. ENDunexplained occurred in 10% of patients. While there was no significant difference in pial arterial collaterals, patients with ENDunexplained exhibited more often unfavorable VO (81% vs. 53%; P < 0.001). Unfavorable VO (aOR [95% CI]; 2.56 [1.02-6.40]; P = 0.045) was an independent predictor of ENDunexplained. ENDunexplained was independently associated with unfavorable functional outcomes at 90 days (aOR [95% CI]; 6.25 [2.06-18.94]; P = 0.001).Unfavorable VO on admission CTA was associated with ENDunexplained. ENDunexplained was independently linked to unfavorable functional outcomes at 90 days. Identifying AIS-LVO patients at risk of ENDunexplained may help to select patients for intensified monitoring and guide to optimal treatment regimes.

  View details for DOI 10.1177/23969873231208277

  View details for PubMedID 38069665

• Pretreatment CT perfusion collateral parameters correlate with penumbra salvage in middle cerebral artery occlusion. Journal of neuroimaging : official journal of the American Society of Neuroimaging Lakhani, D. A., Balar, A. B., Koneru, M., Hoseinyazdi, M., Hyson, N., Cho, A., Greene, C., Xu, R., Luna, L., Caplan, J., Dmytriw, A., Guenego, A., Wintermark, M., Gonzalez, F., Urrutia, V., Huang, J., Nael, K., Rai, A. T., Albers, G. W., Heit, J. J., Yedavalli, V. 2023

  Abstract

  BACKGROUND AND PURPOSE: Acute ischemic stroke due to large vessel occlusion (AIS-LVO) is a major cause of functional dependence. Collateral status (CS) is an important determinant of functional outcomes. Pretreatment CT perfusion (CTP) parameters serve as reliable surrogates of CS. Penumbra Salvage Index (PSI) is another parameter predictive of functional outcomes in AIS-LVO. The aim of this study is to assess the relationship of pretreatment CTP parameters with PSI.METHODS: In this prospectively collected, retrospectively reviewed multicenter analysis, inclusion criteria were as follows: (1) CT angiography confirmed middle cerebral artery (MCA) M1-segment and proximal M2-segment occlusion from 9/1/2017 to 9/22/2022; (2) diagnostic CTP; and (3) available diagnostic Magnetic resonance Imaging (MRI) diffusion-weighted images. Pearson correlation analysis was performed to assess the association between cerebral blood volume (CBV) index and hypoperfusion intensity ratio (HIR) with PSI. p value ≤.05 was considered statistically significant.RESULTS: In total, 131 patients (n = 86, M1 and n = 45, proximal M2 occlusion) met our inclusion criteria. CBV index showed a modest positive correlation with PSI (r = 0.34, p<.001) in patients with proximal MCA occlusion. Similar trends were noted in subgroup analysis of patients with M1 occlusion, and proximal M2 occlusion. Whereas, HIR did not have a strong trend or correlation with PSI.CONCLUSION: CBV index correlates with PSI, whereas HIR does not. Future studies are needed to expand our understanding of the adjunct role of CBV index with other similar pretreatment CTP-based markers in clinical evaluation and decision-making in patients with MCA occlusion.

  View details for DOI 10.1111/jon.13178

  View details for PubMedID 38057941

• Does imaging of the ischemic penumbra have value in acute ischemic stroke with large vessel occlusion? Current opinion in neurology Seners, P., Baron, J., Olivot, J., Albers, G. W. 2023

  Abstract

  PURPOSE OF REVIEW: In this review, we summarize current evidence regarding potential benefits and limitations of using perfusion imaging to estimate presence and extent of irreversibly injured ischemic brain tissue ('core') and severely ischemic yet salvageable tissue ('penumbra') in acute stroke patients with large vessel occlusion (LVO).RECENT FINDINGS: Core and penumbra volumes are strong prognostic biomarkers in LVO patients. Greater benefits of both intravenous thrombolysis and endovascular therapy (EVT) are observed in patients with small core and large penumbra volumes. However, some current definitions of clinically relevant penumbra may be too restrictive and exclude patients who may benefit from reperfusion therapies. Alongside other clinical and radiological factors, penumbral imaging may enhance the discussion regarding the benefit/risk ratio of EVT in common clinical situations, such as patients with large core - for whom EVT's benefit is established but associated with a high rate of severe disability -, or patients with mild symptoms or medium vessel occlusions - for whom EVT's benefit is currently unknown. Beyond penumbral evaluation, perfusion imaging is clinically relevant for optimizing patient's selection for neuroprotection trials.SUMMARY: In an emerging era of precision medicine, perfusion imaging is a valuable tool in LVO-related acute stroke.

  View details for DOI 10.1097/WCO.0000000000001235

  View details for PubMedID 38038427

• Excellent Recanalization and Small Core Volumes Are Associated With Favorable AM-PAC Score in Patients With Acute Ischemic Stroke Secondary to Large Vessel Occlusion. Archives of rehabilitation research and clinical translation Yedavalli, V., Koneru, M., Hoseinyazdi, M., Copeland, K., Xu, R., Luna, L., Caplan, J., Dmytriw, A., Guenego, A., Heit, J., Albers, G., Wintermark, M., Gonzalez, F., Urrutia, V., Huang, J., Leigh, R., Marsh, E., Llinas, R., Hernandez, M. G., Hillis, A. 2023; 5 (4): 100306

  Abstract

  Objective: To assess pretreatment and interventional parameters as predictors of favorable Activity Measure for Post-Acute Care (AM-PAC) scores for optimal discharge planning.Design: In this prospectively collected, retrospectively reviewed multicenter study from 9/1/2017 to 9/22/2022, patients were dichotomized into favorable and unfavorable AM-PAC. Multivariate logistic regression and receiver operator characteristics analyses were performed for the identified significant variables. A P value of ≤.05 was significant.Setting: Hospitalized care.Participants: In total, 229 patients (mean ±SD 70.65 ±15.2 [55.9% women]) met our inclusion criteria. Inclusion criteria were (a) computed tomography (CT) angiography confirmed LVO from 9/1/2017 to 9/22/2022; (b) diagnostic CT perfusion; and (c) available AM-PAC scores.Interventions: None.Main Outcome Measures: Favorable AM-PAC, defined as a daily activity score ≥19 and basic mobility score of ≥17.Results: Patients with favorable AM-PAC were younger (61.3 vs 70.7, P<.001), had lower admission glucose (mean, 124 vs 136, P=.042), lower blood urea nitrogen (mean, 15.59 vs 19.11, P<.001), and lower admission National Institutes of Health Stroke Scale (NIHSS) (mean, 10.58 vs 16.15, P<.001). No differences in sex were noted. Multivariate regression analyses revealed age, admission NIHSS, relative cerebral blood flow (rCBF) <30% volume, and modified thrombolysis in cerebral infarction (mTICI) score to be independent predictors of favorable AM-PAC (P<.047 for all predictors). The combined model revealed an area under the curve (AUC) of 0.83 (IQR 0.75-0.86).Conclusion: Excellent recanalization, smaller core volumes, younger age, and lower stroke severity independently predict favorable outcomes as measured by AM-PAC.

  View details for DOI 10.1016/j.arrct.2023.100306

  View details for PubMedID 38163017

• The Compensation Index Is Better Associated with DSA ASITN Collateral Score Compared to the Cerebral Blood Volume Index and Hypoperfusion Intensity Ratio. Journal of clinical medicine Lakhani, D. A., Balar, A. B., Koneru, M., Wen, S., Hoseinyazdi, M., Greene, C., Xu, R., Luna, L., Caplan, J., Dmytriw, A. A., Guenego, A., Wintermark, M., Gonzalez, F., Urrutia, V., Huang, J., Nael, K., Rai, A. T., Albers, G. W., Heit, J. J., Yedavalli, V. S. 2023; 12 (23)

  Abstract

  Pretreatment CT Perfusion (CTP) parameters serve as reliable surrogates of collateral status (CS). In this study, we aim to assess the relationship between the novel compensation index (CI, Tmax > 4 s/Tmax > 6 s) and already established CTP collateral markers, namely cerebral blood volume (CBV) index and Hypoperfusion Intensity Ratio (HIR), with the reference standard American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score (CS) on DSA.In this retrospective study, inclusion criteria were the following: (a) CT angiography confirmed anterior circulation large vessel occlusion from 9 January 2017 to 10 January 2023; (b) diagnostic CT perfusion; and (c) underwent mechanical thrombectomy with documented DSA-CS. Student t-test, Mann-Whitney-U-test and Chi-square test were used to assess differences. Spearman's rank correlation and logistic regression analysis were used to assess associations. p ≤ 0.05 was considered significant.In total, 223 patients (mean age: 67.8 ± 15.8, 56% female) met our inclusion criteria. The CI (ρ = 0.37, p < 0.001) and HIR (ρ = -0.29, p < 0.001) significantly correlated with DSA-CS. Whereas the CBV Index (ρ = 0.1, p > 0.05) did not correlate with DSA-CS. On multivariate logistic regression analysis taking into account age, sex, ASPECTS, tPA, premorbid mRS, NIH stroke scale, prior history of TIA, stroke, atrial fibrillation, diabetes mellitus, hyperlipidemia, heart disease and hypertension, only CI was not found to be independently associated with DSA-CS (adjusted OR = 1.387, 95% CI: 1.09-1.77, p < 0.01).CI demonstrates a stronger correlation with DSA-CS compared to both the HIR and CBV Index where it may show promise as an additional quantitative pretreatment CS biomarker.

  View details for DOI 10.3390/jcm12237365

  View details for PubMedID 38068416

• Performance of RAPID noncontrast CT stroke platform in large vessel occlusion and intracranial hemorrhage detection. Frontiers in neurology Yedavalli, V., Heit, J. J., Dehkharghani, S., Haerian, H., Mcmenamy, J., Honce, J., Timpone, V. M., Harnain, C., Kesselman, A., Filly, A., Beardsley, A., Sakamoto, B., Song, C., Montuori, J., Navot, B., Mena, F. V., Giurgiutiu, D. V., Kitamura, F., Lima, F. O., Silva, H., Mont'Alverne, F. J., Albers, G. 2023; 14: 1324088

  Abstract

  Noncontrast CT (NCCT) is used to evaluate for intracerebral hemorrhage (ICH) and ischemia in acute ischemic stroke (AIS). Large vessel occlusions (LVOs) are a major cause of AIS, but challenging to detect on NCCT.The purpose of this study is to evaluate an AI software called RAPID NCCT Stroke (RAPID, iSchemaView, Menlo Park, CA) for ICH and LVO detection compared to expert readers.In this IRB approved retrospective, multicenter study, stand-alone performance of the software was assessed based on the consensus of 3 neuroradiologists and sensitivity and specificity were determined. The platform's performance was then compared to interpretation by readers comprised of eight general radiologists (GR) and three neuroradiologists (NR) in detecting ICH and hyperdense vessel sign (HVS) indicating LVO.A total of 244 cases were included. Of the 244, 115 were LVOs and 26 were ICHs. One hundred three cases did not have LVO nor ICH. Stand-alone performance of the software demonstrated sensitivities and specificities of 96.2 and 99.5% for ICH and 63.5 and 95.1% for LVO detection. Compared to all 11 readers and eight GR readers only respectively, the software demonstrated superiority, achieving significantly higher sensitivities (63.5% versus 43.6%, p < 0.0001 and 63.5% versus 40.9%, p = 0.001).The RAPID NCCT Stroke platform demonstrates superior performance to radiologists for detecting LVO from a NCCT. Use of this software platform could lead to earlier LVO detection and expedited transfer of these patients to a thrombectomy capable center.

  View details for DOI 10.3389/fneur.2023.1324088

  View details for PubMedID 38156093

  View details for PubMedCentralID PMC10753184

• Priorities for Advancements in Neuroimaging in the Diagnostic Workup of Acute Stroke. Stroke Samaniego, E. A., Boltze, J., Lyden, P. D., Hill, M. D., Campbell, B. C., Silva, G. S., Sheth, K. N., Fisher, M., Hillis, A. E., Nguyen, T. N., Carone, D., Favilla, C. G., Deljkich, E., Albers, G. W., Heit, J. J., Lansberg, M. G. 2023

  Abstract

  STAIR XII (12th Stroke Treatment Academy Industry Roundtable) included a workshop to discuss the priorities for advancements in neuroimaging in the diagnostic workup of acute ischemic stroke. The workshop brought together representatives from academia, industry, and government. The participants identified 10 critical areas of priority for the advancement of acute stroke imaging. These include enhancing imaging capabilities at primary and comprehensive stroke centers, refining the analysis and characterization of clots, establishing imaging criteria that can predict the response to reperfusion, optimizing the Thrombolysis in Cerebral Infarction scale, predicting first-pass reperfusion outcomes, improving imaging techniques post-reperfusion therapy, detecting early ischemia on noncontrast computed tomography, enhancing cone beam computed tomography, advancing mobile stroke units, and leveraging high-resolution vessel wall imaging to gain deeper insights into pathology. Imaging in acute ischemic stroke treatment has advanced significantly, but important challenges remain that need to be addressed. A combined effort from academic investigators, industry, and regulators is needed to improve imaging technologies and, ultimately, patient outcomes.

  View details for DOI 10.1161/STROKEAHA.123.044985

  View details for PubMedID 37942645

• Brain edema growth after thrombectomy is associated with comprehensive collateral blood flow. Journal of neurointerventional surgery Faizy, T. D., Winkelmeier, L., Mlynash, M., Broocks, G., Heitkamp, C., Thaler, C., van Horn, N., Seners, P., Kniep, H., Stracke, P., Zelenak, K., Lansberg, M. G., Albers, G. W., Wintermark, M., Fiehler, J., Heit, J. J. 2023

  Abstract

  We determined whether a comprehensive assessment of cerebral collateral blood flow is associated with ischemic lesion edema growth in patients successfully treated by thrombectomy.This was a multicenter retrospective study of ischemic stroke patients who underwent thrombectomy treatment of large vessel occlusions. Collateral status was determined using the cerebral collateral cascade (CCC) model, which comprises three components: arterial collaterals (Tan Scale) and venous outflow profiles (Cortical Vein Opacification Score) on CT angiography, and tissue-level collaterals (hypoperfusion intensity ratio) on CT perfusion. Quantitative ischemic lesion net water uptake (NWU) was used to determine edema growth between admission and follow-up non-contrast head CT (ΔNWU). Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC- (poor pial collaterals, tissue-level collaterals, and venous outflow), and CCCmixed (remainder of patients). Primary outcome was ischemic lesion edema growth (ΔNWU). Multivariable regression models were used to assess the primary and secondary outcomes.538 patients were included. 157 patients had CCC+, 274 patients CCCmixed, and 107 patients CCC- profiles. Multivariable regression analysis showed that compared with patients with CCC+ profiles, CCC- (β 1.99, 95% CI 0.68 to 3.30, P=0.003) and CCC mixed (β 1.65, 95% CI 0.75 to 2.56, P<0.001) profiles were associated with greater ischemic lesion edema growth (ΔNWU) after successful thrombectomy treatment. ΔNWU (OR 0.74, 95% CI 0.68 to 0.8, P<0.001) and CCC+ (OR 13.39, 95% CI 4.88 to 36.76, P<0.001) were independently associated with functional independence.A comprehensive assessment of cerebral collaterals using the CCC model is strongly associated with edema growth and functional independence in acute stroke patients successfully treated by endovascular thrombectomy.

  View details for DOI 10.1136/jnis-2023-020921

  View details for PubMedID 37918909

• Semiautomated Detection of Early Infarct Signs on Noncontrast CT Improves Interrater Agreement. Stroke Christensen, S., Demeestere, J., Verhaaren, B. F., Heit, J. J., Von Stein, E. L., Madill, E. S., Kennedy Loube, D., Dugue, R., Rengarajan, S., Mlynash, M., Albers, G. W., Lemmens, R., Lansberg, M. G. 2023

  Abstract

  BACKGROUND: Acute ischemic infarct identification on noncontrast computed tomography (NCCT) is highly variable between raters. A semiautomated method for segmentation of acute ischemic lesions on NCCT may improve interrater reliability.METHODS: Patients with successful endovascular reperfusion from the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) were included. We created relative NCCT (rNCCT) color-gradient overlays by comparing the density of a voxel on NCCT to the homologous region in the contralateral hemisphere. Regions with a relative hypodensity of at least 5% were visualized. We coregistered baseline and follow-up images. Two neuroradiologists and 6 nonradiologists segmented the acute ischemic lesion on the baseline scans with 2 methods: (1) manually outlining hypodense regions on the NCCT (unassisted segmentation) and (2) manually excluding areas deemed outside of the ischemic lesion on the rNCCT color map (rNCCT-assisted segmentation). Voxelwise interrater agreement was quantified using the Dice similarity coefficient and volumetric agreement between raters with the detection index (DI), defined as the true positive volume minus the false positive volume.RESULTS: From a total of 92, we included 61 patients. Median age was 59 (64-77), and 57% were female. Stroke onset was known in 39%. Onset to NCCT was median, 8.5 hours (7-11) and median 10 hours (8.4-11.5) in patients with known and unknown onset, respectively. Compared with unassisted NCCT segmentation, rNCCT-assisted segmentation increased the Dice similarity coefficient by >50% for neuroradiologists (Dice similarity coefficient, 0.38 versus 0.83; P<0.001) and nonradiologists (Dice similarity coefficient, 0.14 versus 0.84; P<0.001), and improved the DI among nonradiologists (mean improvement, 5.8 mL [95% CI, 3.1-8.5] mL, P<0.001) but not among neuroradiologists.CONCLUSIONS: The high variability of manual segmentations of the acute ischemic lesion on NCCT is greatly reduced using semiautomated rNCCT. The rNCCT map may therefore aid acute infarct detection and provide more reliable infarct estimates for clinicians with less experience.

  View details for DOI 10.1161/STROKEAHA.123.044058

  View details for PubMedID 37909206

• Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With A Large Vessel Occlusion. Neurology Seners, P., Yuen, N., Olivot, J. M., Mlynash, M., Heit, J. J., Christensen, S., Escribano Paredes, J. B., Carrera, E., Strambo, D., Michel, P., Salerno, A., Wintermark, M., Chen, H., Albucher, J. F., Cognard, C., Sibon, I., Obadia, M., Savatovsky, J., Lansberg, M. G., Albers, G. W. 2023

  Abstract

  The optimal methods for predicting early infarct growth rate (EIGR) in acute ischemic stroke with a large vessel occlusion (LVO) have not been established. We aimed to study the factors associated with EIGR, with a focus on the collateral circulation as assessed by the Hypoperfusion Intensity Ratio (HIR) on perfusion imaging, and determine whether the associations found are consistent across imaging modalities.Retrospective multicenter international study including anterior circulation LVO-related acute stroke patients with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24hrs from symptom onset. To avoid selection bias, patients were selected from (1) the prospective registries of four comprehensive stroke centers with systematic use of perfusion imaging and including both thrombectomy-treated and untreated patients, and (2) one prospective thrombectomy study where perfusion imaging was acquired per protocol but treatment decisions were made blinded to the results. EIGR was defined as infarct volume on baseline imaging divided by onset-to-imaging time, and fast progressors as EIGR ≥10mL/hr. The HIR, defined as the proportion of Tmax>6s with Tmax>10s volume, was measured on perfusion imaging using RAPID software. The factors independently associated with fast progression were studied using multivariable logistic regression models, with separate analyses for CT- and MRI-assessed patients.Overall, 1127 patients were included (CT, n=471; MRI, n=656). Median age was 74 years (IQR, 62-83), 52% were male, median NIHSS was 16 (IQR, 9-21), median HIR was 0.42 (IQR, 0.26-0.58) and 415 (37%) were fast progressors. The HIR was the primary factor associated with fast progression, with very similar results across imaging modalities: the proportion of fast progressors was 4% in the first HIR quartile (i.e. excellent collaterals), ∼15% in the second, ∼50% in the third, and ∼77% in the fourth (P<0.001 for each imaging modality). Fast progression was independently associated with poor 3-month functional outcome in both the CT and MRI cohorts (P<0.001 and P=0.030, respectively).The HIR is the primary factor associated with fast infarct progression, regardless of imaging modality. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers.

  View details for DOI 10.1212/WNL.0000000000207908

  View details for PubMedID 37813579

• Matched-pair analysis of patients with ischemic stroke undergoing thrombectomy using next-generation balloon guide catheters. Journal of neurointerventional surgery Kim, L. H., Choi, J., Zhou, J., Wolman, D., Pendharkar, A. V., Lansberg, M. G., Albers, G. W., Dodd, R., Do, H. M., Pulli, B., Heit, J. J., Telischak, N. A. 2023

  Abstract

  Balloon guide catheters (BGCs) have not been widely adopted, possibly due to the incompatibility of past-generation BGCs with large-bore intermediate catheters. The next-generation BGC is compatible with large-bore catheters. We compared outcomes of thrombectomy cases using BGCs versus conventional guide catheters.We conducted a retrospective study of 110 thrombectomy cases using BGCs (n=55) and non-BGCs (n=55). Sixty consecutive thrombectomy cases in whom the BOBBY BGC was used at a single institution between February 2021 and March 2022 were identified. Of these, 55 BGC cases were 1:1 matched with non-BGC cases by proceduralists, age, gender, stent retriever + aspiration device versus aspiration-only, and site of occlusion. First-pass effect was defined as Thrombolysis In Cerebral Infarction 2b or higher with a single pass.The BGC and non-BGC cohorts had similar mean age (67.2 vs 68.9 years), gender distribution (43.6% vs 47.3% women), median initial National Institutes of Health Stroke Scale score (14 vs 15), and median pretreatment ischemic core volumes (12 mL vs 11.5 mL). BGC and non-BGC cases had similar rates of single pass (60.0% vs 54.6%), first-pass effect (58.2% vs 49.1%), and complications (1.8% vs 9.1%). In aspiration-only cases, the BGC cohort had a significantly higher rate of first-pass effect (100% vs 50.0%, p=0.01). BGC was associated with a higher likelihood of achieving a modified Rankin Scale score of 2 at discharge (OR 7.76, p=0.02). No additional procedural time was required for BGC cases (46.7 vs 48.2 min).BGCs may be safely adopted with comparable procedural efficacy, benefits to aspiration-only techniques, and earlier functional improvement compared with conventional guide catheters.

  View details for DOI 10.1136/jnis-2023-020635

  View details for PubMedID 37793796

• Larger ischemic cores and poor collaterals among large vessel occlusions presenting in the late evening. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Sreekrishnan, A., Tiedt, S., Seners, P., Yuen, N., Olivot, J., Mlynash, M., Lansberg, M. G., Heit, J. J., Lee, S., Michel, P., Strambo, D., Salerno, A., Paredes, J. B., Carrera, E., Albers, G. W. 2023; 32 (12): 107352

  Abstract

  BACKGROUND: Components critical to cerebral perfusion have been noted to oscillate over a 24-h cycle. We previously reported that ischemic core volume has a diurnal relationship with stroke onset time when examined as dichotomized epochs (i.e. Day, Evening, Night) in a cohort of over 1,500 large vessel occlusion (LVO) patients. In this follow-up analysis, our goal was to explore if there is a sinusoidal relationship between ischemic core, collateral status (as measured by HIR), and stroke onset time.METHODS: We retrospectively examined collection of LVO patients with baseline perfusion imaging performed within 24 h of stroke onset from four international comprehensive stroke centers. Both ischemic core volume and HIR, were utilized as the primary radiographic parameters. To evaluate for differences in these parameters over a continuous 24-h cycle, we conducted a sinusoidal regression analysis after linearly regressing out the confounders age and time to imaging.RESULTS: A total of 1506 LVO cases were included, with a median ischemic core volume of 13.0 cc (IQR: 0.0-42.0) and median HIR of 0.4 (IQR: 0.2-0.6). Ischemic core volume varied by stroke onset time in the unadjusted (p=0.001) and adjusted (p=0.003) sinusoidal regression analysis with a peak in core volume around 7:45PM. HIR similarly varied by stroke onset time in the unadjusted (p=0.004) and adjusted (p=0.002) models with a peak in HIR values at around 8:18PM.CONCLUSION: The results suggest that critical factors to the development of the ischemic core vary by stroke onset time and peak around 8PM. When placed in the context of prior studies, strongly suggest a diurnal component to the development of the ischemic core.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2023.107352

  View details for PubMedID 37801879

• Underlying Causes of TIA and Minor Ischemic Stroke and Risk of Major Vascular Events. JAMA neurology Lavallée, P. C., Charles, H., Albers, G. W., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Labreuche, J., Molina, C., Rothwell, P. M., Steg, P. G., Touboul, P. J., Uchiyama, S., Vicaut, É., Wong, L. K., Amarenco, P. 2023

  Abstract

  The coexistence of underlying causes in patients with transient ischemic attack (TIA) or minor ischemic stroke as well as their associated 5-year risks are not well known.To apply the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other cause, or dissection) grading system to assess coexistence of underlying causes of TIA and minor ischemic stroke and the 5-year risk for major vascular events.This international registry cohort (TIAregistry.org) study enrolled 4789 patients from June 1, 2009, to December 31, 2011, with 1- to 5-year follow-up at 61 sites in 21 countries. Eligible patients had a TIA or minor stroke (with modified Rankin Scale score of 0 or 1) within the last 7 days. Among these, 3847 patients completed the 5-year follow-up by December 31, 2016. Data were analyzed from October 1, 2022, to June 15, 2023.Five-year follow-up.Estimated 5-year risk of the composite outcome of stroke, acute coronary syndrome, or cardiovascular death.A total of 3847 patients (mean [SD] age, 66.4 [13.2] years; 2295 men [59.7%]) in 42 sites were enrolled and participated in the 5-year follow-up cohort (median percentage of 5-year follow-up per center was 92.3% [IQR, 83.4%-97.8%]). In 998 patients with probable or possible causal atherosclerotic disease, 489 (49.0%) had some form of small vessel disease (SVD), including 110 (11.0%) in whom a lacunar stroke was also probably or possibly causal, and 504 (50.5%) had no SVD; 275 (27.6%) had some cardiac findings, including 225 (22.6%) in whom cardiac pathology was also probably or possibly causal, and 702 (70.3%) had no cardiac findings. Compared with patients with none of the 5 ASCOD categories of disease (n = 484), the 5-year rate of major vascular events was almost 5 times higher (hazard ratio [HR], 4.86 [95% CI, 3.07-7.72]; P < .001) in patients with causal atherosclerosis, 2.5 times higher (HR, 2.57 [95% CI, 1.58-4.20]; P < .001) in patients with causal lacunar stroke or lacunar syndrome, and 4 times higher (HR, 4.01 [95% CI, 2.50-6.44]; P < .001) in patients with causal cardiac pathology.The findings of this cohort study suggest that in patients with TIA and minor ischemic stroke, the coexistence of atherosclerosis, SVD, cardiac pathology, dissection, or other causes is substantial, and the 5-year risk of a major vascular event varies considerably across the 5 categories of underlying diseases. These findings further suggest the need for secondary prevention strategies based on pathophysiology rather than a one-size-fits-all approach.

  View details for DOI 10.1001/jamaneurol.2023.3344

  View details for PubMedID 37782494

  View details for PubMedCentralID PMC10546292

• EFFECT OF ANESTHESIA APPROACH ON THROMBECTOMY OUTCOMES IN PATIENTS WITH LARGE ISCHEMIC CORE STROKE: A PRE-SPECIFIED SECONDARY ANALYSIS OF SELECT2 TRIAL Sarraj, A., Abraham, M., Ortega-Gutierrez, S., Hussain, M., Chen, M., Churilov, L., Sitton, C., Pereira, V., Lansberg, M., Hill, M., Albers, G., Ribo, M., Hasssan, A., Campbell, B. SAGE PUBLICATIONS LTD. 2023: 424

  View details for Web of Science ID 001094858602009

• Blood Pressure Management After Endovascular Therapy for Acute Ischemic Stroke: The BEST-II Randomized Clinical Trial. JAMA Mistry, E. A., Hart, K. W., Davis, L. T., Gao, Y., Prestigiacomo, C. J., Mittal, S., Mehta, T., LaFever, H., Harker, P., Wilson-Perez, H. E., Beasley, K. A., Krothapalli, N., Lippincott, E., Stefek, H., Froehler, M., Chitale, R., Fusco, M., Grossman, A., Shirani, P., Smith, M., Jaffa, M. N., Yeatts, S. D., Albers, G. W., Wanderer, J. P., Tolles, J., Lindsell, C. J., Lewis, R. J., Bernard, G. R., Khatri, P. 2023; 330 (9): 821-831

  Abstract

  The effects of moderate systolic blood pressure (SBP) lowering after successful recanalization with endovascular therapy for acute ischemic stroke are uncertain.To determine the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg).Randomized, open-label, blinded end point, phase 2, futility clinical trial that enrolled 120 patients with acute ischemic stroke who had undergone successful endovascular therapy at 3 US comprehensive stroke centers from January 2020 to March 2022 (final follow-up, June 2022).After undergoing endovascular therapy, participants were randomized to 1 of 3 SBP targets: 40 to less than 140 mm Hg, 40 to less than 160 mm Hg, and 40 to 180 mm Hg or less (guideline recommended) group, initiated within 60 minutes of recanalization and maintained for 24 hours.Prespecified multiple primary outcomes for the primary futility analysis were follow-up infarct volume measured at 36 (±12) hours and utility-weighted modified Rankin Scale (mRS) score (range, 0 [worst] to 1 [best]) at 90 (±14) days. Linear regression models were used to test the harm-futility boundaries of a 10-mL increase (slope of 0.5) in the follow-up infarct volume or a 0.10 decrease (slope of -0.005) in the utility-weighted mRS score with each 20-mm Hg SBP target reduction after endovascular therapy (1-sided α = .05). Additional prespecified futility criterion was a less than 25% predicted probability of success for a future 2-group, superiority trial comparing SBP targets of the low- and mid-thresholds with the high-threshold (maximum sample size, 1500 with respect to the utility-weighted mRS score outcome).Among 120 patients randomized (mean [SD] age, 69.6 [14.5] years; 69 females [58%]), 113 (94.2%) completed the trial. The mean follow-up infarct volume was 32.4 mL (95% CI, 18.0 to 46.7 mL) for the less than 140-mm Hg group, 50.7 mL (95% CI, 33.7 to 67.7 mL), for the less than 160-mm Hg group, and 46.4 mL (95% CI, 24.5 to 68.2 mL) for the 180-mm Hg or less group. The mean utility-weighted mRS score was 0.51 (95% CI, 0.38 to 0.63) for the less than 140-mm Hg group, 0.47 (95% CI, 0.35 to 0.60) for the less than 160-mm Hg group, and 0.58 (95% CI, 0.46 to 0.71) for the high-target group. The slope of the follow-up infarct volume for each mm Hg decrease in the SBP target, adjusted for the baseline Alberta Stroke Program Early CT score, was -0.29 (95% CI, -0.81 to ∞; futility P = .99). The slope of the utility-weighted mRS score for each mm Hg decrease in the SBP target after endovascular therapy, adjusted for baseline utility-weighted mRS score, was -0.0019 (95% CI, -∞ to 0.0017; futility P = .93). Comparing the high-target SBP group with the lower-target groups, the predicted probability of success for a future trial was 25% for the less than 140-mm Hg group and 14% for the 160-mm Hg group.Among patients with acute ischemic stroke, lower SBP targets less than either 140 mm Hg or 160 mm Hg after successful endovascular therapy did not meet prespecified criteria for futility compared with an SBP target of 180 mm Hg or less. However, the findings suggested a low probability of benefit from lower SBP targets after endovascular therapy if tested in a future larger trial.ClinicalTrials.gov Identifier: NCT04116112.

  View details for DOI 10.1001/jama.2023.14330

  View details for PubMedID 37668620

• CT perfusion to measure venous outflow in acute ischemic stroke in patients with a large vessel occlusion. Journal of neurointerventional surgery Adusumilli, G., Christensen, S., Yuen, N., Mlynash, M., Faizy, T. D., Albers, G. W., Lansberg, M. G., Fiehler, J., Heit, J. J. 2023

  Abstract

  Robust venous outflow (VO) profiles, measured by degree of venous opacification on pre-thrombectomy CT angiography (CTA) studies, are strongly correlated with favorable outcomes in patients with large vessel occlusion acute ischemic stroke treated by thrombectomy. However, VO measurements are laborious and require neuroimaging expertise.To develop a semi-automated method to measure VO using CTA and CT perfusion imaging studies.We developed a graphical interface using The Visualization Toolkit, allowing for voxel selection at the confluence and bilateral internal cerebral veins on CTA along with arterial input functions (AIFs) from both internal carotid arteries. We extracted concentration-time curves from the CT perfusion study at the corresponding locations associated with AIF and venous output function (VOF). Outcome analyses were primarily conducted by the Mann-Whitney U and Jonckheere-Terpstra tests.Segmentation at the pre-selected AIF and VOF locations was performed on a sample of 97 patients. 65 patients had favorable VO (VO+) and 32 patients had unfavorable VO (VO-). VO+ patients were found to have a significantly shorter VOF time to peak (8.26; 95% CI 7.07 to 10.34) than VO- patients (9.44; 95% CI 8.61 to 10.91), P=0.007. No significant difference was found in VOF curve width and the difference in time between AIF and VOF peaks.Time to peak of VOF at the confluence of sinuses was significantly associated with manually scored venous outflow. Further studies should aim to understand better the association between arterial inflow and venous outflow, and capture quantitative metrics of venous outflow at other locations.

  View details for DOI 10.1136/jnis-2023-020727

  View details for PubMedID 37643804

• USE-Evaluator: Performance metrics for medical image segmentation models supervised by uncertain, small or empty reference annotations in neuroimaging. Medical image analysis Ostmeier, S., Axelrod, B., Isensee, F., Bertels, J., Mlynash, M., Christensen, S., Lansberg, M. G., Albers, G. W., Sheth, R., Verhaaren, B. F., Mahammedi, A., Li, L. J., Zaharchuk, G., Heit, J. J. 2023; 90: 102927

  Abstract

  Performance metrics for medical image segmentation models are used to measure the agreement between the reference annotation and the predicted segmentation. Usually, overlap metrics, such as the Dice, are used as a metric to evaluate the performance of these models in order for results to be comparable. However, there is a mismatch between the distributions of cases and the difficulty level of segmentation tasks in public data sets compared to clinical practice. Common metrics used to assess performance fail to capture the impact of this mismatch, particularly when dealing with datasets in clinical settings that involve challenging segmentation tasks, pathologies with low signal, and reference annotations that are uncertain, small, or empty. Limitations of common metrics may result in ineffective machine learning research in designing and optimizing models. To effectively evaluate the clinical value of such models, it is essential to consider factors such as the uncertainty associated with reference annotations, the ability to accurately measure performance regardless of the size of the reference annotation volume, and the classification of cases where reference annotations are empty. We study how uncertain, small, and empty reference annotations influence the value of metrics on a stroke in-house data set regardless of the model. We examine metrics behavior on the predictions of a standard deep learning framework in order to identify suitable metrics in such a setting. We compare our results to the BRATS 2019 and Spinal Cord public data sets. We show how uncertain, small, or empty reference annotations require a rethinking of the evaluation. The evaluation code was released to encourage further analysis of this topic https://github.com/SophieOstmeier/UncertainSmallEmpty.git.

  View details for DOI 10.1016/j.media.2023.102927

  View details for PubMedID 37672900

• Endovascular Treatment for Acute Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Disease. Seminars in neurology Huo, X., Sun, D., Chen, W., Han, H., Abdalkader, M., Puetz, V., Yi, T., Wang, H., Liu, R., Tong, X., Jia, B., Ma, N., Gao, F., Mo, D., Yan, B., Mitchell, P. J., Leung, T. W., Yavagal, D. R., Albers, G. W., Costalat, V., Fiehler, J., Zaidat, O. O., Jovin, T. G., Liebeskind, D. S., Nguyen, T. N., Miao, Z. 2023

  Abstract

  Intracranial atherosclerotic disease (ICAD) is one of the most common causes of acute ischemic stroke worldwide. Patients with acute large vessel occlusion due to underlying ICAD (ICAD-LVO) often do not achieve successful recanalization when undergoing mechanical thrombectomy (MT) alone, requiring rescue treatment, including intra-arterial thrombolysis, balloon angioplasty, and stenting. Therefore, early detection of ICAD-LVO before the procedure is important to enable physicians to select the optimal treatment strategy for ICAD-LVO to improve clinical outcomes. Early diagnosis of ICAD-LVO is challenging in the absence of consensus diagnostic criteria on noninvasive imaging and early digital subtraction angiography. In this review, we summarize the clinical and diagnostic criteria, prediction of ICAD-LVO prior to the procedure, and EVT strategy of ICAD-LVO and provide recommendations according to the current literature.

  View details for DOI 10.1055/s-0043-1771207

  View details for PubMedID 37549690

• Functional Outcome Prediction in Acute Ischemic Stroke Using a Fused Imaging and Clinical Deep Learning Model. Stroke Liu, Y., Yu, Y., Ouyang, J., Jiang, B., Yang, G., Ostmeier, S., Wintermark, M., Michel, P., Liebeskind, D. S., Lansberg, M. G., Albers, G. W., Zaharchuk, G. 2023

  Abstract

  Predicting long-term clinical outcome based on the early acute ischemic stroke information is valuable for prognostication, resource management, clinical trials, and patient expectations. Current methods require subjective decisions about which imaging features to assess and may require time-consuming postprocessing. This study's goal was to predict ordinal 90-day modified Rankin Scale (mRS) score in acute ischemic stroke patients by fusing a Deep Learning model of diffusion-weighted imaging images and clinical information from the acute period.A total of 640 acute ischemic stroke patients who underwent magnetic resonance imaging within 1 to 7 days poststroke and had 90-day mRS follow-up data were randomly divided into 70% (n=448) for model training, 15% (n=96) for validation, and 15% (n=96) for internal testing. Additionally, external testing on a cohort from Lausanne University Hospital (n=280) was performed to further evaluate model generalization. Accuracy for ordinal mRS, accuracy within ±1 mRS category, mean absolute prediction error, and determination of unfavorable outcome (mRS score >2) were evaluated for clinical only, imaging only, and 2 fused clinical-imaging models.The fused models demonstrated superior performance in predicting ordinal mRS score and unfavorable outcome in both internal and external test cohorts when compared with the clinical and imaging models. For the internal test cohort, the top fused model had the highest area under the curve of 0.92 for unfavorable outcome prediction and the lowest mean absolute error (0.96 [95% CI, 0.77-1.16]), with the highest proportion of mRS score predictions within ±1 category (79% [95% CI, 71%-88%]). On the external Lausanne University Hospital cohort, the best fused model had an area under the curve of 0.90 for unfavorable outcome prediction and outperformed other models with an mean absolute error of 0.90 (95% CI, 0.79-1.01), and the highest percentage of mRS score predictions within ±1 category (83% [95% CI, 78%-87%]).A Deep Learning-based imaging model fused with clinical variables can be used to predict 90-day stroke outcome with reduced subjectivity and user burden.

  View details for DOI 10.1161/STROKEAHA.123.044072

  View details for PubMedID 37485663

• Anatomical predictors of need for decompressive craniectomy after stroke using voxel-based lesion symptom mapping. Journal of neuroimaging : official journal of the American Society of Neuroimaging McCullough-Hicks, M., Topiwala, K., Christensen, S., Ruiz-Betancourt, D., Mlynash, M., Albers, G. W. 2023

  Abstract

  BACKGROUND AND PURPOSE: Malignant cerebral edema (MCE) secondary to ischemic stroke is a highly morbid condition. Decompressive craniectomy (DC) is the only treatment for MCE that has been shown to reduce mortality. We examined whether early infarction and/or hypoperfusion in specific topographic regions was predictive of the need for later DC.METHODS: A retrospective database of patients evaluated for large vessel occlusion (LVO) stroke at Stanford between 2010 and 2019 was used. Thirty patients with LVO and baseline perfusion MRI who underwent DC were evaluated. Propensity matching based on age, lesion size, and recanalization status was performed on the remaining cohort. Baseline masks of apparent diffusion coefficient (ADC)+Tmax >6seconds lesions were generated using automated perfusion software. Voxel-based lesion symptom maping was used to perform logistic regression at each voxel to generate statistical maps of lesion location associated with DC. Hemispheres were combined to increase statistical power.RESULTS: Sixty patients were analyzed. After adjusting for age, lesion size, and recanalization status as covariates, scattered cortical regions, predominately within the temporal and frontal lobe, were mildly to moderately predictive of the need for DC (z-scores: 2.4-6.74, p<.01).CONCLUSIONS: Scattered temporal and frontal lobe regions on baseline diffusion and perfusion MRI were found to be mildly to moderately predictive of the need for subsequent DC in patients with LVO stroke.

  View details for DOI 10.1111/jon.13144

  View details for PubMedID 37400939

• Infarct Core Growth During Interhospital Transfer For Thrombectomy Is Faster At Night. Stroke Seners, P., Mlynash, M., Sreekrishnan, A., Ter Schiphorst, A., Arquizan, C., Costalat, V., Henon, H., Bretzner, M., Heit, J. J., Olivot, J. M., Lansberg, M. G., Albers, G. W. 2023

  Abstract

  Preclinical stroke models have recently reported faster infarct growth (IG) when ischemia was induced during daytime. Considering the inverse rest-activity cycles of rodents and humans, faster IG during the nighttime has been hypothesized in humans.We retrospectively evaluated acute ischemic stroke patients with a large vessel occlusion transferred from a primary to 1 of 3 French comprehensive stroke center, with magnetic resonance imaging obtained at both centers before thrombectomy. Interhospital IG rate was calculated as the difference in infarct volumes on the 2 diffusion-weighted imaging, divided by the time elapsed between the 2 magnetic resonance imaging. IG rate was compared between patients transferred during daytime (7:00-22:59) and nighttime (23:00-06:59) in multivariable analysis adjusting for occlusion site, National Institutes of Health Stroke Scale score, infarct topography, and collateral status.Out of the 329 patients screened, 225 patients were included. Interhospital transfer occurred during nighttime in 31 (14%) patients and daytime in 194 (86%). Median interhospital IG was faster when occurring at night (4.3 mL/h; interquartile range, 1.2-9.5) as compared to the day (1.4 mL/h; interquartile range, 0.4-3.5; P<0.001). In multivariable analysis, nighttime transfer remained independently associated with IG rate (P<0.05).Interhospital IG appeared faster in patients transferred at night. This has potential implications for the design of neuroprotection trials and acute stroke workflow.

  View details for DOI 10.1161/STROKEAHA.123.043643

  View details for PubMedID 37376988

• Endovascular thrombectomy for ischemic stroke with large core volume: An updated, post-TESLA systematic review and meta-analysis of the randomized trials. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Kobeissi, H., Adusumilli, G., Ghozy, S., Kadirvel, R., Brinjikji, W., Albers, G. W., Heit, J. J., Kallmes, D. F. 2023: 15910199231185738

  Abstract

  Limited randomized controlled trials (RCTs) have been performed comparing endovascular thrombectomy (EVT) to medical therapy (MEDT) for acute ischemic stroke with extensive baseline ischemic injury (AIS-EBI). We conducted a systematic review and meta-analysis of RCTs reporting EVT for AIS-EBI.Using the Nested Knowledge AutoLit software, we conducted a systematic literature review from inception to 12 February 2023 within Web of Science, Embase, Scopus, and PubMed databases. Results of the TESLA trial were included on 10 June 2023. We included RCTs that compared EVT to MEDT for AIS with large ischemic core volume. The primary outcome of interest was a modified Rankin Score (mRS) 0-2. Secondary outcomes of interest included early neurological improvement (ENI), mRS 0-3, thrombolysis in cerebral infarction (TICI) 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. A random-effects model was used to calculate risk ratios (RRs) and their corresponding 95% confidence intervals (CIs).We included four RCTs with 1310 patients, 661 of whom underwent EVT and 649 of whom were treated with MEDT. EVT was associated with greater rates of mRS 0-2 (RR = 2.33, 95% CI = 1.75-3.09; P-value < 0.001), mRS 0-3 (RR = 1.68, 95% CI = 1.33-2.12; P-value < 0.001), and ENI (RR = 2.24, 95% CI = 1.55-3.24; P-value < 0.001). Rates of sICH (RR = 1.99, 95% CI = 1.07-3.69; P-value = 0.03) were greater in the EVT group. Mortality (RR = 0.98, 95% CI = 0.83-1.15; P-value = 0.79) was comparable between the EVT and MEDT groups. The rate of successful reperfusion in the EVT group was 79.9% (95% CI = 75.6-83.6).Although the rate of sICH was greater in the EVT group, EVT conferred a greater clinical benefit to MEDT for AIS-EBI based on available RCTs.

  View details for DOI 10.1177/15910199231185738

  View details for PubMedID 37376869

• Pretreatment brain CT perfusion thresholds for predicting final infarct volume in distal medium vessel occlusions. Journal of neuroimaging : official journal of the American Society of Neuroimaging Yedavalli, V., Hamam, O., Mohseni, A., Chen, K., Wang, R., Heo, H., Heit, J., Marsh, E. B., Llinas, R., Urrutia, V., Xu, R., Gonzalez, F., Albers, G., Hillis, A., Nael, K. 2023

  Abstract

  BACKGROUND AND PURPOSE: Quantitative CT perfusion (CTP) thresholds for assessing the extent of ischemia in patients with acute ischemic stroke (AIS) have been established; relative cerebral blood flow (rCBF) <30% is typically used for estimating estimated ischemic core volume and Tmax (time to maximum) >6seconds for critical hypoperfused volume in AIS patients with large vessel occlusion (LVO). In this study, we aimed to identify the optimal threshold values for patients presenting with AIS secondary to distal medium vessel occlusions (DMVOs).METHODS: In this retrospective study, consecutive AIS patients with anterior circulation DMVO who underwent pretreatment CTP and follow-up MRI/CT were included. The CTP data were processed by RAPID (iSchemaView, Menlo Park, CA) to generate estimated ischemic core volumes using rCBF <20%, <30%, <34%, and <38% and critical hypoperfused volumes using Tmax (seconds) >4, >6, >8, and >10. Final infarct volumes (FIVs) were obtained from follow-up MRI/CT within 5days of symptom onset. Diagnostic performance between CTP thresholds and FIV was assessed in the successfully and unsuccessfully recanalized groups.RESULTS: Fifty-five patients met our inclusion criteria (32 female [58.2%], 68.0±12.1years old [mean±SD]). Recanalization was attempted with intravenous tissue-type plasminogen activator and mechanical thrombectomy in 27.7% and 38.1% of patients, respectively. Twenty-five patients (45.4%) were successfully recanalized. In the successfully recanalized patients, no CTP threshold significantly outperformed what is used in LVO setting (rCBF<30%). All rCBF CTP thresholds demonstrated fair diagnostic performances for predicting FIV. In unsuccessfully recanalized patients, all Tmax CTP thresholds strongly predicted FIV with relative superiority of Tmax >10seconds (area under the receiver operating characteristic curve=.875, p=.001).CONCLUSION: In AIS patients with DMVOs, longer Tmax delays than Tmax >6seconds, most notably, Tmax >10seconds, best predict FIV in unsuccessfully recanalized patients. No CTP threshold reliably predicts FIV in the successfully recanalized group nor significantly outperformed rCBF<30%.

  View details for DOI 10.1111/jon.13142

  View details for PubMedID 37357133

• Role of Brain Imaging in the Prediction of Intracerebral Hemorrhage Following Endovascular Therapy for Acute Stroke. Stroke Seners, P., Wouters, A., Maïer, B., Boisseau, W., Gory, B., Heit, J. J., Cognard, C., Mazighi, M., Gaudilliere, B., Lemmens, R., Zaharchuk, G., Albers, G. W., Leigh, R., Olivot, J. M. 2023

  Abstract

  Currently most acute ischemic stroke patients presenting with a large vessel occlusion are treated with endovascular therapy (EVT), which results in high rates of successful recanalization. Despite this success, more than half of EVT-treated patients are significantly disabled 3 months later partly due to the occurrence of post-EVT intracerebral hemorrhage. Predicting post-EVT intracerebral hemorrhage is important for individualizing treatment strategies in clinical practice (eg, safe initiation of early antithrombotic therapies), as well as in selecting the optimal candidates for clinical trials that aim to reduce this deleterious outcome. Emerging data suggest that brain and vascular imaging biomarkers may be particularly relevant since they provide insights into the ongoing acute stroke pathophysiology. In this review/perspective, we summarize the accumulating literature on the role of cerebrovascular imaging biomarkers in predicting post-EVT-associated intracerebral hemorrhage. We focus on imaging acquired before EVT, during the EVT procedure, and in the early post-EVT time frames when new therapeutic therapies could be tested. Accounting for the complex pathophysiology of post-EVT-associated intracerebral hemorrhage, this review may provide some guidance for future prospective observational or therapeutic studies.

  View details for DOI 10.1161/STROKEAHA.123.040806

  View details for PubMedID 37334709

• Consensus Recommendations for Standardized Data Elements, Scales, and Time Segmentations in Studies of Human Circadian/Diurnal Biology and Stroke. Stroke Saver, J. L., Klerman, E. B., Buchan, A. M., Calleja, P., Lizasoain, I., Bahr-Hosseini, M., Lee, S., Liebeskind, D. S., Mergenthaler, P., Mun, K. T., Ning, M., Pelz, D., Ray, D., Rothwell, P. M., Seners, P., Sreekrishnan, A., Sung, E. M., Tiedt, S., Webb, A. J., Wölfer, T. A., Albers, G. W. 2023

  Abstract

  Increasing evidence indicates that circadian and diurnal rhythms robustly influence stroke onset, mechanism, progression, recovery, and response to therapy in human patients. Pioneering initial investigations yielded important insights but were often single-center series, used basic imaging approaches, and used conflicting definitions of key data elements, including what constitutes daytime versus nighttime. Contemporary methodologic advances in human neurovascular investigation have the potential to substantially increase understanding, including the use of large multicenter and national data registries, detailed clinical trial data sets, analysis guided by individual patient chronotype, and multimodal computed tomographic and magnetic resonance imaging. To fully harness the power of these approaches to enhance pathophysiologic knowledge, an important foundational step is to develop standardized definitions and coding guides for data collection, permitting rapid aggregation of data acquired in different studies, and ensuring a common framework for analysis. To meet this need, the Leducq Consortium International pour la Recherche Circadienne sur l'AVC (CIRCA) convened a Consensus Statement Working Group of leading international researchers in cerebrovascular and circadian/diurnal biology. Using an iterative, mixed-methods process, the working group developed 79 data standards, including 48 common data elements (23 new and 25 modified/unmodified from existing common data elements), 14 intervals for time-anchored analyses of different granularity, and 7 formal, validated scales. This portfolio of standardized data structures is now available to assist researchers in the design, implementation, aggregation, and interpretation of clinical, imaging, and population research related to the influence of human circadian/diurnal biology upon ischemic and hemorrhagic stroke.

  View details for DOI 10.1161/STROKEAHA.122.041394

  View details for PubMedID 37272394

• The negative effect of aging on cerebral venous outflow in acute ischemic stroke. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Heitkamp, C., Winkelmeier, L., Heit, J. J., Flottmann, F., Thaler, C., Kniep, H., Broocks, G., Meyer, L., Geest, V., Albers, G. W., Lansberg, M. G., Fiehler, J., Faizy, T. D. 2023: 271678X231179558

  Abstract

  Cortical venous outflow (VO) represents an imaging biomarker of increasing interest in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We conducted a retrospective multicenter cohort study to investigate the effect of aging on VO. A total of 784 patients met the inclusion criteria. Cortical Vein Opacification Score (COVES) was used to assess VO profiles on admission CT angiography. Cerebral microperfusion was determined using the hypoperfusion intensity ratio (HIR) derived from perfusion imaging. Arterial collaterals were assessed using the Tan scale. Multivariable regression analysis was performed to identify independent determinants of VO, HIR and arterial collaterals. In multivariable regression, higher age correlated with worse VO (adjusted odds ratio [95% CI]; 0.83 [0.73-0.95]; P = 0.006) and poorer HIR (β coefficient [95% CI], 0.014 [0.005-0.024]; P = 0.002). The negative effect of higher age on VO was mediated by the extent of HIR (17.3%). We conclude that higher age was associated with worse VO in AIS-LVO, partially explained by the extent of HIR reflecting cerebral microperfusion. Our study underlines the need to assess collateral blood flow beyond the arterial system and provides valuable insights into deteriorated cerebral blood supply in elderly AIS-LVO patients.

  View details for DOI 10.1177/0271678X231179558

  View details for PubMedID 37254736

• Unfavorable Cerebral Venous Outflow is associated with Futile Recanalization in Acute Ischemic Stroke Patients. European journal of neurology Heitkamp, C., Winkelmeier, L., Heit, J. J., Albers, G. W., Lansberg, M. G., Wintermark, M., Broocks, G., van Horn, N., Kniep, H. C., Sporns, P. B., Zelenak, K., Fiehler, J., Faizy, T. D. 2023

  Abstract

  BACKGROUND: Mechanical thrombectomy (MT) has proven to be the standard of care for patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). However, high revascularization rates do not necessarily result in favorable functional outcomes. We aimed to investigate imaging biomarkers associated with futile recanalization, defined as unfavorable functional outcome despite successful recanalization in AIS-LVO patients.METHODS: Retrospective multicenter cohort study of AIS-LVO patients treated by MT. Successful recanalization was defined as modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b-3. A modified Rankin Scale (mRS) score of 3-6 at 90-days was defined as unfavorable functional outcome. Cortical Vein Opacification Score (COVES) was used to assess venous outflow (VO) and the Tan scale was utilized to determine pial arterial collaterals on admission computed tomography angiography (CTA). Unfavorable VO was defined as COVES ≤2. Multivariable regression analysis was performed to investigate vascular imaging factors associated with futile recanalization.RESULTS: Among 539 patients in which successful recanalization was achieved, unfavorable functional outcome was observed in 59% of patients. 58% of patients had unfavorable VO and 31% exhibited poor pial arterial collaterals. In multivariable regression, unfavorable VO was a strong predictor (adjusted odds ratio [95% CI]; 4.79 [2.48-9.23]) of unfavorable functional outcome despite successful recanalization.CONCLUSION: We observe that unfavorable VO on admission CTA is a strong predictor of unfavorable functional outcomes despite successful vessel recanalization in AIS-LVO patients. Assessment of VO profiles could help as a pretreatment imaging biomarker to determine patients at risk for futile recanalization.

  View details for DOI 10.1111/ene.15898

  View details for PubMedID 37243906

• Comprehensive Venous Outflow Predicts Functional Outcomes in Patients with Acute Ischemic Stroke Treated by Thrombectomy. AJNR. American journal of neuroradiology Adusumilli, G., Faizy, T. D., Christensen, S., Mlynash, M., Loh, Y., Albers, G. W., Lansberg, M. G., Fiehler, J., Heit, J. J. 2023

  Abstract

  Cortical venous outflow has emerged as a robust measure of collateral blood flow in acute ischemic stroke. The addition of deep venous drainage to this assessment may provide valuable information to further guide the treatment of these patients.We performed a multicenter retrospective cohort study of patients with acute ischemic stroke treated by thrombectomy between January 2013 and January 2021. The internal cerebral veins were scored on a scale of 0-2. This metric was combined with existing cortical vein opacification scores to create a comprehensive venous outflow score from 0 to 8 and stratify patients as having favorable-versus-unfavorable comprehensive venous outflow. Outcome analyses were primarily conducted using the Mann-Whitney U and χ2 tests.Six hundred seventy-eight patients met the inclusion criteria. Three hundred fifteen were stratified as having favorable comprehensive venous outflow (mean age, 73 years; range, 62-81 years; 170 men), and 363, as having unfavorable comprehensive venous outflow (mean age, 77 years; range, 67-85 years; 154 men). There were significantly higher rates of functional independence (mRS 0-2; 194/296 versus 37/352, 66% versus 11%, P < .001) and excellent reperfusion (TICI 2c/3; 166/313 versus 142/358, 53% versus 40%, P < .001) in patients with favorable comprehensive venous outflow. There was a significant increase in the association of mRS with the comprehensive venous outflow score compared with the cortical vein opacification score (-0.74 versus -0.67, P = .006).A favorable comprehensive venous profile is strongly associated with functional independence and excellent postthrombectomy reperfusion. Future studies should focus on patients with venous outflow status that is discrepant with the eventual outcome.

  View details for DOI 10.3174/ajnr.A7879

  View details for PubMedID 37202117

• Elevated Hypoperfusion Intensity Ratio (HIR) observed in patients with a large vessel occlusion (LVO) presenting in the evening. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Sreekrishnan, A., Seners, P., Yuen, N., Olivot, J., Mlynash, M., Lansberg, M. G., Heit, J. J., Lee, S., Michel, P., Strambo, D., Salerno, A., Paredes, J. B., Carrera, E., Albers, G. W. 2023; 32 (8): 107172

  Abstract

  BACKGROUND: Circadian variability has been implicated in timing of stroke onset, yet the full impact of underlying biological rhythms on acute stroke perfusion patterns is not known. We aimed to describe the relationship between time of stroke onset and perfusion profiles in patients with large vessel occlusion (LVO).METHODS: A retrospective observational study was conducted using prospective registries of four stroke centers across North America and Europe with systematic use of perfusion imaging in clinical care. Included patients had stroke due to ICA, M1 or M2 occlusion and baseline perfusion imaging performed within 24h from last-seen-well (LSW). Stroke onset was divided into eight hour intervals: (1) Night: 23:00-6:59, (2) Day: 7:00-14:59, (3) Evening: 15:00-22:59. Core volume was estimated on CT perfusion (rCBF <30%) or DWI-MRI (ADC <620) and the collateral circulation was estimated with the Hypoperfusion Intensity Ratio (HIR=[Tmax>10s]/[Tmax>6s]). Non-parametric testing was conducted using SPSS to account for the non-normalized dependent variables.RESULTS: A total of 1506 cases were included (median age 74.9 years, IQR 63.0-84.0). Median NIHSS, core volumes, and HIR were 14.0 (IQR 8.0-20.0), 13.0mL (IQR 0.0-42.0), and 0.4 (IQR 0.2-0.6) respectively. Most strokes occurred during the Day (n=666, 44.2%), compared to Night (n=360, 23.9%), and Evening (n=480, 31.9%). HIR was highest, indicating worse collaterals, in the Evening compared to the other timepoints (p=0.006). Controlling for age and time to imaging, Evening strokes had significantly higher HIR compared to Day (p=0.013).CONCLUSION: Our retrospective analysis suggests that HIR is significantly higher in the evening, indicating poorer collateral activation which may lead to larger core volumes in these patients.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2023.107172

  View details for PubMedID 37196564

• Association Between Intravenous Thrombolysis and Clinical Outcomes Among Patients With Ischemic Stroke and Unsuccessful Mechanical Reperfusion. JAMA network open Faizy, T. D., Broocks, G., Heit, J. J., Kniep, H., Flottmann, F., Meyer, L., Sporns, P., Hanning, U., Kaesmacher, J., Deb-Chatterji, M., Vollmuth, P., Lansberg, M. G., Albers, G. W., Fischer, U., Wintermark, M., Thomalla, G., Fiehler, J., Winkelmeier, L. 2023; 6 (5): e2310213

  Abstract

  Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce.To determine whether intravenous thrombolysis (IVT) prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke.Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching.Mechanical thrombectomy with or without IVT.Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death.After matching, 746 patients were compared by treatment arms (median age, 78 [IQR, 68-84] years; 438 women [58.7%]). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio [AOR], 2.63 [95% CI, 1.41-5.11]; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 [95% CI, 1.35-2.92]; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 [95% CI, 0.29-1.81]; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 [95% CI, 0.34-0.86]; P = .01).These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment.

  View details for DOI 10.1001/jamanetworkopen.2023.10213

  View details for PubMedID 37126350

• Imaging Factors Associated With Poor Outcome in Patients With Basilar Artery Occlusion Treated With Endovascular Thrombectomy STROKE-VASCULAR AND INTERVENTIONAL NEUROLOGY Heit, J. J., Mlynash, M., Cereda, C. W., Yuen, N., Lansberg, M. G., Bianco, G., Christensen, S., Qureshi, A. Y., Hinduja, A., Dehkharghani, S., Goldman-Yassen, A. E., Hsieh, K., Giurgiutiu, D., Gibson, D., Carrera, E., Alemseged, F., Faizy, T. D., Fiehler, J., Pileggi, M., Campbell, B., Albers, G. W. 2023; 3 (3)

  View details for DOI 10.1161/SVIN.122.000767

  View details for Web of Science ID 001162312700023

• Visual review of acute stroke neuroimaging prior to transfer acceptance increases likelihood of endovascular therapy. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association McCullough-Hicks, M., Thatikunta, P., Mlynash, M., Albers, G. W., Mijalski-Sells, C. 2023; 32 (7): 107157

  Abstract

  OBJECTIVES: Demand for thrombectomy, and interhospital transfer to comprehensive stroke centers (CSCs), for acute stroke is increasing. There is an urgent need to identify patients most likely to benefit from transfer. We evaluated whether CSC providers' review of neuroimaging prior to transfer acceptance improved patient selection for thrombectomy and correlated with higher rates of treatment.MATERIALS AND METHODS: A retrospective database of all patients transferred to Stanford's CSC for thrombectomy between 2015-2019 was used. Pre-acceptance images, when available for visual review, were reviewed by the CSC stroke team via virtual PACS, RAPID software, or LifeImage platforms.RESULTS: 525 patients met inclusion criteria. 147 (28%) had neuroimaging available for review prior to transfer. Of those who did not recanalize en route, 267 (50.8%) underwent thrombectomy. Patients with imaging available for review prior to acceptance were significantly more likely to receive thrombectomy (68% vs 54%, RR 1.26; p=0.006, 95% CI 1.09-1.48). Patient images that were reviewed via RAPID were CT-based perfusion studies; these were more likely to receive thrombectomy (70% vs 54%, RR 1.30; p=0.01, 1.09-1.56). Patients who received EVT were more likely to have had pre-transfer vessel imaging, regardless of availability for visual review (76% vs 59%, RR 1.44; p<0.001, 1.18-1.76).CONCLUSIONS: Patients with concern for acute stroke transferred for consideration of thrombectomy who had neuroimaging visually reviewed prior to transfer acceptance and did not recanalize by time of arrival were significantly more likely to undergo thrombectomy. Additional prospective studies are needed to confirm our findings.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2023.107157

  View details for PubMedID 37126905

• The Charlotte Large Artery Occlusion Endovascular Therapy Outcome Score Compares Favorably to the Critical Area Perfusion Score for Prognostication Before Basilar Thrombectomy. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Karamchandani, R. R., Satyanarayana, S., Yang, H., Rhoten, J. B., Strong, D., Singh, S., Clemente, J. D., Defilipp, G., Hazim, M., Patel, N. M., Bernard, J., Stetler, W. R., Parish, J. M., Blackwell, T. A., Heit, J. J., Albers, G. W., Saba, K., Guzik, A. K., Wolfe, S. Q., Asimos, A. W. 2023; 32 (7): 107147

  Abstract

  The Critical Area Perfusion Score (CAPS) predicts functional outcomes in vertebrobasilar thrombectomy patients based on computed tomography perfusion (CTP) hypoperfusion. We compared CAPS to the clinical-radiographic Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS).Acute basilar thrombosis patients from January 2017-December 2021 were included in this retrospective analysis from a health system's stroke registry. Inter-rater reliability was assessed for 6 CAPS raters. A logistic regression with CAPS and CLEOS as predictors was performed to predict 90-day modified Rankin Scale (mRS) score 4-6. Area under the curve (AUC) analyses were performed to evaluate prognostic ability.55 patients, mean age 65.8 (± 13.1) years and median NIHSS score 15.55-24, were included. Light's kappa among 6 raters for favorable versus unfavorable CAPS was 0.633 (95% CI 0.497-0.785). Increased CLEOS was associated with elevated odds of a poor outcome (odds ratio (OR) 1.0010, 95% CI 1.0007-1.0014, p<0.01), though CAPS was not (OR 1.0028, 95% CI 0.9420-1.0676, p=0.93). An overall favorable trend was observed for CLEOS (AUC 0.69, 95% CI 0.54-0.84) versus CAPS (AUC 0.49, 95% CI 0.34-0.64; p=0.051). Among 85.5% of patients with endovascular reperfusion, CLEOS had a statistically higher sensitivity than CAPS at identifying poor 90-day outcomes (71% versus 21%, p=0.003).CLEOS demonstrated better predictive ability than CAPS for poor outcomes overall and in patients achieving reperfusion after basilar thrombectomy.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2023.107147

  View details for PubMedID 37119791

• Cerebral Perfusion Imaging and Plateau Waves. Stroke Slawski, D., Lyman, K. A., Thatikunta, P., Gold, C. A., Albers, G. W. 2023

  View details for DOI 10.1161/STROKEAHA.122.042274

  View details for PubMedID 37021565

• Effect of atherosclerosis on 5-year risk of major vascular events in patients with transient ischaemic attack or minor ischaemic stroke: an international prospective cohort study LANCET NEUROLOGY Lavallee, P. C., Charles, H., Albers, G. W., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Labreuche, J., Molina, C., Rothwell, P. M., Steg, P., Touboul, P., Uchiyama, S., Vicaut, E., Wong, L. S., Amarenco, P., TIAregistry Org Investigators 2023; 22 (4): 320-329

  View details for Web of Science ID 000958527500001

• Effect of atherosclerosis on 5-year risk of major vascular events in patients with transient ischaemic attack or minor ischaemic stroke: an international prospective cohort study. The Lancet. Neurology Lavallee, P. C., Charles, H., Albers, G. W., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Labreuche, J., Molina, C., Rothwell, P. M., Steg, P. G., Touboul, P., Uchiyama, S., Vicaut, E., Wong, L. K., Amarenco, P., TIAregistry.org Investigators,, 2023; 22 (4): 320-329

  Abstract

  BACKGROUND: The prevalence of atherosclerosis and the long-term risk of major vascular events in people who have had a transient ischaemic attack or minor ischaemic stroke, regardless of the causal relationship between the index event and atherosclerosis, are not well known. In this analysis, we applied the ASCOD (atherosclerosis, small vessel disease, cardiac pathology, other causes, and dissection) grading system to estimate the 5-year risk of major vascular events according to whether there was a causal relationship between atherosclerosis and the index event (ASCOD grade A1 and A2), no causal relationship (A3), and with or without a causal relationship (A1, A2, and A3). We also aimed to estimate the prevalence of different grades of atherosclerosis and identify associated risk factors.METHODS: We analysed patient data from TIAregistry.org, which is an international, prospective, observational registry of patients with a recent (within the previous 7 days) transient ischaemic attack or minor ischaemic stroke (modified Rankin Scale score of 0-1) from 61 specialised centres in 21 countries in Europe, Asia, the Middle East, and Latin America. Using data from case report forms, we applied the ASCOD grading system to categorise the degree of atherosclerosis in our population (A0: no atherosclerosis; A1 or A2: atherosclerosis with stenosis ipsilateral to the cerebral ischaemic area; A3: atherosclerosis in vascular beds not related to the ischaemic area or ipsilateral plaques without stenosis; and A9: atherosclerosis not assessed). The primary outcome was a composite of non-fatal stroke, non-fatal acute coronary syndrome, or cardiovascular death within 5 years.FINDINGS: Between June 1, 2009, and Dec 29, 2011, 4789 patients were enrolled to TIAregistry.org, of whom 3847 people from 42 centres participated in the 5-year follow-up; 3383 (87·9%) patients had a 5-year follow-up visit (median 92·3% [IQR 83·4-97·8] per centre). 1406 (36·5%) of 3847 patients had no atherosclerosis (ASCOD grade A0), 998 (25·9%) had causal atherosclerosis (grade A1 or A2), and 1108 (28·8%) had atherosclerosis that was unlikely to be causal (grade A3); in 335 (8·7%) patients, atherosclerosis was not assessed (grade A9). The 5-year event rate of the primary composite outcome was 7·7% (95% CI 6·3-9·2; 101 events) in patients categorised with grade A0 atherosclerosis, 19·8% (17·4-22·4; 189 events) in those with grade A1 or A2, and 13·8% (11·8-16·0; 144 events) in patients with grade A3. Compared with patients with grade A0 atherosclerosis, patients categorised as grade A1 or A2 had an increased risk of the primary composite outcome (hazard ratio 2·77, 95% CI 2·18-3·53; p<0·0001), as did patients with grade A3 (1·87, 1·45-2·42; p<0·0001). Except for age, male sex, and multiple infarctions on neuroimaging, most of the risk factors that were identified as being associated with grade A1 or A2 atherosclerosis were modifiable risk factors (ie, hypertension, dyslipidaemia, overweight, smoking cigarettes, and low physical activity; all p values <0·025).INTERPRETATION: In patients with transient ischaemic attack or minor ischaemic stroke, those with atherosclerosis have a much higher risk of major vascular events within 5 years than do those without atherosclerosis. Preventive strategies addressing complications of atherosclerosis should focus on individuals with atherosclerosis rather than grouping together all people who have had a transient ischaemic attack or minor ischaemic stroke (including those without atherosclerosis).FUNDING: AstraZeneca, Sanofi, Bristol Myers Squibb, SOS Attaque Cerebrale Association.

  View details for DOI 10.1016/S1474-4422(23)00067-4

  View details for PubMedID 36931807

• Endovascular Therapy or Medical Management Alone for Isolated Posterior Cerebral Artery Occlusion: A Multicenter Study. Stroke Sabben, C., Charbonneau, F., Delvoye, F., Strambo, D., Heldner, M. R., Ong, E., Ter Schiphorst, A., Henon, H., Ben Hassen, W., Agasse-Lafont, T., Legris, L., Sibon, I., Wolff, V., Sablot, D., Elhorany, M., Preterre, C., Nehme, N., Soize, S., Weisenburger-Lile, D., Triquenot-Bagan, A., Mione, G., Aignatoaie, A., Papassin, J., Poll, R., Béjot, Y., Carrera, E., Garnier, P., Michel, P., Saliou, G., Mordasini, P., Berthezene, Y., Costalat, V., Bricout, N., Albers, G. W., Mazighi, M., Turc, G., Seners, P. 2023; 54 (4): 928-937

  Abstract

  Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown.We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0-2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage, and early neurological deterioration.Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63-82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4-10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66-1.01]; P=0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95-1.43]; P=0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35-4.67]; P=0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64-3.84]; P<0.0001).In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

  View details for DOI 10.1161/STROKEAHA.122.042283

  View details for PubMedID 36729389

• Quantification of Penumbral Volume in Association With Time From Stroke Onset in Acute Ischemic Stroke With Large Vessel Occlusion. JAMA neurology Seners, P., Yuen, N., Mlynash, M., Snyder, S. J., Heit, J. J., Lansberg, M. G., Christensen, S., Albucher, J., Cognard, C., Sibon, I., Obadia, M., Savatovsky, J., Baron, J., Olivot, J., Albers, G. W., Mismatch Prevalence Investigators, Guenego, A., Thalamas, C., Rousseau, V., Drif, A., Sommet, A., Viguier, A., Darcourt, J., Calviere, L., Menegon, P., Raposo, N., Januel, A., Bonneville, F., Tourdias, T., Mazighi, M., Chollet, F., Barbieux, M., Michelozzi, C., Tall, P., Caparros, F., Pouzet, B., Calvas, F., Galitzki, M., Renou, P., Rouanet, F., Berge, J., Marnat, G., Lucas, L., Coignon, C., Sagnier, S., Debruxelle, S., Ledure, S. 2023

  Abstract

  Importance: The benefit of reperfusion therapies for acute ischemic stroke decreases over time. This decreasing benefit is presumably due to the disappearance of salvageable ischemic brain tissue (ie, the penumbra).Objective: To study the association between stroke onset-to-imaging time and penumbral volume in patients with acute ischemic stroke with a large vessel occlusion.Design, Setting, and Participants: A retrospective, multicenter, cross-sectional study was conducted from January 1, 2015, to June 30, 2022. To limit selection bias, patients were selected from (1) the prospective registries of 2 comprehensive centers with systematic use of magnetic resonance imaging (MRI) with perfusion, including both thrombectomy-treated and untreated patients, and (2) 1 prospective thrombectomy study in which MRI with perfusion was acquired per protocol but treatment decisions were made with clinicians blinded to the results. Consecutive patients with acute stroke with intracranial internal carotid artery or first segment of middle cerebral artery occlusion and adequate quality MRI, including perfusion, performed within 24 hours from known symptoms onset were included in the analysis.Exposures: Time from stroke symptom onset to baseline MRI.Main Outcomes and Measures: Penumbral volume, measured using automated software, was defined as the volume of tissue with critical hypoperfusion (time to maximum >6 seconds) minus the volume of the ischemic core. Substantial penumbra was defined as greater than or equal to 15 mL and a mismatch ratio (time to maximum >6-second volume/core volume) greater than or equal to 1.8.Results: Of 940 patients screened, 516 were excluded (no MRI, n=19; no perfusion imaging, n=59; technically inadequate perfusion imaging, n=75; second segment of the middle cerebral artery occlusion, n=156; unwitnessed stroke onset, n=207). Of 424 included patients, 226 (53.3%) were men, and mean (SD) age was 68.9 (15.1) years. Median onset-to-imaging time was 3.8 (IQR, 2.4-5.5) hours. Only 16 patients were admitted beyond 10 hours from symptom onset. Median core volume was 24 (IQR, 8-76) mL and median penumbral volume was 58 (IQR, 29-91) mL. An increment in onset-to-imaging time by 1 hour resulted in a decrease of 3.1 mL of penumbral volume (beta coefficient=-3.1; 95% CI, -4.6 to -1.5; P<.001) and an increase of 3.0 mL of core volume (beta coefficient=3.0; 95% CI, 1.3-4.7; P<.001) after adjustment for confounders. The presence of a substantial penumbra ranged fromapproximately80% in patients imaged at 1 hour to 70% at 5 hours, 60% at 10 hours, and 40% at 15 hours.Conclusions and Relevance: Time is associated with increasing core and decreasing penumbral volumes. Despite this, a substantial percentage of patients have notable penumbra in extended time windows; the findings of this study suggest that a large proportion of patients with large vessel occlusion may benefit from therapeutic interventions.

  View details for DOI 10.1001/jamaneurol.2023.0265

  View details for PubMedID 36939736

• Using Epidemiological Data to Inform Clinical Trial Feasibility Assessments: A Case Study. Stroke Stanton, R. J., Robinson, D. J., Aziz, Y. N., Sucharew, H., Khatri, P., Broderick, J. P., Janis, L. S., Kemp, S., Mlynash, M., Lansberg, M. G., Albers, G. W., Saver, J. L., Flaherty, M. L., Adeoye, O., Woo, D., Ferioli, S., Kissela, B. M., Kleindorfer, D. O. 2023

  Abstract

  Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed.In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan.After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0-2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to <6), the number predicted to be eligible for the trial increased to 4%. At the time of trial conclusion, 57% of the enrolled patients qualified only by the modified criteria, and the trial was stopped at an interim analysis that demonstrated efficacy. We estimated that the Wilcoxon rank-sum value for the unadjusted predicted enrollment would not have crossed the threshold for efficacy and the trial not stopped.Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.

  View details for DOI 10.1161/STROKEAHA.122.041650

  View details for PubMedID 36852687

• Neuroimaging is the new "spatial omic": multi-omic approaches to neuro-inflammation and immuno-thrombosis in acute ischemic stroke. Seminars in immunopathology Maier, B., Tsai, A. S., Einhaus, J. F., Desilles, J., Ho-Tin-Noe, B., Gory, B., Sirota, M., Leigh, R., Lemmens, R., Albers, G., Olivot, J., Mazighi, M., Gaudilliere, B. 2023

  Abstract

  Ischemic stroke (IS) is the leading cause of acquired disability and the second leading cause of dementia and mortality. Current treatments for IS are primarily focused on revascularization of the occluded artery. However, only 10% of patients are eligible for revascularization and 50% of revascularized patients remain disabled at 3 months. Accumulating evidence highlight the prognostic significance of the neuro- and thrombo-inflammatory response after IS. However, several randomized trials of promising immunosuppressive or immunomodulatory drugs failed to show positive results. Insufficient understanding of inter-patient variability in the cellular, functional, and spatial organization of the inflammatory response to IS likely contributed to the failure to translate preclinical findings into successful clinical trials. The inflammatory response to IS involves complex interactions between neuronal, glial, and immune cell subsets across multiple immunological compartments, including the blood-brain barrier, the meningeal lymphatic vessels, the choroid plexus, and the skull bone marrow. Here, we review the neuro- and thrombo-inflammatory responses to IS. We discuss how clinical imaging and single-cell omic technologies have refined our understanding of the spatial organization of pathobiological processes driving clinical outcomes in patients with an IS. We also introduce recent developments in machine learning statistical methods for the integration of multi-omic data (biological and radiological) to identify patient-specific inflammatory states predictive of IS clinical outcomes.

  View details for DOI 10.1007/s00281-023-00984-6

  View details for PubMedID 36786929

• Trial of Endovascular Thrombectomy for Large Ischemic Strokes. The New England journal of medicine Sarraj, A., Hassan, A. E., Abraham, M. G., Ortega-Gutierrez, S., Kasner, S. E., Hussain, M. S., Chen, M., Blackburn, S., Sitton, C. W., Churilov, L., Sundararajan, S., Hu, Y. C., Herial, N. A., Jabbour, P., Gibson, D., Wallace, A. N., Arenillas, J. F., Tsai, J. P., Budzik, R. F., Hicks, W. J., Kozak, O., Yan, B., Cordato, D. J., Manning, N. W., Parsons, M. W., Hanel, R. A., Aghaebrahim, A. N., Wu, T. Y., Cardona-Portela, P., Pérez de la Ossa, N., Schaafsma, J. D., Blasco, J., Sangha, N., Warach, S., Gandhi, C. D., Kleinig, T. J., Sahlein, D., Elijovich, L., Tekle, W., Samaniego, E. A., Maali, L., Abdulrazzak, M. A., Psychogios, M. N., Shuaib, A., Pujara, D. K., Shaker, F., Johns, H., Sharma, G., Yogendrakumar, V., Ng, F. C., Rahbar, M. H., Cai, C., Lavori, P., Hamilton, S., Nguyen, T., Fifi, J. T., Davis, S., Wechsler, L., Pereira, V. M., Lansberg, M. G., Hill, M. D., Grotta, J. C., Ribo, M., Campbell, B. C., Albers, G. W. 2023

  Abstract

  Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations.We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome.The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group.Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

  View details for DOI 10.1056/NEJMoa2214403

  View details for PubMedID 36762865

• Determinants of Infarct Core Growth During Inter-hospital Transfer for Thrombectomy. Annals of neurology Seners, P., Scheldeman, L., Christensen, S., Mlynash, M., Ter Schiphorst, A., Arquizan, C., Costalat, V., Henon, H., Bretzner, M., Heit, J. J., Olivot, J., Lansberg, M. G., Albers, G. W., Infarct-Growth collaborators, Schmitt, P., Sablot, D., Lalu, T., Cordonnier, C., Bricout, N., Leclerc, X., Albucher, J., Cognard, C., Calviere, L. 2023

  Abstract

  OBJECTIVE: Patients with acute ischemic stroke harboring a large vessel occlusion who present to primary stroke centers often require inter-hospital transfer for thrombectomy. We aimed to determine clinical and imaging factors independently associated with fast infarct growth (IG) during inter-hospital transfer.METHODS: We retrospectively analysed data from acute stroke patients with a large vessel occlusion transferred for thrombectomy from a primary stroke center to one of three French comprehensive stroke centers, with an MRI obtained at both the primary and comprehensive center before thrombectomy. Inter-hospital IG rate was defined as the difference in infarct volumes on diffusion-weighted imaging between the primary and comprehensive center, divided by the delay between the two MRI scans. The primary outcome was identification of fast progressors, defined as IG rate ≥5mL/hr. The hypoperfusion intensity ratio (HIR), a surrogate marker of collateral blood flow, was automatically measured on perfusion imaging.RESULTS: A total of 233 patients were included, of whom 27% patients were fast progressors. The percentage of fast progressors was 3% among patients with HIR<0.40 and 71% among those with HIR≥0.40. In multivariable analysis, fast progression was independently associated with HIR, intracranial carotid artery occlusion, and exclusively deep infarct location at the primary center (C-statistic=0.95; 95%CI, 0.93-0.98). IG rate was independently associated with good functional outcome (adjusted OR=0.91; 95%CI 0.83-0.99; P=0.037).INTERPRETATION: Our findings show that a HIR >0.40 is a powerful indicator of fast inter-hospital IG. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.26613

  View details for PubMedID 36748945

• Mechanical Thrombectomy in the Late Presentation of Anterior Circulation Large Vessel Occlusion Stroke: A Guideline From the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Committee STROKE-VASCULAR AND INTERVENTIONAL NEUROLOGY Nguyen, T. N., Castonguay, A. C., Siegler, J. E., Nagel, S., Lansberg, M. G., de Havenon, A., Sheth, S. A., Abdalkader, M., Tsai, J. P., Albers, G. W., Masoud, H. E., Jovin, T. G., Martins, S. O., Nogueira, R. G., Zaidat, O. O. 2023; 3 (1)

  View details for DOI 10.1161/SVIN.122.000512

  View details for Web of Science ID 001157345000020

• Mechanical Thrombectomy in the Late Presentation of Anterior Circulation Large Vessel Occlusion Stroke: A Guideline From the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Committee. Stroke (Hoboken, N.J.) Nguyen, T. N., Castonguay, A. C., Siegler, J. E., Nagel, S., Lansberg, M. G., de Havenon, A., Sheth, S. A., Abdalkader, M., Tsai, J., Albers, G. W., Masoud, H. E., Jovin, T. G., Martins, S. O., Nogueira, R. G., Zaidat, O. O. 2023; 3 (1)

  Abstract

  Recent clinical trials investigating endovascular therapy (EVT) in the extended time window have opened new treatment paradigms for late-presenting patients with large vessel occlusion (LVO) stroke. The aim of this guideline is to provide up to date recommendations for the diagnosis, selection, and medical or endovascular treatment of patients with LVO presenting in the extended time window.The Society of Vascular & Interventional Neurology (SVIN) Guidelines and Practice Clinical Standards (GAPS) committee assembled a writing group and recruited interdisciplinary experts to review and evaluate the current literature. Recommendations were assigned by the writing group using the SVIN-GAPS Class of Recommendation/Level of Evidence algorithm and SVIN GAPS guideline format. The final guideline was approved by all members of the writing group, the GAPS committee, and the SVIN board of directors.Literature review yielded three high quality randomized trials and several observational studies that have been extracted to derive the enclosed summary recommendations. In patients with LVO presenting in the 6-to-24-hour window, and with clinical imaging mismatch as defined by the DAWN and DEFUSE 3 studies, EVT is recommended. Non contrast CT can be used to evaluate infarct size as sole imaging modality for patient selection, particularly when access to CT perfusion or MRI is limited, or if their performance would incur substantial delay to treatment. In addition, several clinical questions were reviewed based on the available evidence and consensus grading.These guidelines provide practical recommendations based on recent evidence on the diagnosis, selection, and treatment of patients with LVO stroke presenting in the extended time window.

  View details for DOI 10.1161/SVIN.122.000512

  View details for PubMedID 39380893

  View details for PubMedCentralID PMC11460660

• Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study. JAMA neurology Sarraj, A., Kleinig, T. J., Hassan, A. E., Portela, P. C., Ortega-Gutierrez, S., Abraham, M. G., Manning, N. W., Siegler, J. E., Goyal, N., Maali, L., Blackburn, S., Wu, T. Y., Blasco, J., Renu, A., Sangha, N. S., Arenillas, J. F., McCullough-Hicks, M. E., Wallace, A., Gibson, D., Pujara, D. K., Shaker, F., de Lera Alfonso, M., Olive-Gadea, M., Farooqui, M., Vivanco Suarez, J. S., Iezzi, Z., Khalife, J., Lechtenberg, C. G., Qadri, S. K., Moussa, R. B., Abdulrazzak, M. A., Almaghrabi, T. S., Mir, O., Beharry, J., Krishnaiah, B., Miller, M., Khalil, N., Sharma, G. J., Katsanos, A. H., Fadhil, A., Duncan, K. R., Hu, Y., Martin-Schild, S. B., Tsivgoulis, G. K., Cordato, D., Furlan, A., Churilov, L., Mitchell, P. J., Arthur, A. S., Parsons, M. W., Grotta, J. C., Sitton, C. W., Ribo, M., Albers, G. W., Campbell, B. C. 2022

  Abstract

  Importance: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.Objective: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.Design, Setting, and Participants: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well.Interventions: Endovascular thrombectomy or medical management (control).Main Outcomes and Measures: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts.Results: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P<.001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P=.003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P=.047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P=.03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P=.04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P=.02).Conclusions and Relevance: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.

  View details for DOI 10.1001/jamaneurol.2022.4714

  View details for PubMedID 36574257

• Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient-level Analysis of EXTEND-IA Trials and SELECT Prospective Cohort. Annals of neurology Sarraj, A., Pujara, D. K., Churilov, L., Sitton, C., Ng, F., Hassan, A. E., Abraham, M. G., Blackburn, S. L., Sharma, G., Yassi, N., Kleinig, T., Shah, D., Wu, T. Y., Tekle, W. G., Budzik, R. F., Hicks, W. J., Vora, N., Edgell, R. C., Haussen, D., Ortega-Gutierrez, S., Toth, G., Maali, L., Ammar Abdulrazzak, M., Al-Shaibi, F., AlMaghrabi, T., Yogendrakumar, V., Shaker, F., Mir, O., Arora, A., Duncan, K., Sundararajan, S., Opaskar, A., Hu, Y., Ray, A., Sunshine, J., Bambakidis, N., Martin-Schild, S., Hussain, M. S., Nogueira, R., Furlan, A., Sila, C. A., Grotta, J. C., Parsons, M., Mitchell, P. J., Donnan, G. A., Davis, S. M., Albers, G. W., Campbell, B. C., SELECT, E. 2022

  Abstract

  INTRODUCTION: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship.METHODS: In a pooled, patient-level analysis of EXTEND-IA trials and SELECT study, we employed a mediation analysis framework to quantify infarct growth and cerebral edema(midline shift) mediation effect on successful reperfusion(mTICI≥2b) association with functional outcome(mRS distribution). Further, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift.RESULTS: 542/665(81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful vs unsuccessful reperfusion. Median(IQR) infarct growth was 12.3(1.8-48.4)ml and median(IQR) midline shift was 0(0,2.2)mm. Of 249(37%) demonstrating a midline shift of ≥1mm, median(IQR) shift was 2.75(1.89, 4.21)mm). Successful reperfusion was associated with reductions in both predefined mediators; infarct growth (beta, -1.19; 95%CI, -1.51to-0.88;p<0.001) and midline shift (aOR:0.36,95%CI:0.23-0.57,p<0.001). Successful reperfusion association with improved functional outcome (acOR:2.68; 95%CI:1.86-3.88,p<0.001), became insignificant (acOR:1.39, 95%CI:0.95-2.04,p=0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect. Analysis considering alternative hypothesis demonstrated consistent results.CONCLUSIONS: In this mediation analysis from a pooled, patient-level cohort, a significant proportion(~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect and identify novel therapeutic targets to further enhance reperfusion benefits. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.26587

  View details for PubMedID 36571388

• Endovascular thrombectomy after acute ischemic stroke of the basilar artery: a meta-analysis of four randomized controlled trials. Journal of neurointerventional surgery Adusumilli, G., Kobeissi, H., Ghozy, S., Hardy, N., Kallmes, K. M., Hutchison, K., Kallmes, D. F., Brinjikji, W., Albers, G. W., Heit, J. J. 2022

  Abstract

  Previous randomized controlled trials (RCTs) and meta-analyses were underpowered to demonstrate the superiority of endovascular thrombectomy (EVT) over medical therapy (MEDT) in the treatment of acute ischemic stroke due to large vessel occlusion of the posterior circulation (PC-LVO). We performed an updated systematic review and meta-analysis after the publication of the BAOCHE and ATTENTION trials to determine whether EVT can benefit patients presenting with PC-LVO.Using Nested Knowledge, we screened literature for RCTs on EVT in PC-LVO. The primary outcome was 90-day modified Rankin Scale (mRS) score 0-3, and secondary outcomes included 90-day mRS score 0-2, 90-day mortality, and rate of symptomatic intracranial hemorrhage (sICH). A random-effects model was used to compute rate ratios (RRs) and their corresponding 95% confidence intervals (CIs).Four RCTs with 988 patients, 556 patients in the EVT arm and 432 patients in the MEDT arm, were included in the meta-analysis. EVT resulted in significantly higher rates of mRS score 0-3 (RR=1.54; 95% CI 1.16 to 2.04; P=0.002) and functional independence (RR=1.83; 95% CI 1.08 to 3.08; P=0.024), and lower rates of mortality (RR=0.76; 95% CI 0.65 to 0.90; P=0.002) at 90-day follow-up compared with MEDT alone. However, EVT patients had higher rates of sICH (RR=7.48; 95% CI 2.27 to 24.61; P<0.001).EVT conferred significant patient benefit over MEDT alone in the treatment of PC-LVO. Future studies should better define patients for whom EVT is futile and determine factors that contribute to higher rates of sICH.

  View details for DOI 10.1136/jnis-2022-019776

  View details for PubMedID 36597942

• Endovascular thrombectomy after acute ischemic stroke of the basilar artery: a meta-analysis of four randomized controlled trials JOURNAL OF NEUROINTERVENTIONAL SURGERY Adusumilli, G., Kobeissi, H., Ghozy, S., Hardy, N., Kallmes, K. M., Hutchison, K., Kallmes, D. F., Brinjikji, W., Albers, G. W., Heit, J. J. 2022

  View details for DOI 10.1136/jnis-2022-019776

  View details for Web of Science ID 000897877200001

• Predicting Hypoperfusion Lesion and Target Mismatch in Stroke from Diffusion-weighted MRI Using Deep Learning. Radiology Yu, Y., Christensen, S., Ouyang, J., Scalzo, F., Liebeskind, D. S., Lansberg, M. G., Albers, G. W., Zaharchuk, G. 2022: 220882

  Abstract

  Background Perfusion imaging is important to identify a target mismatch in stroke but requires contrast agents and postprocessing software. Purpose To use a deep learning model to predict the hypoperfusion lesion in stroke and identify patients with a target mismatch profile from diffusion-weighted imaging (DWI) and clinical information alone, using perfusion MRI as the reference standard. Materials and Methods Imaging data sets of patients with acute ischemic stroke with baseline perfusion MRI and DWI were retrospectively reviewed from multicenter data available from 2008 to 2019 (Imaging Collaterals in Acute Stroke, Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2, and University of California, Los Angeles stroke registry). For perfusion MRI, rapid processing of perfusion and diffusion software automatically segmented the hypoperfusion lesion (time to maximum, ≥6 seconds) and ischemic core (apparent diffusion coefficient [ADC], ≤620 * 10-6 mm2/sec). A three-dimensional U-Net deep learning model was trained using baseline DWI, ADC, National Institutes of Health Stroke Scale score, and stroke symptom sidedness as inputs, with the union of hypoperfusion and ischemic core segmentation serving as the ground truth. Model performance was evaluated using the Dice score coefficient (DSC). Target mismatch classification based on the model was compared with that of the clinical-DWI mismatch approach defined by the DAWN trial by using the McNemar test. Results Overall, 413 patients (mean age, 67 years ± 15 [SD]; 207 men) were included for model development and primary analysis using fivefold cross-validation (247, 83, and 83 patients in the training, validation, and test sets, respectively, for each fold). The model predicted the hypoperfusion lesion with a median DSC of 0.61 (IQR, 0.45-0.71). The model identified patients with target mismatch with a sensitivity of 90% (254 of 283; 95% CI: 86, 93) and specificity of 77% (100 of 130; 95% CI: 69, 83) compared with the clinical-DWI mismatch sensitivity of 50% (140 of 281; 95% CI: 44, 56) and specificity of 89% (116 of 130; 95% CI: 83, 94) (P < .001 for all). Conclusion A three-dimensional U-Net deep learning model predicted the hypoperfusion lesion from diffusion-weighted imaging (DWI) and clinical information and identified patients with a target mismatch profile with higher sensitivity than the clinical-DWI mismatch approach. ClinicalTrials.gov registration nos. NCT02225730, NCT01349946, NCT02586415 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kallmes and Rabinstein in this issue.

  View details for DOI 10.1148/radiol.220882

  View details for PubMedID 36472536

• Percutaneous cervical sympathetic block to treat cerebral vasospasm and delayed cerebral ischemia: a review of the evidence JOURNAL OF NEUROINTERVENTIONAL SURGERY Bombardieri, A., Albers, G. W., Rodriguez, S., Pileggi, M., Steinberg, G. K., Heit, J. J. 2022

  View details for DOI 10.1136/jnis-2022-019838

  View details for Web of Science ID 000894932400001

• Percutaneous cervical sympathetic block to treat cerebral vasospasm and delayed cerebral ischemia: a review of the evidence. Journal of neurointerventional surgery Bombardieri, A. M., Albers, G. W., Rodriguez, S., Pileggi, M., Steinberg, G. K., Heit, J. J. 2022

  Abstract

  Delayed cerebral ischemia (DCI) affects 30% of patients following aneurysmal subarachnoid hemorrhage (aSAH) and is a major driver of morbidity, mortality, and intensive care unit length of stay for these patients. DCI is strongly associated with cerebral arterial vasospasm, reduced cerebral blood flow and cerebral infarction. The current standard treatment with intravenous or intra-arterial calcium channel antagonist and balloon angioplasty or stent has limited efficacy. A simple treatment such as a cervical sympathetic block (CSB) may be an effective therapy but is not routinely performed to treat vasospasm/DCI. CSB consists of injecting local anesthetic at the level of the cervical sympathetic trunk, which temporarily blocks the innervation of the cerebral arteries to cause arterial vasodilatation. CSB is a local, minimally invasive, low cost and safe technique that can be performed at the bedside and may offer significant advantages as complementary treatment in combination with more conventional neurointerventional surgery interventions. We reviewed the literature that describes CSB for vasospasm/DCI prevention or treatment in humans after aSAH. The studies outlined in this review show promising results for a CSB as a treatment for vasospasm/DCI. Further research is required to standardize the technique, to explore how to integrate a CSB with conventional neurointerventional surgery treatments of vasospasm and DCI, and to study its long-term effect on neurological outcomes.

  View details for DOI 10.1136/jnis-2022-019838

  View details for PubMedID 36597947

• Predicting final ischemic stroke lesions from initial diffusion-weighted images using a deep neural network. NeuroImage. Clinical Nazari-Farsani, S., Yu, Y., Armindo, R. D., Lansberg, M., Liebeskind, D. S., Albers, G., Christensen, S., Levin, C. S., Zaharchuk, G. 2022; 37: 103278

  Abstract

  For prognosis of stroke, measurement of the diffusion-perfusion mismatch is a common practice for estimating tissue at risk of infarction in the absence of timely reperfusion. However, perfusion-weighted imaging (PWI) adds time and expense to the acute stroke imaging workup. We explored whether a deep convolutional neural network (DCNN) model trained with diffusion-weighted imaging obtained at admission could predict final infarct volume and location in acute stroke patients.In 445 patients, we trained and validated an attention-gated (AG) DCNN to predict final infarcts as delineated on follow-up studies obtained 3 to 7 days after stroke. The input channels consisted of MR diffusion-weighted imaging (DWI), apparent diffusion coefficients (ADC) maps, and thresholded ADC maps with values less than 620 × 10-6 mm2/s, while the output was a voxel-by-voxel probability map of tissue infarction. We evaluated performance of the model using the area under the receiver-operator characteristic curve (AUC), the Dice similarity coefficient (DSC), absolute lesion volume error, and the concordance correlation coefficient (ρc) of the predicted and true infarct volumes.The model obtained a median AUC of 0.91 (IQR: 0.84-0.96). After thresholding at an infarction probability of 0.5, the median sensitivity and specificity were 0.60 (IQR: 0.16-0.84) and 0.97 (IQR: 0.93-0.99), respectively, while the median DSC and absolute volume error were 0.50 (IQR: 0.17-0.66) and 27 ml (IQR: 7-60 ml), respectively. The model's predicted lesion volumes showed high correlation with ground truth volumes (ρc = 0.73, p < 0.01).An AG-DCNN using diffusion information alone upon admission was able to predict infarct volumes at 3-7 days after stroke onset with comparable accuracy to models that consider both DWI and PWI. This may enable treatment decisions to be made with shorter stroke imaging protocols.

  View details for DOI 10.1016/j.nicl.2022.103278

  View details for PubMedID 36481696

• Cervical sympathectomy to treat cerebral vasospasm: a scoping review. Regional anesthesia and pain medicine Bombardieri, A. M., Heifets, B. D., Treggiari, M., Albers, G. W., Steinberg, G. K., Heit, J. J. 2022

  Abstract

  Delayed cerebral ischemia (DCI) is the second-leading cause of death and disability in patients with aneurysmal subarachnoid hemorrhage (aSAH), and is associated with cerebral arterial vasospasm (CAV). Current treatments for CAV are expensive, invasive, and have limited efficacy. Cervical sympathetic block (CSB) is an underappreciated, but potentially highly effective therapy for CAV.To provide a comprehensive review of the preclinical and human literature pertinent to CSB in the context of CAV.This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. We conducted a literature search using Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus and Web of Science until February 2022, to identify abstracts, conference proceedings, and full-text papers pertinent to cervical sympathectomy and CAV in animal/adult patients.We included six human and six experimental studies. Human studies were mostly prospective observational, except one retrospective and one randomized clinical trial, and used various imaging modalities to measure changes in arterial diameter after the block. Studies that used digital subtraction angiography showed an improvement in cerebral perfusion without change in vessel diameter. Transcranial Doppler studies found an approximately 15% statistically significant decrease in velocities consistent with arterial vasodilatation. Overall, the results suggest an increase in cerebral arterial diameter and neurological improvement in patients receiving a CSB. Animal studies demonstrate that sympathetic system ablation vasodilates cerebral vasculature and decreases the incidence of symptomatic vasospasm.This scoping review suggests that CSB may be a viable option for treatment and prevention of CAV/DCI in patients with aSAH, although the included studies were heterogeneous, mostly observational, and with a small sample size. Further research is needed to standardize the technique and prove its effectiveness to treat patients suffering of CAV/DCI after aSAH.

  View details for DOI 10.1136/rapm-2022-103999

  View details for PubMedID 36424089

• Hypoperfusion Intensity Ratio Is Correlated With the Risk of Parenchymal Hematoma After Endovascular Stroke Treatment. Stroke Winkelmeier, L., Heit, J. J., Adusumilli, G., Geest, V., Christensen, S., Kniep, H., van Horn, N., Steffen, P., Bechstein, M., Sporns, P., Lansberg, M. G., Albers, G. W., Wintermark, M., Fiehler, J., Faizy, T. D. 2022

  Abstract

  BACKGROUND: Parenchymal hematoma (PH) is a major complication after endovascular treatment (EVT) for ischemic stroke. The hypoperfusion intensity ratio (HIR) represents a perfusion parameter reflecting arterial collateralization and cerebral microperfusion in ischemic brain tissue. We hypothesized that HIR correlates with the risk of PH after EVT.METHODS: Retrospective multicenter cohort study of patients with large vessel occlusion who underwent EVT between 2013 and 2021 at one of the 2 comprehensive stroke centers (University Medical Center Hamburg-Eppendorf, Germany and Stanford University School of Medicine, CA). HIR was automatically calculated on computed tomography perfusion studies as the ratio of brain volume with time-to-max (Tmax) delay >10 s over volume with Tmax >6 s. Reperfusion hemorrhages were assessed according to the Heidelberg Bleeding Classification. Primary outcome was PH occurrence (PH+) or absence (PH-) on follow-up imaging. Secondary outcome was good clinical outcome defined as a 90-day modified Rankin Scale score of 0 to 2.RESULTS: A total of 624 patients met the inclusion criteria. We observed PH in 91 (14.6%) patients after EVT. PH+ patients had higher HIR on admission compared with PH- patients (median, 0.6 versus 0.4; P<0.001). In multivariable regression, higher admission blood glucose (adjusted odds ratio [aOR], 1.08 [95% CI, 1.04-1.13]; P<0.001), extensive baseline infarct defined as Alberta Stroke Program Early CT Score ≤5 (aOR, 2.48 [1.37-4.42]; P=0.002), and higher HIR (aOR, 1.22 [1.09-1.38]; P<0.001) were independent determinants of PH after EVT. Both higher HIR (aOR, 0.83 [0.75-0.92]; P<0.001) and PH on follow-up imaging (aOR, 0.39 [0.18-0.80]; P=0.013) were independently associated with lower odds of achieving good clinical outcome.CONCLUSIONS: Poorer (higher) HIR on admission perfusion imaging was strongly associated with PH occurrence after EVT. HIR as a surrogate for cerebral microperfusion might reflect tissue vulnerability for reperfusion hemorrhages. This automated and quickly available perfusion parameter might help to assess the need for intensive medical care after EVT.

  View details for DOI 10.1161/STROKEAHA.122.040540

  View details for PubMedID 36416127

• Cerebral perfusion imaging predicts final infarct volume after basilar artery thrombectomy. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Yuen, N., Mlynash, M., O'Riordan, A., Lansberg, M., Christensen, S., Cereda, C. W., Bianco, G., Giurgiutiu, D. V., Alemseged, F., Pileggi, M., Campbell, B., Albers, G. W., Heit, J. J. 2022; 32 (1): 106866

  Abstract

  Cerebral perfusion imaging may be used to identify the ischemic core in acute ischemic stroke (AIS) patients with a large vessel occlusion of the anterior circulation; however, perfusion parameters that predict the ischemic core in AIS patients with a basilar artery occlusion (BAO) are poorly described. We determined which cerebral perfusion parameters best predict the ischemic core after successful endovascular thrombectomy (EVT) in BAO patients.We performed multicenter retrospective study of BAO patients with perfusion imaging before EVT and a DWI after successful EVT. The ischemic core was defined as regions on CTP, which were co-registered to the final DWI infarct. Various time-to-maximum (Tmax) and cerebral blood flow (CBF) thresholds were compared to final infarct volume to determine the best predictor of the final infarct.28 patients were included in the analysis for this study. Tmax >8s (r2: 0.56; median absolute error, 16.0 mL) and Tmax >10s (r2: 0.73; median absolute error, 11.3 mL) showed the strongest agreement between the pre-EVT CTP study and the final DWI. CBF <38% (r2: 0.76; median absolute error, 8.2 mL) and CBF <34% (r2: 0.76; median absolute error, 9.1 mL) also correlated well with final infarct volume on DWI.Pre-EVT CT perfusion imaging is useful to predict the final ischemic infarct volume in BAO patients. Tmax >8s and Tmax >10s were the strongest predictors of the post-EVT final infarct volume.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2022.106866

  View details for PubMedID 36427471

• Association Between Net Water Uptake and Functional Outcome in Patients With Low ASPECTS Brain Lesions: Results From the I-LAST Study. Neurology Broocks, G., Meyer, L., Elsayed, S., McDonough, R., Bechstein, M., Faizy, T. D., Sporns, P., Schon, G., Minnerup, J., Kniep, H. C., Hanning, U., Barow, E., Schramm, P., Langner, S., Nawabi, J., Papanagiotou, P., Wintermark, M., Lansberg, M. G., Albers, G. W., Heit, J. J., Fiehler, J., Kemmling, A. 2022

  Abstract

  BACKGROUND AND OBJECTIVES: The effect of mechanical thrombectomy (MT) on functional outcome in ischemic stroke patients with low ASPECTS is still uncertain. ASPECTS rating is based on the presence of ischemic hypoattenuation relative to normal, however the degree of hypoattenuation, which directly reflects net uptake of water, is currently not considered as imaging biomarker in stroke triage. We hypothesized that the effect of thrombectomy on functional outcome in low ASPECTS patients depends on early lesion water uptake.METHODS: For this multicenter observational study, anterior circulation stroke patients with ASPECTS≤5 were consecutively analyzed. Net water uptake (NWU) was assessed as quantitative imaging biomarker in admission-CT. Primary endpoint was the rate of favorable functional outcome defined as modified Rankin Scale (mRS) score 0-3 at day 90. The effect of recanalization on functional outcome was analyzed according to the degree of NWU within the early infarct lesion.RESULTS: 254 patients were included, of which 148 (58%) underwent MT. The median ASPECTS was 4 (IQR: 3-5), and the median NWU was 11.4% (IQR: 8.9-15.1%). The rate of favorable outcome was 27.6% in patients with low NWU (<11.4%) versus 6.3% in patients with high NWU (≥11.4%; p<0.0001). In multivariable logistic regression analysis, NWU was an independent predictor of outcome, while vessel recanalization (mTICI≥2b) was only significantly associated with better outcomes if NWU was lower than 12.6%. In inverse-probability weighting analysis, recanalization was associated with 20.7% (p=0.01) increase in favorable outcome in patients with low NWU compared to 9.1% (p=0.06) in patients with high NWU.DISCUSSION: Early NWU was independently associated with clinical outcome, and might serve as an indicator of futile MT in low ASPECTS patients. NWU could be tested as tool to select low ASPECTS patients for MT.

  View details for DOI 10.1212/WNL.0000000000201601

  View details for PubMedID 36414425

• Thrombectomy Outcomes With General vs Non-general Anesthesia: A Pooled, Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study. Neurology Sarraj, A., Albers, G. W., Mitchell, P. J., Hassan, A. E., Abraham, M. G., Blackburn, S., Sharma, G., Yassi, N., Kleinig, T. J., Shah, D. G., Wu, T. Y., Hussain, M. S., Tekle, W. G., Gutierrez, S. O., Aghaebrahim, A. N., Haussen, D. C., Toth, G., Pujara, D., Budzik, R. F., Hicks, W., Vora, N., Edgell, R. C., Slavin, S., Lechtenberg, C. G., Maali, L., Qureshi, A., Rosterman, L., Abdulrazzak, M. A., AlMaghrabi, T., Shaker, F., Mir, O., Arora, A., Martin-Schild, S., Sitton, C. W., Churilov, L., Gupta, R., Lansberg, M. G., Nogueira, R. G., Grotta, J. C., Donnan, G. A., Davis, S. M., Campbell, B. C. 2022

  Abstract

  BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy(EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice.METHODS: In a pooled patient level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II and SELECT, EVT functional outcomes(mRS distribution) were compared between general anesthesia(GA) vs non-general anesthesia(non-GA) in a propensity matched sample. Further, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio(HIR) - Tmax>10s/Tmax>6s(good collaterals - HIR<0.4, poor collaterals - HIR≥0.4) on the association between anesthesia type and EVT outcomes.RESULTS: Of 725 treated with EVT, 299(41%) received GA and 426(59%) non-GA. The baseline characteristics differed in presentation NIHSS(median[IQR]-GA:18[13-22], non-GA:16[11-20],p<0.001) and ischemic core volume(GA:15.0mL[3.2-38.0] vs non-GA:9.0mL[0.0-31.0],p<0.001). Additionally, GA was associated with longer last-known-well(LKW) to arterial access (203min[157-267] vs 186min[138-252],p=0.002), but similar procedural time (35.5min[23-59] vs 34min[22-54],p=0.51). Of 182 matched pairs using propensity scores, baseline characteristics were similar. In the PS-matched pairs, GA was independently associated with worse functional outcomes(adj cOR:0.64,95%CI:0.44-0.93,p=0.021) and higher neurological worsening(GA:14.9% vs non-GA:8.9%, aOR:2.10,95%CI: 1.02-4.33,p=0.045). Patients with poor collaterals had worse functional outcomes with GA(adj cOR:0.47,95%CI:0.29-0.76,p=0.002), while no difference was observed in those with good collaterals(adj. cOR:0.93,95%CI:0.50-1.74,p=0.82), Pinteraction:0.07. No difference was observed in infarct growth overall and in patients with good collaterals, whereas patients with poor collaterals demonstrated larger infarct growth with GA with a significant interaction between collaterals and anesthesia type on infarct growth rate(Pinteraction:0.020).CONCLUSION: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a PS matched analysis from a pooled, patient-level cohort from 3 randomized trials and one prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice.CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that that use of general anesthesia is associated with worse functional outcome in patients undergoing endovascular thrombectomy.TRIAL REGISTRATIONS: EXTEND-IA:ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK:ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II:ClinicalTrials.gov (NCT03340493); SELECT:ClinicalTrials.gov (NCT02446587).

  View details for DOI 10.1212/WNL.0000000000201384

  View details for PubMedID 36289001

• Benefit-Risk Assessment of Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness. Journal of the American Heart Association Raskob, G. E., Ageno, W., Albers, G., Elliott, C. G., Halperin, J., Maynard, G., Steg, P. G., Weitz, J. I., Albanese, J., Yuan, Z., Levitan, B., Lu, W., Suh, E. Y., Spiro, T., Lipardi, C., Barnathan, E. S., Spyropoulos, A. C. 2022: e026229

  Abstract

  Background Venous thromboembolism (VTE) often occurs after hospitalization in medically ill patients, but the population benefit-risk of extended thromboprophylaxis remains uncertain. Methods and Results The MARINER (Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk) study (NCT02111564) was a randomized double-blind trial that compared thromboprophylaxis with rivaroxaban 10mg daily versus placebo for 45days after hospital discharge in medically ill patients with a creatinine clearance ≥50mL/min. The benefit-risk balance in this population was quantified by calculating the between-treatment rate differences in efficacy and safety end points per 10000 patients treated. Clinical characteristics of the study population were consistent with a hospitalized medical population at risk for VTE. Treating 10000 patients with rivaroxaban resulted in 32.5 fewer symptomatic VTE and VTE-related deaths but was associated with 8 additional major bleeding events. The treatment benefit was driven by the prevention of nonfatal symptomatic VTE (26 fewer events). There was no between-treatment difference in the composite of critical site or fatal bleeding. Conclusions Extending thromboprophylaxis with rivaroxaban for 45days after hospitalization provides a positive benefit-risk balance in medically ill patients at risk for VTE who are not at high risk for bleeding. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT02111564.

  View details for DOI 10.1161/JAHA.122.026229

  View details for PubMedID 36205248

• Location-weighted versus Volume-weighted Mismatch at MRI for Response to Mechanical Thrombectomy in Acute Stroke. Radiology Fukutomi, H., Yamamoto, T., Sibon, I., Christensen, S., Raposo, N., Marnat, G., Albucher, J., Olindo, S., Calviere, L., Sagnier, S., Viguier, A., Renou, P., Guenego, A., Poli, M., Darcourt, J., Debruxelles, S., Drif, A., Thalamas, C., Sommet, A., Rousseau, V., Mazighi, M., Bonneville, F., Albers, G. W., Cognard, C., Dousset, V., Olivot, J. M., Tourdias, T., BBS and FRAME investigators, Fontaine, L., Chollet, F., Barbieux, M., Michelozzi, C., Tall, P., Januel, A., Caparros, F., Pouzet, B., Calvas, F., Galitzki, M., Rouanet, F., Ledure, S., Menegon, P., Berge, J., Barreau, X., Gariel, F., Asselineau, J., Perez, P., Mlynash, M. 2022: 220080

  Abstract

  Background A target mismatch profile can identify good clinical response to recanalization after acute ischemic stroke, but does not consider region specificities. Purpose To test whether location-weighted infarction core and mismatch, determined from diffusion and perfusion MRI performed in patients with acute stroke, could improve prediction of good clinical response to mechanical thrombectomy compared with a target mismatch profile. Materials and Methods In this secondary analysis, two prospectively collected independent stroke data sets (2012-2015 and 2017-2019) were analyzed. From the brain before stroke (BBS) study data (data set 1), an eloquent map was computed through voxel-wise associations between the infarction core (based on diffusion MRI on days 1-3 following stroke) and National Institutes of Health Stroke Scale (NIHSS) score. The French acute multimodal imaging to select patients for mechanical thrombectomy (FRAME) data (data set 2) consisted of large vessel occlusion-related acute ischemic stroke successfully recanalized. From acute MRI studies (performed on arrival, prior to thrombectomy) in data set 2, target mismatch and eloquent (vs noneloquent) infarction core and mismatch were computed from the intersection of diffusion- and perfusion-detected lesions with the coregistered eloquent map. Associations of these imaging metrics with early neurologic improvement were tested in multivariable regression models, and areas under the receiver operating characteristic curve (AUCs) were compared. Results Data sets 1 and 2 included 321 (median age, 69 years [IQR, 58-80 years]; 207 men) and 173 (median age, 74 years [IQR, 65-82 years]; 90 women) patients, respectively. Eloquent mismatch was positively and independently associated with good clinical response (odds ratio [OR], 1.14; 95% CI: 1.02, 1.27; P = .02) and eloquent infarction core was negatively associated with good response (OR, 0.85; 95% CI: 0.77, 0.95; P = .004), while noneloquent mismatch was not associated with good response (OR, 1.03; 95% CI: 0.98, 1.07; P = .20). Moreover, adding eloquent metrics improved the prediction accuracy (AUC, 0.73; 95% CI: 0.65, 0.81) compared with clinical variables alone (AUC, 0.65; 95% CI: 0.56, 0.73; P = .01) or a target mismatch profile (AUC, 0.67; 95% CI: 0.59, 0.76; P = .03). Conclusion Location-weighted infarction core and mismatch on diffusion and perfusion MRI scans improved the identification of patients with acute stroke who would benefit from mechanical thrombectomy compared with the volume-based target mismatch profile. Clinical trial registration no. NCT03045146 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Nael in this issue.

  View details for DOI 10.1148/radiol.220080

  View details for PubMedID 36194114

• Risk of subsequent disabling or fatal stroke in patients with transient ischaemic attack or minor ischaemic stroke: an international, prospective cohort study. The Lancet. Neurology Hobeanu, C., Lavallee, P. C., Charles, H., Labreuche, J., Albers, G. W., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Molina, C. A., Rothwell, P. M., Steg, P. G., Touboul, P., Uchiyama, S., Vicaut, E., Wong, K. S., Amarenco, P., TIAregistry.org Investigators,, 2022; 21 (10): 889-898

  Abstract

  BACKGROUND: Patients who have had a transient ischaemic attack or minor stroke have an increased risk of cardiovascular events for the following 5 years. We aimed to assess 5-year functional outcomes in patients with transient ischaemic attack or minor ischaemic stroke and to determine the factors associated with long-term disability.METHODS: We analysed data from patients in TIAregistry.org, an international, prospective, observational registry of patients with transient ischaemic attack or minor ischaemic stroke from 61 specialised centres in 21 countries. Patients aged 18 years or older who had a transient ischaemic attack or minor stroke within the previous 7 days between May 30, 2009, and Dec 30, 2011, with a baseline modified Rankin scale (mRS) score of 0-1, and who had been followed up for 5 years, were eligible for inclusion in this study. We evaluated whether existing comorbidities and stroke recurrence, categorised as disabling (mRS score of >1, including death) or non-disabling (mRS score of 0-1), at 5 years after baseline, were associated with poor functional outcome (defined as an mRS score of >1). We used multivariable generalised equation models for factors associated with poor functional outcome at 5 years and multivariable cause-specific Cox hazard regression models in case of stroke recurrence.FINDINGS: Between May 30, 2009, and Dec 30, 2011, 3847 eligible patients were included in the study, 3105 (80·7%) of whom had an mRS evaluation at 5 years of follow-up. Median follow-up duration was 5·00 years (IQR 4·78-5·00). 710 (22·9%) of 3105 patients had an mRS score greater than 1 at 5 years. Factors associated with poor functional outcome at 5 years were older age (per 10-year increase, odds ratio [OR] 2·18, 95% CI 1·93-2·46; p<0·0001), diabetes of any type (1·45, 1·18-1·78; p=0·0001), history of stroke or transient ischaemic attack before the qualifying event (1·74, 1·37-2·22; p<0·0001), hypertension (1·38, 1·00-1·92; p=0·050), atrial fibrillation or flutter (1·52, 1·04-1·94; p=0·030), congestive heart failure (1·73, 1·22-2·46; p=0·0024), valvular disease (2·47, 1·70-3·58; p<0·0001), stroke as qualifying event (1·31, 1·09-1·57; p=0·0037), history of peripheral artery disease (1·98, 1·28-3·07; p=0·0023), history of coronary artery disease (1·32, 1·00-1·74; p=0·049), intracranial haemorrhage during follow up (4·94, 1·91-12·78; p=0·0013), and living alone (1·32, 1·10-1·59; p=0·0031). Regular physical activity before the index event was associated with reduced risk of poor functional outcome (OR 0·52, 95% CI 0·42-0·66; p<0·0001). 345 recurrent strokes had occurred at 5 years of follow-up, 141 (40·9%) of which were disabling or fatal. Stroke recurrence increased the risk of having a disability at 5 years (OR 3·52, 95% CI 2·37-5·22; p<0·0001). Recurrent disabling or fatal strokes were independently associated with older age (per 10-year increase, hazard ratio [HR] 1·61, 95% CI 1·35-1·92; p<0·0001), diabetes of any type (2·23, 1·56-3·17; p<0·0001), National Institutes of Health Stroke Scale score of greater than 5 at discharge (5·11, 2·15-12·13; p=0·0013), history of coronary artery disease (1·76, 1·17-2·65; p=0·0063), history of stroke or transient ischaemic attack before the qualifying event (1·54, 1·03-2·29; p=0·035), congestive heart failure (1·86, 1·01-3·47; p=0·044), stroke as qualifying event (1·73, 1·22-2·45; p=0·0024), mRS score of greater than 1 at discharge (2·48, 1·27-4·87; p=0·0083), and intracranial haemorrhage during follow-up (17·15, 9·95-27·43; p<0·0001). Regular physical activity before the index event was associated with reduced risk of recurrent disabling stroke at 5 years (HR 0·56, 95% CI 0·31-0·99; p=0·046), and 5-year disability without recurrent stroke (0·61, 0·47-0·79; p=0·0001).INTERPRETATION: We found a substantial burden of disability (mRS score of >1) at 5 years after transient ischaemic attack or minor ischemic stroke, and most predictors of this disability were modifiable risk factors. Patients who did regular physical exercise before the index event had a significantly reduced risk of disability at 5 years compared with patients who did no exercise.FUNDING: AstraZeneca, Sanofi, Bristol Myers Squibb, SOS Attaque Cerebrale Association.

  View details for DOI 10.1016/S1474-4422(22)00302-7

  View details for PubMedID 36115361

• Risk of subsequent disabling or fatal stroke in patients with transient ischaemic attack or minor ischaemic stroke: an international, prospective cohort study LANCET NEUROLOGY Hobeanu, C., Lavallee, P. C., Charles, H., Labreuche, J., Albers, G. W., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Molina, C. A., Rothwell, P. M., Steg, P., Touboul, P., Uchiyama, S., Vicaut, E., Wong, K., Amarenco, P., TIAregistry Org Investigators 2022; 21 (10): 889-898

  View details for Web of Science ID 000888210100018

• Prediction of intracranial atherosclerotic acute large vessel occlusion by severe hypoperfusion volume growth rate. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Sun, D., Huo, X., Ma, N., Gao, F., Mo, D., Han, H., Albers, G. W., Miao, Z. 2022; 31 (11): 106799

  Abstract

  We aimed to investigate whether the time elapsed from stroke onset to imaging (OTI) combined with the parameters generated by automated computed tomography perfusion (CTP) could predict large vessel occlusion (LVO) patients with underlying intracranial atherosclerotic disease (ICAD) before endovascular treatment (EVT).We performed a prospective cohort of LVO patients with automated CTP before EVT from two comprehensive stroke centers. Severe hypoperfusion volume growth rate was defined as the Time-to-Maximum (Tmax) > 10s divided by OTI. We performed receiver operating characteristic analyses to assess the ICAD prediction performance of all the automated CTP parameters, Delong test to compare the area under the curve (AUC) of severe hypoperfusion volume growth rate with the AUC of the other parameters, and logistic regression analysis to find the independent predictors of LVO with underlying ICAD.Of the 204 enrolled LVO patients, 95 ICAD patients and 109 non-ICAD patients were identified. The AUC of severe hypoperfusion volume growth rate was 0.86 (95% confidence interval [CI] 0.81 - 0.91, P < 0.001), the cut-off value with the highest Youden Index was ≤ 11.2 mL/h (sensitivity, 78.95%; specificity, 77.06%; accuracy 77.94%), which was larger than the other parameters except for hypoperfusion intensity ratio (HIR) (All P for Delong test < 0.05). Atrial fibrillation (odds ratio [OR]: 0.09, 95%CI: 0.03 - 0.26, P < 0.001), admission ASPECTS (1-point increased OR: 1.25, 95%CI: 1.03 - 1.53, P = 0.024), and severe hypoperfusion volume growth rate (1 mL/h increased OR: 0.94, 95%CI: 0.90 - 0.98, P = 0.003) were associated with underlying ICAD independently.Severe hypoperfusion volume growth rate showed the best performance for LVO with underlying ICAD prediction. Future larger studies for external validation are needed.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2022.106799

  View details for PubMedID 36174326

• Poor venous outflow profiles increase the risk of reperfusion hemorrhage after endovascular treatment. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Winkelmeier, L., Heit, J. J., Adusumilli, G., Geest, V., Guenego, A., Broocks, G., Pruter, J., Gloyer, N., Meyer, L., Kniep, H., Lansberg, M. G., Albers, G. W., Wintermark, M., Fiehler, J., Faizy, T. D. 2022: 271678X221127089

  Abstract

  To investigate whether unfavorable cerebral venous outflow (VO) predicts reperfusion hemorrhage after endovascular treatment (EVT), we conducted a retrospective multicenter cohort study of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). 629 AIS-LVO patients met inclusion criteria. VO profiles were assessed on admission CT angiography using the Cortical Vein Opacification Score (COVES). Unfavorable VO was defined as COVES ≤2. Reperfusion hemorrhages on follow-up imaging were subdivided into no hemorrhage (noRH), hemorrhagic infarction (HI) and parenchymal hematoma (PH). Patients with PH and HI less frequently achieved good clinical outcomes defined as 90-day modified Rankin Scale scores of ≤2 (PH: 13.6% vs. HI: 24.6% vs. noRH: 44.1%; p<0.001). The occurrence of HI and PH on follow-up imaging was more likely in patients with unfavorable compared to patients with favorable VO (HI: 25.1% vs. 17.4%, p=0.023; PH: 18.3% vs. 8.5%; p=<0.001). In multivariable regression analyses, unfavorable VO increased the likelihood of PH (aOR: 1.84; 95% CI: 1.03-3.37, p=0.044) and HI (aOR: 2.05; 95% CI: 1.25-3.43, p=0.005), independent of age, sex, admission National Institutes Health Stroke Scale scores and arterial collateral status. We conclude that unfavorable VO was associated with the occurrence of HI and PH, both related to worse clinical outcomes.

  View details for DOI 10.1177/0271678X221127089

  View details for PubMedID 36127828

• Outcome prediction value of critical area perfusion score for acute basilar artery occlusion. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Sun, D., Huo, X., Raynald, Mo, D., Gao, F., Ma, N., Albers, G. W., Miao, Z. 2022: 15910199221125853

  Abstract

  PURPOSE: To investigate the performance of the Critical Area Perfusion Score (CAPS), based on computed tomography perfusion (CTP) time to maximum (Tmax) > 10s maps, to predict the outcome in acute basilar artery occlusion (BAO) in patients undergoing endovascular treatment (EVT).METHODS: We perform a retrospective analysis of a prospectively collected database of acute BAO treated with EVT in a comprehensive stroke center. The favorable outcome was defined as the 90-day modified Rankin Scale (mRS) ≤ 3. We performed the logistic regression analysis to find the independent predictors of the favorable outcome. Then, we used receiver operating characteristic analyses to assess the predictive value of the imaging parameters, including CAPS, Posterior Circulation Alberta Stroke Program Early CT Score (PC-ASPECTS), pons midbrain index (PMI), posterior circulation computed tomography angiography (PC-CTA) score, Basilar Artery on Computed Tomography Angiography (BATMAN) score, and CTP parameters. Finally, the Delong test was used to compare the area under the curve (AUC) of CAPS against the other imaging parameters.RESULTS: Of the 65 enrolled patients, the incidence of the favorable outcome was 44.6% (29/65). Low CAPS (per 1- point increased odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.86; P=0.017) and admission National Institutes of Health Stroke Scale (NIHSS) (per 1- point increased OR, 0.80; 95% CI, 0.70-0.91; P=0.001) were independently associated with favorable outcome. The AUC of CAPS was 0.83 (95% CI, 0.74-0.93; P < 0.001) with ≤ 3 cut-off value, 89.66% sensitivity, 77.22% specificity, and 80.00% accuracy, which was greater than the other imaging parameters (All P for Delong test < 0.05).CONCLUSIONS: CAPS was the most accurate imaging-based outcome predictor in acute BAO patients. Future large prospective multicenter studies are needed to verify these results.

  View details for DOI 10.1177/15910199221125853

  View details for PubMedID 36112757

• Venous Outflow Profiles Are Linked to Clinical Outcomes in Ischemic Stroke Patients with Extensive Baseline Infarct. Journal of stroke Winkelmeier, L., Broocks, G., Kniep, H., Geest, V., Reinwald, J., Meyer, L., van Horn, N., Guenego, A., Zelenak, K., Albers, G. W., Lansberg, M., Sporns, P., Wintermark, M., Fiehler, J., Heit, J. J., Faizy, T. D. 2022; 24 (3): 372-382

  Abstract

  BACKGROUND AND PURPOSE: The benefit of endovascular thrombectomy (EVT) treatment is still unclear in stroke patients presenting with extensive baseline infarct. The use of additional imaging biomarkers could improve clinical outcome prediction and individualized EVT selection in this vulnerable cohort. We hypothesized that cerebral venous outflow (VO) may be associated with functional outcomes in patients with low Alberta Stroke Program Early CT Score (ASPECTS).METHODS: We conducted a retrospective multicenter cohort study of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Extensive baseline infarct was defined by an ASPECTS of ≤5 on admission computed tomography (CT). VO profiles were assessed on admission CT angiography using the Cortical Vein Opacification Score (COVES). Favorable VO was defined as COVES ≥3. Multivariable logistic regression was used to determine the association between cerebral VO and good clinical outcomes (90-day modified Rankin Scale score of ≤3).RESULTS: A total of 98 patients met the inclusion criteria. Patients with extensive baseline infarct and favorable VO achieved significantly more often good clinical outcomes compared to patients with unfavorable VO (45.5% vs. 10.5%, P<0.001). Higher COVES were strongly associated with good clinical outcomes (odds ratio, 2.17; 95% confidence interval, 1.15 to 4.57; P=0.024), independent of ASPECTS, National Institutes of Health Stroke Scale, and success of EVT.CONCLUSIONS: Cerebral VO profiles are associated with good clinical outcomes in AIS-LVO patients with extensive baseline infarct. VO profiles could serve as a useful additional imaging biomarker for treatment selection and outcome prediction in low ASPECTS patients.

  View details for DOI 10.5853/jos.2022.01046

  View details for PubMedID 36221940

• Perfusion Imaging and Clinical Outcome in Acute Minor Stroke With Large Vessel Occlusion. Stroke Seners, P., Arquizan, C., Fontaine, L., Ben Hassen, W., Heldner, M. R., Strambo, D., Nagel, S., Carrera, E., Mechtouff, L., McCullough-Hicks, M., Mohammaden, M. H., Cottier, J., Henon, H., Aignatoaie, A., Laksiri, N., Papassin, J., Lucas, L., Garnier, P., Triquenot, A., Mione, G., Hajdu, S., Costalat, V., Potreck, A., Detante, O., Bonneville, F., Berthezene, Y., Bracard, S., Sibon, I., Bricout, N., Boutet, C., Mordasini, P., Michel, P., Oppenheim, C., Olivot, J., Nogueira, R. G., Albers, G. W., Baron, J., Turc, G., MINOR-STROKE-Perfusion Collaborators, Cognard, C., Marnat, G., Menegon, P., Ledure, S., Dargazanli, C., Cho, T., Nighoghossian, N., Eker, O., Gouttard, S., Haussen, D., Debiais, S., Charron, V., Charron, N., Leys, D., Ozsancak, C., Delpech, M., Brunel, H., Papagiannaki, C., Girardin, E., Richard, S., Gory, B., Zbinden, M., Dobrocky, T., Ringelb, P., Mohlenbruch, M. 2022: STROKEAHA122039182

  Abstract

  BACKGROUND: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy.METHODS: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume).RESULTS: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P=0.03. However, mismatch volume modified the effect of bridging on clinical outcome (Pinteraction=0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only (Pinteraction=0.002).CONCLUSIONS: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

  View details for DOI 10.1161/STROKEAHA.122.039182

  View details for PubMedID 35862225

• Benefit of Intravenous Alteplase Before Thrombectomy Depends on ASPECTS. Annals of neurology Broocks, G., Heit, J. J., Kuraitis, G. M., Meyer, L., van Horn, N., Bechstein, M., Thaler, C., Christensen, S., Mlynash, M., Lansberg, M. G., Kemmling, A., Schon, G., Albers, G., Fiehler, J., Wintermark, M., Faizy, T. D. 2022

  Abstract

  PURPOSE: Baseline variables could be used to guide the administration of additional intravenous alteplase (IVT) before mechanical thrombectomy (MT). The aim of this study was to determine how baseline imaging and demographic parameters modify the effect of IVT on clinical outcomes in patients with ischemic stroke due to large vessel occlusion.METHODS: Multicenter retrospective cohort study of ischemic stroke patients triaged by multimodal-CT undergoing MT treatment after direct admission to an MT-eligible center. Inverse-probability weighting analysis (IPW) was used to assess the treatment effect of IVT adjusted for baseline variables. Multivariable logistic regression analysis with IPW-weighting and interaction terms for IVT was performed to predict functional independence (mRS 0-2 at 90-days).RESULTS: 720 patients were included, of which 366 (51%) received IVT. In IPW, the treatment effect of IVT on outcome (mRS 0-2) distinctively varied according to the ASPECTS subgroup (ASPECTS 9-10: +15%, ASPECTS 6-8: +7%, ASPECTS <6: -11%). In multivariable logistic regression analysis, IVT was independently associated with functional independence (aOR: 1.57, 95%CI: 1.16-2.14, p=0.003) and the interaction term was significant for ASPECTS and IVT revealing that IVT was only significantly associated with better outcomes in patients with higher ASPECTS. No other significant baseline variable interaction terms were identified.INTERPRETATION: ASPECTS was the only baseline variable that showed a significant interaction with IVT for outcome prediction. The application of IVT in patients with an ASPECTS of <6 might have detrimental effects on outcome and may only be considered carefully. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.26451

  View details for PubMedID 35801346

• Rivaroxaban Plus Aspirin for Extended Thromboprophylaxis in Acutely Ill Medical Patients: Insights from the MARINER Trial. TH open : companion journal to thrombosis and haemostasis Spyropoulos, A. C., Goldin, M., Ageno, W., Albers, G. W., Elliott, C. G., Hiatt, W. R., Halperin, J. L., Maynard, G., Steg, P. G., Weitz, J. I., Spiro, T. E., Lu, W., Marsigliano, J., Raskob, G. E., Barnathan, E. S. 2022; 6 (3): e177-e183

  Abstract

  Background The MARINER trial evaluated whether postdischarge thromboprophylaxis with rivaroxaban could reduce the primary outcome of symptomatic venous thromboembolism (VTE) or VTE-related death in acutely ill medical patients at risk for VTE. Although aspirin use was not randomized, approximately half of the enrolled patients were receiving aspirin at baseline. We hypothesized that thromboprophylaxis with once-daily rivaroxaban (10mg or, if creatinine clearance was 30-49mL/min, 7.5mg) plus aspirin (R/A) would be superior to placebo without aspirin (no thromboprophylaxis [no TP]). Methods We compared the primary and major secondary outcomes in the intention-to-treat population in four subgroups defined at baseline: (1) R/A ( N =3,159); (2) rivaroxaban alone ( N =2,848); (3) aspirin alone ( N =3,046); and (4) no TP ( N =2,966). Major bleeding (MB) and nonmajor clinically relevant (NMCR) bleeding were assessed in the safety population on treatment plus 2 days. Results Patients on R/A had reduced symptomatic VTE and VTE-related death compared with no TP (0.76 vs 1.28%, p =0.042), and experienced less symptomatic VTE and all-cause mortality ( p =0.005) and all-cause mortality alone ( p =0.01) compared with no TP. Event incidences for rivaroxaban alone (0.91%) or aspirin alone (0.92%) were similar. MB was low in all groups but lowest in the no TP group. NMCR bleeding was increased with R/A compared with no TP ( p =0.009). Limitations Aspirin use was not randomized. Conclusion Extended postdischarge thromboprophylaxis with R/A was associated with less symptomatic VTE and VTE-related death compared with no TP in previously hospitalized medical patients at risk for VTE. NMCR bleeding was increased with R/A compared with no TP. These post hoc findings need confirmation in a prospective trial.

  View details for DOI 10.1055/s-0042-1750379

  View details for PubMedID 36046208

• Intravenous tPA (Tissue-Type Plasminogen Activator) Correlates With Favorable Venous Outflow Profiles in Acute Ischemic Stroke. Stroke Faizy, T. D., Mlynash, M., Marks, M. P., Christensen, S., Kabiri, R., Kuraitis, G. M., Broocks, G., Winkelmeier, L., Geest, V., Nawabi, J., Lansberg, M. G., Albers, G. W., Fiehler, J., Wintermark, M., Heit, J. J. 2022: 101161STROKEAHA122038560

  Abstract

  BACKGROUND: Intravenous tPA (tissue-type plasminogen activator) is often administered before endovascular thrombectomy (EVT). Recent studies have questioned whether tPA is necessary given the high rates of arterial recanalization achieved by EVT, but whether tPA impacts venous outflow (VO) is unknown. We investigated whether tPA improves VO profiles on baseline computed tomography (CT) angiography (CTA) images before EVT.METHODS: Retrospective multicenter cohort study of patients with acute ischemic stroke due to large vessel occlusion undergoing EVT triage. Included patients underwent CT, CTA, and CT perfusion before EVT. VO profiles were determined by opacification of the vein of Labbe, sphenoparietal sinus, and superficial middle cerebral vein on CTA as 0, not visible; 1, moderate opacification; and 2, full. Pial arterial collaterals were graded on CTA, and tissue-level collaterals were assessed on CT perfusion using the hypoperfusion intensity ratio. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analysis, we determined the correlation between tPA administration and favorable VO profiles.RESULTS: Seven hundred seventeen patients met inclusion criteria. Three hundred sixty-five patients received tPA (tPA+), while 352 patients were not treated with tPA (tPA-). Fewer tPA+ patients had atrial fibrillation (n=128 [35%] versus n=156 [44%]; P=0.012) and anticoagulants/antiplatelet treatment before acute ischemic stroke due to large vessel occlusion onset (n=130 [36%] versus n=178 [52%]; P<0.001) compared with tPA- patients. One hundred eighty-five patients (51%) in the tPA+ and 100 patients (28%) in the tPA- group exhibited favorable VO (P<0.001). Multivariable regression analysis showed that tPA administration was a strong independent predictor of favorable VO profiles (OR, 2.6 [95% CI, 1.7-4.0]; P<0.001) after control for favorable pial arterial CTA collaterals, favorable tissue-level collaterals on CT perfusion, age, presentation National Institutes of Health Stroke Scale, antiplatelet/anticoagulant treatment, history of atrial fibrillation and time from symptom onset to imaging.CONCLUSIONS: In patients with acute ischemic stroke due to large vessel occlusion undergoing thrombectomy triage, tPA administration was strongly associated with the presence of favorable VO profiles.

  View details for DOI 10.1161/STROKEAHA.122.038560

  View details for PubMedID 35735008

• Thrombectomy vs Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort. Annals of neurology Sarraj, A., Albers, G. W., Blasco, J., Arenillas, J. F., Ribo, M., Hassan, A. E., Perez de la Ossa, N., Wu, T. Y., Cardona Portela, P., Abraham, M. G., Chen, M., Maali, L., Kleinig, T. J., Cordato, D., Wallace, A. N., Schaafsma, J. D., Sangha, N., Gibson, D. P., Blackburn, S. L., De Lera Alfonso, M., Pujara, D., Shaker, F., McCullough-Hicks, M. E., Moreno Negrete, J. L., Renu, A., Beharry, J., Cappelen-Smith, C., Rodriguez-Esparragoza, L., Olive-Gadea, M., Requena, M., Almaghrabi, T., Mendes Pereira, V., Sitton, C., Martin-Schild, S., Song, S., Ma, H., Churilov, L., Mitchell, P. J., Parsons, M. W., Furlan, A., Grotta, J. C., Donnan, G. A., Davis, S. M., Campbell, B. C., PERFECT-MILD Collaborators 2022

  Abstract

  OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch.METHODS: Pooled cohort of patients with NIHSS<6 and ICA, M1, M2 occlusions from EXTEND-IA, EXTEND-IA-TNK I/II RCTs and prospective data from 15 EVT centers from 10/2010 to 4/2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary endovascular thrombectomy (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and PS matched cohorts. Patients were stratified by target mismatch (mismatch-ratio≥1.8 and mismatch-volume≥15cc). Primary outcome was functional independence (90-day mRS:0-2); Secondary outcomes included safety (sICH, neurological worsening, and mortality).RESULTS: Of 540 patients, 286/540(53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax>6s) volumes of (64[26-96]mL vs MMpri :40[14-76]mL, p<0·001) and higher presentation NIHSS (4(2-5) vs MMpri :3(2-4), p<0·001). Functional independence was similar (EVTpri :77·4% vs MMpri :75.6%, aOR:1.29,95%CI:0.82-2.03,p=0.27). EVT had worse safety: sICH (EVTpri :8.8% vs MMpri :1.3%, p<0.001) and neurological worsening (EVTpri :19.6% vs MMpri :6.7%, p<0.001). In 414(76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri :77·4% vs MMpri :72.7%, aOR:1.68, 95%CI:1.01-2.81,p=0.048), whereas, there was a trend toward less favorable outcomes with primary EVT (EVTpri :77·4% vs MMpri :83.3%, aOR:0.39,95%CI:0.12-1.34,p=0.13) without target mismatch, (pinteraction =0.06). Similar findings were observed in a PS matched subpopulation.INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.26418

  View details for PubMedID 35599458

• Favourable arterial, tissue-level and venous collaterals correlate with early neurological improvement after successful thrombectomy treatment of acute ischaemic stroke. Journal of neurology, neurosurgery, and psychiatry Faizy, T. D., Mlynash, M., Kabiri, R., Christensen, S., Kuraitis, G., Meyer, L., Bechstein, M., Van Horn, N., Lansberg, M. G., Albers, G., Fiehler, J., Wintermark, M., Heit, J. J. 2022

  Abstract

  Early neurological improvement (ENI) after thrombectomy is associated with better long-term outcomes in patients with acute ischaemic stroke due to large vessel occlusion (AIS-LVO). Whether cerebral collaterals influence the likelihood of ENI is poorly described. We hypothesised that favourable collateral perfusion at the arterial, tissue-level and venous outflow (VO) levels is associated with ENI after thrombectomy.Multicentre retrospective study of patients with AIS-LVO treated by thrombectomy. Tissue-level collaterals (TLC) were measured on cerebral perfusion studies by the hypoperfusion intensity ratio. VO and pial arterial collaterals (PAC) were determined by the Cortical Vein Opacification Score and the modified Tan scale on CT angiography, respectively. ENI was defined as improvement of ≥8 points or a National Institutes of Health Stroke Scale score of 0 hour or 1 24 hours after treatment. Multivariable regression analyses were used to determine the association of collateral biomarkers with ENI and good functional outcomes (modified Rankin Scale 0-2).646 patients met inclusion criteria. Favourable PAC (OR: 1.9, CI 1.2 to 3.1; p=0.01), favourable VO (OR: 3.3, CI 2.1 to 5.1; p<0.001) and successful reperfusion (OR: 3.1, CI 1.7 to 5.8; p<0.001) were associated with ENI, but favourable TLC were not (p=0.431). Good functional outcomes at 90-days were associated with favourable TLC (OR: 2.2, CI 1.4 to 3.6; p=0.001), VO (OR: 5.7, CI 3.5 to 9.3; p<0.001) and ENI (OR: 5.7, CI 3.3 to 9.8; p<0.001), but not PAC status (p=0.647).Favourable PAC and VO were associated with ENI after thrombectomy. Favourable TLC predicted longer term functional recovery after thrombectomy, but the impact of TLC on ENI is strongly dependent on vessel reperfusion.

  View details for DOI 10.1136/jnnp-2021-328041

  View details for PubMedID 35577509

• Transient Complete Reversal of Large Area of Restricted Diffusion Seen Early Following Thrombectomy. Stroke Zhou, L. W., Lee, S., Schwartz, N. E., Albers, G. W., Lansberg, M. G. 2022: 101161STROKEAHA122038825

  View details for DOI 10.1161/STROKEAHA.122.038825

  View details for PubMedID 35514284

• Impact of collateral flow on cost-effectiveness of endovascular thrombectomy. Journal of neurosurgery Khunte, M., Wu, X., Avery, E. W., Gandhi, D., Payabvash, S., Matouk, C., Heit, J. J., Wintermark, M., Albers, G. W., Sanelli, P., Malhotra, A. 2022: 1-10

  Abstract

  OBJECTIVE: Acute ischemic stroke patients with large-vessel occlusion and good collateral blood flow have significantly better outcomes than patients with poor collateral circulation. The purpose of this study was to evaluate the cost-effectiveness of endovascular thrombectomy (EVT) based on collateral status and, in particular, to analyze its effectiveness in ischemic stroke patients with poor collaterals.METHODS: A decision analysis study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT based on collateral status. The study was performed over a lifetime horizon with a societal perspective in the US setting. Base-case analysis was done for good, intermediate, and poor collateral status. One-way, two-way, and probabilistic sensitivity analyses were performed.RESULTS: EVT resulted in greater effectiveness of treatment compared to no EVT/medical therapy (2.56 QALYs in patients with good collaterals, 1.88 QALYs in those with intermediate collaterals, and 1.79 QALYs in patients with poor collaterals), which was equivalent to 1050, 771, and 734 days, respectively, in a health state characterized by a modified Rankin Scale (mRS) score of 0-2. EVT also resulted in lower costs in patients with good and intermediate collaterals. For patients with poor collateral status, the EVT strategy had higher effectiveness and higher costs, with an incremental cost-effectiveness ratio (ICER) of $44,326/QALY. EVT was more cost-effective as long as it had better outcomes in absolute numbers in at least 4%-8% more patients than medical management.CONCLUSIONS: EVT treatment in the early time window for good outcome after ischemic stroke is cost-effective irrespective of the quality of collateral circulation, and patients should not be excluded from thrombectomy solely on the basis of collateral status. Despite relatively lower benefits of EVT in patients with poor collaterals, even smaller differences in better outcomes have significant long-term financial implications that make EVT cost-effective.

  View details for DOI 10.3171/2022.2.JNS212887

  View details for PubMedID 35535841

• The Cerebral Collateral Cascade: Comprehensive Blood Flow in Ischemic Stroke. Neurology Faizy, T. D., Mlynash, M., Kabiri, R., Christensen, S., Kuraitis, G. M., Mader, M. M., Flottmann, F., Broocks, G., Lansberg, M. G., Albers, G. W., Marks, M. P., Fiehler, J., Wintermark, M., Heit, J. J. 2022

  Abstract

  Robust cerebral collaterals are associated with favorable outcomes in patients with acute ischemic stroke due to large vessel occlusion treated by thrombectomy. However, collateral status assessment mostly relies on single imaging biomarkers and a more comprehensive holistic approach may provide deeper insights into the biology of collateral perfusion on medical imaging. Comprehensive collateralization is defined as blood flow of cerebral arteries through the brain tissue and into draining veins. We hypothesized that a comprehensive analysis of the cerebral collateral cascade (CCC) on an arterial, tissue and venous level would predict clinical and radiological outcomes.Multicenter retrospective cohort study of acute stroke patients undergoing thrombectomy triage. CCC was determined by quantifying pial arterial collaterals, tissue-level collaterals, and venous outflow. Pial arterial collaterals were determined by CT angiography, tissue-level collaterals were assessed on CT perfusion. Venous outflow was assessed on CT angiography using the cortical vein opacification score. 3 groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC- (poor pial collaterals, tissue-level collaterals, and venous outflow) and CCCmixed (remainder of patients). Primary outcome was functional independence (modified Rankin Scale: 0-2) at 90-days. Secondary outcome was final infarct volume.647 patients met inclusion criteria: 176 CCC+, 345 CCC mixed and 126 CCC-. Multivariable ordinal logistic regression showed that CCC+ predicted good functional outcomes (OR=18.9 [95% CI 8-44.5]; p<0.001) compared to CCC- and CCCmixed patients. CCCmixed patients likely had better functional outcomes compared to CCC- patients (OR=2.5 [95% CI 1.2-5.4]; p=0.014). Quantile regression analysis (50th percentile) showed that CCC+ (β: -78.5, 95% CI -96.0- -61.1; p<0.001) and CCCmixed (β: -64.0, 95% CI -82.4- -45.6; p<0.001) profiles were associated with considerably lower final infarct volumes compared to CCC- profiles.Comprehensive assessment of the collateral blood flow cascade in acute stroke patients is a strong predictor of clinical and radiological outcomes in patients treated by thrombectomy.

  View details for DOI 10.1212/WNL.0000000000200340

  View details for PubMedID 35483902

• Cerebral Hypoperfusion Intensity Ratio Is Linked to Progressive Early Edema Formation. Journal of clinical medicine van Horn, N., Broocks, G., Kabiri, R., Kraemer, M. C., Christensen, S., Mlynash, M., Meyer, L., Lansberg, M. G., Albers, G. W., Sporns, P., Guenego, A., Fiehler, J., Wintermark, M., Heit, J. J., Faizy, T. D. 2022; 11 (9)

  Abstract

  The hypoperfusion intensity ratio (HIR) is associated with collateral status and reflects the impaired microperfusion of brain tissue in patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). As a deterioration in cerebral blood flow is associated with brain edema, we aimed to investigate whether HIR is correlated with the early edema progression rate (EPR) determined by the ischemic net water uptake (NWU) in a multicenter retrospective analysis of AIS-LVO patients anticipated for thrombectomy treatment. HIR was automatically calculated as the ratio of time-to-maximum (TMax) > 10 s/(TMax) > 6 s. HIRs < 0.4 were regarded as favorable (HIR+) and ≥0.4 as unfavorable (HIR-). Quantitative ischemic lesion NWU was delineated on baseline NCCT images and EPR was calculated as the ratio of NWU/time from symptom onset to imaging. Multivariable regression analysis was used to assess the association of HIR with EPR. This study included 731 patients. HIR+ patients exhibited a reduced median NWU upon admission CT (4% (IQR: 2.1-7.6) versus 8.2% (6-10.4); p < 0.001) and less median EPR (0.016%/h (IQR: 0.007-0.04) versus 0.044%/h (IQR: 0.021-0.089; p < 0.001) compared to HIR- patients. Multivariable regression showed that HIR+ (β: 0.53, SE: 0.02; p = 0.003) and presentation of the National Institutes of Health Stroke Scale (β: 0.2, SE: 0.0006; p = 0.001) were independently associated with EPR. In conclusion, favorable HIR was associated with lower early edema progression and decreased ischemic edema formation on baseline NCCT.

  View details for DOI 10.3390/jcm11092373

  View details for PubMedID 35566500

• Accuracy of CT Perfusion-Based Core Estimation of Follow-Up Infarction: Effects of Time-Since-Last-Known-Well. Neurology Sarraj, A., Campbell, B. C., Christensen, S., Sitton, C. W., Khanpara, S., Riascos, R. F., Pujara, D., Shaker, F., Sharma, G., Lansberg, M. G., Albers, G. W., SELECT Investigators 2022

  Abstract

  BACKGROUND AND OBJECTIVES: To assess the accuracy of baseline CT perfusion ischemic core estimates.METHODS: From SELECT, a prospective multicenter cohort study of imaging selection, EVT patients who achieved complete reperfusion (modified Thrombolysis In Cerebral Ischemia (mTICI) score=3) and had follow-up Diffusion Weighted Imaging (DWI) available were evaluated. Follow-up DWI lesions were co-registered to baseline CT Perfusion (CTP). The difference between baseline CTP core (relative Cerebral Blood Flow (rCBF) <30%) volume and follow-up infarct volume was classified as over-estimation (core≥10mL larger than infarct), adequate, or under-estimation (core ≥25 ml smaller than infarct) and spatial overlap was also evaluated.RESULTS: Of 101 included patients, median time from Last Known Well (LKW) to imaging acquisition was 138 (82 - 244) min. The median baseline ischemic core estimate was 9(0-31.9) mL and median follow-up infarct volume was 18.4(5.3-68.7) mL. All 6/101(6%) patients with overestimation of the subsequent infarct volume were imaged within 90 minutes of LKW and achieved rapid reperfusion (within 120 min of CTP). Using rCBF<20% threshold to estimate ischemic core in patients presenting within 90 minutes eliminated overestimation. Volumetric correlation between the ischemic core estimate and follow-up imaging improved as LKW time to imaging acquisition increased - Spearman's rho: <90 min: 0.33 (p=0.049), 90-270 min: 0.63 (p<0.0001), >270 min: 0.86 (p<0.0001). Assessment of the spatial overlap between baseline CTP ischemic core lesion and follow-up infarct demonstrated a median of 3.2(0.0-9.0) mL of estimated core fell outside the subsequent infarct. These regions were predominantly in white matter.DISCUSSION: Significant overestimation of irreversibly injured ischemic core volume was rare, only observed in patients who presented within 90 minutes of LKW and achieved reperfusion within 120 minutes of CTP acquisition, and occurred primarily in white matter. Use of a more conservative (rCBF<20%) threshold for estimating ischemic core in patients presenting within 90 minutes eliminated all significant overestimation cases.

  View details for DOI 10.1212/WNL.0000000000200269

  View details for PubMedID 35450966

• Evaluation of time-resolved whole brain flat panel detector perfusion imaging using RAPID ANGIO in patients with acute stroke: comparison with CT perfusion imaging. Journal of neurointerventional surgery Kurmann, C. C., Kaesmacher, J., Cooke, D. L., Psychogios, M., Weber, J., Lopes, D. K., Albers, G. W., Mordasini, P. 2022

  Abstract

  BACKGROUND: In contrast to conventional CT perfusion (CTP) imaging, flat panel detector CT perfusion (FD-CTP) imaging can be acquired directly in the angiosuite.OBJECTIVE: To evaluate time-resolved whole brain FD-CTP imaging and assess clinically important qualitative and quantitative perfusion parameters in correlation with previously acquired conventional CTP using the new RAPID for ANGIO software.METHODS: We included patients with internal carotid artery occlusions and M1 or M2 occlusions from six centers. All patients underwent mechanical thrombectomy (MT) with preinterventional conventional CTP and FD-CTP imaging. Quantitative performance was determined by comparing volumes of infarct core, penumbral tissue, and mismatch. Eligibility for MT according to the perfusion imaging criteria of DEFUSE 3 was determined for each case from both conventional CTP and FD-CTP imaging.RESULTS: A total of 20 patients were included in the final analysis. Conventional relative cerebral blood flow (rCBF) <30%and FD-CTP rCBF <45% showed good correlation (R2=0.84). Comparisons of conventional CTP Tmax >6s versus FD-CTP Tmax >6s and CTP mismatch versus FD-CTP mismatch showed more variability (R2=0.57, and R2=0.33, respectively). Based on FD-CTP, 16/20 (80%) patients met the inclusion criteria for MT according to the DEFUSE 3 perfusion criteria, in contrast to 18/20 (90%) patients based on conventional CTP. The vessel occlusion could be correctly extrapolated from the hypoperfusion in 18/20 cases (90%).CONCLUSIONS: In our multicenter study, time-resolved whole brain FD-CTP was technically feasible, and qualitative and quantitative perfusion results correlated with those obtained with conventional CTP.

  View details for DOI 10.1136/neurintsurg-2021-018464

  View details for PubMedID 35396333

• Association of Bleeding Severity with Mortality in Extended Thromboprophylaxis of Medically Ill Patients in the MAGELLAN and MARINER Trials. Circulation Spyropoulos, A. C., Raskob, G. E., Cohen, A. T., Ageno, W., Weitz, J. I., Spiro, T. E., Lu, W., Lipardi, C., Albers, G. W., Elliott, C. G., Halperin, J. L., Hiatt, W. R., Maynard, G., Steg, P. G., Sugarmann, C., Barnathan, E. S. 2022

  Abstract

  Background: Extended thromboprophylaxis has not been widely implemented in acutely ill medical patients due to bleeding concerns. The MAGELLAN and MARINER trials evaluated whether rivaroxaban compared with enoxaparin or placebo could prevent venous thromboembolism (VTE) without increased bleeding. We hypothesized that patients with major bleeding (MB) but not those with non-major clinically relevant bleeding (NMCRB), would be at an increased risk of all-cause mortality (ACM). Methods: We evaluated all bleeding events in patients taking at least one dose of study drug and their association with ACM in 4 mutually exclusive groups: (1) no bleeding, or first event was (2) NMCRB, (3) MB, or (4) trivial bleeding. Using a Cox proportional hazards model adjusted for differences in baseline characteristics associated with ACM, we assessed the risk of ACM after such events. Results: Compared to patients with no bleeding, the risk of ACM for patients with NMCRB was not increased in MARINER (HR 0.43, p=0.235) but was increased in MAGELLAN (HR 1.74 p=0.021). MB was associated with a higher incidence of ACM in both studies, while trivial bleeding was not associated with ACM in either study. Conclusions: Patients with MB had an increased risk of ACM, while NMCRB was not consistently associated with an increased risk of death. These results inform the risk-benefit calculus of extended thromboprophylaxis in medically ill patients.

  View details for DOI 10.1161/CIRCULATIONAHA.121.057847

  View details for PubMedID 35389229

• Data Do Not Support Selection by Target Perfusion Mismatch of Patients for Endovascular Stroke Treatment Within the 16-to 24-Hour Interval Response JAMA NEUROLOGY Albers, G. W., Brown, S., Nogueira, R. G. 2022; 79 (4): 418-419

  View details for Web of Science ID 000782625300022

• A Phase III, Prospective, Double-Blind, Randomized, Placebo-Controlled Trial of Thrombolysis in Imaging-Eligible, Late-Window Patients to Assess the Efficacy and Safety of Tenecteplase (TIMELESS): Rationale and Design. International journal of stroke : official journal of the International Stroke Society Albers, G. W., Campbell, B. C., Lansberg, M. G., Broderick, J., Butcher, K., Froehler, M. T., Schwamm, L. H., Nouh, A. M., Liebeskind, D. S., Toy, F., Yang, M., Massaro, L., Schoeffler, M., Purdon, B. 2022: 17474930221088400

  Abstract

  Rationale: While thrombolysis is standard of care for patients with acute ischemic stroke (AIS) within 4.5 hours of symptom onset, the benefit of tenecteplase beyond this time window is less certain.Aim: The TIMELESS trial (NCT03785678) aims to determine if treatment with tenecteplase increases the proportion of good clinical outcomes among patients with stroke due to a large vessel occlusion who present beyond 4.5 hours after symptom onset.Sample size estimates: A total of 456 patients will provide ≥90% power to detect differences in the distribution of modified Rankin Scale scores at Day 90 at the 2-sided 0.049 significance level.Methods and design: TIMELESS is a phase III, double-blind, randomized, placebo-controlled trial of tenecteplase with or without endovascular thrombectomy in patients with AIS and evidence of salvageable tissue via imaging who present within the 4.5-24-hour time window with an internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion.Study outcomes: The primary efficacy objective of tenecteplase compared with placebo will be evaluated with ordinal modified Rankin Scale scores at Day 90. Safety will be evaluated via incidence of symptomatic intracranial hemorrhage, incidence and severity of adverse events and mortality rate.Discussion: Results from TIMELESS will contribute to understanding of the safety and efficacy of tenecteplase administered 4.5-24 hours following symptom onset for patients with an ICA or MCA occlusion.

  View details for DOI 10.1177/17474930221088400

  View details for PubMedID 35262424

• Endovascular Thrombectomy versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE and SELECT Studies. Annals of neurology Sarraj, A., Parsons, M., Bivard, A., Hassan, A. E., Abraham, M. G., Wu, T., Kleinig, T., Lin, L., Chen, C. A., Levi, C., Dong, Q., Cheng, X., Butcher, K. S., Choi, P., Yassi, N., Shah, D., Sharma, G., Pujara, D., Shaker, F., Blackburn, S., Dewey, H., Thijs, V., Sitton, C. W., Donnan, G. A., Mitchell, P. J., Yan, B., Grotta, J. G., Albers, G. W., Davis, S. M., Campbell, B., SELECT Investigators, t. E. 2022

  Abstract

  OBJECTIVE: To evaluate functional and safety outcomes of Endovascular thrombectomy(EVT) vs Medical Management(MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity.METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials(EXTEND-IA, EXTEND-IA-TNK part 1&2) and 2 prospective non-randomized studies(INSPIRE&SELECT), we evaluated EVT association with 90-day functional independence(mRS 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity.RESULTS: We included 517 patients(EVT=195, MM=322), baseline median(IQR) NIHSS was 13(8-19) in EVT vs 10(6-15) in MM, p<0.001. Pre-treatment ischemic core did not differ(EVT=10(0-24)mL vs MM=9(3-21)mL, p=0.59). Compared to MM, EVT was more frequently associated with functional independence(68.3% vs 61.6%, aOR=2.42,95%CI=1.25-4.67, p=0.008,IPTW-OR=1.75,95% CI=1.00-3.75,p=0.05) with a shift towards better mRS outcomes(adjusted cOR=2.02,95%CI:1.23-3.29,p=0.005), and lower mortality(5% vs 10%, aOR=0.32,95%CI=0.12-0.87,p=0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile(EVT=70.7% vs MM=61.3%, aOR=2.29, 95%CI=1.09-4.79,p=0.029, IPTW-OR=2.02,1.08-3.78,p=0.029), whereas no difference was found in those without mismatch(EVT=43.8% vs MM=62.7%,p=0.17, IPTW-OR: 0.71,95% CI=0.18-2.78,p=0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6-10, whereas there was no difference between groups with milder strokes below these thresholds.INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to medical management. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.26331

  View details for PubMedID 35184327

• Data Do Not Support Selection by Target Perfusion Mismatch of Patients for Endovascular Stroke Treatment Within the 16- to 24-Hour Interval-Reply. JAMA neurology Albers, G. W., Brown, S., Nogueira, R. G. 2022

  View details for DOI 10.1001/jamaneurol.2021.5405

  View details for PubMedID 35156998

• Endovascular Therapy Versus Medical Therapy Alone For Basilar Artery Stroke: A Systematic Review And Meta-analysis Through Nested Knowledge Adusumilli, G., Pederson, J., Hardy, N., Kallmes, K., Hutchinson, K., Kobeissi, H., Heiferman, D., Kallmes, D. F., Brinjikji, W., Albers, G. W., Heit, J. J. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.TP147

  View details for Web of Science ID 000788100600432

• Intravenous Glibenclamide For Large Hemispheric Infarction: Baseline Data From Initial Enrollees In The Charm Phase 3 Study Sheth, K. N., Kimberly, W., Albers, G. W., Campbell, B. C., Cordonnier, C., Hinson, H. E., Molyneaux, B. J., Nogueira, R. G., Saver, J. L., Steiner, T., Toyoda, K., Wintermark, M., Hareedy, R., Wald, M., Zhang, R., Ziogas, N. K., Rizzo, M. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.TP20

  View details for Web of Science ID 000788100600308

• Endovascular Thrombectomy Beyond 24 Hours From Last Known Well: A Pooled Multicenter International Cohort Sarraj, A., Hassan, A. E., Abraham, M. G., Cardona Portela, P., Manning, N. W., Cordato, D., Kleinig, T. J., Goyal, N., Blackburn, S., McCullough-Hicks, M. E., Ribo, M., Wu, T. Y., Blasco, J., Sangha, N., Arenillas, J. F., Wallace, A., Pujara, D. K., Shaker, F., de Lera Alfonso, M., Renu, A., Olive Gadea, M., Gibson, D., Lechtenberg, C. G., Maali, L. N., Abdulrazzak, M. A., Almaghrabi, T. S., Beharry, J., Krishnaiah, B., Miller, M., Khalil, N., Sharma, G. J., Katsanos, A. H., Fadhil, A., Duncan, K. R., Hu Yin, Sitton, C. W., Martin-schild, S. B., Tsivgoulis, G. K., Mitchell, P. J., Arthur, A. S., Parsons, M., Grotta, J. C., Campbell, B. C., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.36

  View details for Web of Science ID 000788100600036

• Visual Review Of Neuroimaging Prior To Transfer Acceptance Is Significantly Associated With Higher Rates Of Endovascular Therapy Thatikunta, P., McCullough-Hicks, M. E., Mlynash, M., Albers, G. W., Mijalski Sells, C. M. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.TP49

  View details for Web of Science ID 000788100600335

• The Effect Of Anesthesia On Thrombectomy Outcomes Is Modified By Collateral Flow: Pooled Patient Level Analysis From EXTEND-IA, EXTEND-IA TNK Part I And II, And SELECT Sarraj, A., Albers, G., Hassan, A., Abraham, M. G., Blackburn, S., Hussain, M., Tekle, W., Ortega-Gutierrez, S., Aghaebrahim, A. N., Haussen, D. C., Toth, G., Budzik, R., Pujara, D. K., Hicks, W. J., Vora, N., Edgell, R. C., Slavin, S., Lechtenberg, C. G., Maali, L. N., Qureshi, A. Y., Rosterman, L., Aertker, B., Abdulrazzak, M. A., Mir, O., Parsha, K. N., Reddy, S. S., Alenzi, B., Cai Chunyan, Almaghrabi, T. S., Shaker, F., Kamal, H., Arora, A., Yassi, N., Sharma, G. J., Kleinig, T. J., Shah, D., Wu, T. Y., Martin-schild, S. B., Day, A. L., Sitton, C. W., Mitchell, P. J., Gupta, R., Lansberg, M. G., Nogueira, R. G., Donnan, G. A., Davis, S., Grotta, J. C., Campbell, B. C. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.42

  View details for Web of Science ID 000788100600042

• Anatomical Predictors Of Malignant Cerebral Edema Using Voxel-based Lesion Symptom Mapping Topiwala, K. K., McCullough-Hicks, M. E., Christensen, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.127

  View details for Web of Science ID 000788100600124

• Evaluation Of Flat Panel Detector Whole Brain Perfusion Imaging In Acute Stroke Patients: Comparison With Computer Tomography Perfusion Imaging Kurmann, C., Kaesmacher, J., Cooke, D. L., Psychogios, M., Weber, J., Lopes, D., Albers, G., Mordasini, P. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.128

  View details for Web of Science ID 000788100600125

• Hypoperfusion Lesion And Target Mismatch Prediction In Acute Ischemic Stroke From Baseline Mr Diffusion Imaging Using A 3d Convolutional Neural Network Yu, Y., Gong, E., Ouyang, J., Christensen, S., Scalzo, F., Liebeskind, D. S., Lansberg, M. G., Albers, G., Zaharchuk, G. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.8

  View details for Web of Science ID 000788100600009

• Projections Of Endovascular Therapy-eligible Patients For The Us Population In 2021 Mistry, E., Khoury, J. C., Kissela, B., Kleindorfer, D. O., Alwell, K. S., Jasne, A., Ferioli, S., De Los Rios La Rosa, F., Coleman, E. R., Demel, S. L., Walsh, K. B., Slavin, S. J., Star, M., Haverbusch, M., Mackey, J., Woo, D., Heldner, M., Fischer, U. M., Jadhav, A., Jovin, T. G., Albers, G. W., Nogueira, R. G., Khatri, P. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.132

  View details for Web of Science ID 000788100600129

• Cerebral Perfusion Imaging And Posterior Circulation ASPECTS Identify Stroke Patients Who Benefit From Basilar Artery Thrombectomy Heit, J. J., Bianco, G., Mlynash, M., Yuen, N., Qureshi, A. Y., Hinduja, A., Dehkharghani, S., Goldman-Yassen, A., Hsieh, K., Giurgiutiu, D., Gibson, D., Carrera, E., Alemseged, F., Faizy, T. D., Fiehler, J., Pileggi, M., Lansberg, M. G., Campbell, B., Albers, G. W., Cereda, C. W. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1161/str.53.suppl_1.126

  View details for Web of Science ID 000788100600123

• Cost-effectiveness of thrombectomy in patients with minor stroke and large vessel occlusion: effect of thrombus location on cost-effectiveness and outcomes. Journal of neurointerventional surgery Khunte, M., Wu, X., Koo, A., Payabvash, S., Matouk, C., Heit, J. J., Wintermark, M., Gregory, A. W., Sanelli, P. C., Gandhi, D., Malhotra, A. 1800

  Abstract

  BACKGROUND: To evaluate the cost-effectiveness of endovascular thrombectomy (EVT) to treat large vessel occlusion (LVO) in patients with acute, minor stroke (National Institute of Health Stroke Scale (NIHSS) <6) and impact of occlusion site.METHODS: A Markov decision-analytic model was constructed accounting for both costs and outcomes from a societal perspective. Two different management strategies were evaluated: EVT and medical management. Base case analysis was done for three different sites of occlusion: proximal M1, distal M1 and M2 occlusions. One-way, two-way and probabilistic sensitivity analyses were performed.RESULTS: Base-case calculation showed EVT to be the dominant strategy in 65-year-old patients with proximal M1 occlusion and NIHSS <6, with lower cost (US$37 229 per patient) and higher effectiveness (1.47 quality-adjusted life years (QALYs)), equivalent to 537 days in perfect health or 603 days in modified Rankin score (mRS) 0-2 health state. EVT is the cost-effective strategy in 92.7% of iterations for patients with proximal M1 occlusion using a willingness-to-pay threshold of US$100 000/QALY. EVT was cost-effective if it had better outcomes in 2%-3% more patients than intravenous thrombolysis (IVT) in absolute numbers (base case difference -16%). EVT was cost-effective when the proportion of M2 occlusions was less than 37.1%.CONCLUSIONS: EVT is cost-effective in patients with minor stroke and LVO in the long term (lifetime horizon), considering the poor outcomes and significant disability associated with non-reperfusion. Our study emphasizes the need for caution in interpreting previous observational studies which concluded similar results in EVT versus medical management in patients with minor stroke due to a high proportion of patients with M2 occlusions in the two strategies.

  View details for DOI 10.1136/neurintsurg-2021-018375

  View details for PubMedID 35022300

• Venous outflow profiles are associated with early edema progression in ischemic stroke. International journal of stroke : official journal of the International Stroke Society van Horn, N., Heit, J. J., Kabiri, R., Broocks, G., Christensen, S., Mlynash, M., Meyer, L., Schoenfeld, M. H., Lansberg, M. G., Albers, G. W., Fiehler, J., Wintermark, M., Faizy, T. D. 1800: 17474930211065635

  Abstract

  BACKGROUND: In patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), development of extensive early ischemic brain edema is associated with poor functional outcomes, despite timely treatment. Robust cortical venous outflow (VO) profiles correlate with favorable tissue perfusion. We hypothesized that favorable VO profiles (VO+) correlate with a reduced early edema progression rate (EPR) and good functional outcomes.METHODS: Multicenter, retrospective analysis to investigate AIS-LVO patients treated by mechanical thrombectomy between May 2013 and December 2020. Baseline computed tomography angiography (CTA) was used to determine VO using the cortical vein opacification score (COVES); VO+ was defined as COVES⩾3 and unfavorable as COVES⩽2. EPR was determined as the ratio of net water uptake (NWU) on baseline non-contrast CT and time from symptom onset to admission imaging. Multivariable regression analysis was performed to assess primary (EPR) and secondary outcome (good functional outcomes defined as 0-2 points on the modified Rankin scale).RESULTS: A total of 728 patients were included. Primary outcome analysis showed VO+ (beta: -0.03, SE: 0.009, p=0.002), lower presentation National Institutes of Health Stroke Scale (NIHSS; beta: 0.002, SE: 0.001, p=0.002), and decreased time from onset to admission imaging (beta: -0.00002, SE: 0.00004, p<0.001) were independently associated with reduced EPR. VO+ also predicted good functional outcomes (odds ratio (OR): 5.07, 95% CI: 2.839-9.039, p<0.001), while controlling for presentation NIHSS, time from onset to imaging, general vessel reperfusion, baseline Alberta Stroke Program Early CT Score, infarct core volume, EPR, and favorable arterial collaterals.CONCLUSIONS: Favorable VO profiles were associated with slower infarct edema progression and good long-term functional outcomes as well as better neurological status and ischemic brain alterations at admission.

  View details for DOI 10.1177/17474930211065635

  View details for PubMedID 34983276

• Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis LANCET Jovin, T. G., Nogueira, R. G., Lansberg, M. G., Demchuk, A. M., Martins, S. O., Mocco, J., Ribo, M., Jadhav, A. P., Ortega-Gutierrez, S., Hill, M. D., Lima, F. O., Haussen, D. C., Brown, S., Goyal, M., Siddiqui, A. H., Heit, J. J., Menon, B. K., Kemp, S., Budzik, R., Urra, X., Marks, M. P., Costalat, V., Liebeskind, D. S., Albers, G. W. 2022; 399 (10321): 249-258

  View details for DOI 10.1016/.0140-6736(21)01341-6

  View details for Web of Science ID 000746041700020

• Mechanical Thrombectomy Up to 24Hours in Large Vessel Occlusions and Infarct Velocity Assessment. Journal of the American Heart Association Inoue, M., Yoshimoto, T., Tanaka, K., Koge, J., Shiozawa, M., Nishii, T., Ohta, Y., Fukuda, T., Satow, T., Kataoka, H., Yamagami, H., Ihara, M., Koga, M., Mlynash, M., Albers, G. W., Toyoda, K. 2021: e022880

  Abstract

  Background We retrospectively compared early- (<6hours) versus late- (6-24hours) presenting patients using perfusion-weighted imaging selection and evaluated clinical/radiographic outcomes. Methods and Results Large vessel occlusion patients treated with mechanical thrombectomy from August 2017 to July 2020 within 24hours of onset were retrieved from a single-center database. Perfusion-weighted imaging was analyzed by automated software and final infarct volume was measured semi-automatically within 14days. The primary end point was good outcome (modified Rankin Scale 0-2 at 90days). Secondary end points were excellent outcome (modified Rankin Scale 0-1 at 90days), symptomatic intracranial hemorrhage, and death. Clinical characteristics/radiological values including hypoperfusion volume and infarct growth velocity (baseline volume/onset-to-image time) were compared between the groups. Of 1294 patients, 118 patients were included. The median age was 74years, baseline National Institutes of Health Stroke Scale score was 14, and core volume was 13mL. The late-presenting group had more female patients (67% versus 31%, respectively; P=0.001). No statistically significant differences were seen in good outcome (42% versus 53%, respectively; P=0.30), excellent outcome (26% versus 32%, respectively; P=0.51), symptomatic intracranial hemorrhage (6.5% versus 4.6%, respectively; P=0.74), and death (3.2% versus 5.7%, respectively; P=0.58) between the groups. The late-presenting group had more atherothrombotic cerebral infarction (19% versus 6%, respectively; P=0.03), smaller hypoperfusion volume (median: 77 versus 133mL, respectively; P=0.04), and slower infarct growth velocity (median: 0.6 versus 5.1mL/h, respectively; P=0.03). Conclusions Patients with early- and late-time windows treated with mechanical thrombectomy by automated perfusion-weighted imaging selection have similar outcomes, comparable with those in randomized trials, but different in infarct growth velocities. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02251665.

  View details for DOI 10.1161/JAHA.121.022880

  View details for PubMedID 34889115

• Perfusion Imaging Collateral Scores Predict Infarct Growth in Non-Reperfused DEFUSE 3 Patients. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association MacLellan, A., Mlynash, M., Kemp, S., Ortega-Gutierrez, S., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W., DEFUSE 3 Investigators 2021; 31 (1): 106208

  Abstract

  OBJECTIVE: This study evaluated the associations of perfusion imaging collateral profiles with radiographic and clinical outcome in late presenting, non-reperfused patients in the DEFUSE 3 clinical trial.METHODS: Non-reperfused patients in both treatment arms were included. Baseline ischemic core, Tmax >6s, and Tmax >10s perfusion volumes were calculated with RAPID software; infarct volumes obtained 24 hours after randomization were manually determined from DWI or CT. Substantial infarct growth was defined as a >25mL increase between baseline and 24-hour follow-up. Hypoperfusion Intensity Ratio (HIR) was defined as the proportion of the Tmax >6s lesion with Tmax >10s delay; CBV index was calculated by RAPID from mean CBV values within the Tmax >6s lesion compared to regions of normal CBV.RESULTS: Eighty-four patients were included. ROC analysis showed HIR ≥0.34 (AUC=0.68) and CBV index ≤0.74 (AUC=0.72) optimally predicted substantial infarct growth in follow-up. Median growth was 23.4 versus 73.2mL with HIR threshold of 0.34 (p=0.005), and 24.3 versus 58.7mL with CBV index threshold of 0.74 (p=0.004). If baseline HIR and CBV index were both favorable, median growth was 21.7mL, 40.9mL if one was favorable, and 108.2mL if both were unfavorable (p<0.001). Baseline perfusion profile was not associated with 90-day functional outcome.CONCLUSIONS: Perfusion collateral scores forecast infarct growth in late presenting, non-reperfused ischemic stroke patients. These parameters may be useful for guiding transfer decisions, such as need for repeat imaging upon thrombectomy center arrival, and may help identify slow progressing patients more likely to have persistent salvageable ischemic tissue beyond 24 hours.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2021.106208

  View details for PubMedID 34823091

• Perfusion Imaging Predicts Favorable Outcomes after Basilar Artery Thrombectomy. Annals of neurology Cereda, C. W., Bianco, G., Mlynash, M., Yuen, N., Qureshi, A. Y., Hinduja, A., Dehkharghani, S., Goldman-Yassen, A. E., Hsieh, K. L., Giurgiutiu, D., Gibson, D., Carrera, E., Alemseged, F., Faizy, T. D., Fiehler, J., Pileggi, M., Campbell, B., Albers, G. W., Heit, J. J. 2021

  Abstract

  OBJECTIVE: Perfusion imaging identifies anterior circulation stroke patients who respond favorably to endovascular thrombectomy (ET), but its role in basilar occlusion (BAO) is unknown. We hypothesized that BAO patients with limited regions of severe hypoperfusion (Time-to-maximum [Tmax] delay >10 seconds) would have a favorable response to ET compared to patients with more extensive regions involved.METHODS: We performed a multicenter retrospective cohort study of BAO patients with perfusion imaging prior to ET. We pre-specified a Critical Area Perfusion Score (CAPS; 0-6 points), which quantified severe hypoperfusion (Tmax >10s) in cerebellum (1 point/hemisphere), pons (2 points), midbrain and/or thalamus (2 points). Patients were dichotomized into favorable (CAPS≤3) and unfavorable (CAPS>3) groups. The primary outcome was a favorable functional outcome 90-days after ET (modified Rankin Scale [mRS] 0-3).RESULTS: 103 patients were included. CAPS≤3 patients (87%) had a lower median NIHSS (12.5 [IQR 7-22]) compared to CAPS>3 patients (13%) (23 [IQR 19-36]; p=0.01). Reperfusion was achieved in 84% of all patients with no difference between CAPS groups (p=0.42). 64% of reperfused CAPS≤3 patients had a favorable outcome compared to 8% of non-reperfused CAPS≤3 patients (OR=21.0 [95% CI 2.6-170]; p<0.001). No CAPS>3 patients had a favorable outcome, regardless of reperfusion. In a multivariable regression analysis, CAPS≤3 was a robust independent predictor of favorable outcome after adjustment for reperfusion, age, and pre-ET NIHSS (OR 39.25 [95% CI 1.34->999)]; p=0.04).INTERPRETATION: BAO patients with limited regions of severe hypoperfusion had a favorable response to reperfusion following ET. However, patients with more extensive regions of hypoperfusion in critical brain regions did not benefit from endovascular reperfusion. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.26272

  View details for PubMedID 34786756

• What predicts poor outcome after successful thrombectomy in early time window? Journal of neurointerventional surgery Olivot, J., Heit, J. J., Mazighi, M., Raposo, N., Albucher, J. F., Rousseau, V., Guenego, A., Thalamas, C., Mlynash, M., Drif, A., Christensen, S., Sommet, A., Viguier, A., Darcourt, J., Januel, A., Calviere, L., Menegon, P., Caparros, F., Bonneville, F., Tourdias, T., Sibon, I., Albers, G. W., Cognard, C., FRAME Investigators, Fontaine, L., Chollet, F., Barbieux, M., Michelozzi, C., Tall, P., Pouzet, B., Calvas, F., Galitzki, M., Renou, P., Rouanet, F., Berge, J., Marnat, G., Lucas, L., Coignon, C., Sagnier, S., Debruxelle, S., Ledure, S. 2021

  Abstract

  BACKGROUND: Half of the patients with large vessel occlusion (LVO)-related acute ischemic stroke (AIS) who undergo endovascular reperfusion are dead or dependent at 3 months. We hypothesize that in addition to established prognostic factors, baseline imaging profile predicts outcome among reperfusers.METHODS: Consecutive patients receiving endovascular treatment (EVT) within 6hours after onset with Thrombolysis In Cerebral Infarction (TICI) 2b, 2c and 3 revascularization were included. Poor outcome was defined by a modified Rankin scale (mRS) 3-6 at 90 days. No mismatch (NoMM) profile was defined as a mismatch (MM) ratio ≤1.2 and/or a volume <10mL on pretreatment imaging.RESULTS: 187 patients were included, and 81 (43%) had a poor outcome. Median delay from stroke onset to the end of EVT was 259min (IQR 209-340). After multivariable logistic regression analysis, older age (OR 1.26, 95% CI 1.06 to 1.5; p=0.01), higher National Institutes of Health Stroke Scale (NIHSS) (OR 1.15, 95% CI 1.06 to 1.25; p<0.0001), internal carotid artery (ICA) occlusion (OR 3.02, 95% CI 1.2 to 8.0; p=0.021), and NoMM (OR 4.87, 95% CI 1.09 to 22.8; p=0.004) were associated with poor outcome. In addition, post-EVT hemorrhage (OR 3.64, 95% CI 1.5 to 9.1; p=0.04) was also associated with poor outcome.CONCLUSIONS: The absence of a penumbra defined by a NoMM profile on baseline imaging appears to be an independent predictor of poor outcome after reperfusion. Strategies aiming to preserve the penumbra may be encouraged to improve these patients' outcomes.

  View details for DOI 10.1136/neurintsurg-2021-017946

  View details for PubMedID 34750109

• Cerebral venous outflow profiles are associated with the first pass effect in endovascular thrombectomy. Journal of neurointerventional surgery van Horn, N., Heit, J. J., Kabiri, R., Mader, M. M., Christensen, S., Mlynash, M., Broocks, G., Meyer, L., Nawabi, J., Lansberg, M. G., Albers, G. W., Wintermark, M., Fiehler, J., Faizy, T. D. 2021

  Abstract

  BACKGROUND: Recent studies found that favorable venous outflow (VO) profiles are associated with higher reperfusion rates after mechanical thrombectomy (MT) in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Fewer retrieval attempts and first-pass revascularization during MT lead to better functional outcomes.OBJECTIVE: To examine the hypothesis that favorable VO profiles assessed on baseline CT angiography (CTA) images correlate with successful vessel reperfusion after the first retrieval attempt and fewer retrieval attempts.METHODS: A multicenter retrospective cohort study of patients with AIS-LVO treated by MT. Baseline CTA was used to determine the cortical vein opacification score (COVES). Favorable VO was defined as COVES ≥3. Primary outcomes were successful with excellent vessel reperfusion status, defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3 and 2c/3 after first retrieval attempt.RESULTS: 617 patients were included in this study, of whom 205 (33.2%) had first pass reperfusion. In univariate analysis, ordinal COVES (p=0.011) values were significantly higher in patients with first pass than in those with non-first pass reperfusion, while the number of patients exhibiting favorable pial arterial collaterals using the Maas scale on CTA did not differ (p=0.243). In multivariable logistic regression analysis, higher COVES were independently associated with TICI 2b/3 (OR=1.25, 95%CI 1.1 to 1.42; p=0.001) and TICI 2c/3 (OR=1.2, 95%CI 1.04 to 1.36; p=0.011) reperfusion after one retrieval attempt, controlling for penumbra volume and time from symptom onset to vessel reperfusion.CONCLUSIONS: Favorable VO, classified as higher COVES, is independently associated with successful and excellent first pass reperfusion in patients with AIS-LVO treated by endovascular thrombectomy.

  View details for DOI 10.1136/neurintsurg-2021-018078

  View details for PubMedID 34750110

• ASCOD Phenotyping of Stroke With Anterior Large Vessel Occlusion Treated by Mechanical Thrombectomy. Stroke Fontaine, L., Sibon, I., Raposo, N., Albucher, J., Mazighi, M., Rousseau, V., Darcourt, J., Thalamas, C., Drif, A., Sommet, A., Viguier, A., Guenego, A., Januel, A., Calviere, L., Menegon, P., Bonneville, F., Tourdias, T., Albers, G. W., Cognard, C., Olivot, J., FRAME Investigators, Christensen, S., Mlynash, M., Chollet, F., Barbieux, M., Michelozzi, C., Tall, P., Caparros, F., Pouzet, B., Calvas, F., Galitzki, M., Renou, P., Rouanet, F., Berge, J., Marnat, G., Lucas, L., Coignon, C., Sagnier, S., Debruxelle, S., Ledure, S. 2021: STROKEAHA121035282

  Abstract

  BACKGROUND AND PURPOSE: Determining the mechanism of large vessel occlusion related acute ischemic stroke is of major importance to initiate a tailored secondary prevention strategy. We investigated using the atherosclerosis, small vessel disease, cardiac source, other cause, dissection (ASCOD) classification the distribution of the causes of large vessel occlusion related acute ischemic stroke treated by mechanical thrombectomy.METHODS: This was a predefined substudy of the FRAME (French Acute Multimodal Imaging to Select Patient for Mechanical Thrombectomy). Each patient underwent a systematic etiological workup including brain and vascular imaging, electrocardiogram monitoring lasting at least 24 hours and routine blood tests. Stroke mechanisms were systematically evaluated using the atherosclerosis, small vessel disease, cardiac source, other cause, dissection grading system at 3 months. We defined single potential cause by one cause graded 1 in a single domain, possible cause as a cause graded 1 or 2 regardless of overlap, and no identified cause without grade 1 nor 2 causes.RESULTS: A total of 215 patients (mean age 70±14; 50% male) were included. A single potential cause was identified in 148 (69%). Cardio-embolism (53%) was the most frequent, followed by atherosclerosis (9%), dissection (5%) and other causes (1%). Atrial fibrillation accounted for 88% of C1. Overlap between grade 1 causes was uncommon (3%). Possible causes were identified in 168 patients (83%) and 16 (7%) had no cause identified after the initial evaluation.CONCLUSIONS: Cardio-embolism, especially atrial fibrillation, was the major cause of large vessel occlusion related acute ischemic stroke. This finding emphasizes the yield of paroxysmal atrial fibrillation detection in those patients.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03045146.

  View details for DOI 10.1161/STROKEAHA.121.035282

  View details for PubMedID 34702062

• Prediction of Stroke Infarct Growth Rates by Baseline Perfusion Imaging. Stroke Wouters, A., Robben, D., Christensen, S., Marquering, H. A., Roos, Y. B., van Oostenbrugge, R. J., van Zwam, W. H., Dippel, D. W., Majoie, C. B., Schonewille, W. J., van der Lugt, A., Lansberg, M., Albers, G. W., Suetens, P., Lemmens, R. 2021: STROKEAHA121034444

  Abstract

  BACKGROUND AND PURPOSE: Computed tomography perfusion imaging allows estimation of tissue status in patients with acute ischemic stroke. We aimed to improve prediction of the final infarct and individual infarct growth rates using a deep learning approach.METHODS: We trained a deep neural network to predict the final infarct volume in patients with acute stroke presenting with large vessel occlusions based on the native computed tomography perfusion images, time to reperfusion and reperfusion status in a derivation cohort (MR CLEAN trial [Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands]). The model was internally validated in a 5-fold cross-validation and externally in an independent dataset (CRISP study [CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project]). We calculated the mean absolute difference between the predictions of the deep learning model and the final infarct volume versus the mean absolute difference between computed tomography perfusion imaging processing by RAPID software (iSchemaView, Menlo Park, CA) and the final infarct volume. Next, we determined infarct growth rates for every patient.RESULTS: We included 127 patients from the MR CLEAN (derivation) and 101 patients of the CRISP study (validation). The deep learning model improved final infarct volume prediction compared with the RAPID software in both the derivation, mean absolute difference 34.5 versus 52.4 mL, and validation cohort, 41.2 versus 52.4 mL (P<0.01). We obtained individual infarct growth rates enabling the estimation of final infarct volume based on time and grade of reperfusion.CONCLUSIONS: We validated a deep learning-based method which improved final infarct volume estimations compared with classic computed tomography perfusion imaging processing. In addition, the deep learning model predicted individual infarct growth rates which could enable the introduction of tissue clocks during the management of acute stroke.

  View details for DOI 10.1161/STROKEAHA.121.034444

  View details for PubMedID 34587794

• Distinct intraarterial Clot Localizations affect Tissue-Level Collaterals and Venous Outflow Profiles. European journal of neurology Faizy, T. D., Kabiri, R., Christensen, S., Mlynash, M., Kuraitis, G., Broocks, G., Flottmann, F., Meyer, L., Leischner, H., Lansberg, M. G., Albers, G. W., Marks, M. P., Fiehler, J., Wintermark, M., Heit, J. J. 2021

  Abstract

  BACKGROUND AND AIM: Arterial clot localization affects collateral flow to ischemic brain in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We determined the association between vessel occlusion locations, tissue-level collaterals (TLC) and venous outflow (VO) profiles and their impact on good functional outcomes.MATERIALS AND METHODS: Multicenter retrospective cohort study of consecutive AIS-LVO patients who underwent thrombectomy triage. Baseline CT angiography (CTA) was used to localize vessel occlusion, which was dichotomized into proximal vessel occlusion (PVO; internal carotid artery and proximal M1) and distal vessel occlusion (DVO; distal M1 and M2) and to assess collateral score. TLC were assessed on CT perfusion data using the Hypoperfusion Intensity Ratio (HIR). VO was determined on baseline CTA by the cortical vein opacification score. Primary outcomes were favorable VO and TLC, secondary outcome the Modified Ranking Scale (mRS) after 90 days.RESULTS: 649 patients met inclusion criteria. 376 patients (58%) had a PVO and 273 patients (42%) had a DVO. Multivariable ordinal logistic regression showed that DVO predicted favorable TLC (OR=1.77 [95% CI: 1.24-2.52]; p=0.002) and favorable VO (OR=7.2 [95% CI: 5.2-11.9]; p<0.001). DVO (OR=3.4 [95% CI: 2.1-5.6]; p<0.001), favorable VO (OR=6.4 [95% CI: 3.8-10.6]; p<0.001) and favorable TLC (OR=3.2 [95% CI: 2-5.3]; p<0.001), but not CTA collaterals (OR=1.07 [95% CI: 0.60-1.91]; p=0.813), were predictors of good functional outcome.CONCLUSION: DVO in AIS-LVO patients correlate with favorable TLC and VO profiles, which are associated with good functional outcome.

  View details for DOI 10.1111/ene.15079

  View details for PubMedID 34424584

• Extracellular Vesicle Surface Markers as a Diagnostic Tool in Transient Ischemic Attacks. Stroke Burrello, J., Bianco, G., Burrello, A., Manno, C., Maulucci, F., Pileggi, M., Nannoni, S., Michel, P., Bolis, S., Melli, G., Vassalli, G., Albers, G. W., Cianfoni, A., Barile, L., Cereda, C. W. 2021: STROKEAHA120033170

  Abstract

  BACKGROUND AND PURPOSE: Extracellular vesicles (EVs) are promising biomarkers for cerebral ischemic diseases, but not systematically tested in patients with transient ischemic attacks (TIAs). We aimed at (1) investigating the profile of EV-surface antigens in patients with symptoms suspicious for TIA; (2) developing and validating a predictive model for TIA diagnosis based on a specific EV-surface antigen profile.METHODS: We analyzed 40 subjects with symptoms suspicious for TIA and 20 healthy controls from a training cohort. An independent cohort of 28 subjects served as external validation. Patients were stratified according to likelihood of having a real ischemic event using the Precise Diagnostic Score, defined as: unlikely (score 0-1), possible-probable (score 2-3), or very likely (score 4-8). Serum vesicles were quantified by nanoparticle tracking analysis and EV-surface antigen profile characterized by multiplex flow cytometry.RESULTS: EV concentration increased in patients with very likely or possible-probable TIA (P<0.05) compared with controls. Nanoparticle concentration was directly correlated with the Precise Diagnostic score (R=0.712; P<0.001). After EV immuno-capturing, CD8, CD2, CD62P, melanoma-associated chondroitin sulfate proteoglycan, CD42a, CD44, CD326, CD142, CD31, and CD14 were identified as discriminants between groups. Receiver operating characteristic curve analysis confirmed a reliable diagnostic performance for each of these markers taken individually and for a compound marker derived from their linear combinations (area under the curve, 0.851). Finally, a random forest model combining the expression levels of selected markers achieved an accuracy of 96% and 78.9% for discriminating patients with a very likely TIA, in the training and external validation cohort, respectively.CONCLUSIONS: The EV-surface antigen profile appears to be different in patients with transient symptoms adjudicated to be very likely caused by brain ischemia compared with patients whose symptoms were less likely to due to brain ischemia. We propose an algorithm based on an EV-surface-antigen specific signature that might aid in the recognition of TIA.

  View details for DOI 10.1161/STROKEAHA.120.033170

  View details for PubMedID 34344167

• Standardized Nomenclature for Modified Rankin Scale Global Disability Outcomes: Consensus Recommendations From Stroke Therapy Academic Industry Roundtable XI. Stroke Saver, J. L., Chaisinanunkul, N., Campbell, B. C., Grotta, J. C., Hill, M. D., Khatri, P., Landen, J., Lansberg, M. G., Venkatasubramanian, C., Albers, G. W., XIth Stroke Treatment Academic Industry Roundtable 2021: STROKEAHA121034480

  Abstract

  The modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability, is the most widely employed outcome scale in acute stroke trials. The scale's original development preceded the advent of modern clinimetrics, but substantial subsequent work has been performed to enable the mRS to meet robust contemporary scale standards. Prior research and consensus recommendations have focused on modernizing 2 aspects of the mRS: operationalized assignment of scale scores and statistical analysis of scale distributions. Another important characteristic of the mRS still requiring elaboration and specification to contemporary clinimetric standards is the Naming of scale outcomes. Recent clinical trials have used a bewildering variety, often mutually contradictory, of rubrics to describe scale states. Understanding of the meaning of mRS outcomes by clinicians, patients, and other clinical trial stakeholders would be greatly enhanced by use of a harmonized, uniform set of labels for the distinctive mRS outcomes that would be used consistently across trials. This statement advances such recommended rubrics, developed by the Stroke Therapy Academic Industry Roundtable collaboration using an iterative, mixed-methods process. Specific guidance is provided for health state terms (eg, Symptomatic but Nondisabled for mRS score 1; requires constant care for mRS score 5) and valence terms (eg, excellent for mRS score 1; very poor for mRS score 5) to employ for 23 distinct numeric mRS outcomes, including: all individual 7 mRS levels; all 12 positive and negative dichotomized mRS ranges, positive and negative sliding dichotomies; and utility-weighted analysis of the mRS.

  View details for DOI 10.1161/STROKEAHA.121.034480

  View details for PubMedID 34320814

• Angiography Suite Cone-Beam Computed Tomography Perfusion Imaging in Large-Vessel Occlusion Patients Using RAPID Software: A Pilot Study. Stroke Quispe-Orozco, D., Farooqui, M., Zevallos, C., Schafer, S., Mendez-Ruiz, A., Albers, G., Petersen, N., Ortega-Gutierrez, S. 2021: STROKEAHA121035992

  View details for DOI 10.1161/STROKEAHA.121.035992

  View details for PubMedID 34315250

• Rivaroxaban for Extended Thromboprophylaxis in Acutely Ill Medical Patients 75 Years of Age or Older. Journal of thrombosis and haemostasis : JTH Ageno, W., Lopes, R. D., Goldin, M., Yusen, R. D., Albers, G. W., Elliott, C. G., Halperin, J. L., Hiatt, W. R., Maynard, G., Steg, P. G., Weitz, J. I., Suh, E., Lu, W., Barnathan, E. S., Raskob, G. E., Spyropoulos, A. C. 2021

  Abstract

  BACKGROUND: Although older patients are at increased risk for venous thromboembolism (VTE), thromboprophylaxis is underutilized because of bleeding concerns. The MARINER trial evaluated whether rivaroxaban reduced symptomatic post-discharge VTE in acutely ill medical patients. We hypothesized that rivaroxaban would have a favorable benefit/risk profile in patients ≥75 years of age.METHODS: Patients were randomized in a double-blind manner at hospital discharge to rivaroxaban (10mg/day for creatinine clearance ≥50 ml/min; 7.5mg/day for ≥30-<50ml/min) or placebo for 45 days. Using a Cox proportional hazard model including treatment as a covariate, we compared the risk of the primary efficacy outcome (symptomatic VTE plus VTE-related death in the intention-to-treat population) and safety outcome (ISTH major bleeding in the safety population) in the prespecified subgroups of patients ≥ and <75 years of age.RESULTS: The primary event rate in patients ≥75 years of age was 2-fold higher than that in those <75. The incidence of the primary efficacy outcomes in both age groups was numerically lower with rivaroxaban than with placebo (≥75: 1.2% and 1.6%, HR 0.73 95% CI 0.43, 1.22; <75 0.6% and 0.8%, HR 0.78 95% CI 0.46, 1.32; interaction p-value for age group=0.85). The incidence of major bleeding was low and similar in the two age and treatment groups (interaction p-value for age group=0.35).LIMITATIONS: Subgroup analysis.CONCLUSION: Symptomatic VTE and VTE-related death occur frequently in older patients with acute medical illness. The benefit/risk profile of rivaroxaban in patients ≥75 years of age appears consistent with that observed in the general population.

  View details for DOI 10.1111/jth.15477

  View details for PubMedID 34314574

• Assessment of Optimal Patient Selection for Endovascular Thrombectomy Beyond 6 Hours After Symptom Onset: A Pooled Analysis of the AURORA Database. JAMA neurology Albers, G. W., Lansberg, M. G., Brown, S., Jadhav, A. P., Haussen, D. C., Martins, S. O., Rebello, L. C., Demchuk, A. M., Goyal, M., Ribo, M., Turk, A. S., Liebeskind, D. S., Heit, J. J., Marks, M. P., Jovin, T. G., Nogueira, R. G., AURORA Investigators, Bonafe, A., Budzik, R. F., Bhuva, P., Christensen, S., Cognard, C., Hanel, R. A., Hassan, A. E., Hill, M., Leslie-Mazwi, T., McTaggart, R. A., Millan, M., Ortega-Gutierrez, S., Shuaib, A., Sila, C. A., Torbey, M. T., Kim-Tenser, M., Tsai, J. P., Yavagal, D. R. 2021

  Abstract

  Importance: The optimal imaging approach for identifying patients who may benefit from endovascular thrombectomy (EVT) beyond 6 hours after they were last known well is unclear. Six randomized clinical trials (RCTs) have evaluated the efficacy of EVT vs standard medical care among patients with ischemic stroke.Objective: To assess the benefits of EVT among patients with 3 baseline imaging profiles using a pooled analysis of RCTs.Data Sources: The AURORA (Analysis of Pooled Data from Randomized Studies of Thrombectomy More Than 6 Hours After Last Known Well) Collaboration pooled patient-level data from the included clinical trials.Study Selection: An online database search identified RCTs of endovascular stroke therapy published between January 1, 2010, and March 1, 2021, that recruited patients with ischemic stroke who were randomized between 6 and 24 hours after they were last known well.Data Extraction/Synthesis: Data from the final locked database of each study were provided. Data were pooled, and analyses were performed using mixed-effects modeling with fixed effects for parameters of interest.Main Outcomes and Measures: The primary outcome was reduction in disability measured by the modified Rankin Scale at 90 days. An evaluation was also performed to examine whether the therapeutic response differed based on imaging profile among patients who received treatment based on the time they were last known well. Treatment benefits were assessed among a clinical mismatch subgroup, a target perfusion mismatch subgroup, and an undetermined profile subgroup. The primary end point was assessed among these subgroups and during 3 treatment intervals (tercile 1, 360-574 minutes [6.0-9.5 hours]; tercile 2, 575-762 minutes [9.6-12.7 hours]; and tercile 3, 763-1440 minutes [12.8-24.0 hours]).Results: Among 505 eligible patients, 266 (mean [SD] age, 68.4 [13.8] years; 146 women [54.9%]) were assigned to the EVT group and 239 (mean [SD] age, 68.7 [13.7] years; 126 men [52.7%]) were assigned to the control group. Among 295 patients in the clinical mismatch subgroup and 359 patients in the target perfusion mismatch subgroup, EVT was associated with reductions in disability at 90 days vs no EVT (clinical mismatch subgroup, odds ratio [OR], 3.57; 95% CI, 2.29-5.57; P<.001; target perfusion mismatch subgroup, OR, 3.13; 95% CI, 2.10-4.66; P=.001). Statistically significant benefits were observed in all 3 terciles for both subgroups, with the highest OR observed for tercile 3 (clinical mismatch subgroup, OR, 4.95; 95% CI, 2.20-11.16; P < .001; target perfusion mismatch subgroup, OR, 5.01; 95% CI, 2.37-10.60; P < .001). A total of 132 patients (26.1%) had an undetermined imaging profile and no significant treatment benefit (OR, 1.59; 95% CI, 0.82-3.06; P=.17). The interaction between treatment effects for the clinical and target perfusion mismatch subgroups vs the undetermined profile subgroup was significant (OR, 2.28; 95% CI, 1.11-4.70; P=.03).Conclusions and Relevance: In this study, EVT was associated with similar benefit among patients in the clinical mismatch and target perfusion mismatch subgroups during the 6- to 24-hour treatment interval. These findings support EVT as a treatment for patients meeting the criteria for either of the imaging mismatch profiles within the 6- to 24-hour interval.

  View details for DOI 10.1001/jamaneurol.2021.2319

  View details for PubMedID 34309619

• EXPRESS: A Randomized Controlled Trial to Optimize Patientas Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT2): Study Protocol. International journal of stroke : official journal of the International Stroke Society Sarraj, A., Hassan, A. E., Abraham, M., Ribo, M., Blackburn, S., Chen, M., Hussain, M. S., Pereira, V. M., Ortega, S., Sitton, C., Lavori, P. W., Cai, C., Rahbar, M. H., Pujara, D. K., Shaker, F., Lansberg, M. G., Campbell, B., Grotta, J. C., Albers, G. W. 2021: 17474930211035032

  Abstract

  RATIONALE: Randomized evidence for endovascular thrombectomy(EVT) safety and efficacy in patients with large core strokes is lacking.AIMS: To demonstrate EVT efficacy and safety in patients with large core on non-contrast CT or perfusion imaging(CT/MR) and determine if there is heterogeneity of treatment effect in large cores based on the imaging modality.DESIGN: SELECT2 is a prospective, randomized, multi-center, assessor-blinded controlled trial with adaptive enrichment design, enrolling up to 560 patients.PROCEDURE: Patients who meet the clinical criteria and have anterior circulation large vessel occlusions with large core on either NCCT(ASPECTS 3-5) or perfusion imaging(CTP[rCBF<30%] and/or MRI[ADC <620]a50cc) will be randomized in a 1:1 ratio to undergo EVT or medical management(MM) only up to 24 hours of last known well.STUDY OUTCOMES: The distribution of 90-day mRS scores is the primary outcome. Functional independence(mRS=0-2) rate is a secondary outcome. Other secondary outcomes include safety(symptomatic ICH, neurological worsening, mortality) and imaging outcomes.ANALYSIS: A normal approximation of the Wilcoxon-Mann-Whitney test(the generalized likelihood ratio test) to assess the primary outcome. Functional independence rates, safety and imaging outcomes will also be compared.DISCUSSION: The SELECT2 trial will evaluate EVT safety and efficacy in large cores on either CT or perfusion imaging and may provide randomized evidence to extend EVT eligibility to larger population. Registration: ClinicalTrials.govaNCT03876457.

  View details for DOI 10.1177/17474930211035032

  View details for PubMedID 34282987

• Acute Stroke Imaging Research Roadmap IV: Imaging Selection and Outcomes in Acute Stroke Clinical Trials and Practice. Stroke Campbell, B. C., Lansberg, M. G., Broderick, J. P., Derdeyn, C. P., Khatri, P., Sarraj, A., Saver, J. L., Vagal, A., Albers, G. W., STAIR XI Consortium, Adeoye, O., Ansari, S., Boltze, J., Buchan, A., Chaisinanunkul, N., Chen, C., Davis, T. P., Ermakova, T., Fisher, M., Haddad, W., Hill, M. D., Houser, G., Jadhav, A. P., Kimberly, W. T., Landen, J. W., Liebeskind, D. S., Lyden, P., Lynch, J., Mansi, C., Mocco, J., Nogueira, R. G., Savitz, S. I., Schwamm, L. H., Sheth, K. N., Solberg, Y., Venkatasubramanian, C., Warach, S., Wechsler, L. R., Zhu, B., Ziogas, N. K. 2021: STROKEAHA121035132

  Abstract

  BACKGROUND AND PURPOSE: The Stroke Treatment Academic Industry Roundtable (STAIR) sponsored an imaging session and workshop during the Stroke Treatment Academic Industry Roundtable XI via webinar on October 1 to 2, 2020, to develop consensus recommendations, particularly regarding optimal imaging at primary stroke centers.METHODS: This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss imaging priorities in the light of developments in reperfusion therapies, particularly in an extended time window, and reinvigorated interest in brain cytoprotection trials.RESULTS: The imaging session summarized and compared the imaging components of recent acute stroke trials and debated the optimal imaging strategy at primary stroke centers. The imaging workshop developed consensus recommendations for optimizing the acquisition, analysis, and interpretation of computed tomography and magnetic resonance acute stroke imaging, and also recommendations on imaging strategies for primary stroke centers.CONCLUSIONS: Recent positive acute stroke clinical trials have extended the treatment window for reperfusion therapies using imaging selection. Achieving rapid and high-quality stroke imaging is therefore critical at both primary and comprehensive stroke centers. Recommendations for enhancing stroke imaging research are provided.

  View details for DOI 10.1161/STROKEAHA.121.035132

  View details for PubMedID 34233464

• Perfusion imaging and clinical outcome in acute ischemic stroke with large core. Annals of neurology Seners, P., Oppenheim, C., Turc, G., Albucher, J., Guenego, A., Raposo, N., Christensen, S., Calviere, L., Viguier, A., Darcourt, J., Januel, A., Mlynash, M., Sommet, A., Thalamas, C., Sibon, I., Rousseau, V., Tourdias, T., Menegon, P., Bonneville, F., Mazighi, M., Charron, S., Legrand, L., Cognard, C., Albers, G. W., Baron, J., Olivot, J., FRAME investigators, Chollet, F., Fontaine, L., Barbieux, M., Michelozzi, C., Tall, P., Caparros, F., Pouzet, B., Calvas, F., Galitzki, M., Drif, A., Renou, P., Rouanet, F., Berge, J., Marnat, G., Menegon, P., Lucas, L., Coignon, C., Sagnier, S., Debruxelle, S., Ledure, S. 2021

  Abstract

  OBJECTIVE: Mechanical thrombectomy (MT) is not recommended for acute stroke with large vessel occlusion (LVO) and a large volume of irreversibly injured tissue (core). Perfusion imaging may identify a subset of patients with large core who benefit from MT.METHODS: We compared two cohorts of LVO-related patients with large core (>50ml on diffusion-weighted-imaging or CT-perfusion using RAPID), available perfusion imaging, and treated within 6hrs from onset by either MT+Best Medical Management (BMM) in one prospective study, or BMM alone in the pre-MT era from a prospective registry. Primary outcome was 90-day modified Rankin Scale≤2. We searched for an interaction between treatment group and amount of penumbra as estimated by the mismatch ratio (MMRatio=critical hypoperfusion/core volume).RESULTS: Overall, 107 patients were included (56 MT+BMM+51 BMM): Mean age was 68±15yrs, median core volume 99ml (IQR: 72-131) and MMRatio 1.4 (IQR: 1.0-1.9). Baseline clinical and radiological variables were similar between the 2 groups, except for a higher intravenous thrombolysis rate in the BMM group. The MMRatio strongly modified the clinical outcome following MT (Pinteraction <0.001 for continuous MMRatio); MT was associated with a higher rate of good outcome in patients with, but not in those without, MMRatio>1.2 (adjusted OR [95%CI]=6.8 [1.7-27.0] vs. 0.7 [0.1-6.2], respectively). Similar findings were present for MMRatio≥1.8 in the subgroup with core≥70ml. Parenchymal hemorrhage on follow-up imaging was more frequent in the MT+BMM group regardless of the MMRatio.INTERPRETATION: Perfusion imaging may help select which patients with large core should be considered for MT. Randomized studies are warranted. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.26152

  View details for PubMedID 34216396

• Reexamination of the Embolic Stroke of Undetermined Source Concept. Stroke Albers, G. W., Bernstein, R., Brachmann, J., Camm, A. J., Fromm, P., Goto, S., Granger, C. B., Hohnloser, S. H., Hylek, E., Krieger, D., Passman, R., Pines, J. M., Kowey, P. 2021: STROKEAHA121035208

  Abstract

  Occult atrial fibrillation (AF) is a leading cause of stroke of unclear cause. The optimal approach to secondary stroke prevention for these patients remains elusive. The term embolic stroke of undetermined source (ESUS) was coined to describe ischemic strokes in which the radiographic features demonstrate territorial infarcts resembling those seen in patients with confirmed sources of embolism but without a clear source of embolism detected. It was assumed that patients with ESUS had a high rate of occult AF and would benefit from treatment with direct oral anticoagulants, which are at least as effective as vitamin K antagonists for secondary stroke prevention in patients with AF, but with a much lower risk of intracerebral hemorrhage. Two recent large randomized trials failed to show superiority of direct oral anticoagulants over aspirin in ESUS patients. These findings prompt a reexamination of the ESUS concept, with the goal of improving specificity for detecting patients with a cardioembolic cause. Based on the negative trial results, there is renewed interest in the role of long-term cardiac monitoring for AF in patients who fit the current ESUS definition, as well as the clinical implication of detecting AF. Ongoing trials are exploring these questions. Current ESUS definitions do not accurately detect the patients who should be prescribed direct oral anticoagulants, potentially because occult AF is less common than expected in these patients and/or anticoagulants may be less beneficial in patients with ESUS but no AF than they are for patients with stroke with established AF. More specific criteria to identify patients who may be at higher risk for occult AF and reduce their risk of subsequent stroke have been developed and are being tested in ongoing clinical trials.

  View details for DOI 10.1161/STROKEAHA.121.035208

  View details for PubMedID 34192898

• Optimizing Deep Learning Algorithms for Segmentation of Acute Infarcts on Non-Contrast Material-enhanced CT Scans of the Brain Using Simulated Lesions. Radiology. Artificial intelligence Christensen, S., Mlynash, M., MacLaren, J., Federau, C., Albers, G. W., Lansberg, M. G. 2021; 3 (4): e200127

  Abstract

  Purpose: To test the efficacy of lesion segmentation using a deep learning algorithm on non-contrast material-enhanced CT (NCCT) images with synthetic lesions resembling acute infarcts.Materials and Methods: In this retrospective study, 40 diffusion-weighted imaging (DWI) lesions in patients with acute stroke (median age, 69 years; range, 62-76 years; 17 women; screened between 2011 and 2017) were coregistered to 40 normal NCCT scans (median age, 70 years; range, 55-76 years; 25 women; screened between 2008 and 2011), which produced 640 combinations of DWI-NCCT with and without lesions for training (n = 420), validation (n = 110), and testing (n = 110). The signal intensity on the NCCT scans was depressed by 4 HU (a 13% drop) in the region of the diffusion-weighted lesion. Two U-Net architectures (standard and symmetry aware) were trained with two different training strategies. One was a naive strategy, in which the model started training with random coefficients. The other was a progressive strategy, which started with coefficients derived from a model trained on a dataset with lesions that were depressed by 10 HU. The Dice scores from the two architectures and training strategies were compared from the test dataset.Results: Dice scores of symmetry-aware U-Nets were 25% higher than those of standard U-Nets (median, 0.49 vs 0.65; P < .001). Use of a progressive training strategy had no clear effect on model performance.Conclusion: Symmetry-aware U-Nets offer promise for segmentation of acute stroke lesions on NCCT scans.Keywords: Adults, CT-Quantitative, StrokeSupplemental material is available for this article.©RSNA, 2021.

  View details for DOI 10.1148/ryai.2021200127

  View details for PubMedID 34350404

• Penumbra Consumption Rates Based on Time-to-Maximum Delay and Reperfusion Status: A Post Hoc Analysis of the DEFUSE 3 Trial. Stroke Yaghi, S., Raz, E., Dehkharghani, S., Riina, H., McTaggart, R., Jayaraman, M., Prabhakaran, S., Liebeskind, D. S., Khatri, P., Mac Grory, B., Al-Mufti, F., Lansberg, M., Albers, G., de Havenon, A. 2021: STROKEAHA120033806

  Abstract

  BACKGROUND AND PURPOSE: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (Tmax) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for Tmax delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal.METHODS: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume-baseline core infarct volume)/(Tmax 6 or 10 s volume-baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category.RESULTS: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%-87.7%) versus 5.3% (1.1%-14.6%) of penumbral tissue was consumed based on Tmax >6 s (P<0.001). In the same comparison for Tmax>10 s, we saw a difference of 165.4% (interquartile range, 56.1%-479.8%) versus 25.7% (interquartile range, 3.2%-72.1%; P<0.001). Significant differences were not demonstrated between untreated and TICI 0-2a patients for penumbral consumption based on Tmax >6 s (P=0.52) or Tmax >10 s (P=0.92).CONCLUSIONS: Among extended window endovascular thrombectomy patients, Tmax >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the Tmax >6-s mismatch volume may remain viable in untreated patients at 24 hours.

  View details for DOI 10.1161/STROKEAHA.120.033806

  View details for PubMedID 34157865

• MR perfusion imaging: Half-dose gadolinium is half the quality. Journal of neuroimaging : official journal of the American Society of Neuroimaging Heit, J. J., Christensen, S., Mlynash, M., Marks, M. P., Faizy, T. D., Lansberg, M. G., Wintermark, M., Bammer, R., Albers, G. W. 2021

  Abstract

  BACKGROUND AND PURPOSE: Patients with acute ischemic stroke due to a large vessel occlusion (AIS-LVO) undergo emergent neuroimaging triage for thrombectomy treatment. MRI is often utilized for this evaluation, and cerebral magnetic resonance perfusion (MRP) imaging is used to identify the presence of the salvageable penumbra. To determine if dose reduction is feasible, we assessed whether a half-dose reduction in gadobenate provided sufficient MRP quality in AIS-LVO patients.METHODS: A prospective observational study of all patients presenting to our neurovascular referral center with AIS-LVO was performed. MRP was done with a half-dose of gadolinium (0.1 ml/kg body weight) over a period of 10 months. MRP images were compared to a consecutive historical cohort of full-dose gadolinium (0.2 ml/kg body weight) MRP studies and rated for image quality (poor, borderline, or good) that determined thrombectomy eligibility.RESULTS: Fifty-four half-dose and 127 full-dose patients were included. No differences in patient demographics or stroke presentation details were identified. MRP quality differed between half- and full-dose scans (p < 0.001), which were rated as poor (40.7% vs. 6.3%), borderline (18.5% vs. 26.8%), and good quality (40.7% vs. 66.9%), respectively. MRP image quality was then dichotomized into poor and sufficient (borderline and good) quality groups; half-dose studies were more likely to have poor quality compared to full-dose studies (40.7% vs. 6.3%; p < 0.001).CONCLUSIONS: Half-dose gadolinium administration for MRP in AIS-LVO patients results in poor image quality in a substantial number of studies. MR cerebral perfusion performed with half-dose gadolinium may adversely affect stroke patient triage for thrombectomy.

  View details for DOI 10.1111/jon.12879

  View details for PubMedID 34002424

• Association of Venous Outflow Profiles and Successful Vessel Reperfusion After Thrombectomy. Neurology Faizy, T. D., Kabiri, R., Christensen, S., Mlynash, M., Kuraitis, G., Marc-Daniel Mader, M., Albers, G. W., Lansberg, M. G., Fiehler, P. J., Wintermark, M., Marks, M. P., Heit, J. J. 2021

  Abstract

  OBJECTIVE: Robust arterial collaterals are associated with successful reperfusion after thrombectomy treatment of acute ischemic stroke due to large vessel occlusion (AIS-LVO). Excellent venous outflow (VO) reflects excellent tissue perfusion and collateral status in AIS-LVO patients. To determine whether favorable VO profiles assessed on pre-treatment CT angiography (CTA) images correlate with successful vessel reperfusion after thrombectomy in AIS-LVO patients.METHODS: Multicenter retrospective cohort study of consecutive AIS-LVO patients treated by thrombectomy. Baseline CTA was used to assess collateral status (Tan scale) and VO using the cortical vein opacification score (COVES). Favorable VO was defined as COVES ≥3. Primary outcome was excellent vessel reperfusion status (modified Thrombolysis In Cerebral Infarction [TICI] 2c-3). Secondary outcome was good functional outcome defined as 0-2 on the Modified Ranking Scale (mRS) after 90 days.RESULTS: 565 patients met inclusion criteria. Multivariable logistic regression analysis showed that favorable VO (OR= 2.10 [95% CI 1.39-3.16]; p<0.001) was associated with excellent vessel reperfusion during thrombectomy, regardless of good CTA collateral status (OR= 0.87 [95%CI 0.58-1.34]; p=0.48). A favorable VO profile (OR= 8.9 [95%CI 5.3-14.9]; p<0.001) and excellent vessel reperfusion status (OR = 2.7 [95%CI 1.7-4.4]; p<0.001) were independently associated with good functional outcome adjusted for age, sex, glucose, tPA administration, good CTA collateral status and presentation NIHSS.CONCLUSION: A favorable VO profile is associated with reperfusion success and good functional outcomes in patients with AIS-LVO treated by endovascular thrombectomy.

  View details for DOI 10.1212/WNL.0000000000012106

  View details for PubMedID 33952649

• Circadian Biology and Stroke. Stroke Lo, E. H., Albers, G. W., Dichgans, M., Donnan, G., Esposito, E., Foster, R., Howells, D. W., Huang, Y., Ji, X., Klerman, E. B., Lee, S., Li, W., Liebeskind, D. S., Lizasoain, I., Mandeville, E. T., Moro, M. A., Ning, M., Ray, D., Sakadzic, S., Saver, J. L., Scheer, F. A., Selim, M., Tiedt, S., Zhang, F., Buchan, A. M. 2021: STROKEAHA120031742

  Abstract

  Circadian biology modulates almost all aspects of mammalian physiology, disease, and response to therapies. Emerging data suggest that circadian biology may significantly affect the mechanisms of susceptibility, injury, recovery, and the response to therapy in stroke. In this review/perspective, we survey the accumulating literature and attempt to connect molecular, cellular, and physiological pathways in circadian biology to clinical consequences in stroke. Accounting for the complex and multifactorial effects of circadian rhythm may improve translational opportunities for stroke diagnostics and therapeutics.

  View details for DOI 10.1161/STROKEAHA.120.031742

  View details for PubMedID 33940951

• Selection criteria for large core trials: dogma or data? Journal of neurointerventional surgery Sarraj, A., Campbell, B., Ribo, M., Hussain, M. S., Chen, M., Abraham, M. G., Lansberg, M. G., Mendes Pereira, V., Blackburn, S., Sitton, C. W., Budzik, R. F., Perez de la Ossa, N., Arenillas, J. F., Wu, T., Blasco, J., Mullen, M., Schaafsma, J., Tsai, J. P., Sangha, N., Kozak, O., Gibson, D., Warach, S., Cordato, D., Manning, N. W., Kleinig, T. J., Olivot, J., Elijovich, L., Tsivgoulis, G., Alexandrov, A., Jabbour, P., Yan, B., Kasner, S. E., Arthur, A. S., Parsons, M., Grotta, J. C., Hassan, A. E., Albers, G. W., SELECT2 Investigators and SELECT2 Steering Committee 2021

  View details for DOI 10.1136/neurintsurg-2021-017498

  View details for PubMedID 33879510

• Clinical and Neuroimaging Outcomes of Direct Thrombectomy vs Bridging Therapy in Large Vessel Occlusion: Analysis of the SELECT Cohort Study. Neurology Sarraj, A., Grotta, J., Albers, G. W., Hassan, A. E., Blackburn, S., Day, A., Sitton, C., Abraham, M., Cai, C., Dannenbaum, M., Pujara, D., Hicks, W., Budzik, R., Vora, N., Arora, A., Alenzi, B., Tekle, W. G., Kamal, H., Mir, O., Barreto, A. D., Lansberg, M., Gupta, R., Martin-Schild, S., Savitz, S., Tsivgoulis, G., SELECT investigators 2021

  Abstract

  OBJECTIVE: To evaluate the comparative safety and efficacy of direct endovascular thrombectomy(dEVT) compared to bridging therapy(BT:IV-tPA+EVT) and assess if BT potential benefit relates to stroke severity, size and initial presentation to EVT vs. non-EVT center.METHODS: In a prospective multicenter cohort-study of imaging selection for endovascular thrombectomy[SELECT], anterior-circulation large vessel occlusion (LVO) patients presenting to EVT-capable centers within 4.5hours from last-known-well were stratified into BT vs. dEVT. The primary outcome was 90-day functional independence[modified Rankin Scale(mRS)=0-2]. Secondary outcomes included a shift across 90-day mRS grades, mortality, symptomatic intracranial hemorrhage. We also performed subgroup-analyses according to initial presentation to EVT-capable center (direct versus transfer), stroke severity and baseline infarct core volume.RESULTS: We identified 226 LVOs (54%:men, mean age:65.6±14.6years, median NIHSS-score: 17, 28% received dEVT). Median time from arrival to groin-puncture did not differ in BT-patients when presenting directly[dEVT:1.43 (IQR=1.13-1.90) hours vs. BT:1.58(IQR=1.27-2.02)hours,p=0.40] or transferred to EVT-capable centers[dEVT:1.17 (IQR: 0.90-1.48) hours vs. BT:1.27 (IQR: 0.97-1.87) hours,p=0.24]. BT was associated with higher odds of 90-day functional independence (57% vs. 44%,aOR=2.02,95%CI:1.01-4.03,p=0.046) and functional improvement (adjusted cOR=2.06,95%CI:1.18-3.60,p=0.011), and lower likelihood of 90-day mortality (11% vs. 23%,aOR: 0.20,95%CI:0.07-0.58,p=0.003). No differences in any other outcomes were detected. In subgroup-analyses, BT patients with baseline NIHSS-scores<15 had higher functional independence likelihood compared to dEVT (aOR=4.87,95%CI:1.56-15.18,p=0.006); this association was not evident for patients with NIHSS-scores≥15 (aOR=1.05,95%CI:0.40-2.74,p=0.92). Similarly, functional outcomes improvements with BT were detected in patients with core volume strata (Ischemic core <50cc: aOR: 2.10, 95% CI:1.02-4.33, p=0.044 vs ischemic core ≥50cc: aOR: 0.41,95% CI:0.01-16.02,p=0.64) and transfer status (transferred: aOR: 2.21,95% CI:0.93-9.65,p=0.29 vs direct to EVT center: aOR:1.84,95%CI:0.80-4.23,p=0.15).CONCLUSIONS: Bridging therapy appears to be associated with better clinical outcomes, especially with milder NIHSS-scores, smaller presentation core volumes and those who were "dripped and shipped". We did not observe any potential benefit of bridging therapy in patients with more severe strokes.CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with ischemic stroke from anterior-circulation LVO within 4.5 hours from last-known-well, bridging therapy compared to direct endovascular thrombectomy leads to better 90-day functional outcomes.

  View details for DOI 10.1212/WNL.0000000000012063

  View details for PubMedID 33875560

• Stroke Imaging Utilization According to Age and Severity during the COVID-19 Pandemic. Radiology Kansagra, A. P., Goyal, M. S., Hamilton, S., Albers, G. W. 2021: 204716

  View details for DOI 10.1148/radiol.2021204716

  View details for PubMedID 33847520

• Prediction of Infarct Volume at the 24 Hours after Late Window Presentation with Perfusion Imaging in Patients with Anterior Circulation Large Vessel Occlusion Agarwal, S., Raz, E., Dehkharghani, S., Christensen, S., Lansberg, M., Yaghi, S., de Havenon, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for Web of Science ID 000729283602208

• Venous Outflow Profiles Are Linked to Cerebral Edema Formation at Noncontrast Head CT after Treatment in Acute Ischemic Stroke Regardless of Collateral Vessel Status at CT Angiography. Radiology Faizy, T. D., Kabiri, R., Christensen, S., Mlynash, M., Kuraitis, G., Meyer, L., Marks, M. P., Broocks, G., Flottmann, F., Lansberg, M. G., Albers, G. W., Fiehler, J., Wintermark, M., Heit, J. J. 2021: 203651

  Abstract

  Background Ischemic lesion net water uptake (NWU) at noncontrast head CT enables quantification of cerebral edema in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Purpose To assess whether favorable venous outflow (VO) profiles at CT angiography are associated with reduced NWU and good functional outcomes in patients with AIS due to LVO. Materials and Methods This multicenter retrospective cohort study evaluated consecutive patients with AIS due to LVO who underwent thrombectomy triage between January 2013 and December 2019. Arterial collateral vessel status (Tan scale) and venous output were measured at CT angiography. Venous outflow was graded with use of the cortical vein opacification score, which quantifies opacification of the vein of Labbe, sphenoparietal sinus, and superficial middle cerebral vein. Favorable VO was regarded as a score of 3-6 and unfavorable VO as a score of 0-2. NWU was determined at follow-up noncontrast CT. Multivariable regression analyses were performed to determine the association between favorable VO profiles and NWU after treatment and good functional outcome (modified Rankin Scale, ≤2). Results A total of 580 patients were included. Of the 580 patients, 231 had favorable VO (104 women; median age, 73 years [interquartile range {IQR}, 62-81 years]) and 349 had unfavorable VO (190 women; median age, 77 years [IQR, 66-84 years]). Compared with patients with unfavorable VO, those with favorable VO exhibited lower baseline National Institutes of Health Stroke Scale score (median, 12.5 [IQR, 7-17] vs 17 [IQR, 13-21]), higher Alberta Stroke Program Early CT Score (median, 9 [IQR, 7-10] vs 7 [IQR, 6-8]), and less NWU after treatment (median, 7% [IQR, 4.6%-11.5%] vs 17.9% [IQR, 12.3%-22.2%]). In a multivariable regression analysis, NWU mean difference between patients with unfavorable VO and those with favorable VO was 6.1% (95% CI: 4.9, 7.3; P < .001) regardless of arterial CT angiography collateral vessel status (b coefficient, 0.72 [95% CI: -0.59, 2.03; P = .28]). Favorable VO (odds ratio [OR]: 4.1 [95% CI: 2.2, 7.7]; P < .001) and reduced NWU after treatment (OR: 0.77 [95% CI: 0.73, 0.83]; P < .001) were independently associated with good functional outcomes. Conclusion Favorable venous outflow (VO) correlated with reduced ischemic net water uptake (NWU) after treatment. Reduced NWU and favorable VO were associated with good functional outcomes regardless of CT angiography arterial collateral vessel status. ©RSNA, 2021 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2021203651

  View details for PubMedID 33825511

• Tissue at Risk and Ischemic Core Estimation Using Deep Learning in Acute Stroke. AJNR. American journal of neuroradiology Yu, Y., Xie, Y., Thamm, T., Gong, E., Ouyang, J., Christensen, S., Marks, M. P., Lansberg, M. G., Albers, G. W., Zaharchuk, G. 2021

  Abstract

  BACKGROUND AND PURPOSE: In acute stroke patients with large vessel occlusions, it would be helpful to be able to predict the difference in the size and location of the final infarct based on the outcome of reperfusion therapy. Our aim was to demonstrate the value of deep learning-based tissue at risk and ischemic core estimation. We trained deep learning models using a baseline MR image in 3 multicenter trials.MATERIALS AND METHODS: Patients with acute ischemic stroke from 3 multicenter trials were identified and grouped into minimal (≤20%), partial (20%-80%), and major (≥80%) reperfusion status based on 4- to 24-hour follow-up MR imaging if available or into unknown status if not. Attention-gated convolutional neural networks were trained with admission imaging as input and the final infarct as ground truth. We explored 3 approaches: 1) separate: train 2 independent models with patients with minimal and major reperfusion; 2) pretraining: develop a single model using patients with partial and unknown reperfusion, then fine-tune it to create 2 separate models for minimal and major reperfusion; and 3) thresholding: use the current clinical method relying on apparent diffusion coefficient and time-to-maximum of the residue function maps. Models were evaluated using area under the curve, the Dice score coefficient, and lesion volume difference.RESULTS: Two hundred thirty-seven patients were included (minimal, major, partial, and unknown reperfusion: n = 52, 80, 57, and 48, respectively). The pretraining approach achieved the highest median Dice score coefficient (tissue at risk = 0.60, interquartile range, 0.43-0.70; core = 0.57, interquartile range, 0.30-0.69). This was higher than the separate approach (tissue at risk = 0.55; interquartile range, 0.41-0.69; P = .01; core = 0.49; interquartile range, 0.35-0.66; P=.04) or thresholding (tissue at risk = 0.56; interquartile range, 0.42-0.65; P=.008; core = 0.46; interquartile range, 0.16-0.54; P<.001).CONCLUSIONS: Deep learning models with fine-tuning lead to better performance for predicting tissue at risk and ischemic core, outperforming conventional thresholding methods.

  View details for DOI 10.3174/ajnr.A7081

  View details for PubMedID 33766823

• EXPRESS: Clinical Effectiveness of Endovascular Stroke Treatment in the Early and Extended Time Windows. International journal of stroke : official journal of the International Stroke Society Nogueira, R., Haussen, D. C., Liebeskind, D. S., Jovin, T. G., Gupta, R., Saver, J., Jadhav, A., Budzik, R., Baxter, B., Krajina, A., BonafA, A., Malek, A. R., Narata, A. P., Mohammaden, M. H., Zhang, Y., Morgan, P., Ji, M., Bartolini, B., English, J., Albers, G. W., Mlynash, M., Lansberg, M. G., Frankel, M. R., Pereira, V., Veznedaroglu, E. 2021: 17474930211005740

  Abstract

  BackgroundThe clinical efficacy of mechanical thrombectomy (MT) has been unequivocally demonstrated in multiple randomized clinical trials (RCTs). However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. AimWe aimed to assess the clinical effectiveness of MT in a prospective registry.MethodsA total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label MT registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials according to the basic demographic and clinical criteria without considering specific parenchymal imaging findings. Baseline and outcome variables were compared across the corresponding groups. ResultsAs compared to the treated patients in the actual trials, registry-derived patients tended to be younger and had lower baseline ASPECTS. In addition, time to treatment was earlier and the use of IV-tPA and general anesthesia were higher in DAWN- and DEFUSE 3-registry derived patients versus their corresponding trials. Reperfusion rates were higher in the registry patients. The rates of 90-day good outcome (mRS0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding RCTs (SWIFT-Prime,64.5% vs 60.2%; DAWN,50.4% vs 48.6%; Beyond-DAWN:52.4% vs 48.6%; DEFUSE 3, 52% vs 44.6%, respectively; all P>0.05). Registry-derived patients had significant less disability than the corresponding RCT controls (ordinal mRS shift OR, P<0.05 for all).ConclusionOur study provides favorable generalizability data for the safety and efficacy of thrombectomy in the areal-worlda setting and supports that patients may be safely treated outside the constraints of RCTs.

  View details for DOI 10.1177/17474930211005740

  View details for PubMedID 33705210

• The Cerebral Collateral Cascade: Rethinking the Assessment of Vascular Pathways in Acute Ischemic Stroke Patients. Faizy, T. D., Mlynash, M., Kabiri, R., Christensen, S., Kuraitis, G., Mader, M., Flottmann, F., Broocks, G., Lansberg, M. G., Albers, G., Marks, M., Fiehler, J., Wintermark, M., Heit, J. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P321

  View details for Web of Science ID 000670883500438

• Effect of Premorbid Antiplatelet Medication on Infarct Volume at 24 Hours After Late Window Presentation With Anterior Circulation Large Vessel Occlusion de Havenon, A. H., Christensen, S., Lansberg, M. G., Mlynash, M., Albers, G. W., Yaghi, S. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P513

  View details for Web of Science ID 000670883500628

• Perfusion Imaging Identifies Patients With Mild Deficits Due to Large Vessel Occlusion Who May Benefit From Endovascular Thrombectomy: A Pooled International Cohort Study Sarraj, A., Ribo, M., Blasco, J., Perez de la Ossa, N., Chen, M., Hassan, A. E., Wu, T. Y., Cordato, D., Kleinig, T. J., Schaafsma, J. D., Blackburn, S., Abraham, M. G., Gibson, D., Wallace, A., Pujara, D., Shaker, F., Moreno Negrete, J., Beharry, J., Cappelen-Smith, C., Rodriguez-Esparragoza, L., Olive Gadea, M., Requena, M., Pereira, V., Day, A. L., Sitton, C., Martin-schild, S. B., Song, S., Mitchell, P. J., Parsons, M., Grotta, J. C., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P473

  View details for Web of Science ID 000670883500589

• Validation of Deep Learning Based Critical Hypoperfusion and Ischemic Core Prediction in a Multicenter External Randomized Controlled Trial Yu, Y., Xie, Y., Christensen, S., Gong, E., Lansberg, M. G., Albers, G., Zaharchuk, G. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P325

  View details for Web of Science ID 000670883500442

• Prediction of Stroke Lesion Growth Rates by Baseline Perfusion Imaging Wouters, A., Robben, D., Christensen, S., Marquering, H., Roos, Y., Oostenbrugge, R. V., van Zwam, W., Dippel, D. W., Majoie, C. B., van der Lugt, A., Lansberg, M. G., Albers, G. W., Suetens, P., Lemmens, R. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P333

  View details for Web of Science ID 000670883500450

• Clinical Effectiveness of Endovascular Stroke Treatment in the Early and Extended Time Windows Nogueira, R., Haussen, D. C., Liebeskind, D. S., Jovin, T. G., Gupta, R., Saver, J. L., Jadhav, A., Budzik, R., Baxter, B. W., Krajina, A., Bonafe, A., Malek, A. R., Ana Paula, N., Mohammaden, M., Zhang, Y., Morgan, P., Ji, M., Bartolini, B., English, J., Albers, G., Mlynash, M., Lansberg, M. G., Michael, F., Pereira, V., Veznedaroglu, E. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P467

  View details for Web of Science ID 000670883500583

• Accuracy of CT Perfusion Core Estimates for Predicting Infarct Size in the SELECT Study Sarraj, A., Campbell, B., Sitton, C., Christensen, S., Khanpara, S., Riascos, R., Pujara, D., Shaker, F., Lansberg, M. G., Albers, G., SELECT Investigators LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P331

  View details for Web of Science ID 000670883500448

• Can Deep Learning Find the Ischemic Core on CT? Transfer Learning From Pre-Trained MRI-Based Networks Yu, Y., Christensen, S., Xie, Y., Gong, E., Lansberg, M. G., Albers, G., Zaharchuk, G. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P319

  View details for Web of Science ID 000670883500436

• Prediction of Infarct Volume at the 24 Hours After Late Window Presentation With Perfusion Imaging in Patients With Anterior Circulation Large Vessel Occlusion Agarwal, S., Raz, E., Dehkharghani, S., Christensen, S., Lansberg, M. G., Albers, G., Yaghi, S., De Havenon, A. H. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1161/str.52.suppl_1.P505

  View details for Web of Science ID 000670883500620

• Clinical Outcomes and Identification of Patients With Persistent Penumbral Profiles Beyond 24 Hours From Last Known Well: Analysis From DEFUSE 3. Stroke Sarraj, A., Mlynash, M., Heit, J., Pujara, D., Lansberg, M., Marks, M., Albers, G. W. 2021: STROKEAHA120031147

  Abstract

  BACKGROUND AND PURPOSE: DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) infarct volumes at 24 hours did not significantly differ in the endovascular thrombectomy (EVT) versus medical management (MM) only groups. We hypothesized that this was due to underestimation of the final infarct volume among patients with persistent penumbral tissue 24 hours after randomization that subsequently progressed to infarction. We sought to assess the clinical outcomes in patients with persistent penumbral profile >24 hours from last known well and identify them based on the Persistent Penumbra Index (PPI, time-to-maximum of the residue function >6 s perfusion lesion divided by diffusion-weighted magnetic resonance imaging lesion volume on 24-hour postrandomization imaging).METHODS: Patients were stratified into those with a 24-hour postrandomization penumbral (PPI>1) versus a nonpenumbral (PPI≤1) profile. The primary outcome was 90-day-modified Rankin Scale.RESULTS: One hundred eighty-two patients were randomized (EVT: 92, MM: 90). Twenty-four-hour postrandomization time-to-maximum of the residue function and infarct volumes were assessable for 144 (EVT: 75, MM: 69). Infarct volumes did not differ between EVT and MM (median [interquartile range] mL: 35.0 [17.6-81.6] versus 41.0 [25.4-106.2], P=0.185). Thirty-two patients had persistent penumbral profile (PPI>1), of these 29 (91%) received MM. PPI was 0 (0-0.07) for EVT, and 0.77 (0.23-1.79) for MM, P<0.001. Patients with clinical-imaging mismatch (more severe strokes and smaller infarct volumes) were more likely to have persistent penumbral profile (PPI>1; adjusted odds ratio, 1.20 [1.11-1.30] for every 1-point National Institutes of Health Stroke Scale-increment and adjusted odds ratio, 0.977 [0.964-0.990] for every 10 cc smaller infarct volume, P<0.001). Patients with nonpenumbral profile (PPI≤1) had higher odds of achieving functional independence (39% versus 9%; adjusted odds ratio, 9.9[95% CI, 2.3-42.8], P=0.002), a trend towards lower mortality (12% versus 34%, P=0.002; adjusted odds ratio, 0.34 [95% CI, 0.11-1.03], P=0.057) and early clinical improvement (24-hour National Institutes of Health Stroke Scale-decrease ≥8 points or 0-1): 29% vs 9%, P=0.034) which persisted at discharge and 90-day follow-up. For a given volume, patients with PPI≤1 had significantly higher likelihood of functional independence as compared to those with PPI>1.CONCLUSIONS: Patients with persistent penumbral profile who have salvageable tissue beyond 24 hours from last known well can be identified by PPI and clinical-imaging mismatch. They have a poor prognosis and may benefit from very late window reperfusion therapies. Clinical trials in these patients are warranted.REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

  View details for DOI 10.1161/STROKEAHA.120.031147

  View details for PubMedID 33563012

• The Utility of Domain-Specific End Points in Acute Stroke Trials. Stroke Cramer, S. C., Wolf, S. L., Saver, J. L., Johnston, K. C., Mocco, J., Lansberg, M. G., Savitz, S. I., Liebeskind, D. S., Smith, W., Wintermark, M., Elm, J. J., Khatri, P., Broderick, J. P., Janis, S., NIH StrokeNet Recovery and Rehabilitation Group and the Acute Stroke Group, Chen, D., Dromerick, A., Dunning, K., Grande, A. W., Marshall, R. S., Meinzer, C., Page, S., Reiss, A., Richards, L., Wechsler, L., Winstein, C., Bushnell, C., Edwards, D., Lo, W., Lee, J., Amlie-Lefond, C. M., Albers, G. W., Dempsey, R., Gropen, T. I., Jauch, E. C., Leira, E. C., Martin, R., Meyer, B. C., Schindler, K., Scott, P., Singhal, A. B., Moy, C. S. 2021: STROKEAHA120031939

  View details for DOI 10.1161/STROKEAHA.120.031939

  View details for PubMedID 33563009

• Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Faizy, T. D., Kabiri, R., Christensen, S., Mlynash, M., Kuraitis, G., Broocks, G., Hanning, U., Nawabi, J., Lansberg, M. G., Marks, M. P., Albers, G. W., Fiehler, J., Wintermark, M., Heit, J. J. 2021: 271678X21992200

  Abstract

  Ischemic lesion Net Water Uptake (NWU) quantifies cerebral edema formation and likely correlates with the microvascular perfusion status of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We hypothesized that favorable tissue-level collaterals (TLC) predict less NWU and good functional outcomes. We performed a retrospective multicenter analysis of AIS-LVO patients who underwent thrombectomy triage. TLC were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (HIR; volume ratio of brain tissue with [Tmax>10sec/Tmax>6sec]); favorable TLC were regarded as HIR ≤ 0.4. NWU was determined using a quantitative densitometry approach on follow-up CT. Primary outcome was NWU. Secondary outcome was a good functional outcome (modified Rankin Scale [mRS] 0-2).580 patients met inclusion criteria. Favorable TLC (beta: 4.23, SE: 0.65; p<0.001) predicted smaller NWU after treatment. Favorable TLC (OR: 2.35, [95% CI: 1.31-4.21]; p<0.001), and decreased NWU (OR: 0.75, [95% CI: 0.70-0.79]; p<0.001) predicted good functional outcome, while controlling for age, glucose, CTA collaterals, baseline NIHSS and good vessel reperfusion status.We conclude that favorable TLC predict less ischemic lesion NWU after treatment in AIS-LVO patients. Favorable TLC and decreased NWU were independent predictors of good functional outcome.

  View details for DOI 10.1177/0271678X21992200

  View details for PubMedID 33557694

• Favorable Venous Outflow Profiles Correlate With Favorable Tissue-Level Collaterals and Clinical Outcome. Stroke Faizy, T. D., Kabiri, R. n., Christensen, S. n., Mlynash, M. n., Kuraitis, G. M., Broocks, G. n., Flottmann, F. n., Marks, M. P., Lansberg, M. G., Albers, G. W., Fiehler, J. n., Wintermark, M. n., Heit, J. J. 2021: STROKEAHA120032242

  Abstract

  Patients with acute ischemic stroke due to large vessel occlusion and favorable tissue-level collaterals (TLCs) likely have robust cortical venous outflow (VO). We hypothesized that favorable VO predicts robust TLC and good clinical outcomes.Multicenter retrospective cohort study of consecutive acute ischemic stroke due to large vessel occlusion patients who underwent thrombectomy triage. Included patients had interpretable prethrombectomy computed tomography, computed tomography angiography, and cerebral perfusion imaging. TLCs were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (volume ratio of brain tissue with [Tmax >10 s/Tmax >6 s]). VO was determined by opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein on computed tomography angiography as 0, not visible; 1, moderate opacification; and 2, full. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analyses, we determined the association between VO and (1) favorable TLC status (defined as hypoperfusion intensity ratio ≤0.4) and (2) good functional outcome (modified Rankin Scale score, 0-2).Six hundred forty-nine patients met inclusion criteria. Patients with favorable VO were younger (median age, 72 [interquartile range (IQR), 62-80] versus 77 [IQR, 66-84] years), had a lower baseline National Institutes of Health Stroke Scale (median, 12 [IQR, 7-17] versus 19 [IQR, 13-20]), and had a higher Alberta Stroke Program Early Computed Tomography Score (median, 9 [IQR, 7-10] versus 7 [IQR, 6-9]). Favorable VO strongly predicted favorable TLC (odds ratio, 4.5 [95% CI, 3.1-6.5]; P<0.001) in an adjusted regression analysis. Favorable VO also predicted good clinical outcome (odds ratio, 10 [95% CI, 6.2-16.0]; P<0.001), while controlling for favorable TLC, age, glucose, baseline National Institutes of Health Stroke Scale, and good vessel reperfusion status.In this selective retrospective cohort study of acute ischemic stroke due to large vessel occlusion patients undergoing thrombectomy triage, favorable VO profiles correlated with favorable TLC and were associated with good functional outcomes after treatment. Future prospective studies should independently validate our findings.

  View details for DOI 10.1161/STROKEAHA.120.032242

  View details for PubMedID 33682452

• Ordinal Prediction Model of 90-Day Modified Rankin Scale in Ischemic Stroke. Frontiers in neurology Zhang, M. Y., Mlynash, M., Sainani, K. L., Albers, G. W., Lansberg, M. G. 2021; 12: 727171

  Abstract

  Background and Purpose: Prediction models for functional outcomes after ischemic stroke are useful for statistical analyses in clinical trials and guiding patient expectations. While there are models predicting dichotomous functional outcomes after ischemic stroke, there are no models that predict ordinal mRS outcomes. We aimed to create a model that predicts, at the time of hospital discharge, a patient's modified Rankin Scale (mRS) score on day 90 after ischemic stroke. Methods: We used data from three multi-center prospective studies: CRISP, DEFUSE 2, and DEFUSE 3 to derive and validate an ordinal logistic regression model that predicts the 90-day mRS score based on variables available during the stroke hospitalization. Forward selection was used to retain independent significant variables in the multivariable model. Results: The prediction model was derived using data on 297 stroke patients from the CRISP and DEFUSE 2 studies. National Institutes of Health Stroke Scale (NIHSS) at discharge and age were retained as significant (p < 0.001) independent predictors of the 90-day mRS score. When applied to the external validation set (DEFUSE 3, n = 160), the model accurately predicted the 90-day mRS score within one point for 78% of the patients in the validation cohort. Conclusions: A simple model using age and NIHSS score at time of discharge can predict 90-day mRS scores in patients with ischemic stroke. This model can be useful for prognostication in routine clinical care and to impute missing data in clinical trials.

  View details for DOI 10.3389/fneur.2021.727171

  View details for PubMedID 34744968

• The bright vessel sign on arterial spin labeling MRI for heralding and localizing large vessel occlusions. Journal of neuroimaging : official journal of the American Society of Neuroimaging McCullough-Hicks, M. E., Yu, Y. n., Mlynash, M. n., Albers, G. W., Zaharchuk, G. n. 2021

  Abstract

  The significance of a bright vessel sign (BVS) at the site of a large vessel occlusion (LVO) on MR arterial spin labeling (ASL) sequence is not widely reported. We compared the utility of the ASL BVS to the gradient echo (GRE) susceptibility vessel sign (SVS) in heralding and localizing LVOs in a large cohort; most underwent digital subtraction angiography (DSA) and endovascular therapy for acute stroke.A total of 171 patients with large hemispheric stroke symptoms had baseline and follow-up MRIs with ASL, GRE, and MR angiogram (MRA). Scans were evaluated for (1) presence versus absence and (2) location of ASL BVS and GRE SVS. For patients who underwent DSA, data comparing presence and location of ASL BVS and GRE SVS to occlusions found on angiography, as well as resolution of the signs after successful recanalization, were also evaluated.Compared to MRA, the sensitivity of the ASL BVS for an LVO was .83, significantly better than .67 for GRE SVS (p = .001). Localization of vessel occlusion was correct 60.4% of the time by ASL compared to 64.4% by GRE (p = .502). For the 107 patients who underwent DSA, the sensitivity of ASL BVS was .80 compared to .64 for GRE SVS (p = .009). Localization of LVO found on DSA was correct 63.5% of the time by ASL BVS compared to 72.9% by GRE SVS (p = .251).ASL BVS is significantly more sensitive than GRE SVS for identification of LVO on both MRA and DSA.

  View details for DOI 10.1111/jon.12888

  View details for PubMedID 34015153

• Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis. Lancet (London, England) Jovin, T. G., Nogueira, R. G., Lansberg, M. G., Demchuk, A. M., Martins, S. O., Mocco, J., Ribo, M., Jadhav, A. P., Ortega-Gutierrez, S., Hill, M. D., Lima, F. O., Haussen, D. C., Brown, S., Goyal, M., Siddiqui, A. H., Heit, J. J., Menon, B. K., Kemp, S., Budzik, R., Urra, X., Marks, M. P., Costalat, V., Liebeskind, D. S., Albers, G. W. 2021

  Abstract

  Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days.Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087).These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window.Stryker Neurovascular.

  View details for DOI 10.1016/S0140-6736(21)01341-6

  View details for PubMedID 34774198

• Predictors of Early and Late Infarct Growth in DEFUSE 3. Frontiers in neurology Tate, W. J., Polding, L. C., Christensen, S., Mlynash, M., Kemp, S., Heit, J. J., Marks, M. P., Albers, G. W., Lansberg, M. G. 2021; 12: 699153

  Abstract

  Introduction: The goal of this study is to explore the impact of reperfusion and collateral status on infarct growth in the early and late time windows. Materials and Methods: Seventy patients from the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with baseline, 24-h, and late follow-up scans were evaluated. Scans were taken with DWI or CTP at time of enrollment (Baseline), with DWI or CT 24-h after enrollment (24-h), and with DWI or CT 5 days after enrollment (Late). Early infarct growth (between baseline and 24-h scans) and late infarct growth (between 24-h and late scans) was assessed for each patient. The impact of collateral and reperfusion status on infarct growth was assessed in univariate and multivariate regression. Results: The median early infarct growth was 30.3 ml (IQR 16.4-74.5) and the median late infarct growth was 6.7 ml (IQR -3.5-21.6) in the overall sample. Patients with poor collaterals showed greater early infarct growth (Median 58.5 ml; IQR 18.6-125.6) compared to patients with good collaterals (Median 28.4 ml; IQR 15.8-49.3, unadjusted p = 0.04, adjusted p = 0.06) but showed no difference in late infarct growth. In contrast, patients who reperfused showed no reduction in early infarct growth but showed reduced late infarct growth (Median 1.9 ml; IQR -6.1-8.5) compared to patients without reperfusion (Median 11.2 ml; IQR -1.1-27.2, unadjusted p < 0.01, adjusted p = 0.04). Discussion: In the DEFUSE 3 population, poor collaterals predict early infarct growth and absence of reperfusion predicts late infarct growth. These results highlight the need for timely reperfusion therapy, particularly in patients with poor collaterals and indicate that the 24-h timepoint is too early to assess the full impact of reperfusion therapy on infarct growth. Clinical Trial Registration: http://www.clinicaltrials.gov, Unique identifier [NCT02586415].

  View details for DOI 10.3389/fneur.2021.699153

  View details for PubMedID 34276547

• Quality of Life in Physical, Social, and Cognitive Domains Improves With Endovascular Therapy in the DEFUSE 3 Trial. Stroke Polding, L. C., Tate, W. J., Mlynash, M. n., Marks, M. P., Heit, J. J., Christensen, S. n., Kemp, S. n., Albers, G. W., Lansberg, M. G. 2021: STROKEAHA120031490

  Abstract

  The DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) randomized clinical trial demonstrated the efficacy of endovascular therapy in treating ischemic stroke 6 to 16 hours after onset, resulting in better functional outcomes than standard medical therapy alone. The objective of this secondary analysis is to analyze the effect of late-window endovascular treatment of ischemic stroke on quality of life (QoL) outcomes.Patients (n=182) who presented between 6 and 16 hours after they were last known to be well with acute anterior circulation ischemic stroke were randomized to endovascular thrombectomy plus standard medical therapy or standard medical therapy alone and followed-up through 90 days poststroke. QoL at day 90 was assessed with the QoL in Neurological Disorders measurement tool.Of the 146 subjects alive at day 90, 136 (95%) filled out QoL in Neurological Disorders short forms. Patients treated with endovascular therapy had better QoL scores in each domain: mobility, social participation, cognitive function, and depression (P<0.01 for all). Variables other than endovascular therapy that were independently associated with better QoL included lower baseline National Institutes of Health Stroke Scale, younger age, and male sex. The degree to which the modified Rankin Scale captures differences in QoL between patients varied by domain; the modified Rankin Scale score accounted for a high proportion of the variability in mobility (Rs2=0.82), a moderate proportion in social participation (Rs2=0.62), and a low proportion in cognition (Rs2=0.31) and depression (Rs2=0.19).Patients treated with endovascular therapy 6 to 16 hours after stroke have better QoL than patients treated with medical therapy alone, including better mobility, more social participation, superior cognition, and less depression. The modified Rankin Scale fails to capture patients' outcomes in cognition and depression, which should therefore be assessed with dedicated QoL tools.URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

  View details for DOI 10.1161/STROKEAHA.120.031490

  View details for PubMedID 33596675

• Impact of Clot Shape on Successful M1 Endovascular Reperfusion. Frontiers in neurology Guenego, A., Fahed, R., Sussman, E. S., Leipzig, M., Albers, G. W., Martin, B. W., Marcellus, D. G., Kuraitis, G., Marks, M. P., Lansberg, M. G., Wintermark, M., Heit, J. J. 2021; 12: 642877

  Abstract

  Objectives: The susceptibility-vessel-sign (SVS) allows thrombus visualization, length estimation and composition, and it may impact reperfusion during mechanical thrombectomy (MT). SVS can also describe thrombus shape in the occluded artery: in the straight M1-segment (S-shaped), or in an angulated/traversing a bifurcation segment (A-shaped). We determined whether SVS clot shape influenced reperfusion and outcomes after MT for proximal middle-cerebral-artery (M1) occlusions. Methods: Between May 2015 and March 2018, consecutive patients who underwent MT at one comprehensive stroke center and who had a baseline MRI with a T2* sequence were included. Clinical, procedural and radiographic data, including clot shape on SVS [angulated/bifurcation (A-SVS) vs. straight (S-SVS)] and length were assessed. Primary outcome was successful reperfusion (TICI 2b-3). Secondary outcome were MT complication rates, MT reperfusion time, and clinical outcome at 90-days. Predictors of outcome were assessed with univariate and multivariate analyses. Results: A total of 62 patients were included. 56% (35/62) had an A-SVS. Clots were significantly longer in the A-SVS group (19 mm vs. 8 mm p = 0.0002). Groups were otherwise well-matched with regard to baseline characteristics. There was a significantly lower rate of successful reperfusion in the A-SVS cohort (83%) compared to the S-SVS cohort (96%) in multivariable analysis [OR 0.04 (95% CI, 0.002-0.58), p = 0.02]. There was no significant difference in long term clinical outcome between groups. Conclusion: Clot shape as determined on T2* imaging, in patients presenting with M1 occlusion appears to be a predictor of successful reperfusion after MT. Angulated and bifurcating clots are associated with poorer rates of successful reperfusion.

  View details for DOI 10.3389/fneur.2021.642877

  View details for PubMedID 33597919

• Mismatch Profile Influences Outcome After Mechanical Thrombectomy. Stroke Olivot, J., Albucher, J., Guenego, A., Thalamas, C., Mlynash, M., Rousseau, V., Drif, A., Christensen, S., Sommet, A., Viguier, A., Darcourt, J., Calviere, L., Menegon, P., Raposo, N., Januel, A., Bonneville, F., Tourdias, T., Mazighi, M., Sibon, I., Albers, G. W., Cognard, C., FRAME Investigators*, Chollet, F., Barbieux, M., Michelozzi, C., Tall, P., Caparros, F., Pouzet, B., Calvas, F., Galitzki, M., Renou, P., Rouanet, F., Berge, J., Marnat, G., Lucas, L., Coignon, C., Sagnier, S., Debruxelle, S., Ledure, S. 2020: STROKEAHA120031929

  Abstract

  BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is the recommended treatment for acute ischemic stroke caused by anterior circulation large vessel occlusion. However, despite a high rate of reperfusion, the clinical response to successful MT remains highly variable in the early time window where optimal imaging selection criteria have not been established. We hypothesize that the baseline perfusion imaging profile may help forecast the clinical response to MT in this setting.METHODS: We conducted a prospective multicenter cohort study of patients with large vessel occlusion-related acute ischemic stroke treated by MT within 6 hours. Treatment decisions and the modified Rankin Scale evaluation at 3 months were performed blinded to the results of baseline perfusion imaging. Study groups were defined a posteriori based on predefined imaging profiles: target mismatch (TMM; core volume <70 mL/mismatch ratio >1.2 and mismatch volume >10 mL) versus no TMM or mismatch (MM; mismatch ratio >1.2 and volume >10 mL) versus no MM. Functional recovery (modified Rankin Scale, 0-2) at 3 months was compared based on imaging profile at baseline and whether reperfusion (modified Thrombolysis in Cerebral Infarction 2bc3) was achieved.RESULTS: Two hundred eighteen patients (mean age, 71±15 years; median National Institutes of Health Stroke Scale score, 17 [interquartile range, 12-21]) were enrolled. Perfusion imaging profiles were 71% TMM and 82% MM. The rate of functional recovery was 54% overall. Both TMM and MM profiles were independently associated with a higher rate on functional recovery at 3 months Adjusted odds ratios were 3.3 (95% CI, 1.4-7.9) for TMM and 5.9 (95% CI, 1.8-19.6) for MM. Reperfusion (modified Thrombolysis in Cerebral Infarction 2bc3) was achieved in 86% and was more frequent in TMM and MM patients. Reperfusion was associated with a higher rate of functional recovery in MM and TMM patients but not among those with no MM.CONCLUSIONS: In this cohort study, about 80% of the patients with a large vessel occlusion-related acute ischemic stroke had evidence of penumbra, regardless of infarction volume. Perfusion imaging profiles predict the clinical response to MT.

  View details for DOI 10.1161/STROKEAHA.120.031929

  View details for PubMedID 33349010

• Early Infarct Growth Rate Correlation With Endovascular Thrombectomy Clinical Outcomes: Analysis From the SELECT Study. Stroke Sarraj, A., Hassan, A. E., Grotta, J., Blackburn, S., Day, A., Abraham, M., Sitton, C., Dannenbaum, M., Cai, C., Pujara, D., Hicks, W., Vora, N., Budzik, R., Shaker, F., Arora, A., Riascos, R. F., Kamal, H., Martin-Schild, S., Lansberg, M., Gupta, R., Albers, G. W., SELECT Investigators 2020: STROKEAHA120030912

  Abstract

  BACKGROUND AND PURPOSE: Time elapsed from last-known well (LKW) and baseline imaging results are influential on endovascular thrombectomy (EVT) outcomes.METHODS: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (SELECT [Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke], the early infarct growth rate (EIGR) was defined as ischemic core volume on perfusion imaging (relative cerebral blood flow<30%) divided by the time from LKW to imaging. The optimal EIGR cutoff was identified by maximizing the sum of the sensitivity and specificity to correlate best with favorable outcome and to improve its the predictability. Patients were stratified into slow progressors if EIGR2. The primary outcome was 90-day functional independence (modified Rankin Scale score =0-2).RESULTS: Of 445 consented, 361 (285 EVT, 76 medical management only) patients met the study inclusion criteria. The optimal EIGR was <10 mL/h; 200 EVT patients were slow and 85 fast progressors. Fast progressors had a higher median National Institutes of Health Stroke Scale (19 versus 15, P<0.001), shorter time from LKW to groin puncture (180 versus 266 minutes, P<0.001). Slow progressors had better collaterals on computed tomography perfusion: hypoperfusion intensity ratio (adjusted odds ratio [aOR]: 5.11 [2.43-10.76], P<0.001) and computed tomography angiography: collaterals-score (aOR: 4.43 [1.83-10.73], P=0.001). EIGR independently correlated with functional independence after EVT, adjusting for age, National Institutes of Health Stroke Scale, time LKW to groin puncture, reperfusion (modified Thrombolysis in Cerebral Infarction score of ≥2b), IV-tPA (intravenous tissue-type plasminogen activator), and transfer status (aOR: 0.78 [0.65-0.94], P=0.01). Slow progressors had higher functional independence rates (121 [61%] versus 30 [35%], P<0.001) and had 3.5 times the likelihood of achieving modified Rankin Scale score =0-2 with EVT (aOR=2.94 [95% CI, 1.53-5.61], P=0.001) as compared to fast progressors, who had substantially worse clinical outcomes both in early and late time window. The odds of good outcome decreased by 14% for each 5 mL/h increase in EIGR (aOR, 0.87 [0.80-0.94], P<0.001) and declined more rapidly in fast progressors.CONCLUSIONS: The EIGR strongly correlates with both collateral status and clinical outcomes after EVT. Fast progressors demonstrated worse outcomes when receiving EVT beyond 6 hours of stroke onset as compared to those who received EVT within 6 hours.REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02446587.

  View details for DOI 10.1161/STROKEAHA.120.030912

  View details for PubMedID 33280550

• Renal Safety of Multimodal Brain Imaging Followed by Endovascular Therapy. Stroke Cereda, C. W., Mlynash, M., Cippa, P. E., Kemp, S., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2020: STROKEAHA120030816

  Abstract

  BACKGROUND AND PURPOSE: Contrast-enhanced noninvasive angiography and perfusion imaging are recommended to identify eligible patients for endovascular therapy (EVT) in extended time windows (>6 hours or wake-up). If eligible, additional intraarterial contrast exposure will occur during EVT. We aimed to study the renal safety in the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) population, selected with contrast-enhanced multimodal Imaging and randomized to EVT versus medical management.METHODS: In the randomized DEFUSE 3 trial population, we compared changes in serum creatinine between baseline (before randomization) and 24 hours later. The primary outcome was the relative change in creatinine level between baseline and 24 hours in the EVT versus medical arm. The secondary outcome was a comparison between computed tomography (CT) versus magnetic resonance imaging selection in the EVT arm. The safety outcome was a comparison of the proportion of patients with criteria for contrast-associated kidney injury in the EVT versus medical arm and a comparison between CT versus magnetic resonance imaging selection in the EVT arm.RESULTS: In the DEFUSE 3 population (n=182, age 69±13, 51% female), mean creatinine decreased from a baseline of 0.98±0.33 mg/dL to 0.88±0.28 mg/dL at 24 hours (P<0.001). There was no difference in change between treatment groups: relative to baseline, there was a 6.3% reduction in the EVT group versus 9.2% in the medical group, P=0.294. Absolute decrease -0.08±0.18 in EVT versus -0.12±0.18 in medical, P=0.135; Among patients treated with EVT, there was no difference in 24-hour creatinine level changes between patients who were selected with CT angiography/CT perfusion (-0.08±0.18) versus magnetic resonance imaging (-0.07±0.19), P=0.808 or 6.8% reduction versus 4.8%, P=0.696. In the EVT arm, contrast-associated kidney injury was encountered in 4 out of 91 (4.4%) versus 2/90 (2.2%) in the medical arm P=0.682. In the EVT arm, contrast-associated kidney injury was evenly distributed between magnetic resonance imaging (1/22, 4.6%) versus CT 3 out of 69 (4.4%), P=1.0.CONCLUSIONS: Perfusion imaging before EVT was not associated with evidence of decline in renal function.REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

  View details for DOI 10.1161/STROKEAHA.120.030816

  View details for PubMedID 33250038

• Effect of Sex on Clinical Outcome and Imaging after Endovascular Treatment of Large-Vessel Ischemic Stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Demeestere, J., Christensen, S., Mlynash, M., Federau, C., Albers, G. W., Lemmens, R., Lansberg, M. G. 2020; 30 (2): 105468

  Abstract

  BACKGROUND AND PURPOSE: It is unclear if sex differences explain some of the variability in the outcomes of stroke patients who undergo endovascular treatment (EVT). In this study we assess the effect of sex on radiological and functional outcomes in EVT-treated acute stroke patients and determine if differences in baseline perfusion status between men and women might account for differences in outcomes.METHODS: We included patients from the CRISP (Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke) study, a prospective cohort study of acute stroke patients who underwent EVT up to 18 hours after last seen well. We designed ordinal regression and univariable and multivariable regression models to examine the association between sex and infarct growth, final infarct volume and 90-day mRS score.RESULTS: We included 198 patients. At baseline, women had smaller perfusion lesions, more often had a target mismatch perfusion profile, and had better collateral perfusion. Women experienced less ischemic core growth (median 15 mL vs. 29 mL, p < 0.01) and had smaller final infarct volumes (median 26 mL vs. 50 mL, p < 0.01). Female sex was associated with a favorable shift on the modified Rankin Scale (adjusted cOR 1.79 [1.04 - 3.08; p = 0.04]) and lower odds of severe disability or death (adjusted OR 0.29 [0.10 - 0.81]; p = 0.02).CONCLUSIONS: The results suggest that women have better collaterals and, therefore, more often exhibit a favorable imaging profile on baseline imaging, experience less lesion growth, and have better clinical outcomes following endovascular therapy.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2020.105468

  View details for PubMedID 33227604

• Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study. Journal of neurointerventional surgery Sarraj, A., Pizzo, E., Lobotesis, K., Grotta, J. C., Hassan, A. E., Abraham, M. G., Blackburn, S., Day, A. L., Dannenbaum, M. J., Hicks, W., Vora, N. A., Budzik, R. F., Sharrief, A. Z., Martin-Schild, S., Sitton, C. W., Pujara, D. K., Lansberg, M. G., Gupta, R., Albers, G. W., Kunz, W. G., SELECT Investigators 2020

  Abstract

  BACKGROUND: It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts.METHODS: In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS<6or computed tomography perfusion (CTP) ischemic core volume (rCBF<30%) ≥50cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50000 and $100000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials.RESULTS: From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0-2 (OR 3.27, 95%CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95%CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50000 and $100 000, respectively. EVT was associated with an increment of $29225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86164 and $22501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively.CONCLUSIONS: In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results.CLINICAL TRIAL REGISTRATION: NCT02446587.

  View details for DOI 10.1136/neurintsurg-2020-016766

  View details for PubMedID 33188155

• The Effect of Hyperglycemia on Infarct Growth after Reperfusion: An Analysis of the DEFUSE 3 trial. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Yaghi, S., Dehkharghani, S., Raz, E., Jayaraman, M., Tanweer, O., Grory, B. M., Henninger, N., Lansberg, M. G., Albers, G. W., Havenon, A. d. 2020; 30 (1): 105380

  Abstract

  BACKGROUND AND PURPOSE: Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied.MATERIALS AND METHODS: This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core.RESULTS: We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03).CONCLUSION: In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2020.105380

  View details for PubMedID 33166769

• Correction to: "Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective Multicenter Cohort Study of Imaging Selection". Annals of neurology Sarraj, A., Hassan, A. E., Grotta, J., Sitton, C., Cutter, G., Cai, C., Chen, P. R., Imam, B., Pujara, D., Arora, A., Reddy, S., Parsha, K., Riascos, R. F., Vora, N., Abraham, M., Edgell, R., Hellinger, F., Haussen, D. C., Blackburn, S., Kamal, H., Barreto, A. D., Martin-Schild, S., Lansberg, M., Gupta, R., Savitz, S., Albers, G. W. 2020; 88 (5): 1056-1057

  View details for DOI 10.1002/ana.25843

  View details for PubMedID 33089549

• An International Report on the Adaptations of Rapid Transient Ischaemic Attack Pathways During the COVID-19 Pandemic. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lim, A., Singhal, S., Lavallee, P., Amarenco, P., Rothwell, P. M., Albers, G., Sharma, M., Brown, R. J., Ranta, A., Maddula, M., Kleinig, T., Dawson, J., Elkind, M. S., Guarino, M., Coutts, S. B., Clissold, B., Ma, H., Phan, T. 2020; 29 (11): 105228

  Abstract

  BACKGROUND: This report aims to describe changes that centres providing transient ischaemic attack (TIA) pathway services have made to stay operational in response to the SARS-CoV-2 pandemic.METHODS: An international cross-sectional description of the adaptions of TIA pathways between 30th March and 6th May 2020. Experience was reported from 18 centres with rapid TIA pathways in seven countries (Australia, France, UK, Canada, USA, New Zealand, Italy, Canada) from three continents.RESULTS: All pathways remained active (n = 18). Sixteen (89%) had TIA clinics. Six of these clinics (38%) continued to provide in-person assessment while the majority (63%) used telehealth exclusively. Of these, three reported PPE use and three did not. Five centres with clinics (31%) had adopted a different vascular imaging strategy.CONCLUSION: The COVID pandemic has led TIA clinics around the world to adapt and move to the use of telemedicine for outpatient clinic review and modified investigation pathways. Despite the pandemic, all have remained operational.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2020.105228

  View details for PubMedID 33066882

• ASL BRIGHT VESSEL SIGN SUPERIOR TO GRE SPOT SIGN IN IDENTIFYING PRESENCE OF LARGE VESSEL OCCLUSION Mccullough-Hicks, M., Yu, Y., Mlynash, M., Albers, G., Zaharchuk, G. SAGE PUBLICATIONS LTD. 2020: 283

  View details for Web of Science ID 000587365201308

• EFFECT OF SEX ON CLINICAL OUTCOME AND IMAGING AFTER ENDOVASCULAR TREATMENT OF LARGE-VESSEL ISCHEMIC STROKE IN THE EXTENDED TIME WINDOW Demeestere, J., Christensen, S., Mlynash, M., Albers, G., Lemmens, R., Lansberg, M. SAGE PUBLICATIONS LTD. 2020: 89

  View details for Web of Science ID 000587365200266

• TRAJECTORY OF RECOVERY FOLLOWING CLOT RETRIEVAL- INDIVIDUAL PATIENT DATA ANALYSIS FROM THREE THROMBECTOMY TRIALS (DEFUSE 3, ESCAPE, EXTEND-IA) Han, J., Ma, H., Hill, M., Campbell, B., Albers, G., Goyal, M., Demchuk, A., Davis, S., Donnan, G., Singhal, S., Phan, T. SAGE PUBLICATIONS LTD. 2020: 88–89

  View details for Web of Science ID 000587365200264

• RENAL SAFETY OF MULTIMODAL NEUROIMAGING FOLLOWED BY ENDOVASCULAR THERAPY Cereda, C., Mlynash, M., Cippa, P., Kemp, S., Heit, J., Marks, M., Lansberg, M., Albers, G. SAGE PUBLICATIONS LTD. 2020: 172

  View details for Web of Science ID 000587365200542

• REPERFUSION IS ASSOCIATED WITH FAVORABLE OUTCOMES IN PATIENTS WITH LARGE CORE AND PENUMBRAL TISSUE IN THE FRAME STUDY Olivot, J. M., Albucher, J. F., Guenego, A., Sibon, I., Rousseau, V., Mlynash, M., Christensen, S., Raposo, N., Viguier, A., Thalamas, C., Sommet, A., Drif, A., Darcourt, J., Calviere, L., Menegon, P., Tourdias, T., Januel, A. C., Bonneville, F., Mazighi, M., Albers, G., Cognard, C., FRAME Investigators SAGE PUBLICATIONS LTD. 2020: 175–76

  View details for Web of Science ID 000587365200552

• PROFILING EXTRACELLULAR VESICLE SURFACE MARKERS, AS DIAGNOSTIC TOOL IN TRANSIENT ISCHEMIC ATTACKS (TIAS) Bianco, G., Burrello, J., Burrello, A., Manno, C., Maulucci, F., Padlina, G., Nannoni, S., Michel, P., Bolis, S., Melli, G., Vassalli, G., Cianfoni, A., Albers, G., Barile, L., Cereda, C. SAGE PUBLICATIONS LTD. 2020: 163

  View details for Web of Science ID 000587365200511

• ASCOD PHENOTYPING OF ACUTE BRAIN INFARCTION WITH ANTERIOR LARGE VESSEL OCCLUSION TREATED BY MECHANICAL THROMBECTOMY. Fontaine, L., Sibon, I., Albucher, J. F., Raposo, N., Rousseau, V., Menegon, P., Calviere, L., Sommet, A., Viguier, A., Guenego, A., Thalamas, C., Drif, A., Januel, A. C., Bonneville, F., Mazighi, M., Tourdias, T., Albers, G., Cognard, C., Olivot, J. M. SAGE PUBLICATIONS LTD. 2020: 88

  View details for Web of Science ID 000587365200263

• MECHANICAL THROMBECTOMY MAYBE ASSOCIATED WITH REDUCED DISABILITY IN PATIENTS WITH LARGE CORE BASED ON CTP COMPARED TO MEDICAL THERAPY ALONE Aghaebrahim, A., Desai, S., Monteiro, A., Granja, M., Jadhav, A., Legault, C., Powers, C., Sauvageau, E., Albers, G., Jovin, T., Hanel, R. SAGE PUBLICATIONS LTD. 2020: 176

  View details for Web of Science ID 000587365200553

• Prediction of death after endovascular thrombectomy in the extended window: a secondary analysis of DEFUSE 3 ". Journal of neurointerventional surgery Taussky, P., Agnoletto, G., Grandhi, R., Alexander, M. D., Wong, K., Albers, G. W., de Havenon, A. 2020

  Abstract

  BACKGROUND: The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) clinical trial assessed the use of endovascular thrombectomy (EVT) during the period 6-16hours after last normal in selected patients. This is a secondary cohort analysis of the DEFUSE 3 data assessing potential predictive variables for mortality in the EVT-treated patients.METHODS: The primary outcome was death within 90 days. Patients who died and those who did not were compared statistically. We developed a predictive score using preprocedural variables that were statistically predictive of death in univariate regression analysis (P<0.1).RESULTS: Of the 182 patients in the DEFUSE 3 study, 92 (mean age 69 years; 50% male) met our inclusion criteria, and 15.2% of these patients met the primary outcome. Patient age, baseline National Institutes of Health Stroke Scale (NIHSS) score, wake-up stroke, statin use, and history of diabetes were statistically associated with death. Statin use did not improve the prediction score so was excluded. Thus, our model included four predictors, with one point each given for age >75 years, NIHSS ≥20, wake-up stroke, and diabetes, yielding low (0-1), moderate (2), and high (3-4) risk of death. In the low-risk, moderate-risk, and high-risk categories, 2/52 (3.9%), 3/23 (13.0%), and 9/17 (52.9%) of patients died, respectively (P<0.001).CONCLUSIONS: Despite selective inclusion criteria and overwhelming benefit for EVT, a substantial number of EVT patients in DEFUSE 3 died. The preprocedural variables age, NIHSS, wake-up stroke, and diabetes may predict this risk. Our predictive score provides a basis for future research to determine which factors influence lethal outcome after EVT.

  View details for DOI 10.1136/neurintsurg-2020-016548

  View details for PubMedID 33077580

• Five-year prognosis after TIA or minor ischemic stroke in Asian and non-Asian countries. Neurology Hoshino, T., Uchiyama, S., Wong, L. K., Kitagawa, K., Charles, H., Labreuche, J., Lavallee, P. C., Albers, G. W., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Molina, C., Rothwell, P. M., Gabriel Steg, P., Touboul, P., Vicaut, E., Amarenco, P., TIA registry.org Investigators,, 2020

  Abstract

  OBJECTIVE: We aimed to determine long-term vascular outcomes of Asian patients who experienced TIA or minor ischemic stroke and to compare the outcomes of Asians with those of non-Asians, in the context of modern guideline-based prevention strategies.METHODS: This is a sub-analysis of the TIAregistry.org project, in which 3,847 patients (882 from Asian and 2,965 from non-Asian countries) with a recent TIA or minor ischemic stroke were assessed and treated by specialists at 42 dedicated units from 14 countries and followed for 5 years. The primary outcome was a composite of cardiovascular death, non-fatal stroke, and non-fatal acute coronary syndrome.RESULTS: No differences were observed in the 5-year risk of the primary outcome (14.0% vs 11.7%; hazard ratio [HR], 1.10; 95% CI, 0.88-1.37; p = 0.41) and stroke (10.7% vs 8.5%; HR, 1.17; 95% CI, 0.90-1.51; p = 0.24) between Asian and non-Asian patients. Asians were at higher risk of intracranial hemorrhage (1.8% vs 0.8%; HR, 2.23; 95% CI, 1.09-4.57; p = 0.029). Multivariable analysis showed that the presence of multiple acute infarctions on initial brain imaging was an independent predictor of primary outcome and modified Rankin Scale score of >1 in both Asian (HR, 1.91; 95% CI, 1.11-3.29; p = 0.020) and non-Asian (HR, 1.39; 95% CI, 1.02-1.90; p = 0.037) patients.CONCLUSION: The long-term risk of vascular events in Asian patients was as low as that in non-Asian patients, while Asians had a 2.2-fold higher intracranial hemorrhage risk. Multiple acute infarctions were independently associated with future disability in both groups.CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that among people who experienced TIA or minor stroke, Asians have a similar 5-year risk of cardiovascular death, stroke and acute coronary syndrome as non-Asians.

  View details for DOI 10.1212/WNL.0000000000010995

  View details for PubMedID 33046613

• Circle of Willis variants are not associated with thrombectomy outcomes. Stroke and vascular neurology Seifert-Held, T., Eberhard, K., Christensen, S., Hofer, E., Enzinger, C., Albers, G. W., Lansberg, M. 2020

  Abstract

  BACKGROUND: The circle of Willis (COW) is part of the brain collateral system. The absence of COW segments may affect functional outcome in patients with ischaemic stroke undergoing endovascular therapy.METHODS: In 182 patients in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 Study and the CT Perfusion to Predict Response to Recanalisation in Ischaemic Stroke Project, COW anatomy was evaluated on postinterventional magnetic resonance angiography. The absence of the posterior communicating artery or the first segments of posterior or anterior cerebral arteries ipsilateral to the ischaemic infarction was rated as an incomplete COW. Logistic regression was applied to evaluate an association with the patients' modified Rankin scale (mRS) at 90 days after stroke RESULTS: An incomplete ipsilateral COW was not predictive of the patients' mRS at 90 days after stroke. Significant associations were shown for the patients' baseline National Institutes of Health Stroke Scale (NIHSS), age and reperfusion status. The effect size suggests that a significant association of an incomplete COW with the mRS at 90 days may be obtained in cohorts of more than 3000 patients.CONCLUSIONS: Compared with the established predictors NIHSS, age and reperfusion status, an incomplete COW is not associated with functional outcome after endovascular therapy.

  View details for DOI 10.1136/svn-2020-000491

  View details for PubMedID 33046661

• Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective Multicenter Cohort Study of Imaging Selection (vol 87, pg 419, 2020) ANNALS OF NEUROLOGY Sarraj, A., Hassan, A. E., Grotta, J., Sitton, C., Cutter, G., Cai, C., Chen, P. R., Imam, B., Pujara, D., Arora, A., Reddy, S., Parsha, K., Riascos, R. F., Vora, N., Abraham, M., Edgell, R., Hellinger, F., Haussen, D. C., Blackburn, S., Kamal, H., Barreto, A. D., Martin-Schild, S., Lansberg, M., Gupta, R., Savitz, S., Albers, G. W. 2020

  View details for DOI 10.1002/ana.25843

  View details for Web of Science ID 000560894300001

• Methodologies for pragmatic and efficient assessment of benefits and harms: Application to the SOCRATES trial. Clinical trials (London, England) Evans, S. R., Knutsson, M., Amarenco, P., Albers, G. W., Bath, P. M., Denison, H., Ladenvall, P., Jonasson, J., Easton, J. D., Minematsu, K., Molina, C. A., Wang, Y., Wong, K. L., Johnston, S. C. 2020: 1740774520941441

  Abstract

  BACKGROUND/AIMS: Standard approaches to trial design and analyses can be inefficient and non-pragmatic. Failure to consider a range of outcomes impedes evidence-based interpretation and reduces power. Traditional approaches synthesizing information obtained from separate analysis of each outcome fail to incorporate associations between outcomes and recognize the cumulative nature of outcomes in individual patients, suffer from competing risk complexities during interpretation, and since efficacy and safety analyses are often conducted on different populations, generalizability is unclear. Pragmatic and efficient approaches to trial design and analyses are needed.METHODS: Approaches providing a pragmatic assessment of benefits and harms of interventions, summarizing outcomes experienced by patients, and providing sample size efficiencies are described. Ordinal outcomes recognize finer gradations of patient responses. Desirability of outcome ranking is an ordinal outcome combining benefits and harms within patients. Analysis of desirability of outcome ranking can be based on rank-based methodologies including the desirability of outcome ranking probability, the win ratio, and the proportion in favor of treatment. Partial credit analyses, involving grading the levels of the desirability of outcome ranking outcome similar to an academic test, provides an alternative approach. The methodologies are demonstrated using the acute stroke or transient ischemic attack treated with aspirin or ticagrelor and patient outcomes study (SOCRATES; NCT01994720), a randomized clinical trial.RESULTS: Two 5-level ordinal outcomes were developed for SOCRATES. The first was based on a modified Rankin scale. The odds ratio is 0.86 (95% confidence interval = 0.75, 0.99; p = 0.04) indicating that the odds of worse stroke categorization for a trial participant assigned to ticagrelor is 0.86 times that of a trial participant assigned to aspirin. The 5-level desirability of outcome ranking outcome incorporated and prioritized survival; the number of strokes, myocardial infarction, and major bleeding events; and whether a stroke event was disabling. The desirability of outcome ranking probability and win ratio are 0.504 (95% confidence interval = 0.499, 0.508; p = 0.10) and 1.11 (95% confidence interval = 0.98, 1.26; p = 0.10), respectively, implying that the probability of a more desirable result with ticagrelor is 50.4% and that a more desirable result occurs 1.11 times more frequently on ticagrelor versus aspirin.CONCLUSION: Ordinal outcomes can improve efficiency through required pre-specification, careful construction, and analyses. Greater pragmatism can be obtained by composing outcomes within patients. Desirability of outcome ranking provides a global assessment of the benefits and harms that more closely reflect the experience of patients. The desirability of outcome ranking probability, the proportion in favor of treatment, the win ratio, and partial credit can more optimally inform patient treatment, enhance the understanding of the totality of intervention effects on patients, and potentially provide efficiencies over standard analyses. The methods provide the infrastructure for incorporating patient values and estimating personalized effects.

  View details for DOI 10.1177/1740774520941441

  View details for PubMedID 32666831

• Collateral status contributes to differences between observed and predicted 24-h infarct volumes in DEFUSE 3. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Rao, V. L., Mlynash, M., Christensen, S., Yennu, A., Kemp, S., Zaharchuk, G., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2020: 271678X20918816

  Abstract

  We previously demonstrated that in the DEFUSE 3 trial, the union of the baseline core and the 24-h Tmax>6s perfusion lesion predicts the infarct volume at 24h. Presently, we assessed if collateral robustness measured by the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index accounts for the variance in these predictions. DEFUSE 3 patients underwent MRI/CT perfusion imaging at baseline and 24h post-randomization. We compared baseline and follow-up HIR and CBV index across subgroups stratified by differences between predicted and observed 24-h infarct volumes. Of 123 eligible patients, 34 with 24-h infarcts larger than predicted had less favorable collaterals at baseline (HIR 0.43 vs. 0.32, p=0.006; CBV Index 0.78 vs. 0.85, p=0.001) and 24h (HIR 0.56 vs. 0.07, p=0.004; CBV Index 0.47 vs. 0.73, p=0.006) compared to 71 patients with more accurate infarct volume prediction. Eighteen patients with 24-h infarcts smaller than predicted had similar baseline collateral scores but more favorable 24-h CBV indices (0.81 vs. 0.73, p=0.040). Overall, patients with 24-h infarcts larger than predicted had evidence of less favorable baseline collaterals that fail within 24h, while patients with 24-h infarcts smaller than predicted typically had favorable collaterals that persisted for 24h.

  View details for DOI 10.1177/0271678X20918816

  View details for PubMedID 32423329

• Thrombolysis before Thrombectomy - To Be or DIRECT-MT? The New England journal of medicine Albers, G. W. 2020

  View details for DOI 10.1056/NEJMe2004550

  View details for PubMedID 32374954

• Quality of Life for Younger Versus Older Patients Following Endovascular Thrombectomy in the Extended Window: A Secondary Analysis of DEFUSE 3 de Havenon, A., Majersik, J., Terrill, A., Taylor, K., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000536058002210

• Prognostic value of diffusion-weighted MRI for post-cardiac arrest coma. Neurology Hirsch, K. G., Fischbein, N., Mlynash, M., Kemp, S., Bammer, R., Eyngorn, I., Tong, J., Moseley, M., Venkatasubramanian, C., Caulfield, A. F., Albers, G. 2020

  Abstract

  OBJECTIVE: To validate quantitative diffusion-weighted imaging (DWI) MRI thresholds that correlate with poor outcome in comatose cardiac arrest survivors, we conducted a clinician-blinded study and prospectively obtained MRIs from comatose patients after cardiac arrest.METHODS: Consecutive comatose post-cardiac arrest adult patients were prospectively enrolled. MRIs obtained within 7 days after arrest were evaluated. The clinical team was blinded to the DWI MRI results and followed a prescribed prognostication algorithm. Apparent diffusion coefficient (ADC) values and thresholds differentiating good and poor outcome were analyzed. Poor outcome was defined as a Glasgow Outcome Scale score of ≤2 at 6 months after arrest.RESULTS: Ninety-seven patients were included, and 75 patients (77%) had MRIs. In 51 patients with MRI completed by postarrest day 7, the prespecified threshold of >10% of brain tissue with an ADC <650 *10-6 mm2/s was highly predictive for poor outcome with a sensitivity of 0.63 (95% confidence interval [CI] 0.42-0.80), a specificity of 0.96 (95% CI 0.77-0.998), and a positive predictive value (PPV) of 0.94 (95% CI 0.71-0.997). The mean whole-brain ADC was higher among patients with good outcomes. Receiver operating characteristic curve analysis showed that ADC <650 *10-6 mm2/s had an area under the curve of 0.79 (95% CI 0.65-0.93, p < 0.001). Quantitative DWI MRI data improved prognostication of both good and poor outcomes.CONCLUSIONS: This prospective, clinician-blinded study validates previous research showing that an ADC <650 *10-6 mm2/s in >10% of brain tissue in an MRI obtained by postarrest day 7 is highly specific for poor outcome in comatose patients after cardiac arrest.

  View details for DOI 10.1212/WNL.0000000000009289

  View details for PubMedID 32269116

• CT perfusion core and ASPECT score prediction of outcomes in DEFUSE 3. International journal of stroke : official journal of the International Stroke Society Kim-Tenser, M., Mlynash, M., Lansberg, M. G., Tenser, M., Bulic, S., Jagadeesan, B., Christensen, S., Simpkins, A., Albers, G. W., Marks, M. P. 2020: 1747493020915141

  Abstract

  BACKGROUND: The role of Alberta Stroke Program Early CT Score (ASPECTS) for thrombectomy patient selection and prognostication in late time windows is unknown.AIMS: We compared baseline ASPECTS and core infarction determined by CT perfusion (CTP) as predictors of clinical outcome in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE) 3 trial.METHODS: We included all DEFUSE 3 patients with baseline non-contrast CT and CTP imaging. ASPECTS and core infarction were determined by the DEFUSE 3 core laboratory. Primary outcome was functional independence (modified Rankin Scale (mRS) ≤2). Secondary outcomes included ordinal mRS shift at 90 days and final core infarction volume.RESULTS: Of the 142 patients, 85 patients (60%) had ASPECTS 8-10 and 57 (40%) had ASPECTS 5-7. Thirty-one patients (36%) with ASPECTS 8-10 and 11 patients (19%) with ASPECTS 5-7 were functionally independent at 90 days (p=0.03). In the primary and secondary logistic regression analysis, there was no difference in ordinal mRS shift (p=0.98) or functional independence (mRS≤2; p=0.36) at 90 days between ASPECTS 8-10 and ASPECTS 5-7 patients. Similarly, primary and secondary logistic regression analyses found no difference in ordinal mRS shift (p=1.0) or functional independence (mRS≤2; p=0.87) at 90 days between patients with baseline small core (<50ml) versus medium core (50-70ml).CONCLUSIONS: Higher ASPECTS (8-10) correlated with functional independence at 90 days in the DEFUSE trial. ASPECTS and core infarction volume did not modify the thrombectomy treatment effect, which indicates that patients with a target mismatch profile on perfusion imaging should undergo thrombectomy regardless of ASPECTS or core infarction volume in late time windows.

  View details for DOI 10.1177/1747493020915141

  View details for PubMedID 32233746

• Comparison of Tmax values between full- and half-dose gadolinium perfusion studies. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Christensen, S., Amukotuwa, S., Lansberg, M. G., Kemp, S., Heit, J. J., Mlynash, M., Marks, M. P., Albers, G. W., Bammer, R. 2020: 271678X20914537

  View details for DOI 10.1177/0271678X20914537

  View details for PubMedID 32208802

• Hypoperfusion Intensity Ratio Correlates With Angiographic Collaterals In Acute Ischemic Stroke With M1 Occlusion. European journal of neurology Guenego, A., Fahed, R., Albers, G. W., Kuraitis, G., Sussman, E. S., Martin, B. W., Marcellus, D. G., Olivot, J., Marks, M. P., Lansberg, M. G., Wintermark, M., Heit, J. J. 2020

  Abstract

  PURPOSE: Among patients with an acute ischemic stroke (AIS) secondary to large-vessel-occlusion, the hypoperfusion-intensity-ratio (HIR, TMax>10 volume / TMax>6 volume) is a strong predictor of infarct growth. We studied the correlation between HIR and collaterals assessed with digital-subtraction-angiography (DSA) before thrombectomy.METHODS: Between January 2014 and March 2018, consecutive patients with an AIS and a M1 middle-cerebral-artery occlusion who underwent perfusion imaging and endovascular treatment at our center were screened. Ischemic core (mL), HIR and perfusion mismatch (TMax>6sec minus core volume) were assessed through MRI or CT perfusion. Collaterals were assessed on pre-intervention DSA using the American-Society of Interventional and Therapeutic-Neuroradiology/Society of Interventional-Radiology (ASITN/SIR) scale. Baseline clinical and perfusion characteristics were compared between patients with good (ASITN/SIR 3-4) and those with poor (ASITN/SIR 0-2) DSA collaterals. Correlation between HIR and ASITN/SIR was evaluated using Pearson's correlation. ROC analysis was performed to determine the optimal HIR threshold for the prediction of good DSA collaterals.RESULTS: Ninety-eight patients were included. 49% (48/98) had good DSA collaterals, those patients had significantly smaller hypoperfusion volumes (TMax >6sec 89mL versus 125mL; p=0.007) and perfusion mismatch volumes (72mL versus 89mL; p=0.016). HIR was significantly correlated with DSA collaterals (-0.327 [IC 95%: -0.494 to -0.138; p=0.01]). A HIR cut-off of <0.4 best predicted good DSA collaterals with an odds ratio of 4.3 (1.8-10.1) (Sensitivity=0.792, Specificity=0.560, AUC=0.708).CONCLUSION: HIR is a robust indicator of angiographic collaterals and might be used as a surrogate of collateral assessment in patients undergoing MRI. HIR<0.4 best predicted good DSA collaterals.

  View details for DOI 10.1111/ene.14181

  View details for PubMedID 32068938

• Collateral Status Contributes to Differences Between Observed and Predicted 24-Hour Infarct Volumes in DEFUSE 3 Rao, V., Mlynash, M., Christensen, S., Yennu, A., Kemp, S., Zaharchuk, G., Heit, J., Marks, M., Lansberg, M., Albers, G., DEFUSE 3 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000590040201133

• The Value of Pre-Training for Deep Learning Acute Stroke Triaging Models Yu, Y., Xie, Y., Gong, E., Thamm, T., Ouyang, J., Christensen, S., Lansberg, M., Albers, G., Zaharchuk, G. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000590040201303

• Voxel-Based Lesion Symptom Mapping (VLSM) of NIH Stroke Scale Subscore Deficits McCullough-Hicks, M. E., Christensen, S., Yu, Y., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000590040201313

• Review of Neuroimaging Prior to Transfer Acceptance and Rate of Endovascular Treatment McCullough-Hicks, M. E., Bernier, E., Mlynash, M., Albers, G., Sells, C. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000590040202019

• Unfavorable Baseline Hypoperfusion Intensity Ratio is Associated With Infarct Growth and Poor Outcome in Patients With Distal MCA Occlusions MacLellan, A., Mlynash, M., Kemp, S., Christensen, S., Marks, M., Lansberg, M., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000590040200214

• Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective Multicenter Cohort Study of Imaging Selection. Annals of neurology Sarraj, A., Hassan, A. E., Grotta, J., Sitton, C., Cutter, G., Cai, C., Chen, P. R., Imam, B., Pujara, D., Arora, A., Reddy, S., Parsha, K., Riascos, R. F., Vora, N., Abraham, M., Edgell, R., Hellinger, F., Haussen, D. C., Blackburn, S., Kamal, H., Barreto, A. D., Martin-Schild, S., Lansberg, M., Gupta, R., Savitz, S., Albers, G. W. 2020

  Abstract

  OBJECTIVE: The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are non-contrast CT(CT) and CT-perfusion(CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes.METHODS: A phase-II multicenter, prospective-cohort study of large vessel occlusions who presented up-to-24hours from last-known-well was conducted. Patients received a unified pre-specified imaging evaluation(CT, CT-angiography, and CTP with RAPID software mismatch-determination). The treatment decision, EVT vs Medical Management, was non-randomized and at the treating physicians' discretion. An independent blinded neuroimaging-corelab adjudicated favorable profiles based on pre-defined criteria(CT:ASPECTS≥6, CTP:rCBF(<30%)<70cc with mismatch-ratio≥1.2 and mismatch-volume≥10cc.RESULTS: Of 4722 screened from January/2016-to-February/2018, 361 patients were included. 285(79%) received EVT, of whom, 87.0% had favorable-CTs; 91% favorable-CTPs; 81% both favorable profiles , 16% discordant and 3% both unfavorable. Favorable profiles on the two modalities correlated similarly with 90-day functional independence rates(favorable-CT=56% vs favorable-CTP=57%,aOR=1.91,95%CI=0.40-9.01, p=0.41). Having a favorable profile on both modalities significantly increased the odds of receiving thrombectomy as compared to discordant profiles (aOR:3.97,95% CI=1.97-8.01,p<0.001). 58% of the patients with favorable profiles on both modalities achieved functional independence as compared to 38% in discordant profiles and 0% when both were unfavorable(P<0.001 for trend). In favorable-CT/unfavorable-CTP profiles, EVT was associated with high sICH(24%) and mortality(53%) rates.INTERPRETATION: Patients with favorable imaging profiles on both modalities had higher odds of receiving EVT and high functional independence rates. Patients with discordant profiles achieved reasonable functional independence rates but those with an unfavorable-CTP had higher adverse outcomes. Clinical-Trial-Registration: NCT02446587.https://clinicaltrials.gov/ct2/show/NCT02446587 This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ana.25669

  View details for PubMedID 31916270

• Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill Patients. Journal of the American College of Cardiology Spyropoulos, A. C., Ageno, W. n., Albers, G. W., Elliott, C. G., Halperin, J. L., Hiatt, W. R., Maynard, G. A., Steg, P. G., Weitz, J. I., Lu, W. n., Spiro, T. E., Barnathan, E. S., Raskob, G. E. 2020; 75 (25): 3140–47

  Abstract

  Hospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events. Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown.The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge.MARINER (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients) studied acutely ill medical patients with additional risk factors for venous thromboembolism (VTE). Medically ill patients with a baseline creatinine clearance ≥50 ml/min were randomized in a double-blind fashion to rivaroxaban 10 mg or placebo daily at hospital discharge for 45 days. Exploratory efficacy analyses were performed with the intent-to-treat population including all data through day 45. Time-to-event curves were calculated using the Kaplan-Meier method. A blinded independent committee adjudicated all clinical events.In total, 4,909 patients were assigned to rivaroxaban and 4,913 patients to placebo. The mean age was 67.8 years, 55.5% were men, mean baseline creatinine clearance was 87.8 ml/min, and mean duration of hospitalization was 6.7 days. The pre-specified composite efficacy endpoint (symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death) occurred in 1.28% and 1.77% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 0.72; 95% confidence interval: 0.52 to 1.00; p = 0.049), whereas major bleeding occurred in 0.27% and 0.18% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 1.44; 95% confidence interval: 0.62 to 3.37; p = 0.398).Extended-duration rivaroxaban in hospitalized medically ill patients resulted in a 28% reduction in fatal and major thromboembolic events without a significant increase in major bleeding. (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients [MARINER]; NCT02111564).

  View details for DOI 10.1016/j.jacc.2020.04.071

  View details for PubMedID 32586587

  View details for PubMedCentralID PMC7308003

• Effect of Oxygen Extraction (Brush-Sign) on Baseline Core Infarct Depends on Collaterals (HIR). Frontiers in neurology Guenego, A., Leipzig, M., Fahed, R., Sussman, E. S., Faizy, T. D., Martin, B. W., Marcellus, D. G., Wintermark, M., Olivot, J., Albers, G. W., Lansberg, M. G., Heit, J. J. 2020; 11: 618765

  Abstract

  Objectives: Baseline-core-infarct volume is a critical factor in patient selection and outcome in acute ischemic stroke (AIS) before mechanical thrombectomy (MT). We determined whether oxygen extraction efficiency and arterial collaterals, two different physiologic components of the cerebral ischemic cascade, interacted to modulate baseline-core-infarct volume in patients with AIS-LVO undergoing MT triage. Methods: Between January 2015 and March 2018, consecutive patients with an AIS and M1 occlusion considered for MT with a baseline MRI and perfusion-imaging were included. Variables such as baseline-core-infarct volume [mL], arterial collaterals (HIR: TMax > 10 s volume/TMax > 6 s), high oxygen extraction (HOE, presence of the brush-sign on T2*) were assessed. A linear-regression was used to test the interaction of HOE and HIR with baseline-core-infarct volume, after including potential confounding variables. Results: We included 103 patients. Median age was 70 (58-78), and 63% were female. Median baseline-core-infarct volume was 32 ml (IQR 8-74.5). Seventy six patients (74%) had HOE. In a multivariate analysis both favorable HIR collaterals (p = 0.02) and HOE (p = 0.038) were associated with lower baseline-core-infarct volume. However, HOE significantly interacted with HIR (p = 0.01) to predict baseline-core-infarct volume, favorable collaterals (low HIR) with HOE was associated with small baseline-core-infarct whereas patients with poor collaterals (high HIR) and HOE had large baseline-core-infarct. Conclusion: While HOE under effective collateral blood-flow has the lowest baseline-core-infarct volume of all patients, the protective effect of HOE reverses under poor collateral blood-flow and may be a maladaptive response to ischemic stroke as measured by core infarctions in AIS-LVO patients undergoing MT triage.

  View details for DOI 10.3389/fneur.2020.618765

  View details for PubMedID 33488506

• Tilt-Corrected Region Boundaries May Enhance the Alberta Stroke Program Early Computed Tomography Score for Less Experienced Raters. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Culbertson, C. J., Christensen, S. n., Mlynash, M. n., Heit, J. J., Federau, C. n., Sells, C. M., Legault, C. n., McCaslin, A. F., Werbaneth, K. n., Albers, G. W., Lansberg, M. G. 2020: 104820

  Abstract

  The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to quantify early ischemic changes in the anterior circulation but has limited inter-rater reliability.We investigated whether application of 3-dimensional boundaries outlining the ASPECTS regions improves inter-rater reliability and accuracy.We included all patients from our DEFUSE 2 database who had a pretreatment noncontrast computed tomography scan (NCCT) of acceptable quality. Six raters (2 neuroradiologists, 2 vascular neurologists, and 2 neurology residents) scored ASPECTS of each NCCT without ("CT-native") and with the superimposed boundary template ("CT-template"). Gold-standard ASPECTS were generated by the 2 neuroradiologists through joint adjudication. Inter-rater reliability and accuracy were assessed using the intraclass correlation coefficient (ICC) for full-scale agreements and Gwet's AC1 for dichotomized (ASPECTS 0-6 vs 7-10) agreements.Eighty-two patients were included. Inter-rater reliability improved with higher training level for both CT-native (ICC = .15, .31, .54 for residents, neurologists, and radiologists, respectively) and CT-template (ICC = .18, .33, .56). Use of the boundary template improved correlation with the gold-standard for one resident on full-scale agreement (ICC increased from .01 to .31, P = .01) and another resident on dichotomized agreement (AC1 increased from .36 to .64, P = .01), but resulted in no difference for other raters. The template did not improve ICC between raters of the same training level.Inter-rater reliability of ASPECTS improves with physician training level. Standardized display of ASPECTS region boundaries on NCCT does not improve inter-rater reliability but may improve accuracy for some less experienced raters.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2020.104820

  View details for PubMedID 32307316

• Use of Deep Learning to Predict Final Ischemic Stroke Lesions From Initial Magnetic Resonance Imaging. JAMA network open Yu, Y. n., Xie, Y. n., Thamm, T. n., Gong, E. n., Ouyang, J. n., Huang, C. n., Christensen, S. n., Marks, M. P., Lansberg, M. G., Albers, G. W., Zaharchuk, G. n. 2020; 3 (3): e200772

  Abstract

  Predicting infarct size and location is important for decision-making and prognosis in patients with acute stroke.To determine whether a deep learning model can predict final infarct lesions using magnetic resonance images (MRIs) acquired at initial presentation (baseline) and to compare the model with current clinical prediction methods.In this multicenter prognostic study, a specific type of neural network for image segmentation (U-net) was trained, validated, and tested using patients from the Imaging Collaterals in Acute Stroke (iCAS) study from April 14, 2014, to April 15, 2018, and the Diffusion Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) study from July 14, 2008, to September 17, 2011 (reported in October 2012). Patients underwent baseline perfusion-weighted and diffusion-weighted imaging and MRI at 3 to 7 days after baseline. Patients were grouped into unknown, minimal, partial, and major reperfusion status based on 24-hour imaging results. Baseline images acquired at presentation were inputs, and the final true infarct lesion at 3 to 7 days was considered the ground truth for the model. The model calculated the probability of infarction for every voxel, which can be thresholded to produce a prediction. Data were analyzed from July 1, 2018, to March 7, 2019.Area under the curve, Dice score coefficient (DSC) (a metric from 0-1 indicating the extent of overlap between the prediction and the ground truth; a DSC of ≥0.5 represents significant overlap), and volume error. Current clinical methods were compared with model performance in subgroups of patients with minimal or major reperfusion.Among the 182 patients included in the model (97 women [53.3%]; mean [SD] age, 65 [16] years), the deep learning model achieved a median area under the curve of 0.92 (interquartile range [IQR], 0.87-0.96), DSC of 0.53 (IQR, 0.31-0.68), and volume error of 9 (IQR, -14 to 29) mL. In subgroups with minimal (DSC, 0.58 [IQR, 0.31-0.67] vs 0.55 [IQR, 0.40-0.65]; P = .37) or major (DSC, 0.48 [IQR, 0.29-0.65] vs 0.45 [IQR, 0.15-0.54]; P = .002) reperfusion for which comparison with existing clinical methods was possible, the deep learning model had comparable or better performance.The deep learning model appears to have successfully predicted infarct lesions from baseline imaging without reperfusion information and achieved comparable performance to existing clinical methods. Predicting the subacute infarct lesion may help clinicians prepare for decompression treatment and aid in patient selection for neuroprotective clinical trials.

  View details for DOI 10.1001/jamanetworkopen.2020.0772

  View details for PubMedID 32163165

• Collateral Effect of Covid-19 on Stroke Evaluation in the United States. The New England journal of medicine Kansagra, A. P., Goyal, M. S., Hamilton, S. n., Albers, G. W. 2020

  View details for DOI 10.1056/NEJMc2014816

  View details for PubMedID 32383831

• Response by Dula et al to Letter Regarding Article, "Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort". Stroke Dula, A. N., Mlynash, M. n., Albers, G. W., Warach, S. J. 2020: STROKEAHA120029168

  View details for DOI 10.1161/STROKEAHA.120.029168

  View details for PubMedID 32212895

• National Institutes of Health StrokeNet During the Time of COVID-19 and Beyond. Stroke Broderick, J. P., Elm, J. J., Janis, L. S., Zhao, W. n., Moy, C. S., Dillon, C. R., Chimowitz, M. I., Sacco, R. L., Cramer, S. C., Wolf, S. L., Johnston, K. C., Saver, J. L., Marshall, R. S., Brown, D. n., Wintermark, M. n., Elkind, M. S., Kamel, H. n., Tirschwell, D. L., Longstreth, W. T., Chervin, R. D., Adeoye, O. M., Barreto, A. D., Grotta, J. C., Ramey, S. L., Lo, W. D., Feng, W. n., Schlaug, G. n., Sheth, K. N., Selim, M. n., Naidech, A. M., Lansberg, M. G., Lazar, R. M., Albers, G. W., Griffin, J. S., Sirline, L. P., Frasure, J. n., Wright, C. B., Khatri, P. n. 2020; 51 (8): 2580–86

  View details for DOI 10.1161/STROKEAHA.120.030417

  View details for PubMedID 32716819

• Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial INTERNATIONAL JOURNAL OF STROKE Easton, J., Denison, H., Evans, S. R., Knutsson, M., Amarenco, P., Albers, G. W., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Wong, K., Johnston, S., SOCRATES Steering Comm 2019; 14 (9): 908–14

  View details for DOI 10.1177/1747493019851282

  View details for Web of Science ID 000502477300016

• Benefits of Magnetic Resonance Imaging for Patients Presenting With Low-risk Transient or Persistent Minor Neurologic Deficits. JAMA neurology McCullough-Hicks, M. E., Albers, G. W. 2019

  View details for DOI 10.1001/jamaneurol.2019.2963

  View details for PubMedID 31545348

• Automated Calculation of Alberta Stroke Program Early CT Score. Stroke Albers, G. W., Wald, M. J., Mlynash, M., Endres, J., Bammer, R., Straka, M., Maier, A., Hinson, H. E., Sheth, K. N., Taylor Kimberly, W., Molyneaux, B. J. 2019: STROKEAHA119026430

  Abstract

  Background and Purpose- We compared the Alberta Stroke Program Early CT Score (ASPECTS), calculated using a machine learning-based automatic software tool, RAPID ASPECTS, as well as the median score from 4 experienced readers, with the diffusion-weighted imaging (DWI) ASPECTS obtained following the baseline computed tomography (CT) in patients with large hemispheric infarcts. Methods- CT and magnetic resonance imaging scans from the GAMES-RP study, which enrolled patients with large hemispheric infarctions (82-300 mL) documented on DWI-magnetic resonance imaging, were evaluated by blinded experienced readers to determine both CT and DWI ASPECTS. The CT scans were also evaluated by an automated software program (RAPID ASPECTS). Using the DWI ASPECTS as a reference standard, the median CT ASPECTS of the clinicians and the automated score were compared using the interclass correlation coefficient. Results- The median CT ASPECTS for the clinicians was 5 (interquartile range, 4-7), for RAPID ASPECTS 3 (interquartile range, 1-6), and for DWI ASPECTS 3 (2-4). Median error for RAPID ASPECTS was 1 (interquartile range, -1 to 3) versus 3 (interquartile range, 1-4) for clinicians (P<0.001). The automated score had a higher level of agreement with the median of the DWI ASPECTS, both for the full scale and when dichotomized at <6 versus 6 or more (difference in intraclass correlation coefficient, P=0.001). Conclusions- RAPID ASPECTS was more accurate than experienced clinicians in identifying early evidence of brain ischemia as documented by DWI.

  View details for DOI 10.1161/STROKEAHA.119.026430

  View details for PubMedID 31500555

• Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience JOURNAL OF NEUROINTERVENTIONAL SURGERY Lee, S., Heit, J., Albers, G. W., Wintermark, M., Jiang, B., Bernier, E., Fischbein, N. J., Mlynash, M., Marks, M. P., Do, H. M., Dodd, R. L. 2019; 11 (9): 940–46

  View details for DOI 10.1136/neurintsurg-2019-014862

  View details for Web of Science ID 000490293400019

• Endovascular versus medical therapy for large-vessel anterior occlusive stroke presenting with mild symptoms. International journal of stroke : official journal of the International Stroke Society Wolman, D. N., Marcellus, D. G., Lansberg, M. G., Albers, G., Guenego, A., Marks, M. P., Dodd, R. L., Do, H. M., Wintermark, M., Martin, B. W., Heit, J. J. 2019: 1747493019873510

  Abstract

  BACKGROUND: Acute ischemic stroke patients with a large-vessel occlusion but mild symptoms (NIHSS≤6) pose a treatment dilemma between medical management and endovascular thrombectomy.AIMS: To evaluate the differences in clinical outcomes of endovascular thrombectomy-eligible patients with target-mismatch perfusion profiles who undergo either medical management or endovascular thrombectomy.METHODS: Forty-seven patients with acute ischemic stroke due to large-vessel occlusion, NIHSS≤6, and a target-mismatch perfusion imaging profile were included. Patients underwent medical management or endovascular thrombectomy following treating neurointerventionalist and neurologist consensus. The primary outcome measure was NIHSS shift. Secondary outcome measures were symptomatic intracranial hemorrhage, in-hospital mortality, and 90-day mRS scores. The primary intention-to-treat and as-treated analyses were compared to determine the impact of crossover patient allocation on study outcome measures.RESULTS: Forty-seven patients were included. Thirty underwent medical management (64%) and 17 underwent endovascular thrombectomy (36%). Three medical management patients underwent endovascular thrombectomy due to early clinical deterioration. Presentation NIHSS (P=0.82), NIHSS shift (P=0.62), and 90-day functional independence (mRS 0-2; P=0.25) were similar between groups. Endovascular thrombectomy patients demonstrated an increased overall rate of intracranial hemorrhage (35.3% vs. 10.0%; P=0.04), but symptomatic intracranial hemorrhage was similar between groups (P=0.25). In-hospital mortality was similar between groups (P=0.46), though all two deaths in the medical management group occurred among crossover patients. Endovascular thrombectomy patients demonstrated a longer length of stay (7.6±7.2 vs. 4.3±3.9 days; P=0.04) and a higher frequency of unfavorable discharge to a skilled-nursing facility (P=0.03) rather than home (P=0.05).CONCLUSIONS: Endovascular thrombectomy may pose an unfavorable risk-benefit profile over medical management for endovascular thrombectomy-eligible acute ischemic stroke patients with mild symptoms, which warrants a randomized trial in this subpopulation.

  View details for DOI 10.1177/1747493019873510

  View details for PubMedID 31474193

• Cerebral Blood Flow Predicts the Infarct Core. Stroke Amukotuwa, S., Straka, M., Aksoy, D., Fischbein, N., Desmond, P., Albers, G., Bammer, R. 2019: STROKEAHA119026640

  Abstract

  Background and Purpose- The aim of this study is to determine the spatial and volumetric accuracy of infarct core estimates from relative cerebral blood flow (rCBF) by comparison with near-contemporaneous diffusion-weighted imaging (DWI), and evaluate whether it is sufficient for patient triage to reperfusion therapies. Methods- One hundred ninety-three patients enrolled in the DEFUSE 2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) and SENSE 3 (Sensitivity Encoding) stroke studies were screened, and 119 who underwent acute magnetic resonance imaging with DWI and perfusion imaging within 24 hours of onset were included. Infarct core was estimated using reduced rCBF at 12 thresholds (<0.20-<0.44) and compared against DWI (apparent diffusion coefficient <620 10-6mm2/s). For each threshold, volumetric agreement between the rCBF and DWI core estimates was assessed using Bland-Altman, correlation, and linear regression analyses; spatial agreement was assessed using receiver operating characteristic analysis. Results- An rCBF threshold of 0.32 yielded the smallest mean absolute volume difference (14.7 mL), best linear regression fit (R2=0.84), and best spatial agreement (Youden index, 0.38; 95% CI, 0.34-0.41) between rCBF and DWI, with high correlation (r=0.91, P<0.05), a small mean volume difference (1.3 mL) and no fixed bias (P<0.05). At this threshold, 110 of 119 (92.4%) patients were correctly triaged when applying 70 mL as the volume limit for thrombectomy. Spatial agreement was better for prediction of large infarcts (>70 mL) than small infarcts (≤70 mL), with Youden indices of 0.53 (95% CI, 0.49-0.56) and 0.34 (95% CI, 0.30-0.37), respectively. Conclusions- Strong correlation and agreement with near-contemporaneous DWI indicate that infarct core estimates obtained using rCBF are sufficiently accurate for patient triage to reperfusion therapies. The identified optimal rCBF threshold of 0.32 closely approximates the threshold currently used in clinical practice.

  View details for DOI 10.1161/STROKEAHA.119.026640

  View details for PubMedID 31462191

• Outcomes of Endovascular Thrombectomy vs Medical Management Alone in Patients With Large Ischemic Cores: A Secondary Analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) Study. JAMA neurology Sarraj, A., Hassan, A. E., Savitz, S., Sitton, C., Grotta, J., Chen, P., Cai, C., Cutter, G., Imam, B., Reddy, S., Parsha, K., Pujara, D., Riascos, R., Vora, N., Abraham, M., Kamal, H., Haussen, D. C., Barreto, A. D., Lansberg, M., Gupta, R., Albers, G. W. 2019

  Abstract

  Importance: The efficacy and safety of endovascular thrombectomy (EVT) in patients with large ischemic cores remains unknown, to our knowledge.Objective: To compare outcomes in patients with large ischemic cores treated with EVT and medical management vs medical management alone.Design, Setting, and Participants: This prespecified analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) trial, a prospective cohort study of imaging selection that was conducted in 9 US comprehensive stroke centers, enrolled patients between January 2016 and February 2018, and followed them up for 90 days. Patients with moderate to severe stroke and anterior circulation large-vessel occlusion presenting up to 24 hours from the time they were last known to be well were eligible for the cohort. Of these, patients with large ischemic cores on computed tomography (CT) (Alberta Stroke Program Early CT Score <6) or CT perfusion scanning (a volume with a relative cerebral blood flow <30% of ≥50 cm3) were included in analyses.Exposures: Endovascular thrombectomy with medical management (MM) or MM only.Main Outcomes and Measures: Functional outcomes at 90 days per modified Rankin scale; safety outcomes (mortality, symptomatic intracerebral hemorrhage, and neurological worsening).Results: A total of 105 patients with large ischemic cores on either CT or CT perfusion images were included: 71 with Alberta Stroke Program Early CT Scores of 5 or less (EVT, 37; MM, 34), 74 with cores of 50 cm3 or greater on CT perfusion images (EVT, 39; MM, 35), and 40 who had large cores on both CT and CT perfusion images (EVT, 14; MM, 26). The median (interquartile range) age was 66 (60-75) years; 45 patients (43%) were female. Nineteen of 62 patients (31%) who were treated with EVT achieved functional independence (modified Rankin Scale scores, 0-2) vs 6 of 43 patients (14%) treated with MM only (odds ratio [OR], 3.27 [95% CI, 1.11-9.62]; P=.03). Also, EVT was associated with better functional outcomes (common OR, 2.12 [95% CI, 1.05-4.31]; P=.04), less infarct growth (44 vs 98 mL; P=.006), and smaller final infarct volume (97 vs 190 mL; P=.001) than MM. In the odds of functional independence, there was a 42% reduction per 10-cm3 increase in core volume (adjusted OR, 0.58 [95% CI, 0.39-0.87]; P=.007) and a 40% reduction per hour of treatment delay (adjusted OR, 0.60 [95% CI, 0.36-0.99]; P=.045). Of 10 patients who had EVT with core volumes greater than 100 cm3, none had a favorable outcome.Conclusions and Relevance: Although the odds of good outcomes for patients with large cores who receive EVT markedly decline with increasing core size and time to treatment, these data suggest potential benefits. Randomized clinical trials are needed.

  View details for DOI 10.1001/jamaneurol.2019.2109

  View details for PubMedID 31355873

• Thrombectomy Results in Reduced Hospital Stay, More Home-Time, and More Favorable Living Situations in DEFUSE 3. Stroke Tate, W. J., Polding, L. C., Kemp, S., Mlynash, M., Heit, J. J., Marks, M. P., Albers, G. W., Lansberg, M. G. 2019: STROKEAHA119025165

  Abstract

  Background and Purpose- The DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) demonstrated that endovascular thrombectomy in the 6- to 16-hour time window improves functional outcomes of patients with evidence of salvageable tissue on baseline computed tomography or magnetic resonance imaging. The purpose of this study is to assess the effect of endovascular therapy on length of hospital stay, home-time during the first 3 months poststroke, and living situation poststroke in DEFUSE 3. Methods- Duration of hospital stay and home-time (number of days during the 90-day poststroke period that the patient resides in their own home or in that of a relative) were compared between treatment groups using the Wilcoxon rank-sum test. Patient living situation was assessed at discharge, 30 days, and 90 days on an ordinal 4-point scale (home, acute rehabilitation unit, institutionalized care, or hospice/death) and differences between groups were analyzed using the Cochran-Armitage trend test. Results- Median length of hospital stay was 9.1 (interquartile range, 6.2-15.0) days in the medical group versus 6.5 (interquartile range, 3.7-9.3) days in the endovascular group ( P<0.001). Median home-time during the first 90 days after stroke was 0 (interquartile range, 0-53) days in the medical group versus 55 (interquartile range, 0-83) days in the endovascular group ( P<0.001). The endovascular group had more favorable living situations at time of discharge ( P<0.001), 30 days ( P<0.001), and 90 days ( P<0.001) poststroke. Conclusions- Endovascular thrombectomy resulted in reduced hospital stay, more home-time, and more desirable living situations in the 90 days after stroke. These results provide evidence that endovascular therapy in the delayed time window can improve quality of life for stroke patients and reduce healthcare costs. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for DOI 10.1161/STROKEAHA.119.025165

  View details for PubMedID 31288666

• The feasibility of deep learning to predict final stroke lesion using baseline diffusion-weighted imaging only in non-recanalized acute ischemic stroke patients Yu, Y., Xie, Y., Thamm, T., Gong, E., Christensen, S., Lansberg, M. G., Albers, G. W., Zaharchuk, G. SAGE PUBLICATIONS INC. 2019: 231–32

  View details for Web of Science ID 000473954100265

• Clinical validation of penumbra and ischemic core prediction from deep learning algorithm using baseline multimodal MRI in acute ischemic stroke patients: A multi-center study Yu, Y., Xie, Y., Thamm, T., Gong, E., Huang, C., Christensen, S., Lansberg, M. G., Albers, G. W., Zaharchuk, G. SAGE PUBLICATIONS INC. 2019: 10–11

  View details for Web of Science ID 000473954100011

• Deep learning-based penumbra estimation using DWI and ASL for acute ischemic stroke patients Xie, Y., Yu, Y., Thamm, T., Gong, E., Ouyang, J., Huang, C., Christensen, S., Albers, G., Zaharchuk, G. SAGE PUBLICATIONS INC. 2019: 622

  View details for Web of Science ID 000473954100806

• Time Course for Benefit and Risk of Clopidogrel and Aspirin after Acute Transient Ischemic Attack and Minor Ischemic Stroke: A Secondary Analysis from the POINT Randomized Trial. Circulation Johnston, S. C., Elm, J. J., Easton, J. D., Farrant, M., Barsan, W. G., Kim, A. S., Lindblad, A. S., Palesch, Y. Y., Zurita, K. G., Albers, G. W., Cucchiara, B. L., Kleindorfer, D. O., Lutsep, H. L., Pearson, C., Sethi, P., Vora, N., POINT and Neurological Emergencies Treatment Trials Network Investigators 2019

  Abstract

  BACKGROUND: In patients with acute minor ischemic stroke or high-risk transient ischemic attack enrolled in the POINT trial, the combination of clopidogrel and aspirin for 90 days reduced major ischemic events but increased major hemorrhage compared to aspirin alone.METHODS: In a secondary analysis of POINT (N=4,881), we assessed the time course for benefit and risk from the combination of clopidogrel and aspirin. The primary efficacy outcome was a composite of ischemic stroke, myocardial infarction, or ischemic vascular death. The primary safety outcome was major hemorrhage. Risks and benefits were estimated for delayed times of treatment initiation using left-truncated models.RESULTS: Through 90 days, the rate of major ischemic events was initially high then decreased markedly, while the rate of major hemorrhage remained low but relatively constant throughout. Using a model-based approach, the optimal change-point for major ischemic events was 21 days (0-21 days HR 0.65 for clopidogrel-aspirin vs. aspirin, 95% CI 0.50-0.85, p=0.0015, compared to 22-90 days HR 1.38, 95% CI 0.81-2.35, p=0.24). Models showed benefits of clopidogrel-aspirin for treatment delayed as long as 3 days after symptom onset.CONCLUSIONS: The benefit of clopidogrel-aspirin occurs predominantly within the first 21 days, and outweighs the low, but ongoing risk of major hemorrhage. When considered with the results of CHANCE, a similar trial treating with clopidogrel-aspirin for 21 days and showing no increase in major hemorrhage, these results suggest limiting clopidogrel-aspirin use to 21 days may maximize benefit and reduce risk after high-risk TIA or minor ischemic stroke.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT00991029.

  View details for DOI 10.1161/CIRCULATIONAHA.119.040713

  View details for PubMedID 31238700

• Advanced Brain Imaging in Late-Arriving Drip and Ship Patients With Known Large Vessel Occlusion. Stroke Albers, G. W., Molina, C. A., Selim, M. H., Jovin, T. G. 2019: STROKEAHA118020574

  View details for DOI 10.1161/STROKEAHA.118.020574

  View details for PubMedID 31216963

• Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window: A Subanalysis From the DEFUSE 3 Trial JAMA NEUROLOGY Sarraj, A., Mlynash, M., Savitz, S. I., Heit, J. J., Lansberg, M. G., Marks, M. P., Albers, G. W. 2019; 76 (6): 682–89

  View details for DOI 10.1001/jamaneurol.2019.0118

  View details for Web of Science ID 000474834200011

• Thrombectomy with Conscious Sedation Compared with General Anesthesia: A DEFUSE 3 Analysis AMERICAN JOURNAL OF NEURORADIOLOGY Powers, C. J., Dornbos, D., Mlynash, M., Gulati, D., Torbey, M., Nimjee, S. M., Lansberg, M. G., Albers, G. W., Marks, M. P. 2019; 40 (6): 1001–5

  View details for DOI 10.3174/ajnr.A6059

  View details for Web of Science ID 000476574200012

• Artificial Neural Network Computer Tomography Perfusion Prediction of Ischemic Core STROKE Kasasbeh, A. S., Christensen, S., Parsons, M. W., Campbell, B., Albers, G. W., Lansberg, M. G. 2019; 50 (6): 1578–81

  View details for DOI 10.1161/STROKEAHA.118.022649

  View details for Web of Science ID 000470074200063

• Response by de Havenon et al to Letter Regarding Article, "Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome" STROKE de Havenon, A., Albers, G. W., Heit, J. J. 2019; 50 (6): E166

  View details for DOI 10.1161/STROKEAHA.119.025713

  View details for Web of Science ID 000470074200014

• Collateral blood flow measurement with intravoxel incoherent motion perfusion imaging in hyperacute brain stroke NEUROLOGY Federau, C., Wintermark, M., Christensen, S., Mlynash, M., Marcellus, D. G., Zhu, G., Martin, B. W., Lansberg, M. G., Albers, G. W., Heit, J. J. 2019; 92 (21): E2462–E2471

  View details for DOI 10.1212/WNL.0000000000007538

  View details for Web of Science ID 000480767200007

• Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study STROKE Heit, J. J., Mlynash, M., Kemp, S. M., Lansberg, M. G., Christensen, S., Marks, M. P., Ortega-Gutierrez, S., Albers, G. W. 2019; 50 (5): 1172–77

  View details for DOI 10.1161/STROKEAHA.119.024928

  View details for Web of Science ID 000469350000042

• Collateral blood flow measurement with intravoxel incoherent motion perfusion imaging in hyperacute brain stroke. Neurology Federau, C., Wintermark, M., Christensen, S., Mlynash, M., Marcellus, D. G., Zhu, G., Martin, B. W., Lansberg, M. G., Albers, G. W., Heit, J. J. 2019

  Abstract

  OBJECTIVE: To determine if intravoxel incoherent motion (IVIM) magnetic resonance perfusion can measure the quality of the collateral blood flow in the penumbra in hyperacute stroke.METHODS: A 6 b values IVIM MRI sequence was acquired in stroke patients with large vessel occlusion imaged <16 hours of last seen well. IVIM perfusion measures were evaluated in regions of interest drawn in the infarct core (D < 600 mm2/s), in the corresponding region in the contralateral hemisphere, and in the dynamic susceptibility contrast penumbra. In patients with a penumbra >15 mL, images were reviewed for the presence of a penumbra perfusion lesion on the IVIM f map, which was correlated with infarct size metrics. Statistical significance was tested using Student t test, Mann-Whitney U test, and Fisher exact test.RESULTS: A total of 34 patients were included. In the stroke core, IVIM f was significantly lower (4.6 ± 3.3%) compared to the healthy contralateral region (6.3 ± 2.2%, p < 0.001). In the 25 patients with a penumbra >15 mL, 9 patients had an IVIM penumbra perfusion lesion (56 ± 76 mL), and 16 did not. Patients with an IVIM penumbra perfusion lesion had a larger infarct core (82 ± 84 mL) at baseline, a larger infarct growth (68 ± 40 mL), and a larger final infarct size (126 ± 81 mL) on follow-up images compared to the patients without (resp. 20 ± 17 mL, p < 0.05; 13 ± 19 mL, p < 0.01; 29 ± 24 mL, p < 0.05). All IVIM penumbra perfusion lesions progressed to infarction despite thrombectomy treatment.CONCLUSIONS: IVIM is a promising tool to assess the quality of the collateral blood flow in hyperacute stroke. IVIM penumbra perfusion lesion may be a marker of nonsalvageable tissue despite treatment with thrombectomy, suggesting that the IVIM penumbra perfusion lesion might be counted to the stroke core, together with the DWI lesion.

  View details for PubMedID 31019105

• STAIR X. Stroke Demchuk, A. M., Albers, G. W., Nogueira, R. G., STAIR X Consortium *, STAIR X (Stroke Treatment Academic Industry Roundtable) writing contributors, Alexandrov, A. V., Arbe-Barnes, S., Baron, J., Boltze, J., Broderick, J. P., Broschat, K., Campbell, B. C., Derdeyn, C. P., Elkind, M. S., Emberson, J. R., En'Wezoh, D., Furlan, A. J., Gorelick, P. B., Hancock, A. M., Hill, M. D., Holt, B., Khatri, P., Kim, W., Kjos, D., Kleindorfer, D., Lansberg, M. G., Liberman, M., Liebeskind, D. S., Luby, M., Lyden, P., Lynch, J. K., Mocco, J., Palesch, Y. Y., Pereira, V. M., Sanossian, N., Savitz, S. I., Schwamm, L. H., Selim, M., Sheth, K. N., Simpkins, A. N., Singhal, A., Solberg, Y., Steinberg, G. K., Tymianski, M., Warach, S., Wechsler, L. R., Wright, C., Yoo, A. J., Zaidat, O. O. 2019: STROKEAHA119024337

  View details for DOI 10.1161/STROKEAHA.119.024337

  View details for PubMedID 31112484

• Baseline Perfusion Imaging Collateral Scores Predict Infarct Growth in DEFUSE 3 MacLellan, A., Mlynash, M., Heit, J., Marks, M., Lansberg, M., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000475965907014

• Design of a Phase III Study of Intravenous Glibenclamide (BIIB093) for Large Hemispheric Infarction: the CHARM Study Sheth, K. N., Kimberley, W., Albers, G. W., Hinson, H. E., Molyneaux, B. J., Nogueira, R., Saver, J., Steiner, T., Toyoda, K., Wintermark, M., Elkins, J., Deykin, A., Wald, M., Landen, J. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000475965901294

• Association of Thrombectomy With Stroke Outcomes Among Patient Subgroups Secondary Analyses of the DEFUSE 3 Randomized Clinical Trial JAMA NEUROLOGY Lansberg, M. G., Mlynash, M., Hamilton, S., Yeatts, S. D., Christensen, S., Kemp, S., Lavori, P. W., Ortega-Gutierrez, S., Broderick, J., Heit, J., Marks, M. P., Albers, G. W., Ortega-Gutierrez, S., Leira, E., McTaggart, R., Yaghi, S., Torbey, M., Powers, C. J., Kim-Tenser, M., Tenser, M., Lansberg, M., Marks, M., Leslie-Mazwi, T., Hurst, R., Kasner, S., Sarraj, A., Spiegel, G., Ansari, S. A., Prabhakaran, S., Altschul, D., de Havenon, A., Park, M., Fifi, J., Tuhrim, S., Hoesch, R., Blatter, D., Kayan, Y., Young, M., Stephens, R., Finch, I., Afshinnik, A., Ryan, R., Chaudhary, N., Brown, D., Feske, S., Aziz-Sultan, A., Smith, W., Cooke, D., Warach, S., Miley, J., Ahmed, A., Bradbury, E., Bozorgchami, H., Priest, R., Gropen, T., Harrigan, M., Kalafut, M., Ammirati, G., Meyer, B., Khalessi, A., Schlaug, G., Sen, S., Moftakhar, R., Streib, C., Jagadeesan, B. D., Toth, G., Uchino, K., Hsia, A., Liu, A., Jagadeesan, B. D., Streib, C., Vagal, A., Ringer, A. J., Willey, J. Z., Meyers, P. M., Zaidat, O. O., Froehler, M., Leifer, D., Patsalides, A., Lowenkopf, T., Deshmukh, V., Tirschwell, D., Hallam, D., DEFUSE 3 Investigators 2019; 76 (4): 447–53

  View details for DOI 10.1001/jamaneurol.2018.4587

  View details for Web of Science ID 000463873600013

• Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study. Stroke Heit, J. J., Mlynash, M., Kemp, S. M., Lansberg, M. G., Christensen, S., Marks, M. P., Ortega-Gutierrez, S., Albers, G. W. 2019: STROKEAHA119024928

  Abstract

  Background and Purpose- Thrombectomy in late time windows leads to improved outcomes in patients with ischemic stroke due to large vessel occlusion. We determined whether patients with rapid neurological improvement (RNI) 24 hours after thrombectomy were more likely to have a favorable clinical outcome in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3). Methods- All patients who underwent thrombectomy in DEFUSE 3 were included. RNI was defined as a reduction of ≥8 on the National Institutes of Health Stroke Scale or National Institutes of Health Stroke Scale zero to one 24 hours after thrombectomy. Clinical outcomes were assessed by an ordinal analysis modified Rankin Scale score and a dichotomous analysis for 90-day independence (modified Rankin Scale score, 0-2). Results- Ninety-one patients in DEFUSE 3 underwent thrombectomy with follow-up data; 31 patients (34%) experienced RNI (RNI+) after thrombectomy and 60 patients (66%) did not (RNI-). Patient demographics and stroke presentation and imaging details were similar between RNI+ and RNI- patients. Reperfusion (Thrombolysis in Cerebral Infarction 2b-3) after thrombectomy was achieved in 26 (84%) RNI+ and 43 (72%) RNI- ( P=0.2). Symptomatic intracranial hemorrhage occurred in no RNI+ and 8% of RNI- patients ( P=0.2). RNI was associated with a favorable modified Rankin Scale shift at day 90 (odds ratio, 3.8; CI, 1.7-8.6; P=0.001) and higher rates of modified Rankin Scale zero to 2 (61% versus 37%; odds ratio, 2.7; CI, 1.1-6.7; P=0.03). Mortality was 3% in RNI+ versus 18% in RNI- ( P=0.05). RNI+ patients had lower median 24-hour National Institutes of Health Stroke Scale (5 [interquartile range (IQR), 1-7] versus 13 [IQR, 7.5-21]; P<0.001), smaller 24-hour infarction volume (21 [IQR, 5-32] versus 65 [IQR, 27-145] mL; P<0.001), and less 24-hour infarct growth (8 [IQR, 1-18] versus 37 [IQR, 16-105] mL; P<0.001) compared with RNI- patients. Hospital stay was shorter in RNI+ (3.7 [IQR, 2.9-7.1] versus 7.4 [IQR, 5.2-12.1] days in RNI-; P<0.001). Conclusions- RNI following thrombectomy correlates with favorable clinical and radiographic outcomes and reduced hospital length of stay. RNI was a favorable prognostic sign following late-window thrombectomy in DEFUSE 3. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for PubMedID 30932783

• Hypoperfusion Intensity Ratio Is Correlated With Patient Eligibility for Thrombectomy STROKE Guenego, A., Marcellus, D. G., Martin, B. W., Christensen, S., Albers, G. W., Lansberg, M. G., Marks, M. P., Wintermark, M., Heit, J. J. 2019; 50 (4): 917–22

  View details for DOI 10.1161/STROKEAHA.118.024134

  View details for Web of Science ID 000469347900033

• Response to letter by Samuels et al. International journal of stroke : official journal of the International Stroke Society Brinjikji, W., Albers, G. W., Koch, S., Rabinstein, A. A. 2019: 1747493019840929

  View details for DOI 10.1177/1747493019840929

  View details for PubMedID 30935348

• Validation and iteration of CT perfusion defined malignant profile thresholds for acute ischemic stroke. International journal of stroke : official journal of the International Stroke Society Keenan, K. J., Christensen, S., Inoue, M., Mlynash, M., Albers, G. W., Smith, W. S. 2019: 1747493019832987

  Abstract

  BACKGROUND: Malignant profile computed tomography perfusion (CTP) lesions are associated with poor outcomes after administration of intravenous tissue-plasminogen activator (IV-tPA) for ischemic stroke.AIMS: To determine whether published CTP-based lesion thresholds predictive of poor outcomes in a predominantly 8cm of CTP anatomic coverage cohort would predict poor outcomes in an independent 4cm of CTP anatomic coverage cohort and to generate optimized 4cm CTP thresholds.METHODS: Ischemic stroke patients with baseline CTP imaging with 4cm of anatomic coverage before receiving IV-tPA at a single institution were retrospectively studied. Perfusion lesion time to maximum of tissue residue function (Tmax) and cerebral blood flow (CBF) volumes were determined using RAPID automated software. Fisher's exact tests assessed associations between lesion thresholds and outcomes. Receiver operating characteristic (ROC) curves generated optimized thresholds for 4cm of CTP coverage.RESULTS: Sixty-three patients were included. Poor outcomes were associated with published thresholds of Tmax >6s>103mL, Tmax>8s>86mL, and Tmax>10s>78mL but not CBF core >53mL. Thresholds optimized for 4cm of CTP coverage and associated with poor outcomes were Tmax>6s>100mL, Tmax>8s>65mL, Tmax>10s>46mL, and CBF core >39mL.CONCLUSIONS: We validated the ability of published CTP Tmax lesion volume thresholds to predict poor outcomes despite IV-tPA in an independent cohort using only 4cm of CTP anatomical coverage. A CBF>39mL threshold, rather than the predominantly 8cm CTP coverage derived CBF threshold of >53mL, was associated with poor outcomes in this 4cm CTP coverage cohort.

  View details for DOI 10.1177/1747493019832987

  View details for PubMedID 30794104

• Time to Loading Dose and Risk of Recurrent Events in the SOCRATES Trial. Stroke Molina, C. A., Johnston, S. C., Ladenvall, P., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Knutsson, M., Minematsu, K., Rother, J., Wang, Y., Wong, K. S., SOCRATES Steering Committee and Investigators 2019: STROKEAHA118022675

  Abstract

  Background and Purpose- Recurrent ischemia risk is high in the acute period after cerebral ischemic events. Effects of antiplatelet agents may vary by time to loading dose (TLD). We explored the risk of recurrent events and safety and efficacy of ticagrelor versus aspirin in relation to TLD. Methods- We randomized 13 199 patients with noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to 90-day ticagrelor or aspirin treatment within 24 hours of symptom onset. For this analysis, 13 126 patients were categorized by TLD as <12 hours or ≥12 hours from start of index event. The primary end point was the composite of stroke, myocardial infarction, or death within 90 days. Major bleeding was the primary safety end point. Results- TLD was <12 hours in 4403 (33.5%) and ≥12 hours in 8723 (66.5%). The Kaplan-Meier% for the primary end point for all patients with TLD<12 hours was 7.5% versus 6.9% in TLD≥12 hours. Among patients with TLD<12 hours, the primary end point occurred in 147/2196 (6.8%) randomized to ticagrelor and in 184/2207 (8.3%) randomized to aspirin (hazard ratio, 0.79; 95% CI, 0.64-0.98; P=0.036). Among patients with TLD≥12 hours, the primary end point occurred in 6.7% patients randomized to ticagrelor versus 7.0% to aspirin (hazard ratio, 0.95; 95% CI, 0.81-1.12; P=0.55). There was no significant treatment-by-TLD interaction. Major bleeding rates were comparable on ticagrelor and aspirin, regardless of TLD. Conclusions- The event rate for the primary end point was higher in patients treated early (<12 hours) versus later (≥12 hours). In this exploratory analysis, a larger numerical difference in the primary end point was observed among patients on ticagrelor than on aspirin when TLD was <12 hours compared with ≥12 hours, although the interaction terms for treatment-by-TLD were not significant. For major bleeding, no relation to TLD was observed. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01994720.

  View details for PubMedID 30776996

• Persistent Target Mismatch Profile >24 Hours After Stroke Onset in DEFUSE 3. Stroke Christensen, S., Mlynash, M., Kemp, S., Yennu, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023392

  Abstract

  Background and Purpose- Efficacy of endovascular thrombectomy has been demonstrated up to 24 hours after stroke onset in patients selected with perfusion imaging. We hypothesized that a persistent favorable perfusion profile exists in some patients beyond 24 hours from the onset and can be predicted by a lower baseline hypoperfusion intensity ratio, which indicates favorable collaterals. Methods- We identified control arm patients from the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with a diffusion weighted imaging and perfusion magnetic resonance imaging performed 24 hours following randomization and compared imaging and clinical variables between patients with persistent mismatch versus patients who no longer had a mismatch 24 hours after randomization. Results- Eighteen percent of the control arm patients had a persistent favorable profile >38 hours after last known well time. These patients had similar baseline diffusion weighted imaging and Tmax >6 seconds volumes as patients whose initially favorable perfusion profile became unfavorable (diffusion weighted imaging lesion 7 versus 17 mL; P=0.17, Tmax >6 seconds 98 versus 100 mL; P=0.48) yet experienced less infarct growth (15 versus 59 mL; P<0.001) and had 3-fold smaller infarct volumes (15 versus 59 mL; P<0.001) 24 hours after randomization. Patients with a persistent favorable perfusion profile had a significantly lower hypoperfusion intensity ratio on baseline imaging (0.2 versus 0.4; P<0.01). Favorable clinical outcome at 90 days occurred in only 10% of the persistent mismatch patients. Conclusions- About 20% of patients with a middle cerebral artery or internal carotid artery occlusion who present in an extended time window and are not treated with thrombectomy have a persistent mismatch for at least an additional 24 hours. These patients have a favorable hypoperfusion intensity ratio at presentation, may experience delayed infarct expansion, and have poor clinical outcomes. Clinical trials are needed to determine if patients with a favorable perfusion profile benefit from reperfusion beyond 24 hours. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for PubMedID 30735466

• Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window: A Subanalysis From the DEFUSE 3 Trial. JAMA neurology Sarraj, A., Mlynash, M., Savitz, S. I., Heit, J. J., Lansberg, M. G., Marks, M. P., Albers, G. W. 2019

  Abstract

  Importance: Although thrombectomy benefit was maintained in transfer patients with ischemic stroke in early-window trials, overall functional independence rates were lower in thrombectomy and medical management-only groups.Objective: To evaluate whether the imaging-based selection criteria used in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) trial would lead to comparable outcome rates and treatment benefits in transfer vs direct-admission patients.Design, Setting, and Participants: Subgroup analysis of DEFUSE 3, a prospective, randomized, multicenter, blinded-end point trial. Patients were enrolled between May 2016 and May 2017 and were followed up for 90 days. The trial comprised 38 stroke centers in the United States and 182 patients with stroke with a large-vessel anterior circulation occlusion and initial infarct volume of less than 70 mL, mismatch ratio of at least 1.8, and mismatch volume of at least 15 mL, treated within 6 to 16 hours from last known well. Patients were stratified based on whether they presented directly to the study site or were transferred from a primary center. Data were analyzed between July 2018 and October 2018.Interventions or Exposures: Endovascular thrombectomy plus standard medical therapy vs standard medical therapy alone.Main Outcomes and Measures: The primary outcome was the distribution of 90-day modified Rankin Scale scores.Results: Of the 296 patients who consented, 182 patients were randomized (66% were transfer patients and 34% directly presented to a study site). Median age was 71 years (interquartile range [IQR], 60-79 years) vs 70 years (IQR, 59-80 years); 69 transfer patients were women (57%) and 23 of the direct group were women (37%). Transfer patients had longer median times from last known well to study site arrival (9.43 vs 9 hours) and more favorable collateral profiles (based on hypoperfusion intensity ratio): median for transfer, 0.35 (IQR, 0.18-0.47) vs 0.42 (IQR, 0.25-0.56) for direct (P=.05). The primary outcome (90-day modified Rankin Scale score shift) did not differ in the direct vs transfer groups (direct OR, 2.9; 95% CI, 1.2-7.2; P=.01; transfer OR, 2.6; 95% CI, 1.3-4.8; P=.009). The overall functional independence rate (90-day modified Rankin Scale score 0-2) in the thrombectomy group did not differ (direct 44% vs transfer 45%) nor did the treatment effect (direct OR, 2.0; 95% CI, 0.9-4.4 vs transfer OR, 3.1; 95% CI, 1.6-6.1). Thrombectomy reperfusion rates, mortality, and symptomatic intracranial hemorrhage rates did not differ.Conclusions and Relevance: In late-window patients selected by penumbral mismatch criteria, both the favorable outcome rate and treatment effect did not decline in transfer patients. These results have health care implications indicating transferring potential candidates for late-window thrombectomy is associated with substantial clinical benefits and should be encouraged.Trial Registration: ClinicalTrials.gov identifier: NCT02586415.

  View details for PubMedID 30734042

• Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3. Stroke Rao, V., Christensen, S., Yennu, A., Mlynash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023177

  Abstract

  Background and Purpose- Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume. Methods- Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses. Results- Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization ( r=0.83; P<0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization ( r=0.77; P<0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125; r=0.83; P<0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes. Conclusions- The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for PubMedID 30727840

• DEFUSE 3 Non-DAWN Patients. Stroke Leslie-Mazwi, T. M., Hamilton, S., Mlynash, M., Patel, A. B., Schwamm, L. H., Lansberg, M. G., Marks, M., Hirsch, J. A., Albers, G. W. 2019: STROKEAHA118023310

  Abstract

  Background and Purpose- DAWN (Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) established thrombectomy for patients with emergent large vessel occlusions presenting 6 to 24 hours after symptom onset. Given the greater inclusivity of DEFUSE 3, we evaluated the effect of thrombectomy in DEFUSE 3 patients who would have been excluded from DAWN. Methods- Eligibility criteria of the DAWN trial were applied to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large, National Institutes of Health Stroke Scale (NIHSS) score 6 to 9, and modified Rankin Scale score of 2. Subgroups were compared with the DEFUSE 3 non-DAWN and entire DEFUSE 3 cohorts. Results- There were 71 DEFUSE 3 non-DAWN patients; 31 patients with NIHSS 6 to 9, 33 with core too large, and 13 with premorbid modified Rankin Scale score of 2 (some patients met multiple criteria). For core-too-large patients, median 24-hour infarct volume was 119 mL (interquartile range, 74.6-180) versus 31.5 mL (interquartile range, 17.6-64.3) for core-not-too-large patients ( P<0.001). Complications and functional outcomes were similar between the groups. Thrombectomy in core-too-large patients compared with the remaining DEFUSE 3 non-DAWN patients conveyed benefit for functional outcome (odds ratio, 20.9; CI, 1.3-337.8). Comparing the NIHSS 6 to 9 group with the NIHSS ≥10 patients, modified Rankin Scale score 0 to 2 outcomes were achieved in 74% versus 22% ( P<0.001), with mortality in 6% versus 23% ( P=0.024), respectively. For patients with NIHSS 6 to 9 compared with the remaining DEFUSE 3 non-DAWN patients, thrombectomy trended toward a better chance of functional outcome (odds ratio, 1.86; CI, 0.36-9.529). Conclusions- Patients with pretreatment core infarct volumes <70 mL but too large for inclusion by DAWN criteria demonstrate benefit from endovascular therapy. More permissive pretreatment core thresholds in core-clinical mismatch selection paradigms may be appropriate. In contrast to data supporting a beneficial treatment effect across the full range of NIHSS scores in the entire DEFUSE 3 population, only a trend toward benefit of thrombectomy in patients with NIHSS 6 to 9 was found in this small subgroup.

  View details for PubMedID 30727856

• Results From DEFUSE 3. Stroke de Havenon, A., Mlynash, M., Kim-Tenser, M. A., Lansberg, M. G., Leslie-Mazwi, T., Christensen, S., McTaggart, R. A., Alexander, M., Albers, G., Broderick, J., Marks, M. P., Heit, J. J., DEFUSE 3 Investigators 2019: STROKEAHA118023407

  Abstract

  Background and Purpose- The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. We sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window. Methods- This is a prespecified analysis of DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). We included patients with computed tomography angiography as their baseline imaging and rated collateral status using the validated scales described by Tan and Maas. The primary outcome is functional independence (modified Rankin scale score of ≤2). Additional outcomes include the full range of the modified Rankin scale, baseline ischemic core volume, change from baseline in the ischemic core volume at 24 hours, and death at 90 days. Results- Of the 130 patients in our cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis (30% versus 39%; P=0.3) or after adjustment for treatment arm (odds ratio [95% CI], 0.61 [0.26-1.45]). Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant ( P=0.8). Collateral status also did not affect the rate of stroke-related death (n [%], good versus poor collaterals, 18/97 [19%] versus 8/33 [24%], P=0.5]. Conclusions- In DEFUSE 3 patients, good leptomeningeal collaterals on single phase computed tomography angiography were not predictive of functional independence or death and did not impact the treatment effect of endovascular thrombectomy. These unexpected findings require further study to confirm their validity and to better understand the role of collaterals for stroke patients with anterior circulation large vessel occlusion in the late therapeutic window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

  View details for PubMedID 30726184

• DEFUSE 3 Trial Outcomes not Affected by the Enrollment Rates of the Participating Centers. Mlynash, M., Lansberg, M. G., Kemp, S., Christensen, S., Heit, J. J., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733402235

• Ischemic Core Volume Modifies the Association Between ASPECT Score and Clinical Outcome. Sarraj, A., Hassan, A., Grotta, J., Sitton, C., Chen, P. R., Cai Chunyan, Cutter, G., Pujara, D., Imam, B., Reddy, S., Kamal, H., Abraham, M., McCullough, L., Lansberg, M., Savitz, S., Albers, G., Gupta, R. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733403006

• Early Infarct Growth Correlates With Both Collateral Status and Clinical Outcomes After Thrombecomy Sarraj, A., Savitz, S., Sitton, C., Hassan, A., Cai Chunyuan, Pujara, D., Grotta, J., Imam, B., Chen, P. R., Cutter, G., Reddy, S., Kamal, H., Abraham, M., McCullough, L., Lansberg, M., Gupta, R., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400160

• Comparison of Predicted vs. Actual Enrollment Into the NIH StrokeNet DEFUSE 3 Trial: Effectiveness of a Population-Based Epidemiology Feasibility Assessment in Improving Enrollment Into Clinical Trials. Kleindorfer, D. O., Moomaw, C. J., Mlynash, M., Broderick, J. P., Khatri, P., Saver, J. L., Alwell, K., Kemp, S., Janis, S., Moy, C., Woo, D., Flaherty, M. L., Ferioli, S., Adeoye, O., Kissela, B. M., Lansberg, M., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733401331

• Baseline Perfusion Imaging Collateral Scores Predict Infarct Growth in DEFUSE 3 MacLellan, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Michael, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400155

• Deep Learning Based Prediction of Tissue Status From Native CT Perfusion Images. Robben, D., Christensen, S., Boers, A. M., Marquering, H. A., Majoie, C. B., van Oostenbrugge, R. J., Roos, Y. B., Dippel, D. W., van Zwam, W. H., van der Lugt, A., Lansberg, M. G., Albers, G. W., Suetens, P., Lemmens, R. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733401351

• Endovascular Thrombectomy May Be Safe and Effective in Patients With Large Core Lesions on Either Simple CT or Perfusion Images Sarraj, A., Hassan, A., Grotta, J., Sitton, C., Chen, P. R., Vora, N., Cai Chuyan, Cutter, G., Pujara, D., Imam, B., Reddy, S., Kamal, H., Abraham, M., McCullough, L., Lansberg, M., Savitz, S., Gupta, R., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400005

• Evaluating the Generalizability of the Common Odds Ratio: A Demonstration using Two Trials of Endovascular Therapy. Yeatts, S. D., Mlynash, M., Lavori, P. W., Albers, G. W., Lansberg, M. G., Broderick, J. P., Palesch, Y. Y., Hamilton, S. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733401165

• Endovascular Thrombectomy May Be Safe and Effective in Patients With Large Core and Early Presentation Sarraj, A., Hassan, A., Sitton, C., Chen, P. R., Cai Chunyan, Cutter, G., Pujara, D., Imam, B., Reddy, S., Kamal, H., Gutierrez, O., Abraham, M., Edgell, R., McCullough, L., Savitz, S., Albers, G., Gupta, R., Grotta, J. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400110

• Optimizing CT Perfusion Thresholds for Identification of Ischemic Core in Hyperacute Stroke. Legault, C., Lansberg, M., Heit, J., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733401337

• Late Window Transfer Patients had Favorable Outcomes Following Thrombectomy in DEFUSE 3 Sarraj, A., Mlynash, M., Heit, J., Marks, M., Lansberg, M., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400112

• Selection Criteria for Thrombectomy in Pediatric Stroke: A Single-Center Series Lee, S., Heit, J. J., Albers, G. W., Wintermark, M., Elbers, J., Bernier, E., Jiang, B., Marks, M. P., Do Huy, M., Dodd, R. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733401386

• A Closer Look at Late Window Thrombectomy Selection Lesile-Mazwi, T. M., Hamilton, S., Mlynash, M., Patel, A. B., Schwamm, L. H., Lansberg, M. G., Marks, M. P., Hirsch, J. A., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733401369

• CT Perfusion Collateral Score Predicts Which Patients Will Maintain a Penumbral Profile on MRI for Greater than 24 Hours Christensen, S., Mlynash, M., Kemp, S., Yennu, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G., DEFUSE 3 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400161

• Correlation between Modified Rankin Scale and Quality of Life in DEFUSE 3 Polding, L. C., Tate, W. J., Mlynash, M., Marks, M. P., Heit, J. J., Kemp, S., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400174

• Combination of Tmax and Relative CBV Perfusion Parameters More Accurately Predicts CTA Collaterals Than a Single Perfusion Parameter in DEFUSE 3. Mlynash, M., Lansberg, M. G., Kemp, S., Christensen, S., Yennu, A., Heit, J. J., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733403010

• Union of Ischemic Core and Hypoperfusion Volume Correlates With 24-hour Infarct Size in DEFUSE 3 Rao, V., Christensen, S., Yennu, A., Mylnash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733402495

• Later Imaging More Accurately Captures Infarct Growth in DEFUSE 3 Tate, W. J., Polding, L. C., Christensen, S., Mlynash, M., Heit, J. J., Marks, M. M., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733402494

• Early Dramatic Improvement on the National Institutes of Health Stroke Scale Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study. Heit, J. J., Mlynash, M., Kemp, S., Lansberg, M. G., Christiansen, S., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733402332

• Improved Quality of Life With Endovascular Therapy in the DEFUSE 3 Trial Polding, L. C., Tate, W. J., Mlynash, M., Marks, M. P., Heit, J. J., Kemp, S., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400006

• Thrombectomy Results in Reduced Hospital Stay, More Time at Home, and More Favorable Living Situations for Patients in the DEFUSE 3 Trial. Tate, W. J., Polding, L. C., Kemp, S., Mlynash, M., Heit, J. J., Marks, M. P., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400173

• Results From the DEFUSE 3 Trial: Good Leptomeningeal Collaterals Are Associated With Reduced Core Infarct Size but Not Improved Neurologic Outcome de Havenon, A., Mlynash, M., Kim-Tenser, M. A., Lansberg, M., Leslie-Mazwi, T., Christensen, S., McTaggart, R., Alexander, M., Albers, G., Broderick, J., Marks, M. P., Heit, J., DEFUSE 3 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000478733400007

• Association of Thrombectomy With Stroke Outcomes Among Patient Subgroups: Secondary Analyses of the DEFUSE 3 Randomized Clinical Trial. JAMA neurology Lansberg, M. G., Mlynash, M., Hamilton, S., Yeatts, S. D., Christensen, S., Kemp, S., Lavori, P. W., Gutierrez, S. O., Broderick, J., Heit, J., Marks, M. P., Albers, G. W., DEFUSE 3 Investigators 2019

  Abstract

  Importance: The DEFUSE 3 randomized clinical trial previously demonstrated benefit of endovascular thrombectomy for acute ischemic stroke in the 6- to 16-hour time window. For treatment recommendations, it is important to know if the treatment benefit was universal.Objective: To determine the outcomes among patients who may have a reduced effect of thrombectomy, including those who are older, have milder symptoms, or present late.Design, Setting, and Participants: DEFUSE 3 was a randomized, open-label, blinded end point trial conducted from May 2016 to May 2017. This multicenter study included 38 sites in the United States. Of 296 patients who were enrolled in DEFUSE 3, 182 patients met all inclusion criteria and were randomized and included in the intention-to-treat analysis, which was conducted in August 2017. These patients had acute ischemic strokes due to an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion computed tomography or magnetic resonance imaging. The study was stopped early for efficacy.Interventions: Endovascular thrombectomy plus medical management vs medical management alone.Main Outcomes and Measures: Functional outcome at day 90, assessed on the modified Rankin Scale. Multivariate ordinal logistic regression was used to calculate the adjusted proportional association between endovascular treatment and clinical outcome (shift in the distribution of modified Rankin Scale scores expressed as a common odds ratio) among patients of different ages, baseline stroke severities, onset-to-treatment times, locations of the arterial occlusion, and imaging modalities used to document the presence of salvageable tissue (computed tomography vs magnetic resonance imaging).Results: This study included 182 patients (median [interquartile range] age, 70 [59-80] years; median [interquartile range] National Institutes of Health Stroke Scale score, 16 [11-21], and 92 women [51%]). In the overall cohort, independent predictors of better functional outcome were younger age, lower baseline National Institutes of Health Stroke Scale score, and lower serum glucose level. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1 (95% CI, 1.8-5.4). There was no significant interaction between this treatment effect and age (P=.93), National Institutes of Health Stroke Scale score (P=.87), time to randomization (P=.56), imaging modality (P=.49), or location of the arterial occlusion (P=.54).Conclusions and Relevance: Endovascular thrombectomy, initiated up to 16 hours after last known well time in patients with salvageable tissue on perfusion imaging, benefits patients with a broad range of clinical features. Owing to the small sample size of this study, a pooled analysis of late time window endovascular stroke trials is needed to confirm these results.Trial Registration: ClinicalTrials.gov identifier: NCT02586415.

  View details for PubMedID 30688974

• Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke. JAMA neurology Boers, A. M., Jansen, I. G., Brown, S., Lingsma, H. F., Beenen, L. F., Devlin, T. G., Roman, L. S., Heo, J., Ribo, M., Almekhlafi, M. A., Liebeskind, D. S., Teitelbaum, J., Cuadras, P., du Mesnil de Rochemont, R., Beaumont, M., Brown, M. M., Yoo, A. J., Donnan, G. A., Mas, J. L., Oppenheim, C., Dowling, R. J., Moulin, T., Agrinier, N., Lopes, D. K., Aja Rodriguez, L., Compagne, K. C., Al-Ajlan, F. S., Madigan, J., Albers, G. W., Soize, S., Blasco, J., Davis, S. M., Nogueira, R. G., Davalos, A., Menon, B. K., van der Lugt, A., Muir, K. W., Roos, Y. B., White, P., Mitchell, P. J., Demchuk, A. M., van Zwam, W. H., Jovin, T. G., van Oostenbrugge, R. J., Dippel, D. W., Campbell, B. C., Guillemin, F., Bracard, S., Hill, M. D., Goyal, M., Marquering, H. A., Majoie, C. B. 2019

  Abstract

  Importance: The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke.Objective: To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke.Design, Setting, and Participants: Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017.Main Outcome and Measure: The 90-day functional outcome via the modified Rankin Scale (mRS).Results: Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P=.007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P<.001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P<.001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome.Conclusions and Relevance: In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.

  View details for PubMedID 30615038

• Thrombectomy with Conscious Sedation Compared with General Anesthesia: A DEFUSE 3 Analysis. AJNR. American journal of neuroradiology Powers, C. J., Dornbos, D. n., Mlynash, M. n., Gulati, D. n., Torbey, M. n., Nimjee, S. M., Lansberg, M. G., Albers, G. W., Marks, M. P. 2019

  Abstract

  The optimal patient sedation during mechanical thrombectomy for ischemic stroke in the extended time window is unknown. The purpose of this study was to assess the impact of patient sedation on outcome in patients undergoing thrombectomy 6-16 hours from stroke onset.Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) was a multicenter, randomized, open-label trial of thrombectomy for ICA and M1 occlusions in patients 6-16 hours from stroke onset. Subjects underwent thrombectomy with either general anesthesia or conscious sedation at the discretion of the treating institution.Of the 92 patients who were randomized to intervention, 26 (28%) underwent thrombectomy with general anesthesia and 66 (72%) underwent thrombectomy with conscious sedation. Baseline clinical and imaging characteristics were similar among all groups. Functional independence at 90 days was 23% for general anesthesia, 53% for conscious sedation, and 17% for medical management (P = .009 for general anesthesia versus conscious sedation). Conscious sedation was associated with a shorter time from arrival in the angiosuite to femoral puncture (median, 14 versus 18 minutes; P = 0.05) and a shorter time from femoral puncture to reperfusion (median, 36 versus 48 minutes; P = .004). Sixty-six patients were treated at sites that exclusively used general anesthesia (n = 14) or conscious sedation (n = 52). For these patients, functional independence at 90 days was significantly higher in the conscious sedation subgroup (58%) compared with the general anesthesia subgroup (21%) (P = .03).Patients who underwent thrombectomy with conscious sedation in the extended time window experienced a higher likelihood of functional independence at 90 days, a lower NIHSS score at 24 hours, and a shorter time from femoral puncture to reperfusion compared with those who had general anesthesia. This effect remained robust in institutions that only treated patients with a single anesthesia technique.

  View details for PubMedID 31072970

• Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort. Stroke Dula, A. N., Mlynash, M. n., Zuck, N. D., Albers, G. W., Warach, S. J. 2019: STROKEAHA119028205

  Abstract

  Background and Purpose- Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). Methods- DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results- All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9-18.4) in women versus 12.6 mL (2.7-29.6) in men, for Tmax>6 seconds 89.0 mL (63.8-131.7) versus 133.9 mL (87.0-175.4), and for mismatch 82.1mL (53.8-112.8) versus 108.2 (64.1-149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15-0.46) versus 0.39 (0.26-0.57), P=0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (P=0.003). Conclusions- In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

  View details for DOI 10.1161/STROKEAHA.119.028205

  View details for PubMedID 31826731

• Factors that may contribute to poor outcome despite good reperfusion after acute endovascular stroke therapy INTERNATIONAL JOURNAL OF STROKE Rabinstein, A. A., Albers, G. W., Brinjikji, W., Koch, S. 2019; 14 (1): 23–31

  Abstract

  Endovascular therapy with mechanical thrombectomy is a formidable treatment for severe acute ischemic stroke caused by occlusion of a proximal intracranial artery. Its strong beneficial effect is explained by the high rates of very good and excellent reperfusion achieved with current endovascular techniques. However, there is a sizable proportion of patients who do not experience clinical improvement despite successful recanalization of the occluded artery and reperfusion of the ischemic territory. Factors such as baseline reserve, collateral flow, anesthesia and systemic factors have been identified as potential culprits for lack of improvement in the setting of timely and successful revascularization. Older age, baseline disability and perhaps radiological markers of chronic brain injury can affect the prognosis of patients treated with endovascular therapy. Collateral flow is a major determinant of outcome after endovascular therapy and it is manifested by the size of the core in relation to the volume of the salvageable tissue. Parenchymal and vascular imaging can help assess the quality of collateral flow, but the optimal radiological strategy for daily practice (i.e. the optimal combination of rapid availability and diagnostic precision) has not been established. A sizable body of observational evidence indicates that acute hypertension, hyperglycemia and fever are associated with worse outcomes after a stroke even after optimal reperfusion with endovascular therapy. Lastly, current randomized controlled trials in anesthesia for stroke demonstrate similar rates of good functional outcome between general anesthesia and conscious sedation suggesting equipoise exists.

  View details for PubMedID 30188259

• Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial. International journal of stroke : official journal of the International Stroke Society Easton, J. D., Denison, H. n., Evans, S. R., Knutsson, M. n., Amarenco, P. n., Albers, G. W., Ladenvall, P. n., Minematsu, K. n., Molina, C. A., Wang, Y. n., Wong, K. L., Johnston, S. C. 2019: 1747493019851282

  Abstract

  Adjudication of endpoints is a standard procedure in cardiovascular clinical trials. However, several studies indicate that the benefit of adjudication in estimating treatment effect may be limited.This post hoc analysis of SOCRATES (NCT01994720) compared the treatment effects and investigated the agreement of clinical event assessment by site investigators and independent adjudicators.SOCRATES compared ticagrelor and aspirin in 13,199 patients with acute minor stroke or high-risk transient ischemic attack. The primary endpoint was stroke, myocardial infarction, or death. Stroke was the major component of the primary endpoint and a secondary endpoint. The endpoints were adjudicated by a blinded independent committee. We compared the treatment effect on the primary endpoint and stroke alone based on the investigators' and adjudicators' assessments, and investigated the agreement rate on the stroke endpoint and major hemorrhages.The hazard ratios (95% confidence interval) for ticagrelor versus aspirin therapy for the primary endpoint were 0.89 (0.78-1.01) when calculated on adjudicator-assessed events and 0.88 (0.78-1.00) for investigator-assessed events. The hazard ratios (95% confidence intervals) for stroke were 0.86 (0.75-0.99) based on the adjudicators' diagnoses and 0.85 (0.75-0.97) based on the investigators' diagnoses. The overall agreement between adjudicator- and investigator-diagnosed stroke was 91%, and for major hemorrhages was 88%.In SOCRATES, there was no clinically meaningful difference in the estimated treatment effect, on either the primary endpoint or stroke, by using investigator- or adjudicator-assessed events. Double-blind treatment outcome studies with stroke endpoints may not benefit from adjudication.ClinicalTrials.gov Identifier: NCT01994720.

  View details for PubMedID 31092152

• Artificial Neural Network Computer Tomography Perfusion Prediction of Ischemic Core. Stroke Kasasbeh, A. S., Christensen, S. n., Parsons, M. W., Campbell, B. n., Albers, G. W., Lansberg, M. G. 2019: STROKEAHA118022649

  Abstract

  Background and Purpose- Computed tomography perfusion (CTP) is a useful tool in the evaluation of acute ischemic stroke, where it can provide an estimate of the ischemic core and the ischemic penumbra. The optimal CTP parameters to identify the ischemic core remain undetermined. Methods- We used artificial neural networks (ANNs) to optimally predict the ischemic core in acute stroke patients, using diffusion-weighted imaging as the gold standard. We first designed an ANN based on CTP data alone and next designed an ANN based on clinical and CTP data. Results- The ANN based on CTP data predicted the ischemic core with a mean absolute error of 13.8 mL (SD, 13.6 mL) compared with diffusion-weighted imaging. The area under the receiver operator characteristic curve was 0.85. At the optimal threshold, the sensitivity for predicting the ischemic core was 0.90 and the specificity was 0.62. Combining CTP data with clinical data available at time of presentation resulted in the same mean absolute error (13.8 mL) but lower SD (12.4 mL). The area under the curve, sensitivity, and specificity were 0.87, 0.91, and 0.65, respectively. The maximal Dice coefficient was 0.48 in the ANN based on CTP data exclusively. Conclusions- An ANN that integrates clinical and CTP data predicts the ischemic core with accuracy.

  View details for PubMedID 31092162

• Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience. Journal of neurointerventional surgery Lee, S. n., Heit, J. J., Albers, G. W., Wintermark, M. n., Jiang, B. n., Bernier, E. n., Fischbein, N. J., Mlynash, M. n., Marks, M. P., Do, H. M., Dodd, R. L. 2019

  Abstract

  The extended time window for endovascular therapy in adult stroke represents an opportunity for stroke treatment in children for whom diagnosis may be delayed. However, selection criteria for pediatric thrombectomy has not been defined.We performed a retrospective cohort study of patients aged <18 years presenting within 24 hours of acute large vessel occlusion. Patient consent was waived by our institutional IRB. Patient data derived from our institutional stroke database was compared between patients with good and poor outcome using Fisher's exact test, t-test, or Mann-Whitney U-test.Twelve children were included: 8/12 (66.7%) were female, mean age 9.7±5.0 years, median National Institutes of Health Stroke Scale (NIHSS) 11.5 (IQR 10-14). Stroke etiology was cardioembolic in 75%, dissection in 16.7%, and cryptogenic in 8.3%. For 2/5 with perfusion imaging, Tmax >4 s appeared to better correlate with NIHSS. Nine patients (75%) were treated: seven underwent thrombectomy alone; one received IV alteplase and thrombectomy, and one received IV alteplase alone. Favorable outcome was achieved in 78% of treated patients versus 0% of untreated patients (P=0.018). All untreated patients had poor outcome, with death (n=2) or severe disability (n=1) at follow-up. Among treated patients, older children (12.8±2.9 vs 4.2±5.0 years, P=0.014) and children presenting as outpatient (100% vs 0%, P=0.028) appeared to have better outcomes.Perfusion imaging is feasible in pediatric stroke and may help identify salvageable tissue in extended time windows, though penumbral thresholds may differ from adult values. Further studies are needed to define criteria for thrombectomy in this unique population.

  View details for PubMedID 31097548

• Comparison of T2*GRE and DSC-PWI for hemorrhage detection in acute ischemic stroke patients: Pooled analysis of the EPITHET, DEFUSE 2, and SENSE 3 stroke studies. International journal of stroke : official journal of the International Stroke Society Amukotuwa, S. A., Fischbein, N. J., Albers, G. W., Davis, S. n., Donnan, G. A., Andre, J. B., Bammer, R. n. 2019: 1747493019858781

  Abstract

  The objective of this study was to compare the diagnostic performance of the baseline pre-contrast images of dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) with conventional T2*gradient recalled echo (GRE) imaging for detection of hemorrhage in acute ischemic stroke patients.T2*GRE and DSC-PWI from 393 magnetic resonance imaging scans from 221 patients enrolled in three prospective stroke studies were independently evaluated by two readers blinded to clinical and other imaging data. Agreement between T2*GRE and DSC-PWI for the presence of hemorrhage, and acute hemorrhagic transformation, was assessed using the kappa statistic. Inter-reader agreement was also assessed using the kappa statistic.Agreement between the baseline images of DSC-PWI and T2*GRE regarding the presence of hemorrhage was almost perfect (kreader 1 : 0.90, 95% confidence interval 0.86-0.95 and kreader 2 : 0.91, 95% confidence interval 0.87-0.96). Agreement between the sequences was still higher for detection of acute hemorrhagic transformation (kreader 1 : 0.94, 95% confidence interval 0.91-0.98 and kreader 2 : 0.95, 95% confidence interval 0.92-0.98). Inter-reader agreement for detection of hemorrhage was also almost perfect for both T2*GRE (k: 0.95, 95% confidence interval 0.91-0.98) and DSC-PWI (k: 0.96, 95% confidence interval 0.93-0.99). Acute hemorrhagic transformation detected on T2*GRE was missed on DSC-PWI by one or both readers in 5/393 (1.3%) scans.The almost perfect statistical agreement between DSC-PWI and conventional T2*GRE suggests that DSC-PWI is sufficient for hemorrhage screening prior to thrombolysis in stroke patients. T2*GRE can therefore be omitted when DSC-PWI is included, thereby shortening the acute ischemic stroke magnetic resonance imaging protocol and expediting treatment. Trial registration: ClinicalTrials.gov Identifier: NCT02586415.

  View details for DOI 10.1177/1747493019858781

  View details for PubMedID 31291850

• Thrombectomy for acute ischemic stroke in nonagenarians compared with octogenarians. Journal of neurointerventional surgery Sussman, E. S., Martin, B. n., Mlynash, M. n., Marks, M. P., Marcellus, D. n., Albers, G. n., Lansberg, M. n., Dodd, R. n., Do, H. M., Heit, J. J. 2019

  Abstract

  Multiple randomized trials have shown that endovascular thrombectomy (EVT) leads to improved outcomes in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Elderly patients were poorly represented in these trials, and the efficacy of EVT in nonagenarian patients remains uncertain.We performed a retrospective cohort study at a single center. Inclusion criteria were: age 80-99, LVO, core infarct <70 mL, and salvageable penumbra. Patients were stratified into octogenarian (80-89) and nonagenarian (90-99) cohorts. The primary outcome was the ordinal score on the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included dichotomized functional outcome (mRS ≤2 vs mRS ≥3), successful revascularization, symptomatic intracranial hemorrhage (ICH), and mortality.108 patients met the inclusion criteria, including 79 octogenarians (73%) and 29 nonagenarians (27%). Nonagenarians were more likely to be female (86% vs 58%; p<0.01); there were no other differences between groups in terms of demographics, medical comorbidities, or treatment characteristics. Successful revascularization (TICI 2b-3) was achieved in 79% in both cohorts. Median mRS at 90 days was 5 in octogenarians and 6 in nonagenarians (p=0.09). Functional independence (mRS ≤2) at 90 days was achieved in 12.5% and 19.7% of nonagenarians and octogenarians, respectively (p=0.54). Symptomatic ICH occurred in 21.4% and 6.4% (p=0.03), and 90-day mortality rate was 63% and 40.9% (p=0.07) in nonagenarians and octogenarians, respectively.Nonagenarians may be at higher risk of symptomatic ICH than octogenarians, despite similar stroke- and treatment-related factors. While there was a trend towards higher mortality and worse functional outcomes in nonagenarians, the difference was not statistically significant in this relatively small retrospective study.

  View details for DOI 10.1136/neurintsurg-2019-015147

  View details for PubMedID 31350369

• Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke. Stroke Thamm, T. n., Guo, J. n., Rosenberg, J. n., Liang, T. n., Marks, M. P., Christensen, S. n., Do, H. M., Kemp, S. M., Adair, E. n., Eyngorn, I. n., Mlynash, M. n., Jovin, T. G., Keogh, B. P., Chen, H. J., Lansberg, M. G., Albers, G. W., Zaharchuk, G. n. 2019: STROKEAHA119026499

  Abstract

  Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730.

  View details for DOI 10.1161/STROKEAHA.119.026499

  View details for PubMedID 31619150

• Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials JOURNAL OF NEUROINTERVENTIONAL SURGERY Boers, A. M., Jansen, I. H., Beenen, L. M., Devlin, T. G., San Roman, L., Heo, J., Ribo, M., Brown, S., Almekhlafi, M. A., Liebeskind, D. S., Teitelbaum, J., Lingsma, H. F., van Zwam, W. H., Cuadras, P., de Rochemont, R., Beaumont, M., Brown, M. M., Yoo, A. J., van Oostenbrugge, R. J., Menon, B. K., Donnan, G. A., Mas, J., Roos, Y. M., Oppenheim, C., van der Lugt, A., Dowling, R. J., Hill, M. D., Davalos, A., Moulin, T., Agrinier, N., Demchuk, A. M., Lopes, D. K., Aja Rodriguez, L., Dippel, D. J., Campbell, B. V., Mitchell, P. J., Al-Ajlan, F. S., Jovin, T. G., Madigan, J., Albers, G. W., Soize, S., Guillemin, F., Reddy, V. K., Bracard, S., Blasco, J., Muir, K. W., Nogueira, R. G., White, P. M., Goyal, M., Davis, S. M., Marquering, H. A., Majoie, C. M. 2018; 10 (12): 1137–42

  Abstract

  Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement.To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality.Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated.Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14-120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15-131) vs 22 mL (IQR 8-71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively).In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.

  View details for PubMedID 29627794

• Response by Demeestere et al to Letter Regarding Article, "Alberta Stroke Program Early CT Score Versus Computed Tomographic Perfusion to Predict Functional Outcome After Successful Reperfusion in Acute Ischemic Stroke". Stroke Demeestere, J., Albers, G. W., Lansberg, M., Lemmens, R. 2018: STROKEAHA118023955

  View details for PubMedID 30580744

• Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data. The Lancet. Neurology Campbell, B. C., Majoie, C. B., Albers, G. W., Menon, B. K., Yassi, N., Sharma, G., van Zwam, W. H., van Oostenbrugge, R. J., Demchuk, A. M., Guillemin, F., White, P., Davalos, A., van der Lugt, A., Butcher, K. S., Cherifi, A., Marquering, H. A., Cloud, G., Macho Fernandez, J. M., Madigan, J., Oppenheim, C., Donnan, G. A., Roos, Y. B., Shankar, J., Lingsma, H., Bonafe, A., Raoult, H., Hernandez-Perez, M., Bharatha, A., Jahan, R., Jansen, O., Richard, S., Levy, E. I., Berkhemer, O. A., Soudant, M., Aja, L., Davis, S. M., Krings, T., Tisserand, M., San Roman, L., Tomasello, A., Beumer, D., Brown, S., Liebeskind, D. S., Bracard, S., Muir, K. W., Dippel, D. W., Goyal, M., Saver, J. L., Jovin, T. G., Hill, M. D., Mitchell, P. J., HERMES collaborators, Berkhemer, O. A., Fransen, P. S., Beumer, D., van den Berg, L. A., Lingsma, H. F., Yoo, A. J., Schonewille, W. J., Vos, J. A., Nederkoorn, P. J., Wermer, M. J., van Walderveen, M. A., Staals, J., Hofmeijer, J., van Oostayen, J. A., Lycklama A Nijeholt, G. J., Boiten, J., Brouwer, P. A., Emmer, B. J., de Bruijn, S. F., van Dijk, L. C., Kappelle, J., Lo, R. H., van Dijk, E. J., de Vries, J., de Kort, P. L., van Rooij, W. J., van den Berg, J. S., van Hasselt, B. A., Aerden, L. A., Dallinga, R. J., Visser, M. C., Bot, J. C., Vroomen, P. C., Eshghi, O., Schreuder, T. H., Heijboer, R. J., Keizer, K., Tielbeek, A. V., den Hertog, H. M., Gerrits, D. G., van den Berg-Vos, R. M., Karas, G. B., Steyerberg, E. W., Flach, Z., Marquering, H. A., Sprengers, M. E., Jenniskens, S. F., Beenen, L. F., van den Berg, R., Koudstaal, P. J., van Zwam, W. H., Roos, Y. B., van der Lugt, A., van Oostenbrugge, R. J., Majoie, C. B., Dippel, D. W., Brown, M. M., Liebig, T., Stijnen, T., Andersson, T., Mattle, H., Wahlgren, N., van der Heijden, E., Ghannouti, N., Fleitour, N., Hooijenga, I., Puppels, C., Pellikaan, W., Geerling, A., Lindl-Velema, A., van Vemde, G., de Ridder, A., Greebe, P., de Bont-Stikkelbroeck, J., de Meris, J., Janssen, K., Struijk, W., Licher, S., Boodt, N., Ros, A., Venema, E., Slokkers, I., Ganpat, R., Mulder, M., Saiedie, N., Heshmatollah, A., Schipperen, S., Vinken, S., van Boxtel, T., Koets, J., Boers, M., Santos, E., Borst, J., Jansen, I., Kappelhof, M., Lucas, M., Geuskens, R., Barros, R. S., Dobbe, R., Csizmadia, M., Hill, M. D., Goyal, M., Demchuk, A. M., Menon, B. K., Eesa, M., Ryckborst, K. J., Wright, M. R., Kamal, N. R., Andersen, L., Randhawa, P. A., Stewart, T., Patil, S., Minhas, P., Almekhlafi, M., Mishra, S., Clement, F., Sajobi, T., Shuaib, A., Montanera, W. J., Roy, D., Silver, F. L., Jovin, T. G., Frei, D. F., Sapkota, B., Rempel, J. L., Thornton, J., Williams, D., Tampieri, D., Poppe, A. Y., Dowlatshahi, D., Wong, J. H., Mitha, A. P., Subramaniam, S., Hull, G., Lowerison, M. W., Sajobi, T., Salluzzi, M., Wright, M. R., Maxwell, M., Lacusta, S., Drupals, E., Armitage, K., Barber, P. A., Smith, E. E., Morrish, W. F., Coutts, S. B., Derdeyn, C., Demaerschalk, B., Yavagal, D., Martin, R., Brant, R., Yu, Y., Willinsky, R. A., Montanera, W. J., Weill, A., Kenney, C., Aram, H., Stewart, T., Stys, P. K., Watson, T. W., Klein, G., Pearson, D., Couillard, P., Trivedi, A., Singh, D., Klourfeld, E., Imoukhuede, O., Nikneshan, D., Blayney, S., Reddy, R., Choi, P., Horton, M., Musuka, T., Dubuc, V., Field, T. S., Desai, J., Adatia, S., Alseraya, A., Nambiar, V., van Dijk, R., Wong, J. H., Mitha, A. P., Morrish, W. F., Eesa, M., Newcommon, N. J., Shuaib, A., Schwindt, B., Butcher, K. S., Jeerakathil, T., Buck, B., Khan, K., Naik, S. S., Emery, D. J., Owen, R. J., Kotylak, T. B., Ashforth, R. A., Yeo, T. A., McNally, D., Siddiqui, M., Saqqur, M., Hussain, D., Kalashyan, H., Manosalva, A., Kate, M., Gioia, L., Hasan, S., Mohammad, A., Muratoglu, M., Williams, D., Thornton, J., Cullen, A., Brennan, P., O'Hare, A., Looby, S., Hyland, D., Duff, S., McCusker, M., Hallinan, B., Lee, S., McCormack, J., Moore, A., O'Connor, M., Donegan, C., Brewer, L., Martin, A., Murphy, S., O'Rourke, K., Smyth, S., Kelly, P., Lynch, T., Daly, T., O'Brien, P., O'Driscoll, A., Martin, M., Daly, T., Collins, R., Coughlan, T., McCabe, D., Murphy, S., O'Neill, D., Mulroy, M., Lynch, O., Walsh, T., O'Donnell, M., Galvin, T., Harbison, J., McElwaine, P., Mulpeter, K., McLoughlin, C., Reardon, M., Harkin, E., Dolan, E., Watts, M., Cunningham, N., Fallon, C., Gallagher, S., Cotter, P., Crowe, M., Doyle, R., Noone, I., Lapierre, M., Cote, V. A., Lanthier, S., Odier, C., Durocher, A., Raymond, J., Weill, A., Daneault, N., Deschaintre, Y., Jankowitz, B., Baxendell, L., Massaro, L., Jackson-Graves, C., Decesare, S., Porter, P., Armbruster, K., Adams, A., Billigan, J., Oakley, J., Ducruet, A., Jadhav, A., Giurgiutiu, D., Aghaebrahim, A., Reddy, V., Hammer, M., Starr, M., Totoraitis, V., Wechsler, L., Streib, S., Rangaraju, S., Campbell, D., Rocha, M., Gulati, D., Silver, F. L., Krings, T., Kalman, L., Cayley, A., Williams, J., Stewart, T., Wiegner, R., Casaubon, L. K., Jaigobin, C., Del Campo, J. M., Elamin, E., Schaafsma, J. D., Willinsky, R. A., Agid, R., Farb, R., Ter Brugge, K., Sapkoda, B. L., Baxter, B. W., Barton, K., Knox, A., Porter, A., Sirelkhatim, A., Devlin, T., Dellinger, C., Pitiyanuvath, N., Patterson, J., Nichols, J., Quarfordt, S., Calvert, J., Hawk, H., Fanale, C., Frei, D. F., Bitner, A., Novak, A., Huddle, D., Bellon, R., Loy, D., Wagner, J., Chang, I., Lampe, E., Spencer, B., Pratt, R., Bartt, R., Shine, S., Dooley, G., Nguyen, T., Whaley, M., McCarthy, K., Teitelbaum, J., Tampieri, D., Poon, W., Campbell, N., Cortes, M., Dowlatshahi, D., Lum, C., Shamloul, R., Robert, S., Stotts, G., Shamy, M., Steffenhagen, N., Blacquiere, D., Hogan, M., AlHazzaa, M., Basir, G., Lesiuk, H., Iancu, D., Santos, M., Choe, H., Weisman, D. C., Jonczak, K., Blue-Schaller, A., Shah, Q., MacKenzie, L., Klein, B., Kulandaivel, K., Kozak, O., Gzesh, D. J., Harris, L. J., Khoury, J. S., Mandzia, J., Pelz, D., Crann, S., Fleming, L., Hesser, K., Beauchamp, B., Amato-Marzialli, B., Boulton, M., Lopez-Ojeda, P., Sharma, M., Lownie, S., Chan, R., Swartz, R., Howard, P., Golob, D., Gladstone, D., Boyle, K., Boulos, M., Hopyan, J., Yang, V., Da Costa, L., Holmstedt, C. A., Turk, A. S., Navarro, R., Jauch, E., Ozark, S., Turner, R., Phillips, S., Shankar, J., Jarrett, J., Gubitz, G., Maloney, W., Vandorpe, R., Schmidt, M., Heidenreich, J., Hunter, G., Kelly, M., Whelan, R., Peeling, L., Burns, P. A., Hunter, A., Wiggam, I., Kerr, E., Watt, M., Fulton, A., Gordon, P., Rennie, I., Flynn, P., Smyth, G., O'Leary, S., Gentile, N., Linares, G., McNelis, P., Erkmen, K., Katz, P., Azizi, A., Weaver, M., Jungreis, C., Faro, S., Shah, P., Reimer, H., Kalugdan, V., Saposnik, G., Bharatha, A., Li, Y., Kostyrko, P., Santos, M., Marotta, T., Montanera, W., Sarma, D., Selchen, D., Spears, J., Heo, J. H., Jeong, K., Kim, D. J., Kim, B. M., Kim, Y. D., Song, D., Lee, K., Yoo, J., Bang, O. Y., Rho, S., Lee, J., Jeon, P., Kim, K. H., Cha, J., Kim, S. J., Ryoo, S., Lee, M. J., Sohn, S., Kim, C., Ryu, H., Hong, J., Chang, H., Lee, C., Rha, J., Davis, S. M., Donnan, G. A., Campbell, B. C., Mitchell, P. J., Churilov, L., Yan, B., Dowling, R., Yassi, N., Oxley, T. J., Wu, T. Y., Silver, G., McDonald, A., McCoy, R., Kleinig, T. J., Scroop, R., Dewey, H. M., Simpson, M., Brooks, M., Coulton, B., Krause, M., Harrington, T. J., Steinfort, B., Faulder, K., Priglinger, M., Day, S., Phan, T., Chong, W., Holt, M., Chandra, R. V., Ma, H., Young, D., Wong, K., Wijeratne, T., Tu, H., Mackay, E., Celestino, S., Bladin, C. F., Loh, P. S., Gilligan, A., Ross, Z., Coote, S., Frost, T., Parsons, M. W., Miteff, F., Levi, C. R., Ang, T., Spratt, N., Kaauwai, L., Badve, M., Rice, H., de Villiers, L., Barber, P. A., McGuinness, B., Hope, A., Moriarty, M., Bennett, P., Wong, A., Coulthard, A., Lee, A., Jannes, J., Field, D., Sharma, G., Salinas, S., Cowley, E., Snow, B., Kolbe, J., Stark, R., King, J., Macdonnell, R., Attia, J., D'Este, C., Saver, J. L., Goyal, M., Diener, H. C., Levy, E. I., Bonafe, A., Mendes Pereira, V., Jahan, R., Albers, G. W., Cognard, C., Cohen, D. J., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., von Kummer, R., Smith, W., Turjman, F., Hamilton, S., Chiacchierini, R., Amar, A., Sanossian, N., Loh, Y., Devlin, T., Baxter, B., Hawk, H., Sapkota, B., Quarfordt, S., Sirelkhatim, A., Dellinger, C., Barton, K., Reddy, V. K., Ducruet, A., Jadhav, A., Horev, A., Giurgiutiu, D., Totoraitis, V., Hammer, M., Jankowitz, B., Wechsler, L., Rocha, M., Gulati, D., Campbell, D., Star, M., Baxendell, L., Oakley, J., Siddiqui, A., Hopkins, L. N., Snyder, K., Sawyer, R., Hall, S., Costalat, V., Riquelme, C., Machi, P., Omer, E., Arquizan, C., Mourand, I., Charif, M., Ayrignac, X., Menjot de Champfleur, N., Leboucq, N., Gascou, G., Moynier, M., du Mesnil de Rochemont, R., Singer, O., Berkefeld, J., Foerch, C., Lorenz, M., Pfeilschifer, W., Hattingen, E., Wagner, M., You, S. J., Lescher, S., Braun, H., Dehkharghani, S., Belagaje, S. R., Anderson, A., Lima, A., Obideen, M., Haussen, D., Dharia, R., Frankel, M., Patel, V., Owada, K., Saad, A., Amerson, L., Horn, C., Doppelheuer, S., Schindler, K., Lopes, D. K., Chen, M., Moftakhar, R., Anton, C., Smreczak, M., Carpenter, J. S., Boo, S., Rai, A., Roberts, T., Tarabishy, A., Gutmann, L., Brooks, C., Brick, J., Domico, J., Reimann, G., Hinrichs, K., Becker, M., Heiss, E., Selle, C., Witteler, A., Al Boutros, S., Danch, M., Ranft, A., Rohde, S., Burg, K., Weimar, C., Zegarac, V., Hartmann, C., Schlamann, M., Goricke, S., Ringlestein, A., Wanke, I., Monninghoff, C., Dietzold, M., Budzik, R., Davis, T., Eubank, G., Hicks, W. J., Pema, P., Vora, N., Mejilla, J., Taylor, M., Clark, W., Rontal, A., Fields, J., Peterson, B., Nesbit, G., Lutsep, H., Bozorgchami, H., Priest, R., Ologuntoye, O., Barnwell, S., Dogan, A., Herrick, K., Takahasi, C., Beadell, N., Brown, B., Jamieson, S., Hussain, M. S., Russman, A., Hui, F., Wisco, D., Uchino, K., Khawaja, Z., Katzan, I., Toth, G., Cheng Ching, E., Bain, M., Man, S., Farrag, A., George, P., John, S., Shankar, L., Drofa, A., Dahlgren, R., Bauer, A., Itreat, A., Taqui, A., Cerejo, R., Richmond, A., Ringleb, P., Bendszus, M., Mohlenbruch, M., Reiff, T., Amiri, H., Purrucker, J., Herweh, C., Pham, M., Menn, O., Ludwig, I., Acosta, I., Villar, C., Morgan, W., Sombutmai, C., Hellinger, F., Allen, E., Bellew, M., Gandhi, R., Bonwit, E., Aly, J., Ecker, R. D., Seder, D., Morris, J., Skaletsky, M., Belden, J., Baker, C., Connolly, L. S., Papanagiotou, P., Roth, C., Kastrup, A., Politi, M., Brunner, F., Alexandrou, M., Merdivan, H., Ramsey, C., Given Ii, C., Renfrow, S., Deshmukh, V., Sasadeusz, K., Vincent, F., Thiesing, J. T., Putnam, J., Bhatt, A., Kansara, A., Caceves, D., Lowenkopf, T., Yanase, L., Zurasky, J., Dancer, S., Freeman, B., Scheibe Mirek, T., Robison, J., Rontal, A., Roll, J., Clark, D., Rodriguez, M., Fitzsimmons, B., Zaidat, O., Lynch, J. R., Lazzaro, M., Larson, T., Padmore, L., Das, E., Farrow Schmidt, A., Hassan, A., Tekle, W., Cate, C., Jansen, O., Cnyrim, C., Wodarg, F., Wiese, C., Binder, A., Riedel, C., Rohr, A., Lang, N., Laufs, H., Krieter, S., Remonda, L., Diepers, M., Anon, J., Nedeltchev, K., Kahles, T., Biethahn, S., Lindner, M., Chang, V., Gachter, C., Esperon, C., Guglielmetti, M., Arenillas Lara, J. F., Martinez Galdamez, M., Calleja Sanz, A. I., Cortijo Garcia, E., Garcia Bermejo, P., Perez, S., Mulero Carrillo, P., Crespo Vallejo, E., Ruiz Pinero, M., Lopez Mesonero, L., Reyes Munoz, F. J., Brekenfeld, C., Buhk, J., Krutzelmann, A., Thomalla, G., Cheng, B., Beck, C., Hoppe, J., Goebell, E., Holst, B., Grzyska, U., Wortmann, G., Starkman, S., Duckwiler, G., Jahan, R., Rao, N., Sheth, S., Ng, K., Noorian, A., Szeder, V., Nour, M., McManus, M., Huang, J., Tarpley, J., Tateshima, S., Gonzalez, N., Ali, L., Liebeskind, D., Hinman, J., Calderon Arnulphi, M., Liang, C., Guzy, J., Koch, S., DeSousa, K., Gordon Perue, G., Haussen, D., Elhammady, M., Peterson, E., Pandey, V., Dharmadhikari, S., Khandelwal, P., Malik, A., Pafford, R., Gonzalez, P., Ramdas, K., Andersen, G., Damgaard, D., Von Weitzel Mudersbach, P., Simonsen, C., Ruiz de Morales Ayudarte, N., Poulsen, M., Sorensen, L., Karabegovich, S., Hjorringgaard, M., Hjort, N., Harbo, T., Sorensen, K., Deshaies, E., Padalino, D., Swarnkar, A., Latorre, J. G., Elnour, E., El Zammar, Z., Villwock, M., Farid, H., Balgude, A., Cross, L., Hansen, K., Holtmannspotter, M., Kondziella, D., Hoejgaard, J., Taudorf, S., Soendergaard, H., Wagner, A., Cronquist, M., Stavngaard, T., Cortsen, M., Krarup, L. H., Hyldal, T., Haring, H., Guggenberger, S., Hamberger, M., Trenkler, J., Sonnberger, M., Nussbaumer, K., Dominger, C., Bach, E., Jagadeesan, B. D., Taylor, R., Kim, J., Shea, K., Tummala, R., Zacharatos, H., Sandhu, D., Ezzeddine, M., Grande, A., Hildebrandt, D., Miller, K., Scherber, J., Hendrickson, A., Jumaa, M., Zaidi, S., Hendrickson, T., Snyder, V., Killer Oberpfalzer, M., Mutzenbach, J., Weymayr, F., Broussalis, E., Stadler, K., Jedlitschka, A., Malek, A., Mueller Kronast, N., Beck, P., Martin, C., Summers, D., Day, J., Bettinger, I., Holloway, W., Olds, K., Arkin, S., Akhtar, N., Boutwell, C., Crandall, S., Schwartzman, M., Weinstein, C., Brion, B., Prothmann, S., Kleine, J., Kreiser, K., Boeckh Behrens, T., Poppert, H., Wunderlich, S., Koch, M. L., Biberacher, V., Huberle, A., Gora Stahlberg, G., Knier, B., Meindl, T., Utpadel Fischler, D., Zech, M., Kowarik, M., Seifert, C., Schwaiger, B., Puri, A., Hou, S., Wakhloo, A., Moonis, M., Henniger, N., Goddeau, R., Massari, F., Minaeian, A., Lozano, J. D., Ramzan, M., Stout, C., Patel, A., Tunguturi, A., Onteddu, S., Carandang, R., Howk, M., Ribo, M., Sanjuan, E., Rubiera, M., Pagola, J., Flores, A., Muchada, M., Meler, P., Huerga, E., Gelabert, S., Coscojuela, P., Tomasello, A., Rodriguez, D., Santamarina, E., Maisterra, O., Boned, S., Sero, L., Rovira, A., Molina, C. A., Millan, M., Munoz, L., Perez de la Ossa, N., Gomis, M., Dorado, L., Lopez-Cancio, E., Palomeras, E., Munuera, J., Garcia Bermejo, P., Remollo, S., Castano, C., Garcia-Sort, R., Cuadras, P., Puyalto, P., Hernandez-Perez, M., Jimenez, M., Martinez-Pineiro, A., Lucente, G., Davalos, A., Chamorro, A., Urra, X., Obach, V., Cervera, A., Amaro, S., Llull, L., Codas, J., Balasa, M., Navarro, J., Arino, H., Aceituno, A., Rudilosso, S., Renu, A., Macho, J. M., San Roman, L., Blasco, J., Lopez, A., Macias, N., Cardona, P., Quesada, H., Rubio, F., Cano, L., Lara, B., de Miquel, M. A., Aja, L., Serena, J., Cobo, E., Albers, G. W., Lees, K. R., Arenillas, J., Roberts, R., Minhas, P., Al-Ajlan, F., Salluzzi, M., Zimmel, L., Patel, S., Eesa, M., Marti-Fabregas, J., Jankowitz, B., Serena, J., Salvat-Plana, M., Lopez-Cancio, E., Bracard, S., Ducrocq, X., Anxionnat, R., Baillot, P., Barbier, C., Derelle, A., Lacour, J., Richard, S., Samson, Y., Sourour, N., Baronnet-Chauvet, F., Clarencon, F., Crozier, S., Deltour, S., Di Maria, F., Le Bouc, R., Leger, A., Mutlu, G., Rosso, C., Szatmary, Z., Yger, M., Zavanone, C., Bakchine, S., Pierot, L., Caucheteux, N., Estrade, L., Kadziolka, K., Leautaud, A., Renkes, C., Serre, I., Desal, H., Guillon, B., Boutoleau-Bretonniere, C., Daumas-Duport, B., De Gaalon, S., Derkinderen, P., Evain, S., Herisson, F., Laplaud, D., Lebouvier, T., Lintia-Gaultier, A., Pouclet-Courtemanche, H., Rouaud, T., Rouaud Jaffrenou, V., Schunck, A., Sevin-Allouet, M., Toulgoat, F., Wiertlewski, S., Gauvrit, J., Ronziere, T., Cahagne, V., Ferre, J., Pinel, J., Raoult, H., Mas, J., Meder, J., Al Najjar-Carpentier, A., Birchenall, J., Bodiguel, E., Calvet, D., Domigo, V., Godon-Hardy, S., Guiraud, V., Lamy, C., Majhadi, L., Morin, L., Naggara, O., Trystram, D., Turc, G., Berge, J., Sibon, I., Menegon, P., Barreau, X., Rouanet, F., Debruxelles, S., Kazadi, A., Renou, P., Fleury, O., Pasco-Papon, A., Dubas, F., Caroff, J., Godard Ducceschi, S., Hamon, M., Lecluse, A., Marc, G., Giroud, M., Ricolfi, F., Bejot, Y., Chavent, A., Gentil, A., Kazemi, A., Osseby, G., Voguet, C., Mahagne, M., Sedat, J., Chau, Y., Suissa, L., Lachaud, S., Houdart, E., Stapf, C., Buffon Porcher, F., Chabriat, H., Guedin, P., Herve, D., Jouvent, E., Mawet, J., Saint-Maurice, J., Schneble, H., Turjman, F., Nighoghossian, N., Berhoune, N., Bouhour, F., Cho, T., Derex, L., Felix, S., Gervais-Bernard, H., Gory, B., Manera, L., Mechtouff, L., Ritzenthaler, T., Riva, R., Salaris Silvio, F., Tilikete, C., Blanc, R., Obadia, M., Bartolini, M. B., Gueguen, A., Piotin, M., Pistocchi, S., Redjem, H., Drouineau, J., Neau, J., Godeneche, G., Lamy, M., Marsac, E., Velasco, S., Clavelou, P., Chabert, E., Bourgois, N., Cornut-Chauvinc, C., Ferrier, A., Gabrillargues, J., Jean, B., Marques, A., Vitello, N., Detante, O., Barbieux, M., Boubagra, K., Favre Wiki, I., Garambois, K., Tahon, F., Ashok, V., Voguet, C., Coskun, O., Guedin, P., Rodesch, G., Lapergue, B., Bourdain, F., Evrard, S., Graveleau, P., Decroix, J. P., Wang, A., Sellal, F., Ahle, G., Carelli, G., Dugay, M., Gaultier, C., Lebedinsky, A. P., Lita, L., Musacchio, R. M., Renglewicz-Destuynder, C., Tournade, A., Vuillemet, F., Montoro, F. M., Mounayer, C., Faugeras, F., Gimenez, L., Labach, C., Lautrette, G., Denier, C., Saliou, G., Chassin, O., Dussaule, C., Melki, E., Ozanne, A., Puccinelli, F., Sachet, M., Sarov, M., Bonneville, J., Moulin, T., Biondi, A., De Bustos Medeiros, E., Vuillier, F., Courtheoux, P., Viader, F., Apoil-Brissard, M., Bataille, M., Bonnet, A., Cogez, J., Kazemi, A., Touze, E., Leclerc, X., Leys, D., Aggour, M., Aguettaz, P., Bodenant, M., Cordonnier, C., Deplanque, D., Girot, M., Henon, H., Kalsoum, E., Lucas, C., Pruvo, J., Zuniga, P., Bonafe, A., Arquizan, C., Costalat, V., Machi, P., Mourand, I., Riquelme, C., Bounolleau, P., Arteaga, C., Faivre, A., Bintner, M., Tournebize, P., Charlin, C., Darcel, F., Gauthier-Lasalarie, P., Jeremenko, M., Mouton, S., Zerlauth, J., Lamy, C., Herve, D., Hassan, H., Gaston, A., Barral, F., Garnier, P., Beaujeux, R., Wolff, V., Herbreteau, D., Debiais, S., Murray, A., Ford, G., Muir, K. W., White, P., Brown, M. M., Clifton, A., Freeman, J., Ford, I., Markus, H., Wardlaw, J., Lees, K. R., Molyneux, A., Robinson, T., Lewis, S., Norrie, J., Robertson, F., Perry, R., Dixit, A., Cloud, G., Clifton, A., Madigan, J., Roffe, C., Nayak, S., Lobotesis, K., Smith, C., Herwadkar, A., Kandasamy, N., Goddard, T., Bamford, J., Subramanian, G., Lenthall, R., Littleton, E., Lamin, S., Storey, K., Ghatala, R., Banaras, A., Aeron-Thomas, J., Hazel, B., Maguire, H., Veraque, E., Harrison, L., Keshvara, R., Cunningham, J. 2018

  Abstract

  BACKGROUND: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.METHODS: In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mum2/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.FINDINGS: We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30-0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69-0·86] per 10 mL, pinteraction=0·29; diffusion MRI OR 0·87 [0·81-0·94] per 10 mL, pinteraction=0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.INTERPRETATION: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions.FUNDING: Medtronic.

  View details for PubMedID 30413385

• Alberta Stroke Program Early CT Score Versus Computed Tomographic Perfusion to Predict Functional Outcome After Successful Reperfusion in Acute Ischemic Stroke. Stroke Demeestere, J., Scheldeman, L., Cornelissen, S. A., Heye, S., Wouters, A., Dupont, P., Christensen, S., Mlynash, M., Albers, G. W., Lansberg, M., Lemmens, R. 2018; 49 (10): 2361–67

  Abstract

  Background and Purpose- We aimed to compare the ability of conventional Alberta Stroke Program Early CT Score (ASPECTS), automated ASPECTS, and ischemic core volume on computed tomographic perfusion to predict clinical outcome in ischemic stroke because of large vessel occlusion ≤18 hours after symptom onset. Methods- We selected patients with acute ischemic stroke from the CRISP study (Computed Tomographic Perfusion to Predict Response to Recanalization in Ischemic Stroke Project) with successful reperfusion (modified treatment in cerebral ischemia score 2b or 3). We used e-ASPECTS software to calculate automated ASPECTS and RAPID software to estimate ischemic core volumes. We studied associations between these imaging characteristics and good outcome (modified Rankin Scale score, 0-2) or poor outcome (modified Rankin Scale score, 4-6) in univariable and multivariable analysis, after adjustment for relevant clinical confounders. Results- We included 156 patients. Conventional and automated ASPECTS was not associated with good or poor outcome in univariable analysis ( P=nonsignificant for all). Automated ASPECTS was associated with good outcome in multivariable analysis ( P=0.02) but not with poor outcome. Ischemic core volume was associated with good ( P<0.01) and poor outcome ( P=0.04) in univariable and multivariable analysis ( P=0.03 and P=0.02, respectively). Computed tomographic perfusion predicted good outcome with an area under the curve of 0.62 (95% CI, 0.53-0.71) and optimal cutoff core volume of 15 mL. Conclusions- Ischemic core volume assessed on computed tomographic perfusion is a predictor of clinical outcome among patients in whom endovascular reperfusion is achieved ≤18 hours after symptom onset. In this population, conventional or automated ASPECTS did not predict outcome.

  View details for PubMedID 30355098

• KEY SUBGROUP ANALYSES FROM THE SELECT STUDY Sarraj, A., Grotta, J., Hassan, A., Abraham, M., Haussen, D., Vora, N., Hellinger, F., Edgell, R., Gupta, R., Albers, G. SAGE PUBLICATIONS LTD. 2018: 228

  View details for Web of Science ID 000448113303244

• Relative cerebral blood volume is associated with collateral status and infarct growth in stroke patients in SWIFT PRIME JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Arenillas, J. F., Cortijo, E., Garcia-Bermejo, P., Levy, E. I., Jahan, R., Liebeskind, D., Goyal, M., Saver, J. L., Albers, G. W. 2018; 38 (10): 1839–47

  Abstract

  We aimed to evaluate how predefined candidate cerebral perfusion parameters correlate with collateral circulation status and to assess their capacity to predict infarct growth in patients with acute ischemic stroke (AIS) eligible for endovascular therapy. Patients enrolled in the SWIFT PRIME trial with baseline computed tomography perfusion (CTP) scans were included. RAPID software was used to calculate mean relative cerebral blood volume (rCBV) in hypoperfused regions, and hypoperfusion index ratio (HIR). Blind assessments of collaterals were performed using CT angiography in the whole sample and cerebral angiogram in the endovascular group. Reperfusion was assessed on 27-h CTP; infarct volume was assessed on 27-h magnetic resonance imaging/CT scans. Logistic and rank linear regression models were conducted. We included 158 patients. High rCBV ( p = 0.03) and low HIR ( p = 0.03) were associated with good collaterals. A positive association was found between rCBV and better collateral grades on cerebral angiography ( p = 0.01). Baseline and 27-h follow-up CTP were available for 115 patients, of whom 74 (64%) achieved successful reperfusion. Lower rCBV predicted a higher infarct growth in successfully reperfused patients ( p = 0.038) and in the endovascular treatment group ( p = 0.049). Finally, rCBV and HIR may serve as markers of collateral circulation in AIS patients prior to endovascular therapy.Unique identifier: NCT0165746.

  View details for PubMedID 29135347

  View details for PubMedCentralID PMC6168913

• Regional Contributions to Poststroke Disability in Endovascular Therapy. Interventional neurology Sheth, S. A., Malhotra, K., Liebeskind, D. S., Liang, C. W., Yoo, A. J., Jahan, R., Nogueira, R. G., Pereira, V., Gralla, J., Albers, G., Goyal, M., Saver, J. L. 2018; 7 (6): 533-543

  Abstract

  The relative contribution of each Alberta Stroke Program Early CT Score (ASPECTS) region to poststroke disability likely varies across regions. Determining the relative weights of each ASPECTS region may improve patient selection for endovascular stroke therapy (EST).In the combined Solitaire Flow Restoration with the Intention for Thrombectomy (SWIFT), Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), and Solitaire Flow Restoration with the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) databases, we identified patients treated with the Solitaire stent retriever. Using 24-h CT scan, a multivariate ordinal regression was used to determine the relative contribution of each ASPECTS region to clinical outcome separately in each hemisphere. The coefficients from the regression were used to create a weighted ASPECTS (wASPECTS), which was compared with the original ASPECTS to predict 90-day modified Rankin Scale disability outcomes in an independent validation cohort.Among 342 patients treated with EST, the average age was 67 years, 57% were female, and the median National Institutes of Health Stroke Scale (NIHSS) score was 17 (IQR 13-20). The median ASPECTS at presentation was 8 (IQR 7-10). The most commonly involved ASPECTS regions on 24-h CT were the lentiform nuclei (70%), insula (55%), and caudate (52%). In multivariate analysis, preservation of M6 (β = 9.7) and M4 (β = 4.4) regions in the right hemisphere was most strongly predictive of good outcome. For the left hemisphere, M6 (β = 5.5), M5 (β = 4.1), and M3 (β = 3.1) generated the greatest parameter estimates, though they did not reach statistical significance. A wASPECTS incorporating all 20 parameter estimates resulted in improved discrimination against the original ASPECTS in the independent cohort (C-statistic 0.78 vs. 0.67, right hemisphere).For both right and left hemisphere, preservation of the high cortical regions was more strongly associated with improved outcomes compared to the deep regions. Our findings support taking into consideration the location and relative weightings of the involved ASPECTS regions when evaluating a patient for EST.

  View details for DOI 10.1159/000492400

  View details for PubMedID 30410533

  View details for PubMedCentralID PMC6216699

• Endovascular thrombectomy in patients with large infarctions: reasons for restraint. The Lancet. Neurology Albers, G. W. 2018; 17 (10): 836–37

  View details for PubMedID 30264719

• Volumetric and Spatial Accuracy of Computed Tomography Perfusion Estimated Ischemic Core Volume in Patients With Acute Ischemic Stroke. Stroke Hoving, J. W., Marquering, H. A., Majoie, C. B., Yassi, N., Sharma, G., Liebeskind, D. S., van der Lugt, A., Roos, Y. B., van Zwam, W., van Oostenbrugge, R. J., Goyal, M., Saver, J. L., Jovin, T. G., Albers, G. W., Davalos, A., Hill, M. D., Demchuk, A. M., Bracard, S., Guillemin, F., Muir, K. W., White, P., Mitchell, P. J., Donnan, G. A., Davis, S. M., Campbell, B. C. 2018; 49 (10): 2368–75

  Abstract

  Background and Purpose- The volume of estimated ischemic core using computed tomography perfusion (CTP) imaging can identify ischemic stroke patients who are likely to benefit from reperfusion, particularly beyond standard time windows. We assessed the accuracy of pretreatment CTP estimated ischemic core in patients with successful endovascular reperfusion. Methods- Patients from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) and EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) databases who had pretreatment CTP, >50% angiographic reperfusion, and follow-up magnetic resonance imaging at 24 hours were included. Ischemic core volume on baseline CTP data was estimated using relative cerebral blood flow <30% (RAPID, iSchemaView). Follow-up diffusion magnetic resonance imaging was registered to CTP, and the diffusion lesion was outlined using a semiautomated algorithm. Volumetric and spatial agreement (using Dice similarity coefficient, average Hausdorff distance, and precision) was assessed, and expert visual assessment of quality was performed. Results- In 120 patients, median CTP estimated ischemic core volume was 7.8 mL (IQR, 1.8-19.9 mL), and median diffusion lesion volume at 24 hours was 30.8 mL (IQR, 14.9-67.6 mL). Median volumetric difference was 4.4 mL (IQR, 1.2-12.0 mL). Dice similarity coefficient was low (median, 0.24; IQR, 0.15-0.37). The median precision (positive predictive value) of 0.68 (IQR, 0.40-0.88) and average Hausdorff distance (median, 3.1; IQR, 1.8-5.7 mm) indicated reasonable spatial agreement for regions estimated as ischemic core at baseline. Overestimation of total ischemic core volume by CTP was uncommon. Expert visual review revealed overestimation predominantly in white matter regions. Conclusions- CTP estimated ischemic core volumes were substantially smaller than follow-up diffusion-weighted imaging lesions at 24 hours despite endovascular reperfusion within 2 hours of imaging. This may be partly because of infarct growth. Volumetric CTP core overestimation was uncommon and not related to imaging-to-reperfusion time. Core overestimation in white matter should be a focus of future efforts to improve CTP accuracy.

  View details for PubMedID 30355095

• Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness NEW ENGLAND JOURNAL OF MEDICINE Spyropoulos, A. C., Ageno, W., Albers, G. W., Elliott, C., Halperin, J. L., Hiatt, W. R., Maynard, G. A., Steg, P., Weitz, J. I., Suh, E., Spiro, T. E., Barnathan, E. S., Raskob, G. E., Jure, H., Alvarisqueta, A., Cartasegna, L., Hominal, M., Cursack, G., Alzogaray, M., Maillo, M., Parody, M., Caccavo, A., Dran, R., Muntaner, J., Casas, M., Schmidberg, J., Sarjanovich, R., Gabito, A., Garrido, M., Amuchastegui, M., Fernandez, A., Loureyro, J., Giumelli, C., Heazlewood, V., Karrasch, J., Colquhoun, D., White, H., Sabet, A., Bowler, S., Carroll, P., Khalafallah, A., Baker, R., Hedger, S., Simpson, F., Jackson, D., Chong Beng, Eichinger-Hasenauer, S., Siostrzonek, P., Gary, T., Hoppe, U., Dosta, N., Krivenchuk, V., Prystrom, A., Gorokhovsky, S., Yanushko, V., Skrahin, A., Kulik, A., Maslianski, B., Yakubtsevich, R., Timkin, I., Moguchaya, O., Tanaskovic, N., Miljkovic, S., Stojkovic, S., Kovacevic-Preradovic, T., Jovic, D., Basagic, E., Radjen, M., Mutapcic, M., Rizvanovic-Vojic, E., Galic, K., Terzic, I., Pojskic, B., Stevanovic, D., Cehajic, M., Trbojevic, S., Rech, R., Annichino-Bizzacchi, J., Stelmach, R., Blanco, D., Castro, I., Backes, L., Saraiva, J., Ramacciotti, E., de Barros e Silva, P., Reis, G., Vieira, M., Leaes, P., Zimmermann, S., Van Bellen, B., Precoma, D., Silvestrini, L., Hernandes, M., Kyoleyan, M., Kalinova, T., Tiholov, R., Petrov, I., Mihov, A., Chompalova, B., Velikov, C., Pencheva, G., Atanasov, P., Raev, D., Kinova, E., Peltegov, V., Marchev, S., Mincheva, V., Siulemezova, S., Ayryanova, I., Grigorov, M., Naydenova, I., Koteva, N., Dimov, B., Runev, N., Getov, D., Metev, H., Donchev, K., Taseva, M., Hadzhieva, A., Benov, H., Stoyanov, M., Tisheva-Gospodinova, S., Mihaylova, N., Abadzhiev, S., Atzev, B., Georgiev, R., Mollov, M., Stoikov, A., Mazhdrakov, G., Karastanev, K., Dube, F., Roth, S., Mansour, S., Carrier, M., Wu, C., Dolan, S., Pesant, Y., Pietrangelo, M., Dresser, G., Kahn, S., Kruisselbrink, R., Cadena Bonfanti, A., Botero, R., Quintero Ossa, A., Poveda, C., Cedano, J., Gomez Isaza, L., Villaquiran Torres, C., MARINER Investigators 2018; 379 (12): 1118–27

  View details for DOI 10.1056/NEJMoa1805090

  View details for Web of Science ID 000445020900006

• Use of Imaging to Select Patients for Late Window Endovascular Therapy. Stroke Albers, G. W. 2018; 49 (9): 2256-2260

  View details for DOI 10.1161/STROKEAHA.118.021011

  View details for PubMedID 30355004

• Hypoperfusion Ratio predicts infarct growth during transfer for thrombectomy. Annals of neurology Guenego, A., Mlynash, M., Christensen, S., Kemp, S., Heit, J. J., Lansberg, M. G., Albers, G. W. 2018

  Abstract

  We hypothesized that automated assessment of collaterals on computed-tomography (CT) perfusion can predict the rate of infarct growth during transfer from a primary to a comprehensive stroke center for endovascular stroke treatment. We identified consecutive patients (N=28) and assessed their collaterals based on the hypoperfusion intensity ratio (HIR) prior to transfer. Infarct growth rate was strongly correlated with HIR (r= 0.78, p<0.001). ROC analysis identified an HIR of ≥0.5 as optimal for predicting infarct growth. Patients with HIR ≥ 0.5 had a median infarct growth rate of 10.1 mL/h (IQR: 6.4-18.4) compared with 0.9 mL/h (IQR: 0-2.8), p< 0.001) in patients with a HIR < 0.5. Patients with an HIR above ≥ 0.5 had an 83% probability of significant core growth, whereas patients with HIR <0.5 had an 88% probability of core stability. These preliminary data have the potential to guide decision making regarding whether repeat brain imaging should be performed after transfer to a comprehensive stroke center. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30168180

• Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness. The New England journal of medicine Spyropoulos, A. C., Ageno, W., Albers, G. W., Elliott, C. G., Halperin, J. L., Hiatt, W. R., Maynard, G. A., Steg, P. G., Weitz, J. I., Suh, E., Spiro, T. E., Barnathan, E. S., Raskob, G. E., MARINER Investigators 2018

  Abstract

  Background Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. Methods In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. Results Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). Conclusions Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. (Funded by Janssen Research and Development; MARINER ClinicalTrials.gov number, NCT02111564 .).

  View details for PubMedID 30145946

• Endovascular Treatment in the DEFUSE 3 Study. Stroke Marks, M. P., Heit, J. J., Lansberg, M. G., Kemp, S., Christensen, S., Derdeyn, C. P., Rasmussen, P. A., Zaidat, O. O., Broderick, J. P., Yeatts, S. D., Hamilton, S., Mlynash, M., Albers, G. W. 2018

  Abstract

  BACKGROUND AND PURPOSE: Endovascular therapy in an extended time window has been shown to be beneficial in selected patients. This study correlated angiographic outcomes of patients randomized to endovascular therapy with clinical and imaging outcomes in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3).METHODS: Angiograms were assessed for the primary arterial occlusive lesion and the modified Thrombolysis in Cerebral Infarction (TICI) score at baseline and the final modified TICI score. Clinical outcomes were assessed using an ordinal analysis of 90-day modified Rankin Scale and a dichotomous analysis for functional independence (modified Rankin Scale score of 0-2). TICI scores were correlated with outcome, types of device used for thrombectomy, and 24-hour follow-up imaging.RESULTS: TICI 2B-3 reperfusion was achieved in 70 of 92 patients (76%). TICI 2B-3 reperfusion showed a more favorable distribution of Rankin scores compared with TICI 0-2A; odds ratio, 2.77; 95% confidence interval, 1.17-6.56; P=0.019. Good functional outcome (90-day modified Rankin Scale score of 0-2) increased with better TICI scores (P=0.0028). There was less disability comparing TICI 3 patients to TICI 2B patients (P=0.037). Successful reperfusion (TICI 2B-3) was independent of the device used, the site of occlusion (internal carotid artery or M1) or adjunctive use of carotid angioplasty and stenting. Significantly less infarct growth at 24 hours was seen in TICI 3 patients compared with TICI 0-2A (P=0.0015) and TICI 2B (P=0.0002) patients.CONCLUSIONS: Thrombectomy in an extended time window demonstrates similar rates of TICI 2B-3 reperfusion to earlier time window studies. Successful reperfusion was independent of the device used, the site of occlusion or adjunctive use of carotid angioplasty and stenting. TICI 3 reperfusion was more likely to result in low rates of infarct growth at 24 hours and good functional outcome at 90 days.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02586415.

  View details for DOI 10.1161/STROKEAHA.118.022147

  View details for PubMedID 29986935

• Efficacy and Safety of Ticagrelor in Relation to Aspirin Use Within the Week Before Randomization in the SOCRATES Trial STROKE Wong, K., Amarenco, P., Albers, G. W., Denison, H., Easton, J., Evans, S. R., Held, P., Himmelmann, A., Kasner, S. E., Knutsson, M., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Johnston, S., SOCRATES Steering Comm 2018; 49 (7): 1678–85

  Abstract

  SOCRATES (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), comparing ticagrelor with aspirin in patients with acute cerebral ischemia, found a nonsignificant 11% relative risk reduction for stroke, myocardial infarction, or death (P=0.07). Aspirin intake before randomization could enhance the effect of ticagrelor by conferring dual antiplatelet effect during a high-risk period for subsequent stroke. Therefore, we explored the efficacy and safety of ticagrelor versus aspirin in the patients who received any aspirin the week before randomization.A prespecified subgroup analysis in SOCRATES (n=13 199), randomizing patients with acute ischemic stroke (National Institutes of Health Stroke Scale score of ≤5) or transient ischemic attack (ABCD2 score of ≥4) to 90-day treatment with ticagrelor or aspirin. Patients in the prior-aspirin group had received any aspirin within the week before randomization. Primary end point was time to stroke, myocardial infarction, or death. Safety end point was PLATO (Study of Platelet Inhibition and Patient Outcomes) major bleeding.The 4232 patients in the prior-aspirin group were older, had more vascular risk factors, and vascular disease than the other patients. In the prior-aspirin group, the primary end point occurred in 138/2130 (6.5%) of patients on ticagrelor and in 177/2102 (8.3%) on aspirin (hazard ratio, 0.76; 95% confidence interval, 0.61-0.95; P=0.02); in patients with no prior-aspirin usage an event occurred in 304/4459 (6.9%) and 320/4508 (7.1%) on ticagrelor and aspirin, respectively (hazard ratio, 0.96; 95% confidence interval, 0.82-1.12; P=0.59). The treatment-by-prior-aspirin interaction was not statistically significant (P=0.10). In the prior-aspirin group, major bleeding occurred in 0.7% and 0.4% of patients on ticagrelor and aspirin, respectively (hazard ratio, 1.58; 95% confidence interval, 0.68-3.65; P=0.28).In this secondary analysis from SOCRATES, fewer primary end points occurred on ticagrelor treatment than on aspirin in patients receiving aspirin before randomization, but there was no significant treatment-by-prior-aspirin interaction. A new study will investigate the benefit-risk of combining ticagrelor and aspirin in patients with acute cerebral ischemia (URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429).URL: https://www.clinicaltrials.gov. Unique identifier: NCT01994720.

  View details for PubMedID 29915123

  View details for PubMedCentralID PMC6019568

• Multimodal magnetic resonance imaging to identify stroke onset within 6 h in patients with large vessel occlusions EUROPEAN STROKE JOURNAL Wouters, A., Dupont, P., Christensen, S., Norrving, B., Laage, R., Thomalla, G., Kemp, S., Lansberg, M., Thijs, V., Albers, G. W., Lemmens, R. 2018; 3 (2): 185–92

  View details for DOI 10.1177/2396987317753486

  View details for Web of Science ID 000432064200011

• Multimodal magnetic resonance imaging to identify stroke onset within 6 h in patients with large vessel occlusions. European stroke journal Wouters, A., Dupont, P., Christensen, S., Norrving, B., Laage, R., Thomalla, G., Kemp, S., Lansberg, M., Thijs, V., Albers, G. W., Lemmens, R. 2018; 3 (2): 185-192

  Abstract

  Mechanical thrombectomy within 6 h after stroke onset improves the outcome in patients with large vessel occlusions. The aim of our study was to establish a model based on diffusion weighted and perfusion weighted imaging to provide an accurate prediction for the 6 h time-window in patients with unknown time of stroke onset.A predictive model was designed based on data from the DEFUSE 2 study and validated in a subgroup of patients with large vessel occlusions from the AXIS 2 trial.We constructed the model in 91 patients from DEFUSE 2. The following parameters were independently associated with <6 h time-window and included in the model: interquartile range and median relative diffusion weighted imaging, hypoperfusion intensity ratio, core volume and the interaction between median relative diffusion weighted imaging and hypoperfusion intensity ratio as predictors of the 6 h time-window. The area under the curve was 0.80 with a positive predictive value of 0.90 (95%CI 0.79-0.96). In the validation cohort (N = 90), the area under the curve was 0.73 (P for difference = 0.4) with a positive predictive value of 0.85 (95%CI 0.69-0.95).After validation in a larger independent dataset the model can be considered to select patients for endovascular treatment in whom stroke onset is unknown.In patients with large vessel occlusion and unknown time of stroke onset an automated multivariate imaging model is able to select patients who are likely within the 6 h time-window.

  View details for DOI 10.1177/2396987317753486

  View details for PubMedID 31008349

  View details for PubMedCentralID PMC6460412

• Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke. The New England journal of medicine Amarenco, P., Lavallee, P. C., Monteiro Tavares, L., Labreuche, J., Albers, G. W., Abboud, H., Anticoli, S., Audebert, H., Bornstein, N. M., Caplan, L. R., Correia, M., Donnan, G. A., Ferro, J. M., Gongora-Rivera, F., Heide, W., Hennerici, M. G., Kelly, P. J., Kral, M., Lin, H., Molina, C., Park, J. M., Purroy, F., Rothwell, P. M., Segura, T., Skoloudik, D., Steg, P. G., Touboul, P., Uchiyama, S., Vicaut, E., Wang, Y., Wong, L. K., TIAregistry.org Investigators,, 2018

  Abstract

  Background After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. Methods We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. Results A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. Conclusions In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

  View details for PubMedID 29766771

• Thrombectomy for Stroke with Selection by Perfusion Imaging REPLY NEW ENGLAND JOURNAL OF MEDICINE Albers, G. W., Marks, M. P., Lansberg, M. G. 2018; 378 (19): 1849–50

  View details for Web of Science ID 000431774400020

• Automated DWI analysis can identify patients within the thrombolysis time window of 4.5 hours. Neurology Wouters, A., Cheng, B., Christensen, S., Dupont, P., Robben, D., Norrving, B., Laage, R., Thijs, V. N., Albers, G. W., Thomalla, G., Lemmens, R. 2018; 90 (18): e1570–e1577

  Abstract

  OBJECTIVE: To develop an automated model based on diffusion-weighted imaging (DWI) to detect patients within 4.5 hours after stroke onset and compare this method to the visual DWI-FLAIR (fluid-attenuated inversion recovery) mismatch.METHODS: We performed a subanalysis of the "DWI-FLAIR mismatch for the identification of patients with acute ischemic stroke within 4.5 hours of symptom onset" (PRE-FLAIR) and the "AX200 for ischemic stroke" (AXIS 2) trials. We developed a prediction model with data from the PRE-FLAIR study by backward logistic regression with the 4.5-hour time window as dependent variable and the following explanatory variables: age and median relative DWI (rDWI) signal intensity, interquartile range (IQR) rDWI signal intensity, and volume of the core. We obtained the accuracy of the model to predict the 4.5-hour time window and validated our findings in an independent cohort from the AXIS 2 trial. We compared the receiver operating characteristic curve to the visual DWI-FLAIR mismatch.RESULTS: In the derivation cohort of 118 patients, we retained the IQR rDWI as explanatory variable. A threshold of 0.39 was most optimal in selecting patients within 4.5 hours after stroke onset resulting in a sensitivity of 76% and specificity of 63%. The accuracy was validated in an independent cohort of 200 patients. The predictive value of the area under the curve of 0.72 (95% confidence interval 0.64-0.80) was similar to the visual DWI-FLAIR mismatch (area under the curve = 0.65; 95% confidence interval 0.58-0.72; p for difference = 0.18).CONCLUSIONS: An automated analysis of DWI performs at least as good as the visual DWI-FLAIR mismatch in selecting patients within the 4.5-hour time window.

  View details for PubMedID 29618622

• Design and Implementation of a Novel Acute Stroke Code for the Extended Window of Endovascular Treatment Legault, C., Dujari, S., Shen, S. H., Wagner, A. M., Albers, G., Bernier, E., Callagy, P., Vora, N. LIPPINCOTT WILLIAMS & WILKINS. 2018

  View details for Web of Science ID 000453090803006

• Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke STROKE Tsai, J. P., Mlynash, M., Christensen, S., Kemp, S., Kim, S., Mishra, N. K., Federau, C., Nogueira, R. G., Jovin, T. G., Devlin, T. G., Akhtar, N., Yavagal, D. R., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W., Lansberg, M. G., CRISP Investigators 2018; 49 (4): 952-+

  Abstract

  This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke.We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0-2) at day 90 and radiographic outcomes at day 5.Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence (P=0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P=0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49-166] versus 43 [18-81] mL; P=0.006) and larger final infarct volumes (110 [61-155] versus 48 [21-99] mL; P=0.001).Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

  View details for PubMedID 29581341

• Late Window Paradox STROKE Albers, G. W. 2018; 49 (3): 768–71

  View details for PubMedID 29367336

• Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials INTERNATIONAL JOURNAL OF STROKE Hacke, W., Lyden, P., Emberson, J., Baigent, C., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S. M., Donnan, G. A., Grotta, J. C., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M. G., Lindley, R. I., Olivot, J., Parsons, M., Sandercock, P. G., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J. M., Whiteley, W. N., del Zoppo, G., Lees, K. R., Stroke Thrombolysis Trialists' 2018; 13 (2): 175–89

  Abstract

  Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0-1) at 3-6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0-1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21-1.68 and 1.43, 1.23-1.65, respectively), but not in those outside the age-revised label (1.06, 0.90-1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76-1.25 and 1.01, 0.86-1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99-1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19-2.01 and 1.37, 1.17-1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97-1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77-1.26 and 1.02, 0.87-1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98-1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

  View details for DOI 10.1177/1747493017744464

  View details for Web of Science ID 000426007700011

  View details for PubMedID 29171359

• Early Cerebral Vein After Endovascular Ischemic Stroke Treatment Predicts Symptomatic Reperfusion Hemorrhage. Stroke Cartmell, S. C., Ball, R. L., Kaimal, R. n., Telischak, N. A., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018

  Abstract

  Parenchymal hemorrhage (PH) after endovascular mechanical thrombectomy in acute ischemic stroke leads to worse outcomes. Better clinical and imaging biomarkers of symptomatic reperfusion PH are needed to identify patients at risk. We identified clinical and imaging predictors of reperfusion PH after endovascular mechanical thrombectomy with attention to early cerebral veins (ECVs) on postreperfusion digital subtraction angiography.We performed a retrospective cohort study of consecutive acute ischemic stroke patients undergoing endovascular mechanical thrombectomy at our neurovascular referral center. Clinical and imaging characteristics were collected from patient health records, and random forest variable importance measures were used to identify predictors of symptomatic PH. Predictors of secondary outcomes, including 90-day mortality, functional dependence (modified Rankin Scale score, >2), and National Institutes of Health Stroke Scale shift, were also determined. Diagnostic test characteristics of ECV for symptomatic PH were determined using a receiver operating characteristic analysis. Differences between patients with and without symptomatic PH were assessed with Fisher exact test and the Wilcoxon rank sum (Mann-Whitney U test) test at the 0.05 significance level.Of 64 patients with anterior circulation large-vessel occlusion identified, 6 (9.4%) developed symptomatic PH. ECV was the strongest predictor of symptomatic PH with more than twice the importance of the next best predictor, male sex. Although ECV was also predictive of 90-day mortality and functional dependence, other characteristics were more important than ECV for these outcomes. The sensitivity and specificity of ECV alone for subsequent hemorrhage were both 0.83, with an area under the curve of 0.83 and 95% confidence interval of 0.66 to 1.00.ECV on postendovascular mechanical thrombectomy digital subtraction angiography is highly diagnostic of subsequent symptomatic reperfusion hemorrhage in this data set. This finding has important implications for post-treatment management of blood pressure and anticoagulation.

  View details for PubMedID 29739912

• Regional Contributions to Poststroke Disability in Endovascular Therapy INTERVENTIONAL NEUROLOGY Sheth, S. A., Malhotra, K., Liebeskind, D. S., Liang, C. W., Yoo, A. J., Jahan, R., Nogueira, R. G., Pereira, V., Gralla, J., Albers, G., Goyal, M., Saver, J. L., SWIFT STAR SWIFT PRIME Investigato 2018; 7 (6): 533–43

  View details for DOI 10.1159/000492400

  View details for Web of Science ID 000447256900029

• Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? Journal of neurointerventional surgery Wolman, D. N., Iv, M. n., Wintermark, M. n., Zaharchuk, G. n., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018

  Abstract

  Acute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).This retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.Two hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529).AIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.

  View details for PubMedID 29555872

• Reduced Intravoxel Incoherent Motion Microvascular Perfusion Predicts Delayed Cerebral Ischemia and Vasospasm After Aneurysm Rupture. Stroke Heit, J. J., Wintermark, M. n., Martin, B. W., Zhu, G. n., Marks, M. P., Zaharchuk, G. n., Dodd, R. L., Do, H. M., Steinberg, G. K., Lansberg, M. G., Albers, G. W., Federau, C. n. 2018

  Abstract

  Proximal artery vasospasm and delayed cerebral ischemia (DCI) after cerebral aneurysm rupture result in reduced cerebral perfusion and microperfusion and significant morbidity and mortality. Intravoxel incoherent motion (IVIM) magnetic resonance imaging extracts microvascular perfusion information from a multi-b value diffusion-weighted sequence. We determined whether decreased IVIM perfusion may identify patients with proximal artery vasospasm and DCI.We performed a pilot retrospective cohort study of patients with ruptured cerebral aneurysms. Consecutive patients who underwent a brain magnetic resonance imaging with IVIM after ruptured aneurysm treatment were included. Patient demographic, treatment, imaging, and outcome data were determined by electronic medical record review. Primary outcome was DCI development with proximal artery vasospasm that required endovascular treatment. Secondary outcomes included mortality and clinical outcomes at 6 months.Sixteen patients (11 females, 69%;P=0.9) were included. There were no differences in age, neurological status, or comorbidities between patients who subsequently underwent endovascular treatment of DCI (10 patients; DCI+ group) and those who did not (6 patients; DCI- group). Compared with DCI- patients, DCI+ patients had decreased IVIM perfusion fractionf(0.09±0.03 versus 0.13±0.01;P=0.03), reduced diffusion coefficientD(0.82±0.05 versus 0.92±0.07×10-3mm2/s;P=0.003), and reduced blood flow-related parameterfD* (1.18±0.40 versus 1.83±0.40×10-3mm2/s;P=0.009). IVIM pseudodiffusion coefficientD* did not differ between DCI- (0.011±0.002) and DCI+ (0.013±0.005 mm2/s;P=0.4) patients. No differences in mortality or clinical outcome were identified.Decreased IVIM perfusion fractionfand blood flow-related parameterfD* correlate with DCI and proximal artery vasospasm development after cerebral aneurysm rupture.

  View details for DOI 10.1161/STROKEAHA.117.020395

  View details for PubMedID 29439196

• Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. The New England journal of medicine Albers, G. W., Marks, M. P., Kemp, S. n., Christensen, S. n., Tsai, J. P., Ortega-Gutierrez, S. n., McTaggart, R. A., Torbey, M. T., Kim-Tenser, M. n., Leslie-Mazwi, T. n., Sarraj, A. n., Kasner, S. E., Ansari, S. A., Yeatts, S. D., Hamilton, S. n., Mlynash, M. n., Heit, J. J., Zaharchuk, G. n., Kim, S. n., Carrozzella, J. n., Palesch, Y. Y., Demchuk, A. M., Bammer, R. n., Lavori, P. W., Broderick, J. P., Lansberg, M. G. 2018; 378 (8): 708–18

  Abstract

  Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms.We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90.The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18).Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).

  View details for PubMedID 29364767

• A Comparison of Relative Time to Peak and Tmax for Mismatch-Based Patient Selection FRONTIERS IN NEUROLOGY Wouters, A., Christensen, S., Straka, M., Mlynash, M., Liggins, J., Bammer, R., Thijs, V., Lemmens, R., Albers, G. W., Lansberg, M. G. 2017; 8: 539

  Abstract

  The perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch profile is used to select patients for endovascular treatment. A PWI map of Tmax is commonly used to identify tissue with critical hypoperfusion. A time to peak (TTP) map reflects similar hemodynamic properties with the added benefit that it does not require arterial input function (AIF) selection and deconvolution. We aimed to determine if TTP could substitute Tmax for mismatch categorization.Imaging data of the DEFUSE 2 trial were reprocessed to generate relative TTP (rTTP) maps. We identified the rTTP threshold that yielded lesion volumes comparable to Tmax > 6 s and assessed the effect of reperfusion according to mismatch status, determined based on Tmax and rTTP volumes.Among 102 included cases, the Tmax > 6 s lesion volumes corresponded most closely with rTTP > 4.5 s lesion volumes: median absolute difference 6.9 mL (IQR: 2.3-13.0). There was 94% agreement in mismatch classification between Tmax and rTTP-based criteria. When mismatch was assessed by Tmax criteria, the odds ratio (OR) for favorable clinical response associated with reperfusion was 7.4 (95% CI 2.3-24.1) in patients with mismatch vs. 0.4 (95% CI 0.1-2.6) in patients without mismatch. When mismatch was assessed with rTTP criteria, these ORs were 7.2 (95% CI 2.3-22.2) and 0.3 (95% CI 0.1-2.2), respectively.rTTP yields lesion volumes that are comparable to Tmax and reliably identifies the PWI/DWI mismatch profile. Since rTTP is void of the problems associated with AIF selection, it is a suitable substitute for Tmax that could improve the robustness and reproducibility of mismatch classification in acute stroke.

  View details for PubMedID 29081762

• A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3) INTERNATIONAL JOURNAL OF STROKE Albers, G. W., Lansberg, M. G., Kemp, S., Tsai, J. P., Lavori, P., Christensen, S., Mlynash, M., Kim, S., Hamilton, S., Yeatts, S. D., Palesch, Y., Bammer, R., Broderick, J., Marks, M. P. 2017; 12 (8): 896–905

  Abstract

  Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0-2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test).

  View details for PubMedID 28946832

• Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) CIRCULATION Easton, J., Aunes, M., Albers, G. W., Amarenco, P., Bokelund-Singh, S., Denison, H., Evans, S. R., Held, P., Jahreskog, M., Jonasson, J., Minematsu, K., Molina, C. A., Wang, Y., Wong, K., Johnston, S., SOCRATES Steering Comm 2017; 136 (10): 907-+

  Abstract

  Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH).An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population.A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor.Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

  View details for PubMedID 28655834

• Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source. Stroke Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Hill, M. D., Jonasson, J., Kasner, S. E., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Wong, K. S., Johnston, S. C. 2017; 48 (9): 2480-2487

  Abstract

  Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis.We randomized 13 199 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.ESUS was identified in 4329 (32.8%) patients. There was no treatment-by-ESUS category interaction (P=0.83). Hazard ratio in ESUS patients was 0.87 (95% confidence interval, 0.68-1.10; P=0.24). However, hazard ratio was 0.51 (95% confidence interval, 0.29-0.90; P=0.02) in ESUS patients with ipsilateral stenosis <50% or aortic arch atherosclerosis (n=961) and 0.98 (95% confidence interval, 0.76-1.27; P=0.89) in the remaining ESUS patients (n=3368; P for heterogeneity =0.04).In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca).URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

  View details for DOI 10.1161/STROKEAHA.117.017217

  View details for PubMedID 28720658

• Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis Individual Patient Data Meta-Analysis STROKE Charidimou, A., Turc, G., Oppenheim, C., Yan, S., Scheitz, J. F., Erdur, H., Klinger-Gratz, P. P., El-Koussy, M., Takahashi, W., Moriya, Y., Wilson, D., Kidwell, C. S., Saver, J. L., Sallem, A., Moulin, S., Edjlali-Goujon, M., Thijs, V., Fox, Z., Shoamanesh, A., Albers, G. W., Mattle, H. P., Benavente, O. R., Jaeger, H., Ambler, G., Aoki, J., Baron, J., Kimura, K., Kakuda, W., Takizawa, S., Jung, S., Nolte, C. H., Lou, M., Cordonnier, C., Werring, D. J. 2017; 48 (8): 2084-+

  Abstract

  We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome.We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2).In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH (P=0.014), PH (P=0.013), and PHr (P<0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively).Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

  View details for DOI 10.1161/STROKEAHA.116.012992

  View details for Web of Science ID 000406128300033

  View details for PubMedID 28720659

• MR perfusion lesions after TIA or minor stroke are associated with new infarction at 7 days NEUROLOGY Lee, J., Inoue, M., Mlynash, M., Mann, S. K., Cereda, C. W., Ke, M., Albers, G. W., Olivot, J. M. 2017; 88 (24): 2254–59

  Abstract

  To investigate the relationship between acute perfusion-weighted imaging (PWI) lesions occurring within the first hours after a TIA or a minor brain infarction (BI) and the incidence of new BI detected on a systematic MRI at 1 week.Consecutive patients who experienced a TIA or BI with a neurologic deficit that lasted <24 hours, did not receive any revascularization therapy (thrombolysis/thrombectomy), and underwent DWI/PWI at baseline and fluid-attenuated inversion recovery (FLAIR)/DWI 1 week after symptom onset were enrolled. Investigators blinded to clinical information independently assessed the presence of acute ischemic lesions on baseline DWI/PWI and follow-up DWI and FLAIR. Baseline and follow-up MRIs were then compared to determine the occurrence and location of new infarctions.Sixty-four patients met the inclusion criteria. Median (IQR) ABCD2 score was 4 (3-5). Median delay from onset to baseline and follow-up MRI was 5 (2-10) hours and 6 (5-7) days, respectively. MRI revealed an acute ischemic lesion on DWI and/or PWI in 38 patients. Nine patients (14%) had a new infarction on follow-up MRI. Each had a PWI and 4 had a DWI lesion on baseline MRI. All new BIs except one were asymptomatic and in the same location as the acute PWI lesion.Our results showed that 30% of the acute focal PWI lesions detected after a TIA are associated with a new BI at 1 week. Those new BIs may result from the progression of the initial ischemic injury.

  View details for PubMedID 28500226

• Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org. Stroke Hoshino, T., Uchiyama, S., Wong, L. K., Sissani, L., Albers, G. W., Bornstein, N. M., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Labreuche, J., Lavallée, P. C., Molina, C., Rothwell, P. M., Steg, P. G., Touboul, P., Vicaut, É., Amarenco, P. 2017

  Abstract

  This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians.The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome.Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P=0.38) and stroke (6.0% versus 4.8%; P=0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63-0.98; P=0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P<0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P=0.02). In multivariable analysis, multiple acute infarcts (P=0.005) and alcohol consumption (P=0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis (P<0.001), ABCD(2) score (P<0.001), atrial fibrillation (P=0.008), extracranial stenosis (P=0.03), and previous stroke or TIA (P=0.03) were independent predictors in non-Asians.The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians.

  View details for DOI 10.1161/STROKEAHA.117.016874

  View details for PubMedID 28584002

• Efficacy of Stent-Retriever Thrombectomy in Magnetic Resonance Imaging Versus Computed Tomographic Perfusion-Selected Patients in SWIFT PRIME Trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke). Stroke Menjot de Champfleur, N., Saver, J. L., Goyal, M., Jahan, R., Diener, H. C., Bonafe, A., Levy, E. I., Pereira, V. M., Cognard, C., Yavagal, D. R., Albers, G. W. 2017; 48 (6): 1560-1566

  Abstract

  The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI).Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP.MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital (P=0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group (P=0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P=0.02; CTP, P=0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups.Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

  View details for DOI 10.1161/STROKEAHA.117.016669

  View details for PubMedID 28465460

• Wake-Up Stroke: Current Understanding. Topics in magnetic resonance imaging : TMRI Tsai, J. P., Albers, G. W. 2017; 26 (3): 97-102

  Abstract

  Patients with wake-up strokes account for approximately 1 in 5 individuals presenting with an acute ischemic stroke. However, they are commonly excluded from acute stroke treatment. This article reviews the current understanding of wake-up strokes. A comparison of wake-up and awake-onset strokes demonstrated that they are physiologically, clinically, and radiologically similar. Use of advanced CT and MRI techniques may help extend acute stroke treatment options to patients with wake-up stroke.

  View details for DOI 10.1097/RMR.0000000000000126

  View details for PubMedID 28277462

• CT Perfusion to Predict Response to Recanalization in Ischemic Stroke. Annals of neurology Lansberg, M. G., Christensen, S., Kemp, S., Mlynash, M., Mishra, N., Federau, C., Tsai, J. P., Kim, S., Nogueria, R. G., Jovin, T., Devlin, T. G., Akhtar, N., Yavagal, D. R., Haussen, D., Dehkharghani, S., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W. 2017

  Abstract

  To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging.Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1-20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5-27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4-140).The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856.

  View details for DOI 10.1002/ana.24953

  View details for PubMedID 28486789

• Symptomatic Patients Remain at Substantial Risk of Arterial Disease Complications Before and After Endarterectomy or Stenting STROKE Hobeanu, C., Lavallee, P. C., Rothwell, P. M., Sissani, L., Albers, G. W., Bornstein, N. M., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Labreuche, J., Molina, C., Steg, P. G., Touboul, P., Uchiyama, S., Vicaut, E., Wong, L. K., Amarenco, P. 2017; 48 (4): 1005-1010

  Abstract

  After carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with transient ischemic attack or minor ischemic stroke, recurrent stroke risk falls to a low rate on modern medical treatment.We used data from 4583 patients with recent transient ischemic attack or minor stroke enrolled in the TIAregistry.org to perform a nested case-control analysis to evaluate pre- and post-CEA/CAS risk. Cases were defined as patients with a CEA/CAS during the 1-year follow-up period. For each case, 2 controls with a follow-up time greater than the time from qualifying event to CEA/CAS were randomly selected, matched by age and sex. Primary outcome was defined as major vascular events (MVE, including stroke, cardiovascular death, and myocardial infarction).The median delay from symptom onset of qualifying event to CEA/CAS was 11 days (interquartile range, 6-23). Overall, patients with CEA/CAS had a higher 1-year risk of MVE than other patients (14.8% versus 5.8%; adjusted hazard ratio, 2.40; 95% confidence interval, 1.61-3.60; P<0.001). During the matched preprocedural period, MVE occurred in 14 (7.5%) cases and in 13 (3.5%) controls, with an adjusted odds ratio =2.46 (95% confidence interval, 1.07-5.64; P=0.03). In the postprocedural period, the risk of MVE was also higher in cases than in controls (adjusted P<0.03).Patients with CEA/CAS had a higher 12-month risk of MVE, as well as during pre- and postprocedural periods. These results suggest that patients in whom CEA/CAS is anticipated are likely to be an informative population for inclusion in studies testing new antithrombotic strategies started soon after symptom onset.

  View details for DOI 10.1161/STROKEAHA.116.015171

  View details for Web of Science ID 000398207000042

  View details for PubMedID 28289241

• Predictive Value of RAPID Assessed Perfusion Thresholds on Final Infarct Volume in SWIFT PRIME (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment) STROKE Mokin, M., Levy, E. I., Saver, J. L., Siddiqui, A. H., Goyal, M., Bonafe, A., Cognard, C., Jahan, R., Albers, G. W. 2017; 48 (4): 932-938

  Abstract

  Computed tomography perfusion imaging can estimate the size of the ischemic core, which can be used for the selection of patients for endovascular therapy. The relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) thresholds chosen to identify ischemic core influence the accuracy of prediction. We aimed to analyze the accuracy of various rCBV and rCBF thresholds for predicting the 27-hour infarct volume using RAPID automated analysis software from the SWIFT PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment) data.Patients from the SWIFT PRIME study who achieved complete reperfusion based on time until the residue function reached its peak >6 s perfusion maps obtained at 27 hours were included. Patients from both the intravenous tissue-type plasminogen activator only and endovascular groups were included in analysis. Final infarct volume was determined on magnetic resonance imaging (fluid-attenuated inversion recovery images) or computed tomography scans obtained 27 hours after symptom onset. The predicted ischemic core volumes on rCBV and rCBF maps using thresholds ranging between 0.2 and 0.8 were compared with the actual infarct volume to determine the most accurate thresholds.Among the 47 subjects, the following baseline computed tomography perfusion thresholds most accurately predicted the actual 27-hour infarct volume: rCBV=0.32, median absolute error (MAE)=9 mL; rCBV=0.34, MAE=9 mL; rCBF=0.30, MAE=8.8 mL; rCBF=0.32, MAE=7 mL; and rCBF=0.34, MAE=7.3.Brain regions with rCBF 0.30 to 0.34 or rCBV 0.32 to 0.34 thresholds provided the most accurate prediction of infarct volume in patients who achieved complete reperfusion with MAEs of ≤9 mL.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

  View details for DOI 10.1161/STROKEAHA.116.015472

  View details for Web of Science ID 000398207000032

  View details for PubMedID 28283606

• Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. The Lancet. Neurology Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Hill, M. D., Jonasson, J., Kasner, S. E., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Wong, K. S., Johnston, S. C. 2017

  Abstract

  Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial.SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720.Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0·88]; p=0·003). In 10 118 patients with no ipsilateral stenosis, 339 (6·7%) of 5047 patients in the ticagrelor group had an occurrence of stroke, myocardial infarction, or death within 90 days compared with 350 (6·9%) of 5071 in the aspirin group (0·97 [0·84-1·13]; p=0·72). There were no significant differences in the proportion of life-threatening bleeding or major or minor bleeding events in patients with ipsilateral stenosis in the ticagrelor group compared with the aspirin group.In this prespecified exploratory analysis, ticagrelor was superior to aspirin at preventing stroke, myocardial infarction, or death at 90 days in patients with acute ischaemic stroke or transient ischaemic attack when associated with ipsilateral atherosclerotic stenosis. An understanding of stroke mechanisms and causes is important to deliver safe and efficacious treatments for early stroke prevention.AstraZeneca.

  View details for DOI 10.1016/S1474-4422(17)30038-8

  View details for PubMedID 28238711

• Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke). Stroke Shireman, T. I., Wang, K., Saver, J. L., Goyal, M., Bonafé, A., Diener, H., Levy, E. I., Pereira, V. M., Albers, G. W., Cognard, C., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., Devlin, T. G., Lopes, D. K., Reddy, V. K., Du Mesnil De Rochemont, R., Jahan, R., Vilain, K. A., House, J., Lee, J., Cohen, D. J. 2017; 48 (2): 379-387

  Abstract

  Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions.In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors.Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates.Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

  View details for DOI 10.1161/STROKEAHA.116.014735

  View details for PubMedID 28028150

• Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients From the SOCRATES Trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) STROKE Wang, Y., Minematsu, K., Wong, K. S., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Jonasson, J., Molina, C. A., Johnston, S. C. 2017; 48 (1): 167-?

  Abstract

  In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis.Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model.A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61).The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

  View details for DOI 10.1161/STROKEAHA.116.014891

  View details for Web of Science ID 000391944900030

  View details for PubMedID 27899747

• Current Imaging Strategies for Patient Selection in Acute Ischemic Stroke Trials NEUROPROTECTIVE THERAPY FOR STROKE AND ISCHEMIC DISEASE Tsai, J. P., Albers, G. W., Lapchak, P. A., Zhang, J. H. 2017: 751–74

  View details for DOI 10.1007/978-3-319-45345-3_33

  View details for Web of Science ID 000414951200034

• Power of an Adaptive Trial Design for Endovascular Stroke Studies Simulations Using IMS (Interventional Management of Stroke) III Data STROKE Lansberg, M. G., Bhat, N. S., Yeatts, S. D., Palesch, Y. Y., Broderick, J. P., Albers, G. W., Lai, T. L., Lavori, P. W. 2016; 47 (12): 2931-2937

  Abstract

  Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies.We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design.The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%).These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern.

  View details for DOI 10.1161/STROKEAHA.116.015436

  View details for Web of Science ID 000389424200022

  View details for PubMedID 27895297

  View details for PubMedCentralID PMC5134921

• Functional Neurologic Outcomes Change Over the First 6 Months After Cardiac Arrest. Critical care medicine Tong, J. T., Eyngorn, I., Mlynash, M., Albers, G. W., Hirsch, K. G. 2016; 44 (12): e1202-e1207

  Abstract

  To determine the longitudinal changes in functional outcome and compare ordinal outcome scale assessments in comatose cardiac arrest survivors.Prospective observational study of comatose cardiac arrest survivors. Subjects who survived to 1 month were included.Academic medical center ICU.Ninety-eight consecutive patients who remained comatose after resuscitation from cardiac arrest; 45 patients survived to 1 month.None.Patients' functional neurologic outcomes were assessed by phone call or in-person clinic visit at 1, 3, 6, and 12 months postcardiac arrest using the modified Rankin Scale, Glasgow Outcome Scale, and Barthel Index. A "good" outcome was defined as modified Rankin Scale 0-3, Barthel Index 70-100, and Glasgow Outcome Scale 4-5. Changes in dichotomized outcomes and shifts on each outcome scale were analyzed. The mean age of survivors was 51 ± 19 years and 18 (40%) were women. Five (19%) out of 26 patients with data available at all timepoints improved to good modified Rankin Scale outcome and none worsened to poor outcome between postarrest months 1 and 6 (p = 0.06). Thirteen patients (50%) improved on the modified Rankin Scale by 1-3 points and four (15%) worsened by 1-2 points between months 1 and 6 (overall improvement by 0.5 points; 95% CI, 0-1; p = 0.04). From postarrest months 6 to 12, there was no change in the number of patients with good versus poor outcomes. The modified Rankin Scale and Barthel Index were more sensitive to detecting changes in outcome than the Glasgow Outcome Scale.In initially comatose cardiac arrest survivors, improvements in functional status occur over the first 6 months after the event. There was no significant change in outcome between postarrest months 6 and 12. The modified Rankin Scale is a sensitive outcome scale in this population.

  View details for PubMedID 27495816

• Optimal Computed Tomographic Perfusion Scan Duration for Assessment of Acute Stroke Lesion Volumes STROKE Kasasbeh, A. S., Christensen, S., Straka, M., Mishra, N., Mlynash, M., Bammer, R., Albers, G. W., Lansberg, M. G. 2016; 47 (12): 2966-2971

  Abstract

  The minimal scan duration needed to obtain reliable lesion volumes with computed tomographic perfusion (CTP) has not been well established in the literature.We retrospectively assessed the impact of gradual truncation of the scan duration on acute ischemic lesion volume measurements. For each scan, we identified its optimal scan time, defined as the shortest scan duration that yields measurements of the ischemic lesion volumes similar to those obtained with longer scanning, and the relative height of the fitted venous output function at its optimal scan time.We analyzed 70 computed tomographic perfusion scans of acute stroke patients. An optimal scan time could not be determined in 11 scans (16%). For the other 59 scans, the median optimal scan time was 32.7 seconds (90th percentile 52.6 seconds; 100th percentile 68.9 seconds), and the median relative height of the fitted venous output function at the optimal scan times was 0.39 (90th percentile 0.02; 100th percentile 0.00). On the basis of a linear model, the optimal scan time was T0 plus 1.6 times the width of the venous output function (P<0.001; R(2)=0.49).This study shows how the optimal duration of a computed tomographic perfusion scan relates to the arrival time and width of the contrast bolus. This knowledge can be used to optimize computed tomographic perfusion scan protocols and to determine whether a scan is of sufficient duration. Provided a baseline (T0) of 10 seconds, a total scan duration of 60 to 70 seconds, which includes the entire downslope of the venous output function in most patients, is recommended.

  View details for DOI 10.1161/STROKEAHA.116.014177

  View details for Web of Science ID 000389424200027

  View details for PubMedID 27895299

  View details for PubMedCentralID PMC5134896

• Comparison of stroke volume evolution on diffusion-weighted imaging and fluid-attenuated inversion recovery following endovascular thrombectomy. International journal of stroke Federau, C., Christensen, S., Mlynash, M., Tsai, J., Kim, S., Zaharchuk, G., Inoue, M., Straka, M., Mishra, N. K., Kemp, S., Lansberg, M. G., Albers, G. W. 2016

  Abstract

  To compare the evolution of the infarct lesion volume on both diffusion-weighted imaging and fluid-attenuated inversion recovery in the first five days after endovascular thrombectomy.We included 109 patients from the CRISP and DEFUSE 2 studies. Stroke lesion volumes obtained on diffusion-weighted imaging and fluid-attenuated inversion recovery images both early post-procedure (median 18 h after symptom onset) and day 5, were compared using median, interquartile range, and correlation plots. Patients were dichotomized based on the time after symptom onset of their post procedure images (≥18 h vs. <18 h), and the degree of reperfusion (on Tmax>6 s; ≥ 90% vs. < 90%).Early post-procedure, median infarct lesion volume was 19 ml [(IQR) 7-43] on fluid-attenuated inversion recovery, and 23 ml [11-64] on diffusion-weighted imaging. On day 5, median infarct lesion volume was 52 ml [20-118] on fluid-attenuated inversion recovery, and 37 ml [16-91] on diffusion-weighted imaging. Infarct lesion volume on early post-procedure diffusion-weighted imaging, compared to fluid-attenuated inversion recovery, correlated better with day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesions (r = 0.88 and 0.88 vs. 0.78 and 0.77; p < 0.0001). Median lesion growth was significantly smaller on diffusion-weighted imaging when the early post-procedure scan was obtained ≥18 h post stroke onset (5 ml [-1-13]), compared to <18 h (13 ml [2-47]; p = 0.03), but was not significantly different on fluid-attenuated inversion recovery (≥18 h: 26 ml [12-57]; <18 h: 21 ml [5-57]; p = 0.65). In the <90% reperfused group, the median infarct growth was significantly larger for diffusion-weighted imaging and fluid-attenuated inversion recovery (diffusion-weighted imaging: 23 ml [8-57], fluid-attenuated inversion recovery: 41 ml [13-104]) compared to ≥90% (diffusion-weighted imaging: 6 ml [2-24]; p = 0.003, fluid-attenuated inversion recovery: 19 ml [8-46]; p = 0.001).Early post-procedure lesion volume on diffusion-weighted imaging is a better estimate of day 5 infarct volume than fluid-attenuated inversion recovery. However, both early post-procedure diffusion-weighted imaging and fluid-attenuated inversion recovery underestimate day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesion volumes, especially in patients who do not reperfuse.

  View details for PubMedID 27811306

• Desmoteplase 3 to 9 Hours After Major Artery Occlusion Stroke: The DIAS-4 Trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke). Stroke; a journal of cerebral circulation von Kummer, R., Mori, E., Truelsen, T., Jensen, J. S., Grønning, B. A., Fiebach, J. B., Lovblad, K., Pedraza, S., Romero, J. M., Chabriat, H., Chang, K., Dávalos, A., Ford, G. A., Grotta, J., Kaste, M., Schwamm, L. H., Shuaib, A., Albers, G. W. 2016

  Abstract

  The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window.Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events.In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms.Late treatment with intravenous 90 µg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.

  View details for PubMedID 27803391

• Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies LANCET NEUROLOGY Kelly, P. J., Albers, G. W., Chatzikonstantinou, A., De Marchis, G. M., Ferrari, J., George, P., Katan, M., Knoflach, M., Kim, J. S., Li, L., Lee, E., Olivot, J., Purroy, F., Raposo, N., Rothwell, P. M., Sharma, V. K., Song, B., Tsivgoulis, G., Walsh, C., Xu, Y., Merwick, A. 2016; 15 (12): 1236-1245

  View details for Web of Science ID 000386315700019

• A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Cereda, C. W., Christensen, S., Campbell, B. C., Mishra, N. K., Mlynash, M., Levi, C., Straka, M., Wintermark, M., Bammer, R., Albers, G. W., Parsons, M. W., Lansberg, M. G. 2016; 36 (10): 1780-1789

  Abstract

  Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages.

  View details for DOI 10.1177/0271678X15610586

  View details for Web of Science ID 000385349400011

  View details for PubMedID 26661203

  View details for PubMedCentralID PMC5076783

• Stroke Treatment Academic Industry Roundtable: The Next Generation of Endovascular Trials. Stroke; a journal of cerebral circulation Jovin, T. G., Albers, G. W., Liebeskind, D. S. 2016; 47 (10): 2656-2665

  Abstract

  The STAIR (Stroke Treatment Academic Industry Roundtable) meeting aims to advance acute stroke therapy development through collaboration between academia, industry, and regulatory institutions. In pursuit of this goal and building on recently available level I evidence of benefit from endovascular therapy (ET) in large vessel occlusion stroke, STAIR IX consensus recommendations were developed that outline priorities for future research in ET.Three key directions for advancing the field were identified: (1) development of systems of care for ET in large vessel occlusion stroke, (2) development of therapeutic approaches adjunctive to ET, and (3) exploring clinical benefit of ET in patient population insufficiently studied in recent trials. Methodological issues such as optimal trial design and outcome measures have also been addressed.Development of systems of care strategies should be geared both toward ensuring broad access to ET for eligible patients and toward shortening time to reperfusion to the minimum possible. Adjunctive therapy development includes neuroprotective approaches, adjuvant microcirculatory/collateral enhancing strategies, and periprocedural management. Future research priorities seeking to expand the eligible patient population are to determine benefit of ET in patients presenting beyond conventional time windows, in patients with large baseline ischemic core lesions, and in other important subgroups.Research priorities in ET for large vessel occlusion stroke are to improve systems of care, investigate effective adjuvant therapies, and explore whether patient eligibility could be expanded.

  View details for DOI 10.1161/STROKEAHA.116.013578

  View details for PubMedID 27586682

• Prediction of Stroke Onset Is Improved by Relative Fluid-Attenuated Inversion Recovery and Perfusion Imaging Compared to the Visual Diffusion-Weighted Imaging/Fluid-Attenuated Inversion Recovery Mismatch. Stroke; a journal of cerebral circulation Wouters, A., Dupont, P., Norrving, B., Laage, R., Thomalla, G., Albers, G. W., Thijs, V., Lemmens, R. 2016; 47 (10): 2559-2564

  Abstract

  Acute stroke patients with unknown time of symptom onset are ineligible for thrombolysis. The diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) mismatch is a reasonable predictor of stroke within 4.5 hours of symptom onset, and its clinical usefulness in selecting patients for thrombolysis is currently being investigated. The accuracy of the visual mismatch rating is moderate, and we hypothesized that the predictive value of stroke onset within 4.5 hours could be improved by including various clinical and imaging parameters.In this study, 141 patients in whom magnetic resonance imaging was obtained within 9 hours after symptom onset were included. Relative FLAIR signal intensity was calculated in the region of nonreperfused core. Mean Tmax was calculated in the total region with Tmax >6 s. Mean relative FLAIR, mean Tmax, lesion volume with Tmax >6 s, age, site of arterial stenosis, core volume, and location of infarct were analyzed by logistic regression to predict stroke onset time before or after 4.5 hours.Receiver-operating characteristic curve analysis revealed an area under the curve of 0.68 (95% confidence interval 0.59-0.78) for the visual diffusion-weighted imaging/FLAIR mismatch, thereby correctly classifying 69% of patients with an onset time before or after 4.5 hours. Age, relative FLAIR, and Tmax increased the accuracy significantly (P<0.01) to an area under the curve of 0.82 (95% confidence interval 0.74-0.89). This new predictive model correctly categorized 77% of patients according to stroke onset before versus after 4.5 hours.In patients with unknown stroke onset, the accuracy of predicting time from symptom onset within 4.5 hours is improved by obtaining relative FLAIR and perfusion imaging.

  View details for DOI 10.1161/STROKEAHA.116.013903

  View details for PubMedID 27601375

• Analysis of perfusion MRI in stroke: To deconvolve, or not to deconvolve. Magnetic resonance in medicine Meijs, M., Christensen, S., Lansberg, M. G., Albers, G. W., Calamante, F. 2016; 76 (4): 1282-1290

  Abstract

  There is currently controversy regarding the benefits of deconvolution-based parameters in stroke imaging, with studies suggesting a similar infarct prediction using summary parameters. We investigate here the performance of deconvolution-based parameters and summary parameters for dynamic-susceptibility contrast (DSC) MRI analysis, with particular emphasis on precision.Numerical simulations were used to assess the contribution of noise and arterial input function (AIF) variability to measurement precision. A realistic AIF range was defined based on in vivo data from an acute stroke clinical study. The simulated tissue curves were analyzed using two popular singular value decomposition (SVD) based algorithms, as well as using summary parameters.SVD-based deconvolution methods were found to considerably reduce the AIF-dependency, but a residual AIF bias remained on the calculated parameters. Summary parameters, in turn, show a lower sensitivity to noise. The residual AIF-dependency for deconvolution methods and the large AIF-sensitivity of summary parameters was greatly reduced when normalizing them relative to normal tissue.Consistent with recent studies suggesting high performance of summary parameters in infarct prediction, our results suggest that DSC-MRI analysis using properly normalized summary parameters may have advantages in terms of lower noise and AIF-sensitivity as compared to commonly used deconvolution methods. Magn Reson Med 76:1282-1290, 2016. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26024

  View details for PubMedID 26519871

• Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. The Lancet. Neurology Whiteley, W. N., Emberson, J., Lees, K. R., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M. G., Lindley, R. I., Lyden, P., Olivot, J. M., Parsons, M., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., del Zoppo, G. J., Sandercock, P., Hacke, W., Baigent, C. 2016; 15 (9): 925-933

  Abstract

  Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4·5 h of acute ischaemic stroke. However, alteplase also increases the risk of intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients.We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24-36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale [NIHSS]); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90-180 days.Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 [6·8%] of 3391 patients allocated alteplase vs 44 [1·3%] of 3365 patients allocated control; odds ratio [OR] 5·55 [95% CI 4·01-7·70]; absolute excess 5·5% [4·6-6·4]); of SITS-MOST haemorrhage (124 [3·7%] of 3391 vs 19 [0·6%] of 3365; OR 6·67 [4·11-10·84]; absolute excess 3·1% [2·4-3·8]); and of fatal intracerebral haemorrhage (91 [2·7%] of 3391 vs 13 [0·4%] of 3365; OR 7·14 [3·98-12·79]; absolute excess 2·3% [1·7-2·9]). However defined, the proportional increase in intracerebral haemorrhage was similar irrespective of treatment delay, age, or baseline stroke severity, but the absolute excess risk of intracerebral haemorrhage increased with increasing stroke severity: for SITS-MOST intracerebral haemorrhage the absolute excess risk ranged from 1·5% (0·8-2·6%) for strokes with NIHSS 0-4 to 3·7% (2·1-6·3%) for NIHSS 22 or more (p=0·0101). For patients treated within 4·5 h, the absolute increase in the proportion (6·8% [4·0% to 9·5%]) achieving a modified Rankin Scale of 0 or 1 (excellent outcome) exceeded the absolute increase in risk of fatal intracerebral haemorrhage (2·2% [1·5% to 3·0%]) and the increased risk of any death within 90 days (0·9% [-1·4% to 3·2%]).Among patients given alteplase, the net outcome is predicted both by time to treatment (with faster time increasing the proportion achieving an excellent outcome) and stroke severity (with a more severe stroke increasing the absolute risk of intracerebral haemorrhage). Although, within 4·5 h of stroke, the probability of achieving an excellent outcome with alteplase treatment exceeds the risk of death, early treatment is especially important for patients with severe stroke.UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.

  View details for DOI 10.1016/S1474-4422(16)30076-X

  View details for PubMedID 27289487

• Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology Leigh, R., Christensen, S., Campbell, B. C., Marks, M. P., Albers, G. W., Lansberg, M. G. 2016; 87 (3): 263-269

  Abstract

  This study sought to confirm the relationship between the degree of blood-brain barrier (BBB) damage and the severity of intracranial hemorrhage (ICH) in a population of patients who received endovascular therapy.The degree of BBB disruption on pretreatment MRI scans was analyzed, blinded to follow-up data, in the DEFUSE 2 cohort in which patients had endovascular therapy within 12 hours of stroke onset. BBB disruption was compared with ICH grade previously established by the DEFUSE 2 core lab. A prespecified threshold for predicting parenchymal hematoma (PH) was tested.Of the 108 patients in the DEFUSE 2 trial, 100 had adequate imaging and outcome data and were included in this study; 24 developed PH. Increasing amounts of BBB disruption on pretreatment MRIs was associated with increasing severity of ICH grade (p = 0.004). BBB disruption on the pretreatment scan was associated with PH (p = 0.020) with an odds ratio for developing PH of 1.69 for each 10% increase in BBB disruption (95% confidence interval 1.09-2.64), although a reliably predictive threshold was not identified.The amount of BBB disruption on pretreatment MRI is associated with the severity of ICH after acute intervention. This relationship has now been identified in patients receiving IV, endovascular, and combined therapies. Further study is needed to determine its role in guiding treatment.

  View details for DOI 10.1212/WNL.0000000000002862

  View details for PubMedID 27316247

• Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack NEW ENGLAND JOURNAL OF MEDICINE Johnston, S. C., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Jonasson, J., Minematsu, K., Molina, C. A., Wang, Y., Wong, K. S. 2016; 375 (1): 35-43

  Abstract

  Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

  View details for DOI 10.1056/NEJMoa1603060

  View details for PubMedID 27160892

• Evolution of Volume and Signal Intensity on Fluid-attenuated Inversion Recovery MR Images after Endovascular Stroke Therapy RADIOLOGY Federau, C., Mlynash, M., Christensen, S., Zaharchuk, G., Cha, B., Lansberg, M. G., Wintermark, M., Albers, G. W. 2016; 280 (1): 184-192

  Abstract

  Purpose To analyze both volume and signal evolution on magnetic resonance (MR) fluid-attenuated inversion recovery (FLAIR) images between the images after endovascular therapy and day 5 (which was the prespecified end point for infarct volume in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution [DEFUSE 2] trial) in a subset of patients enrolled in the DEFUSE 2 study. Materials and Methods This study was approved by the local ethics committee at all participating sites. Informed written consent was obtained from all patients. In this post hoc analysis of the DEFUSE 2 study, 35 patients with FLAIR images acquired both after endovascular therapy (median time after symptom onset, 12 hours) and at day 5 were identified. Patients were separated into two groups based on the degree of reperfusion achieved on time to maximum greater than 6-second perfusion imaging (≥90% vs <90%). After coregistration and signal normalization, lesion volumes and signal intensity were assessed by using FLAIR imaging for the initial lesion (ie, visible after endovascular therapy) and the recruited lesion (the additional lesion visible on day 5, but not visible after endovascular therapy). Statistical significance was assessed by using Wilcoxon signed-rank, Mann-Whitney U, and Fisher exact tests. Results All 35 patients had FLAIR lesion growth between the after-revascularization examination and day 5. Median lesion growth was significantly larger in patients with <90% reperfusion (27.85 mL) compared with ≥90% (8.12 mL; P = .003). In the initial lesion, normalized signal did not change between after endovascular therapy (median, 1.60) and day 5 (median, 1.58) in the ≥90% reperfusion group (P = .97), but increased in the <90% reperfusion group (from 1.60 to 1.73; P = .01). In the recruited lesion, median normalized signal increased significantly in both groups between after endovascular therapy and day 5 (after endovascular therapy, from 1.19 to 1.56, P < .001; and day 5, from 1.18 to 1.63, P < .001). Conclusion Patients with ≥90% reperfusion after endovascular therapy have significantly less lesion growth on FLAIR images between after therapy and day 5 compared with patients who have <90% reperfusion. Therefore, the effect of reperfusion therapies on lesion volumes are likely more apparent at day 5 than after therapy. (©) RSNA, 2016.

  View details for DOI 10.1148/radiol.2015151586

  View details for Web of Science ID 000378721900020

  View details for PubMedID 26761721

• The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE Design, rationale, and clinical implications THROMBOSIS AND HAEMOSTASIS Raskob, G. E., Spyropoulos, A. C., Zrubek, J., Ageno, W., Albers, G., Elliott, C. G., Halperin, J., Haskell, L., Hiatt, W. R., Maynard, G. A., Peters, G., Spiro, T., Steg, P. G., Suh, E. Y., Weitz, J. I. 2016; 115 (6): 1240-1248

  Abstract

  Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.

  View details for DOI 10.1160/TH15-09-0756

  View details for Web of Science ID 000377237400020

  View details for PubMedID 26842902

• Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials Consensus Recommendations and Further Research Priorities STROKE Warach, S. J., Luby, M., Albers, G. W., Bammer, R., Bivard, A., Campbell, B. C., Derdeyn, C., Heit, J. J., Khatri, P., Lansberg, M. G., Liebeskind, D. S., Majoie, C. B., Marks, M. P., Menon, B. K., Muir, K. W., Parsons, M. W., Vagal, A., Yoo, A. J., Alexandrov, A. V., Baron, J., Fiorella, D. J., Furlan, A. J., Puig, J., Schellinger, P. D., Wintermark, M. 2016; 47 (5): 1389-1398

  Abstract

  The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

  View details for DOI 10.1161/STROKEAHA.115.012364

  View details for PubMedID 27073243

• Diagnostic Yield of Echocardiography in Transient Ischemic Attack JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Wilson, C. A., Tai, W., Desai, J. A., Mulvihill, I., Olivot, J., Murphy, S., Coutts, S. B., Albers, G. W., Kelly, P., Cucchiara, B. L. 2016; 25 (5): 1135-1140

  Abstract

  Echocardiography is often performed to identify a cardiac source of embolism (CSE) causing transient ischemic attack (TIA). However, the diagnostic yield of echocardiography in TIA remains uncertain, and its role in routine evaluation of TIA is controversial.Patients with acute TIA were prospectively enrolled at 4 stroke centers. A CSE was defined using the Causative Classification of Stroke system; patent foramen ovale was considered a relevant CSE only if the patient underwent closure or was placed on anticoagulation. Patients with a known CSE at time of admission were excluded from analysis of the yield of echocardiography.A total of 869 patients were enrolled at stroke centers, and 129 had a known CSE at presentation. Of the 740 remaining patients, 603 (81%) underwent echocardiography. A potential CSE was identified in 60 (10%) of these patients. The most common CSEs noted on echocardiography were complex aortic arch atherosclerosis and patent foramen ovale. History of coronary artery disease (P < .001), lack of prior stroke or TIA (P = .007), and presence of acute infarction on magnetic resonance imaging (MRI) (P < .001) were predictors of CSE on echocardiography. The yield of echocardiography was 29% in patients with both history of coronary artery disease and acute infarction on MRI, 14% with one of these features, and 5% with neither of these features (P < .0001). A CSE identified by echocardiography prompted initiation of anticoagulation in 15 of the 603 (2.5%) subjects.Echocardiography demonstrates a relevant CSE in a significant portion of patients with TIA. However, changes in antithrombotic therapy resulting from echocardiography are infrequent.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2016.01.011

  View details for Web of Science ID 000375144200021

  View details for PubMedID 26915604

• One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke NEW ENGLAND JOURNAL OF MEDICINE Amarenco, P., Lavallee, P. C., Labreuche, J., Albers, G. W., Bornstein, N. M., Canhao, P., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Molina, C., Rothwell, P. M., Sissani, L., Skoloudik, D., Steg, P. G., Touboul, P., Uchiyama, S., Vicaut, E., Wong, L. K. 2016; 374 (16): 1533-1542

  Abstract

  Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists.We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD(2) score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year.From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan-Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan-Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD(2) score of 6 or 7 were each associated with more than a doubling of the risk of stroke.We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD(2) score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.).

  View details for DOI 10.1056/NEJMoa1412981

  View details for Web of Science ID 000374383900006

  View details for PubMedID 27096581

• Association Between Time From Stroke Onset and Fluid-Attenuated Inversion Recovery Lesion Intensity Is Modified by Status of Collateral Circulation STROKE Wouters, A., Dupont, P., Christensen, S., Norrving, B., Laage, R., Thomalla, G., Albers, G., Thijs, V., Lemmens, R. 2016; 47 (4): 1018-1022

  View details for DOI 10.1161/STROKEAHA.115.012010

  View details for Web of Science ID 000372853200018

• Effect of endovascular reperfusion in relation to site of arterial occlusion. Neurology Lemmens, R., Hamilton, S. A., Liebeskind, D. S., Tomsick, T. A., Demchuk, A. M., Nogueira, R. G., Marks, M. P., Jahan, R., Gralla, J., Yoo, A. J., Yeatts, S. D., Palesch, Y. Y., Saver, J. L., Pereira, V. M., Broderick, J. P., Albers, G. W., Lansberg, M. G. 2016; 86 (8): 762-770

  Abstract

  To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL).We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions.Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7).The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

  View details for DOI 10.1212/WNL.0000000000002399

  View details for PubMedID 26802090

• Multi-Center Study of Diffusion-Weighted Imaging in Coma After Cardiac Arrest. Neurocritical care Hirsch, K. G., Mlynash, M., Eyngorn, I., Pirsaheli, R., Okada, A., Komshian, S., Chen, C., Mayer, S. A., Meschia, J. F., Bernstein, R. A., Wu, O., Greer, D. M., Wijman, C. A., Albers, G. W. 2016; 24 (1): 82-89

  Abstract

  The ability to predict outcomes in acutely comatose cardiac arrest survivors is limited. Brain diffusion-weighted magnetic resonance imaging (DWI MRI) has been shown in initial studies to be a simple and effective prognostic tool. This study aimed to determine the predictive value of previously defined DWI MRI thresholds in a multi-center cohort.DWI MRIs of comatose post-cardiac arrest patients were analyzed in this multi-center retrospective observational study. Poor outcome was defined as failure to regain consciousness within 14 days and/or death during the hospitalization. The apparent diffusion coefficient (ADC) value of each brain voxel was determined. ADC thresholds and brain volumes below each threshold were analyzed for their correlation with outcome.125 patients were included in the analysis. 33 patients (26 %) had a good outcome. An ADC value of less than 650 × 10(-6) mm(2)/s in ≥10 % of brain volume was highly specific [91 % (95 % CI 75-98)] and had a good sensitivity [72 % (95 % CI 61-80)] for predicting poor outcome. This threshold remained an independent predictor of poor outcome in multivariable analysis (p = 0.002). An ADC value of less than 650 × 10(-6) mm(2)/s in >22 % of brain volume was needed to achieve 100 % specificity for poor outcome.In patients who remain comatose after cardiac arrest, quantitative DWI MRI findings correlate with early recovery of consciousness. A DWI MRI threshold of 650 × 10(-6) mm(2)/s in ≥10 % of brain volume can differentiate patients with good versus poor outcome, though in this patient population the threshold was not 100 % specific for poor outcome.

  View details for DOI 10.1007/s12028-015-0179-9

  View details for PubMedID 26156112

• Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrollment decision making. International journal of stroke Luby, M., Warach, S. J., Albers, G. W., Baron, J., Cognard, C., Dávalos, A., Donnan, G. A., Fiebach, J. B., Fiehler, J., Hacke, W., Lansberg, M. G., Liebeskind, D. S., Mattle, H. P., Oppenheim, C., Schellinger, P. D., Wardlaw, J. M., Wintermark, M. 2016; 11 (2): 180-190

  Abstract

  For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials.STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials.We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy.Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes.

  View details for DOI 10.1177/1747493015616634

  View details for PubMedID 26783309

  View details for PubMedCentralID PMC4762013

• Prognostic Value of Quantitative Diffusion-Weighted MRI in Patients with Traumatic Brain Injury JOURNAL OF NEUROIMAGING Shakir, A., Aksoy, D., Mlynash, M., Harris, O. A., Albers, G. W., Hirsch, K. G. 2016; 26 (1): 103-108

  Abstract

  Data about the predictive value of quantitative diffusion-weighted MRI in traumatic brain injury (TBI) patients is lacking. This study aimed to determine if specific apparent diffusion coefficient (ADC) thresholds could be determined that correlate with outcome in moderate-severe TBI.This retrospective observational study investigated patients with moderate-severe TBI. MRIs obtained post-injury days 1-13 were analyzed. MRIs were obtained on a 1.5T scanner; 20-23 contiguous diffusion-weighted imaging (DWI) sections with a spin-echo echo planar imaging DWI 256×256 reconstructed matrix; field of view 24×24 cm; slice thickness/gap of 5/1.5 or 5/2.5 mm. The ADC value of each brain tissue voxel was determined. The percentage of voxels below different ADC thresholds was calculated and correlated with outcome. A good outcome was defined as discharge to home or a rehabilitation facility.Seventy-six patients were analyzed. Thirty-five patients (46%) had a good outcome. The timing of MRI scans did not differ between groups, but the mean age did (42±18 years vs. 56±19 years, p<.01, good vs. poor outcome). Patients with poor outcome had significantly higher percentage of brain volume with ADC < 400×10(-6) mm2 /second (.85±.67% vs. .60±.29%, poor vs. good outcome, p<.05). Using a ROC curve analysis and Youden's index, an ADC <400×10(-6) mm2 /second in ≥.49% of brain was 85% sensitive and 46% specific for poor outcome (p<.05).Quantitative MRI offers additional prognostic information in acute TBI. A whole brain tissue ADC threshold of <400×10(-6) mm2 /second in ≥.49% of brain may be a novel prognostic biomarker.

  View details for DOI 10.1111/jon.12286

  View details for Web of Science ID 000368012400014

• Prediction of final infarct volume on subacute MRI by quantifying cerebral edema in ischemic stroke. Journal of cerebral blood flow and metabolism Tipirneni-Sajja, A., Christensen, S., Straka, M., Inoue, M., Lansberg, M. G., Mlynash, M., Bammer, R., Parsons, M. W., Donnan, G. A., Davis, S. M., Albers, G. W. 2016: 271678X16683960-?

  Abstract

  Final infarct volume in stroke trials is assessed on images obtained between 30 and 90 days after stroke onset. Imaging at such delayed timepoints is problematic because patients may be lost to follow-up or die before the scan. Obtaining an early assessment of infarct volume on subacute scans avoids these limitations; however, it overestimates true infarct volume because of edema. The aim of this study was to develop a novel approach to quantify edema so that final infarct volumes can be approximated on subacute scans. We analyzed data from 20 stroke patients (median age, 75 years) who had baseline, subacute (fu5d) and late (fu90d) MRI scans. Edema displaces CSF from sulci and ventricles; therefore, edema volume was estimated as change in CSF volume between baseline and spatially coregistered fu5d ADC maps. The median (interquartile range, IQR) estimated edema volume was 13.3 (7.5-37.7) mL. The fu5d lesion volumes correlated well with fu90d infarct volumes with slope: 1.24. With edema correction, fu5d infarct volumes are in close agreement, slope: 0.97 and strongly correlated with actual fu90d volumes. The median (IQR) difference between actual and predicted infarct volumes was 0.1 (-3.0-5.7) mL. In summary, this novel technique for estimation of edema allows final infarct volume to be predicted from subacute MRI.

  View details for DOI 10.1177/0271678X16683960

  View details for PubMedID 28155584

• Magnetic resonance imaging-based endovascular versus medical stroke treatment for symptom onset up to 12?h. International journal of stroke Wouters, A., Lemmens, R., Christensen, S., Wilms, G., Dupont, P., Mlynash, M., Schneider, A., Laage, R., Cereda, C. W., Lansberg, M. G., Albers, G. W., Thijs, V. 2016; 11 (1): 127-133

  Abstract

  Recent trials have shown a clear benefit of endovascular therapy for stroke patients presenting within 6 h after stroke onset. Imaging-based selection may identify a cohort with a favorable response to endovascular therapy, in an even later time window.We performed an indirect comparison between outcomes seen in DEFUSE 2, a prospective cohort study of patients who received a baseline MRI before endovascular therapy, and a control group from AXIS 2 receiving standard medical care up to 12 h after symptom onset.Patients from AXIS 2 with a confirmed large vessel occlusion were selected as a control group for DEFUSE 2-patients. The primary endpoint was good functional outcome at day 90 (Modified Rankin Score 0-2). We performed a stratified analysis based on the presence of the target mismatch for both studies and reperfusion status in DEFUSE 2.We compared good functional outcome in 108 patients from AXIS 2 and 99 patients from DEFUSE 2. In DEFUSE 2-patients with the target mismatch profile in whom reperfusion was achieved, the rate of good functional outcome was increased compared to target mismatch patients in AXIS 2, 54% versus 29% (OR 3.2, 95% CI 1.1-9.4). In target mismatch patients treated between 6 and 12 h after stroke onset, this association between study and good functional outcome remained present (OR 9.0, 95% CI 1.1-75.8).This indirect comparison suggests that endovascular treatment resulting in substantial reperfusion is associated with improved outcome in target mismatch patients even beyond 6 h after stroke onset. Confirmation is needed from future clinical trials that randomize patients beyond the 6 h time window.

  View details for DOI 10.1177/1747493015607503

  View details for PubMedID 26763028

• Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME. Annals of neurology Albers, G. W., Goyal, M., Jahan, R., Bonafe, A., Diener, H., Levy, E. I., Pereira, V. M., Cognard, C., Cohen, D. J., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., Baxter, B. W., Devlin, T. G., Lopes, D. K., Reddy, V. K., de Rochemont, R. d., Singer, O. C., Bammer, R., Saver, J. L. 2016; 79 (1): 76-89

  Abstract

  Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile.Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent-retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6-second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI).A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6ml (interquartile range = 0-16). Ischemic core volumes correlated with 27-hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6-second lesion volumes correlated with 27-hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow-up Tmax > 6-second volume (ie, predicted infarct volume) correlated with the 27-hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13ml.Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27-hour infarct volume in acute stroke patients who were treated with reperfusion therapies. ANN NEUROL 2016;79:76-89.

  View details for DOI 10.1002/ana.24543

  View details for PubMedID 26476022

• Inter-rater agreement analysis of the Precise Diagnostic Score for suspected transient ischemic attack. International journal of stroke Cereda, C. W., George, P. M., Inoue, M., Vora, N., Olivot, J., Schwartz, N., Lansberg, M. G., Kemp, S., Mlynash, M., Albers, G. W. 2016; 11 (1): 85-92

  Abstract

  No definitive criteria are available to confirm the diagnosis of transient ischemic attack. Inter-rater agreement between physicians regarding the diagnosis of transient ischemic attack is low, even among vascular neurologists. We developed the Precise Diagnostic Score, a diagnostic score that consists of discrete and well-defined clinical and imaging parameters, and investigated inter-rater agreement in patients with suspected transient ischemic attack.Fellowship-trained vascular neurologists, blinded to final diagnosis, independently reviewed retrospectively identical history, physical examination, routine diagnostic studies, and brain magnetic resonance imaging (diffusion and perfusion images) from consecutive patients with suspected transient ischemic attack. Each patient was rated using the 8-point Precise Diagnostic Score score, composed of a clinical score (0-4 points) and an imaging score (0-4 points). The composite Precise Diagnostic Score determines a Precise Diagnostic Score Likelihood of Brain Ischemia Scale: 0-1 = unlikely, 2 = possible, 3 = probable, 4-8 = very likely.Three raters reviewed data from 114 patients. Using Precise Diagnostic Score, all three raters scored a similar percentage of the clinical events as being "probable" or "very likely" caused by brain ischemia: 57, 55, and 58%. Agreement was high for both total Precise Diagnostic Score (intraclass correlation coefficient of 0.94) and for the Likelihood of Brain Ischemia Scale (agreement coefficient of 0.84).Compared with prior studies, inter-rater agreement for the diagnosis of transient brain ischemia appears substantially improved with the Precise Diagnostic Score scoring system. This score is the first to include specific criteria to assess the clinical relevance of diffusion-weighted imaging and perfusion lesions and supports the added value of magnetic resonance imaging for assessing patients with suspected transient ischemic attack.

  View details for DOI 10.1177/1747493015607507

  View details for PubMedID 26763024

• Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report. Journal of the American Heart Association Albers, G. W., Bernstein, R. A., Brachmann, J., Camm, J., Easton, J. D., Fromm, P., Goto, S., Granger, C. B., Hohnloser, S. H., Hylek, E., Jaffer, A. K., Krieger, D. W., Passman, R., Pines, J. M., Reed, S. D., Rothwell, P. M., Kowey, P. R. 2016; 5 (3)

  View details for DOI 10.1161/JAHA.115.002944

  View details for PubMedID 27068633

• Standards and Barriers in Acute Stroke Therapy: A Leap Forward in the Evolution of Endovascular Interventions for Stroke. Journal of the American College of Cardiology Albers, G. W., Halperin, J. L. 2015; 66 (22): 2506-9

  View details for DOI 10.1016/j.jacc.2015.09.069

  View details for PubMedID 26653624

• Novel TIA biomarkers identified by mass spectrometry-based proteomics INTERNATIONAL JOURNAL OF STROKE George, P. M., Mlynash, M., Adams, C. M., Kuo, C. J., Albers, G. W., Olivot, J. 2015; 10 (8): 1204-1211

  Abstract

  Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment.Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics.Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen.Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found.Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum biomarker for transient ischemic attack. This unbiased proteomic approach may be a promising method to identify novel biomarkers to more precisely diagnose transient ischemic attacks.

  View details for DOI 10.1111/ijs.12603

  View details for Web of Science ID 000367673700011

• The association between lesion location and functional outcome after ischemic stroke. International journal of stroke : official journal of the International Stroke Society Yassi, N., Churilov, L., Campbell, B. C., Sharma, G., Bammer, R., Desmond, P. M., Parsons, M. W., Albers, G. W., Donnan, G. A., Davis, S. M. 2015; 10 (8): 1270-6

  Abstract

  Infarct location has a critical effect on patient outcome after ischemic stroke, but the study of its role independent of overall lesion volume is challenging. We performed a retrospective, hypothesis-generating study of the effect of infarct location on three-month functional outcome in a pooled analysis of the EPITHET and DEFUSE studies.Posttreatment MRI diffusion lesions were manually segmented and transformed into standard-space. A novel composite brain atlas derived from three standard brain atlases and encompassing 132 cortical and sub-cortical structures was used to segment the transformed lesion into different brain regions, and calculate the percentage of each region infarcted. Classification and Regression Tree (CART) analysis was performed to determine the important regions in each hemisphere associated with nonfavorable outcome at day 90 (modified Rankin score [mRS] > 1).Overall, 152 patients (82 left hemisphere) were included. Median diffusion lesion volume was 37·0 ml, and median baseline National Institutes of Health Stroke Score was 13. In the left hemisphere, the strongest determinants of nonfavorable outcome were infarction of the uncinate fasciculus, followed by precuneus, angular gyrus and total diffusion lesion volume. In the right hemisphere, the strongest determinants of nonfavorable outcome were infarction of the parietal lobe followed by the putamen.Assessment of infarct location using CART demonstrates regional characteristics associated with poor outcome. Prognostically important locations include limbic, default-mode and language areas in the left hemisphere, and visuospatial and motor regions in the right hemisphere.

  View details for DOI 10.1111/ijs.12537

  View details for PubMedID 26045301

• Novel TIA biomarkers identified by mass spectrometry-based proteomics. International journal of stroke : official journal of the International Stroke Society George, P. M., Mlynash, M., Adams, C. M., Kuo, C. J., Albers, G. W., Olivot, J. M. 2015; 10 (8): 1204-11

  Abstract

  Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment.Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics.Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen.Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found.Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum biomarker for transient ischemic attack. This unbiased proteomic approach may be a promising method to identify novel biomarkers to more precisely diagnose transient ischemic attacks.

  View details for DOI 10.1111/ijs.12603

  View details for PubMedID 26307429

• Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: rationale and design. International journal of stroke : official journal of the International Stroke Society Johnston, S. C., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Held, P., Jonasson, J., Minematsu, K., Molina, C. A., Wong, L. K. 2015; 10 (8): 1304-8

  Abstract

  The risk of recurrent ischemia is high in the acute period after ischemic stroke and transient ischemic attack. Aspirin is recommended by guidelines for this indication, but more intensive antiplatelet therapy may be justified.We aim to evaluate whether ticagrelor, a potent antiplatelet agent that blocks the P2Y12 receptor without requiring metabolic activation, reduces the risk of major vascular events compared with aspirin when randomization occurs within 24 h after symptom onset of a nonsevere ischemic stroke or high-risk transient ischemic attack.Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) is a randomized, double-blind, event-driven trial and will include an estimated 13,600 participants randomized in 33 countries worldwide to collect 844 primary events.The primary endpoint is the composite of stroke (ischemic or hemorrhagic), myocardial infarction, and death. Time to the first primary endpoint will be compared in the treatment groups during 90-day follow-up, with major hemorrhage serving as the primary safety endpoint. Participants will be followed for an additional 30 days after the randomized treatment period.The SOCRATES trial fulfills an important clinical need by evaluating a potent antiplatelet agent as a superior alternative to current standard of care in patients presenting acutely with ischemic stroke or transient ischemic attack.

  View details for DOI 10.1111/ijs.12610

  View details for PubMedID 26311628

• Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: rationale and design INTERNATIONAL JOURNAL OF STROKE Johnston, S. C., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Held, P., Jonasson, J., Minematsu, K., Molina, C. A., Wong, L. K. 2015; 10 (8): 1304-1308

  View details for DOI 10.1111/ijs.12610

  View details for Web of Science ID 000367673700027

• The association between lesion location and functional outcome after ischemic stroke INTERNATIONAL JOURNAL OF STROKE Yassi, N., Churilov, L., Campbell, B. C., Sharma, G., Bammer, R., Desmond, P. M., Parsons, M. W., Albers, G. W., Donnan, G. A., Davis, S. M., Investigators, E. P. 2015; 10 (8): 1270-1276

  Abstract

  Infarct location has a critical effect on patient outcome after ischemic stroke, but the study of its role independent of overall lesion volume is challenging. We performed a retrospective, hypothesis-generating study of the effect of infarct location on three-month functional outcome in a pooled analysis of the EPITHET and DEFUSE studies.Posttreatment MRI diffusion lesions were manually segmented and transformed into standard-space. A novel composite brain atlas derived from three standard brain atlases and encompassing 132 cortical and sub-cortical structures was used to segment the transformed lesion into different brain regions, and calculate the percentage of each region infarcted. Classification and Regression Tree (CART) analysis was performed to determine the important regions in each hemisphere associated with nonfavorable outcome at day 90 (modified Rankin score [mRS] > 1).Overall, 152 patients (82 left hemisphere) were included. Median diffusion lesion volume was 37·0 ml, and median baseline National Institutes of Health Stroke Score was 13. In the left hemisphere, the strongest determinants of nonfavorable outcome were infarction of the uncinate fasciculus, followed by precuneus, angular gyrus and total diffusion lesion volume. In the right hemisphere, the strongest determinants of nonfavorable outcome were infarction of the parietal lobe followed by the putamen.Assessment of infarct location using CART demonstrates regional characteristics associated with poor outcome. Prognostically important locations include limbic, default-mode and language areas in the left hemisphere, and visuospatial and motor regions in the right hemisphere.

  View details for DOI 10.1111/ijs.12537

  View details for Web of Science ID 000367673700020

• Ultra-acute CT perfusion imaging: A stroke in the scanner. Neurology Christensen, S., Obi, C., Albers, G., Lansberg, M. 2015; 85 (19): 1725-6

  View details for DOI 10.1212/WNL.0000000000002109

  View details for PubMedID 26553942

  View details for PubMedCentralID PMC4653113

• Yield of CT perfusion for the evaluation of transient ischaemic attack. International journal of stroke Kleinman, J. T., Mlynash, M., Zaharchuk, G., Ogdie, A. A., Straka, M., Lansberg, M. G., Schwartz, N. E., Singh, P., Kemp, S., Bammer, R., Albers, G. W., Olivot, J. 2015; 10: 25-29

  Abstract

  BACKGROUND: Magnetic resonance diffusion-weighted imaging and perfusion-weighted imaging are able to identify ischaemic 'footprints' in transient ischaemic attack. Computed tomography perfusion (CTP) may be useful for patient triage and subsequent management. To date, less than 100 cases have been reported, and none have compared computed tomography perfusion to perfusion-weighted imaging (PWI). We sought to define the yield of computed tomography perfusion for the evaluation of transient ischaemic attack. METHODS: Consecutive patients with a discharge diagnosis of possible or definite transient ischaemic event who underwent computed tomography perfusion were included in this study. The presence of an ischaemic lesion was assessed on noncontrast computed tomography, automatically deconvolved CTP(TMax) (Time till the residue function reaches its maximum), and when available on diffusion-weighted imaging and PWI(TMax) maps. RESULTS: Thirty-four patients were included and 17 underwent magnetic resonance imaging. Median delay between onset and computed tomography perfusion was 4·4 h (Interquartile range [IQR]: 1·9-9·6), and between computed tomography perfusion and magnetic resonance imaging was 11 h (Interquartile range: 3·8-22). Noncontrast computed tomography was negative in all cases, while CTP(TMax) identified an ischaemic lesion in 12/34 patients (35%). In the subgroup of patients with multimodal magnetic resonance imaging, an ischaemic lesion was found in six (35%) patients using CTP(TMax) versus nine (53%) on magnetic resonance imaging (five diffusion-weighted imaging, nine perfusion-weighted imaging). The additional yield of CTP(TMax) over computed tomography angiography was significant in the evaluation of transient ischaemic attack (12 vs. 3, McNemar, P = 0·004). CONCLUSIONS: CTP(TMax) found an ischaemic lesion in one-third of acute transient ischaemic attack patients. Computed tomography perfusion may be an acceptable substitute when magnetic resonance imaging is unavailable or contraindicated, and has additional yield over computed tomography angiography. Further studies evaluating the outcome of patients with computed tomography perfusion lesions in transient ischaemic attack are justified at this time.

  View details for DOI 10.1111/j.1747-4949.2012.00941.x

  View details for PubMedID 23228203

• Relationships Between Imaging Assessments and Outcomes in Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke STROKE Albers, G. W., Goyal, M., Jahan, R., Bonafe, A., Diener, H., Levy, E. I., Pereira, V. M., Cognard, C., Yavagal, D. R., Saver, J. L. 2015; 46 (10): 2786-2794

  View details for DOI 10.1161/STROKEAHA.115.010710

  View details for PubMedID 26316344

• Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology Lansberg, M. G., Cereda, C. W., Mlynash, M., Mishra, N. K., Inoue, M., Kemp, S., Christensen, S., Straka, M., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2015; 85 (8): 708-714

  Abstract

  To evaluate whether time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on MRI.Patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion-diffusion target mismatch were included. Reperfusion was defined as a decrease in the perfusion lesion volume of at least 50% between baseline and early follow-up. Good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. Lesion growth was defined as the difference between the baseline and the early follow-up diffusion-weighted imaging lesion volumes.Among 78 patients with the target mismatch profile (mean age 66 ± 16 years, 54% women), reperfusion was associated with increased odds of good functional outcome (adjusted odds ratio 3.7, 95% confidence interval 1.2-12, p = 0.03) and attenuation of lesion growth (p = 0.02). Time to treatment did not modify these effects (p value for the time × reperfusion interaction is 0.6 for good functional outcome and 0.3 for lesion growth). Similarly, in the subgroup of patients with reperfusion (n = 46), time to treatment was not associated with good functional outcome (p = 0.2).The association between endovascular reperfusion and improved functional and radiologic outcomes is not time-dependent in patients with a perfusion-diffusion mismatch. Proof that patients with mismatch benefit from endovascular therapy in the late time window should come from a randomized placebo-controlled trial.

  View details for DOI 10.1212/WNL.0000000000001853

  View details for PubMedID 26224727

• Imaging in StrokeNet Realizing the Potential of Big Data STROKE Liebeskind, D. S., Albers, G. W., Crawford, K., Derdeyn, C. P., George, M. S., Palesch, Y. Y., Toga, A. W., Warach, S., Zhao, W., Brott, T. G., Sacco, R. L., Khatri, P., Saver, J. L., Cramer, S. C., Wolf, S. L., Broderick, J. P., Wintermark, M. 2015; 46 (7): 2000-2006

  View details for DOI 10.1161/STROKEAHA.115.009479

  View details for PubMedID 26045600

• The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion INTERNATIONAL JOURNAL OF STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirnini, A., Liggins, J., Bammer, R., Lansberg, M. G., Kemp, S., Zaharchuk, G., Straka, M., Albers, G. W. 2015; 10 (5): 723-729

  Abstract

  The degree of variability in the rate of early diffusion-weighted imaging expansion in acute stroke has not been well characterized.We hypothesized that patients with slowly expanding diffusion-weighted imaging lesions would have more penumbral salvage and better clinical outcomes following endovascular reperfusion than patients with rapidly expanding diffusion-weighted imaging lesions.In the first part of this substudy of DEFUSE 2, growth curves were constructed for patients with >90% reperfusion and <10% reperfusion. Next, the initial growth rate was determined in all patients with a clearly established time of symptom onset, assuming a lesion volume of 0 ml just prior to symptom onset. Patients who achieved reperfusion (>50% reduction in perfusion-weighted imaging after endovascular therapy) were categorized into tertiles according to their initial diffusion-weighted imaging growth rates. For each tertile, penumbral salvage [comparison of final volume to the volume of perfusion-weighted imaging (Tmax > 6 s)/diffusion-weighted imaging mismatch prior to endovascular therapy], favorable clinical response (National Institutes of Health Stroke Scale improvement of ≥8 points or 0-1 at 30 days), and good functional outcome (90-day modified Rankin score of ≤2) were calculated. A multivariate model assessed whether infarct growth rates were an independent predictor of clinical outcomes.Sixty-five patients were eligible for this study; the median initial growth rate was 3·1 ml/h (interquartile range 0·7-10·7). Target mismatch patients (n = 42) had initial growth rates that were significantly slower than the growth rates in malignant profile (n = 9 patients, P < 0·001). In patients who achieved reperfusion (n = 38), slower early diffusion-weighted imaging growth rates were associated with better clinical outcomes (P < 0·05) and a trend toward more penumbral salvage (n = 31, P = 0·103). A multivariate model demonstrated that initial diffusion-weighted imaging growth rate was an independent predictor of achieving a 90-day modified Rankin score of ≤2.The growth rate of early diffusion-weighted imaging lesions in acute stroke patients is highly variable; malignant profile patients have higher growth rates than patients with target mismatch. A slower rate of early diffusion-weighted imaging growth is associated with a greater degree of penumbral salvage and improved clinical outcomes following endovascular reperfusion.

  View details for DOI 10.1111/ijs.12436

  View details for Web of Science ID 000356718000025

  View details for PubMedID 25580662

  View details for PubMedCentralID PMC4478123

• A score based on age and DWI volume predicts poor outcome following endovascular treatment for acute ischemic stroke INTERNATIONAL JOURNAL OF STROKE Liggins, J. T., Yoo, A. J., Mishra, N. K., Wheeler, H. M., Straka, M., Leslie-Mazwi, T. M., Chaudhry, Z. A., Kemp, S., Mlynash, M., Bammer, R., Albers, G. W., Lansberg, M. G. 2015; 10 (5): 705-709

  Abstract

  The Houston Intra-Arterial Therapy score predicts poor functional outcome following endovascular treatment for acute ischemic stroke based on clinical variables. The present study sought to (a) create a predictive scoring system that included a neuroimaging variable and (b) determine if the scoring systems predict the clinical response to reperfusion.Separate datasets were used to derive (n = 110 from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 study) and validate (n = 125 from Massachusetts General Hospital) scoring systems that predict poor functional outcome, defined as a modified Rankin Scale score of 4-6 at 90 days.Age (P < 0·001; β = 0·087) and diffusion-weighted imaging volume (P = 0·023; β = 0·025) were the independent predictors of poor functional outcome. The Stanford Age and Diffusion-Weighted Imaging score was created based on the patient's age (0-3 points) and diffusion-weighted imaging lesion volume (0-1 points). The percentage of patients with a poor functional outcome increased significantly with the number of points on the Stanford Age and Diffusion-Weighted Imaging score (P < 0·01 for trend). The area under the receiver operating characteristic curve for the Stanford Age and Diffusion-Weighted Imaging score was 0·82 in the derivation dataset. In the validation cohort, the area under the receiver operating characteristic curve was 0·69 for the Stanford Age and Diffusion-Weighted Imaging score and 0·66 for the Houston Intra-Arterial Therapy score (P = 0·45 for the difference). Reperfusion, but not the interactions between the prediction scores and reperfusion, were predictors of outcome (P > 0·5).The Stanford Age and Diffusion-Weighted Imaging and Houston Intra-Arterial Therapy scores can be used to predict poor functional outcome following endovascular therapy with good accuracy. However, these scores do not predict the clinical response to reperfusion. This limits their utility as tools to select patients for acute stroke interventions.

  View details for DOI 10.1111/ijs.12207

  View details for Web of Science ID 000356718000022

  View details for PubMedID 24207136

• Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke NEW ENGLAND JOURNAL OF MEDICINE Saver, J. L., Goyal, M., Bonafe, A., Diener, H., Levy, E. I., Pereira, V. M., Albers, G. W., Cognard, C., Cohen, D. J., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., Baxter, B. W., Devlin, T. G., Lopes, D. K., Reddy, V. K., de Rochemont, R. d., Singer, O. C., Jahan, R. 2015; 372 (24): 2285-2295

  Abstract

  Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome.We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]).The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12).In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).

  View details for DOI 10.1056/NEJMoa1415061

  View details for Web of Science ID 000356019200004

  View details for PubMedID 25882376

• Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation INTERNATIONAL JOURNAL OF STROKE Tu, H. T., Campbell, B. C., Christensen, S., Desmond, P. M., De Silva, D. A., Parsons, M. W., Churilov, L., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2015; 10 (4): 534-540

  Abstract

  BACKGROUND: Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. METHODS: Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial; before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from >4 to >8 s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria. RESULTS: Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum >8 s, volume 48 vs. 29 ml, P = 0·02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0·001), larger infarcts (median volume 75 vs. 23 ml, P = 0·001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0·03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0·03), and higher mortality (36% vs. 16%, P = 0·03) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6·05, 95% confidence interval 1·60-22·83) but not poor functional outcome (modified Rankin scale 3-6, odds ratio = 0·99, 95% confidence interval 0·35-2·80) or mortality (odds ratio = 2·54, 95% confidence interval 0·86-7·49) three-months following stroke, after adjusting for other baseline imbalances. CONCLUSION: Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes.

  View details for DOI 10.1111/ijs.12007

  View details for Web of Science ID 000354494000023

  View details for PubMedID 23489996

• Reperfusion versus recanalization: the winner is…. Stroke; a journal of cerebral circulation Tsai, J. P., Albers, G. W. 2015; 46 (6): 1433-1434

  View details for DOI 10.1161/STROKEAHA.115.009268

  View details for PubMedID 25908456

• Safety and efficacy of desmoteplase given 3-9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial LANCET NEUROLOGY Albers, G. W., von Kummer, R., Truelsen, T., Jensen, J. S., Ravn, G. M., Gronning, B. A., Chabriat, H., Chang, K., Davalos, A. E., Ford, G. A., Grotta, J., Kaste, M., Schwamm, L. H., Shuaib, A. 2015; 14 (6): 575-584

  Abstract

  Current treatment of ischaemic stroke with thrombolytic therapy is restricted to 3-4·5 h after symptom onset. We aimed to assess the safety and efficacy of desmoteplase, a fibrin-dependent plasminogen activator, given between 3 h and 9 h after symptom onset in patients with occlusion or high-grade stenosis in major cerebral arteries.In a prospective, double-blind, multicentre, parallel-group, randomised trial, we enrolled patients from 77 hospitals in 17 countries who had ischaemic stroke and occlusion or high-grade stenosis in major cerebral arteries. We randomly assigned patients in a 1:1 ratio, using computer-generated randomisation lists with stratification for baseline National Institutes of Health Stroke Scale and age, to treatment with desmoteplase (90 μg/kg) given 3-9 h after symptom onset or to placebo. Patients, investigators, staff, and the funder were masked to treatment assignment. The primary outcome was a favourable modified Rankin Scale score (0-2) at day 90 in all treated patients who had at least one postbaseline measurement of the modified Rankin Scale. Safety was assessed in all randomly assigned patients who received study drugs. This trial is registered with ClinicalTrials.gov, number NCT00790920.Between Feb 6, 2009, and Nov 27, 2013, we enrolled 492 patients and randomly assigned 247 to desmoteplase and 245 to placebo (236 in the desmoteplase group and 237 in the placebo group were included in the analysis of the primary endpoint). Median time from stroke onset to treatment was 6·9 h (IQR 5·7-8·0) for placebo and 7·0 h (6·0-7·9) for desmoteplase. Modified Rankin Scale score (0-2) at day 90 occurred in 121 (51%) patients given desmoteplase and 118 (50%) patients given placebo (adjusted odds ratio 1·20, 95% CI 0·79-1·81, p=0·40). 24 (10%) of 240 patients given desmoteplase died compared with 23 (10%) of 238 patients given placebo. Serious adverse events occurred in 64 (27%) of 240 patients receiving desmoteplase compared with 69 (29%) of 238 patients receiving placebo; frequency of symptomatic intracranial haemorrhage (six [3%] patients in the desmoteplase group vs five [2%] in the placebo group), symptomatic cerebral oedema (five [2%] vs four [2%]), and major haemorrhage (ten [4%] vs 15 [6%]) was much the same between treatment groups.Treatment with desmoteplase did not cause safety concerns and did not improve functional outcome when given to patients who had ischaemic stroke and major cerebral artery occlusion beyond 3 h of symptom onset.H Lundbeck A/S.

  View details for DOI 10.1016/S1474-4422(15)00047-2

  View details for Web of Science ID 000354829900009

  View details for PubMedID 25937443

• Reperfusion of Very Low Cerebral Blood Volume Lesion Predicts Parenchymal Hematoma After Endovascular Therapy STROKE Mishra, N. K., Christensen, S., Wouters, A., Campbell, B. C., Straka, M., Mlynash, M., Kemp, S., Cereda, C. W., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2015; 46 (5): 1245-1249

  Abstract

  Ischemic stroke patients with regional very low cerebral blood volume (VLCBV) on baseline imaging have increased risk of parenchymal hemorrhage (PH) after intravenous alteplase-induced reperfusion. We developed a method for automated detection of VLCBV and examined whether patients with reperfused-VLCBV are at increased risk of PH after endovascular reperfusion therapy.Receiver operating characteristic analysis was performed to optimize a relative CBV threshold associated with PH in patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study. Regional reperfused-VLCBV was defined as regions with low relative CBV on baseline imaging that demonstrated normal perfusion (Tmax <6 s) on coregistered early follow-up magnetic resonance imaging. The association between VLCBV, regional reperfused-VLCBV and PH was assessed in univariate and multivariate analyses.In 91 patients, the greatest area under the curve for predicting PH occurred at an relative CBV threshold of <0.42 (area under the curve, 0.77). At this threshold, VLCBV lesion volume ≥3.55 mL optimally predicted PH with 94% sensitivity and 63% specificity. Reperfused-VLCBV lesion volume was more specific (0.74) and equally sensitive (0.94). In total, 18 patients developed PH, of whom 17 presented with VLCBV (39% versus 2%; P=0.001), all of them had regional reperfusion (47% versus 0%; P=0.01), and 71% received intravenous alteplase. VLCBV lesion (odds ratio, 33) and bridging with intravenous alteplase (odds ratio, 3.8) were independently associated with PH. In a separate model, reperfused-VLCBV remained the single independent predictor of PH (odds ratio, 53).These results suggest that VLCBV can be used for risk stratification of patients scheduled to undergo endovascular therapy in trials and routine clinical practice.

  View details for DOI 10.1161/STROKEAHA.114.008171

  View details for PubMedID 25828235

• Apparent diffusion coefficient threshold for delineation of ischemic core. International journal of stroke Purushotham, A., Campbell, B. C., Straka, M., Mlynash, M., Olivot, J., Bammer, R., Kemp, S. M., Albers, G. W., Lansberg, M. G. 2015; 10 (3): 348-353

  Abstract

  MRI-based selection of patients for acute stroke interventions requires rapid accurate estimation of the infarct core on diffusion-weighted MRI. Typically used manual methods to delineate restricted diffusion lesions are subjective and time consuming. These limitations would be overcome by a fully automated method that can rapidly and objectively delineate the ischemic core. An automated method would require predefined criteria to identify the ischemic core.The aim of this study is to determine apparent diffusion coefficient-based criteria that can be implemented in a fully automated software solution for identification of the ischemic core.Imaging data from patients enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study who had early revascularization following intravenous thrombolysis were included. The patients' baseline restricted diffusion and 30-day T2 -weighted fluid-attenuated inversion recovery lesions were manually delineated after coregistration. Parts of the restricted diffusion lesion that corresponded with 30-day infarct were considered ischemic core, whereas parts that corresponded with normal brain parenchyma at 30 days were considered noncore. The optimal apparent diffusion coefficient threshold to discriminate core from noncore voxels was determined by voxel-based receiver operating characteristics analysis using the Youden index.51 045 diffusion positive voxels from 14 patients who met eligibility criteria were analyzed. The mean DWI lesion volume was 24 (± 23) ml. Of this, 18 (± 22) ml was ischemic core and 3 (± 5) ml was noncore. The remainder corresponded to preexisting gliosis, cerebrospinal fluid, or was lost to postinfarct atrophy. The apparent diffusion coefficient of core was lower than that of noncore voxels (P < 0·0001). The optimal threshold for identification of ischemic core was an apparent diffusion coefficient ≤620 × 10(-6 ) mm(2) /s (sensitivity 69% and specificity 78%).Our data suggest that the ischemic core can be identified with an absolute apparent diffusion coefficient threshold. This threshold can be implemented in image analysis software for fully automated segmentation of the ischemic core.

  View details for DOI 10.1111/ijs.12068

  View details for PubMedID 23802548

• Solitaire (TM) with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke INTERNATIONAL JOURNAL OF STROKE Saver, J. L., Goyal, M., Bonafe, A., Diener, H., Levy, E. I., Pereira, V. M., Albers, G. W., Cognard, C., Cohen, D. J., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., Devlin, T. G., Lopes, D. K., Reddy, V., de Rochemont, R. d., Jahan, R. 2015; 10 (3): 439-448

  Abstract

  Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions.The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke.The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled.Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset.The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure.Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2).

  View details for DOI 10.1111/ijs.12459

  View details for Web of Science ID 000351395300035

• Interhospital variation in reperfusion rates following endovascular treatment for acute ischemic stroke. Journal of neurointerventional surgery Liggins, J. T., Mlynash, M., Jovin, T. G., Straka, M., Kemp, S., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2015; 7 (4): 231-233

  Abstract

  Patients who have successful reperfusion following endovascular therapy for acute ischemic stroke have improved clinical outcomes. We sought to determine if the chance of successful reperfusion differs among hospitals, and if hospital site is an independent predictor of reperfusion.Nine hospitals recruited patients in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), a prospective cohort study of endovascular stroke treatment conducted between 2008 and 2011. Patients were included for analysis if they had a baseline Thrombolysis in Cerebral Infarction (TICI) score of 0 or 1. Successful reperfusion was defined as a TICI reperfusion score of 2b or 3 at completion of the procedure. Collaterals were assessed using the Collateral Flow Grading System and were dichotomized as poor (0-2) or good (3-4). The association between hospital site and successful reperfusion was first assessed in an unadjusted analysis and subsequently in a multivariate analysis that adjusted for predictors of successful reperfusion.36 of 89 patients (40%) achieved successful reperfusion. The rate of reperfusion varied from 0% to 77% among hospitals in the univariate analysis (χ(2) p<0.001) but hospital site did not remain as an independent predictor of reperfusion in multivariate analysis (p=0.81) after adjustment for the presence of good collaterals (p<0.01) and use of the Merci retriever (p<0.05).Reperfusion rates vary among hospitals, which may be related to differences in treatment protocols and patient characteristics. Additional studies are needed to identify all of the factors that underlie this variability as this could lead to strategies that reduce interhospital variability in reperfusion rates and improve clinical outcomes.

  View details for DOI 10.1136/neurintsurg-2014-011115

  View details for PubMedID 24662608

• TIA triage in emergency department using acute MRI (TIA-TEAM): A feasibility and safety study. International journal of stroke Vora, N., Tung, C. E., Mlynash, M., Garcia, M., Kemp, S., Kleinman, J., Zaharchuk, G., Albers, G., Olivot, J. 2015; 10 (3): 343-347

  Abstract

  Positive diffusion weighted imaging (DWI) on MRI is associated with increased recurrent stroke risk in TIA patients. Acute MRI aids in TIA risk stratification and diagnosis.To evaluate the feasibility and safety of TIA triage directly from the emergency department (ED) with acute MRI and neurological consultation.Consecutive ED TIA patients assessed by a neurologist underwent acute MRI/MRA of head/neck per protocol and were hospitalized if positive DWI, symptomatic vessel stenosis, or per clinical judgment. Stroke neurologist adjudicated the final TIA diagnosis as definite, possible, or not a cerebrovascular event. Stroke recurrence rates were calculated at 7, 90, 365 days and compared with predicted stroke rates derived from historical DWI and ABCD(2) score data.One hundred twenty-nine enrolled patients had a mean age of 69 years (±17) and median ABCD(2) score of 3 (interquartile range [IQR] 3-4). During triage, 112 (87%) patients underwent acute MRI after a median of 16 h (IQR 10-23) from symptom onset. No patients experienced a recurrent event before imaging. Twenty-four (21%) had positive DWI and 8 (7%) had symptomatic vessel stenosis. Of the total cohort, 83 (64%) were discharged and 46 (36%) were hospitalized. By one-year follow-up, one patient in each group had experienced a stroke. Of 92 patients with MRI and index cerebrovascular event, recurrent stroke rates were 1·1% at 7 and 90 days. These were similar to predicted recurrence rates.TIA triage in the ED using a protocol with neurological consultation and acute MRI is feasible and safe. The majority of patients were discharged without hospitalization and rates of recurrent stroke were not higher than predicted.

  View details for DOI 10.1111/ijs.12390

  View details for PubMedID 25367837

• Alberta Stroke Program Early Computed Tomographic Scoring Performance in a Series of Patients Undergoing Computed Tomography and MRI: Reader Agreement, Modality Agreement, and Outcome Prediction. Stroke; a journal of cerebral circulation McTaggart, R. A., Jovin, T. G., Lansberg, M. G., Mlynash, M., Jayaraman, M. V., Choudhri, O. A., Inoue, M., Marks, M. P., Albers, G. W. 2015; 46 (2): 407-412

  Abstract

  In this study, we compare the performance of pretreatment Alberta Stroke Program Early Computed Tomographic scoring (ASPECTS) using noncontrast CT (NCCT) and MRI in a large endovascular therapy cohort.Prospectively enrolled patients underwent baseline NCCT and MRI and started endovascular therapy within 12 hours of stroke onset. Inclusion criteria for this analysis were evaluable pretreatment NCCT, diffusion-weighted MRI (DWI), and 90-day modified Rankin Scale scores. Two expert readers graded ischemic change on NCCT and DWI using the ASPECTS. ASPECTS scores were analyzed with the full scale or were trichotomized (0-4 versus 5-7 versus 8-10) or dichotomized (0-7 versus 8-10). Good functional outcome was defined as a 90-day modified Rankin Scale score of 0 to 2.Seventy-four patients fulfilled our study criteria. The full-scale inter-rater agreement for CT-ASPECTS and DWI-ASPECTS was 0.579 and 0.867, respectively. DWI-ASPECTS correlated with functional outcome (P=0.004), whereas CT-ASPECTS did not (P=0.534). Both DWI-ASPECTS and CT-ASPECTS correlated with DWI volume. The receiver operating characteristic analysis revealed that DWI-ASPECTS outperformed both CT-ASPECTS and the time interval between symptom onset and start of the procedure for predicting good functional outcome (modified Rankin Scale score, ≤2) and DWI volume ≥70 mL.Inter-rater agreement for DWI-ASPECTS was superior to that for CT-ASPECTS. DWI-ASPECTS outperformed NCCT ASPECTS for predicting functional outcome at 90 days.

  View details for DOI 10.1161/STROKEAHA.114.006564

  View details for PubMedID 25538199

• Transient global amnes a associated with a unilateral infarction of the fornix: case report and review of the literature FRONTIERS IN NEUROLOGY Gupta, M., Kantor, M. A., Tung, C. E., Zhang, N., Albers, G. W. 2015; 5

  View details for DOI 10.3389/fneur.2014.00291

  View details for Web of Science ID 000363751300002

• Selection for delayed intravenous alteplase treatment based on a prognostic score INTERNATIONAL JOURNAL OF STROKE Fulton, R. L., Lees, K. R., Bluhmki, E., Biegert, G., Albers, G. W., Davis, S. M., Donnan, G. A., Grotta, J. C., Hacke, W., Kaste, M., von Kummer, R., Shuaib, A., Toni, D. 2015; 10 (1): 90-94

  Abstract

  Approved use of intravenous alteplase for ischemic stroke offers net benefit. Pooled randomized controlled trial analysis suggests additional patients could benefit but others be harmed with treatment initiated beyond 4·5 h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection.We selected 500 patients treated by intravenous alteplase and 500 controls from Virtual International Stroke Trials Archive, matching modified Rankin score outcomes to those from pooled randomized controlled trial 4·5-6 h data. We ranked patients by prognostic score. We chose limits to optimize our sample for a net treatment benefit significant at P = 0·01 by Cochran-Mantel-Haenszel test and by ordinal regression. For validation, we had these applied to the pooled randomized controlled trial data for 4·5-6 h, testing for net benefit by Cochran-Mantel-Haenszel test, ordinal regression, and also by dichotomized outcomes: modified Rankin score 0-1, mortality and parenchymal hemorrhage type 2 bleeds. All analyses were adjusted for age and National Institutes of Health Stroke Scale.In the training dataset, limits of 56-95 on a prognostic score retained 714 patients in whom there was net benefit significant at P = 0·01. When applied to the 1120 patients in the pooled randomized controlled trial 4·5-6 h dataset, score limits of 56-95 retained 711 patients and gave odds ratio for improved modified Rankin score distribution of 1·13, 95% confidence interval 0·87-1·47, Cochran-Mantel-Haenszel P = 0·89. More patients achieved modified Rankin score 0-1 (odds ratio 1·44, 1·02-2·05, P = 0·04) but mortality and parenchymal hemorrhage type 2 bleeds were increased: odds ratio 1·56, 1·01-2·40, P = 0·04; odds ratio 15·6, 3·7-65·8, P = 0·0002, respectively.Selection of patients between 4·5 and 6 h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

  View details for DOI 10.1111/j.1747-4949.2012.00943.x

  View details for Web of Science ID 000346156500024

  View details for PubMedID 23294942

• Computed Tomography Perfusion Imaging in the Selection of Acute Stroke Patients to Undergo Emergent Carotid Endarterectomy ANNALS OF VASCULAR SURGERY Devlin, T. G., Phade, S. V., Hutson, R. K., Fugate, M. W., Major, G. R., Albers, G. W., Sirelkhatim, A. A., Sapkota, B. L., Quartfordt, S. D., Baxter, B. W. 2015; 29 (1)

  Abstract

  Severe acute stroke patients with critical carotid stenosis or occlusion without intracranial thrombus typically do not undergo emergent carotid thromboendarterectomy (CEA) because of the risk of reperfusion-related intracranial hemorrhage. Past studies have not consistently demonstrated benefit of early operative intervention. Cerebral computed tomography (CT), cervical and cerebral CT angiography (CTA), and cerebral CT perfusion (CTP) imaging may identify a subset of acute stroke patients without intracranial thrombus who may benefit from emergent CEA. Acute stroke patients underwent unenhanced brain CT imaging to exclude pathology that would contraindicate emergent therapy. Emergent CTAs of the intracranial and extracranial vessels were utilized to identify patients who presented with stroke symptoms based on the presence of isolated extracranial carotid disease in the absence of intracranial thromboembolism. CTP was then used to assess the extent of potentially reversible cerebral ischemia (penumbral tissue). Patients with isolated extracranial carotid lesions with significant reversible ischemia in the absence of large areas of irreversible cerebral damage underwent emergent CEA to salvage ischemic penumbra. In 1 year, 3 patients presented with large acute strokes in which CTA disclosed symptomatic extracranial internal carotid artery preocclusive or occlusive lesions without intracranial thromboembolic occlusions. CTP indicated a large area of ischemic penumbra with limited permanent injury. Mean age, time to presentation, and National Institutes of Health stroke score (NIHSS) were 66 years, 4.2 hr, and 19.3. All patients underwent emergent CEA with cervical carotid thrombectomy. Average time from stroke symptom onset to revascularization was 12.5 (range 5.9-19.0) hr. There were no perioperative deaths. At day 5, the mean NIHSS decreased to 7.6 and at day 30 was 4.7. The modified Rankin scale score dropped from a poststroke, preoperative level of 5 to 2.3 by day 30. Emergent CEA should be considered in patients presenting with large acute strokes based on favorable CT, CTA, and CTP findings. Emergent clot localization and physiological assessment of brain "tissue at risk" relative to irreversible cerebral infarction using CT, CTA, and CTP is now available. Utilization of this information by an experienced stroke team of neurologists, radiologists, and surgeons may aid in the recognition of a select group of patients in which emergent CEA may drive to improved outcomes.

  View details for DOI 10.1016/j.avsg.2014.07.023

  View details for Web of Science ID 000346239900027

  View details for PubMedID 25194548

• Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome JOURNAL OF NEUROINTERVENTIONAL SURGERY Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 6 (10): 724-728

  Abstract

  To understand how three commonly used measures of endovascular therapy correlate with clinical outcome and infarct growth.Prospectively enrolled patients underwent baseline MRI and started endovascular therapy within 12 h of stroke onset. The final angiogram was given a primary arterial occlusive lesion (AOL) recanalization score (0-3), a Thrombolysis in Myocardial Infarction (TIMI) score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) score (0-3). The scores were dichotomized into poor revascularization (AOL 0-2, TIMI 0-1 and TICI 0-2a) versus good revascularization (AOL 3, TIMI 2-3, TICI 2b-3). Patients were classified according to whether or not they had target mismatch (TMM). Good outcome was defined as a 90-day modified Rankin Scale score of 0-2.Endovascular treatment was attempted in 100. A good outcome was achieved in 57% of patients with a TICI score of 2b-3 and in 24% of patients with a TICI score of 0-2a (p=0.001). Patients with TIMI scores of 2-3 and an AOL score of 3 had lower rates of good outcome (44% and 47%, respectively), which were not significantly better than those with TIMI scores of 0-1 or AOL scores of 0-2. In patients with TMM, these rates of good outcome improved with all the scoring systems and were significantly better for TIMI and TICI scores. Patients with a TICI score of 2a had rates of good functional outcome and lesion growth which were not different from those with TICI scores of 0-1 but were significantly worse than those with TICI scores of 2b-3.TIMI 2-3 and TICI 2b-3 reperfusion scores demonstrated improved outcome in patients with tissue mismatch with a small infarct core and a larger hypoperfused region but AOL scores did not. Patients with a TICI score of 2a had a poorer outcome and more lesion growth than those with TICI scores of 2b-3.

  View details for DOI 10.1136/neurintsurg-2013-010973

  View details for Web of Science ID 000344939800007

  View details for PubMedCentralID PMC4090292

• Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome. Journal of neurointerventional surgery Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 6 (10): 724-728

  Abstract

  To understand how three commonly used measures of endovascular therapy correlate with clinical outcome and infarct growth.Prospectively enrolled patients underwent baseline MRI and started endovascular therapy within 12 h of stroke onset. The final angiogram was given a primary arterial occlusive lesion (AOL) recanalization score (0-3), a Thrombolysis in Myocardial Infarction (TIMI) score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) score (0-3). The scores were dichotomized into poor revascularization (AOL 0-2, TIMI 0-1 and TICI 0-2a) versus good revascularization (AOL 3, TIMI 2-3, TICI 2b-3). Patients were classified according to whether or not they had target mismatch (TMM). Good outcome was defined as a 90-day modified Rankin Scale score of 0-2.Endovascular treatment was attempted in 100. A good outcome was achieved in 57% of patients with a TICI score of 2b-3 and in 24% of patients with a TICI score of 0-2a (p=0.001). Patients with TIMI scores of 2-3 and an AOL score of 3 had lower rates of good outcome (44% and 47%, respectively), which were not significantly better than those with TIMI scores of 0-1 or AOL scores of 0-2. In patients with TMM, these rates of good outcome improved with all the scoring systems and were significantly better for TIMI and TICI scores. Patients with a TICI score of 2a had rates of good functional outcome and lesion growth which were not different from those with TICI scores of 0-1 but were significantly worse than those with TICI scores of 2b-3.TIMI 2-3 and TICI 2b-3 reperfusion scores demonstrated improved outcome in patients with tissue mismatch with a small infarct core and a larger hypoperfused region but AOL scores did not. Patients with a TICI score of 2a had a poorer outcome and more lesion growth than those with TICI scores of 2b-3.

  View details for DOI 10.1136/neurintsurg-2013-010973

  View details for PubMedID 24353330

• Lipoprotein Phospholipase A2 Mass and Activity Are Not Associated with the Diagnosis of Acute Brain Ischemia CEREBROVASCULAR DISEASES Tai, W., Garcia, M., Mlynash, M., Kemp, S., Albers, G. W., Olivot, J. 2014; 38 (5): 324-327

  View details for DOI 10.1159/000368218

  View details for Web of Science ID 000348046700002

• Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials LANCET Emberson, J., Lees, K. R., Lyden, P., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M., Lindley, R. I., Murray, G., Olivot, J. M., Parsons, M., Tilley, B., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J., Baigent, C., Sandercock, P., Hacke, W. 2014; 384 (9958): 1929-1935

  Abstract

  Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase.We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3-6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality.Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35-2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05-1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95-1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01-7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11-10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98-12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99-1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3-6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h.Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits.UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.

  View details for DOI 10.1016/S0140-6736(14)60584-5

  View details for Web of Science ID 000345450100028

  View details for PubMedCentralID PMC4441266

• Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet Emberson, J., Lees, K. R., Lyden, P., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M., Lindley, R. I., Murray, G., Olivot, J. M., Parsons, M., Tilley, B., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J., Baigent, C., Sandercock, P., Hacke, W. 2014; 384 (9958): 1929-1935

  Abstract

  Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase.We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3-6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality.Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35-2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05-1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95-1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01-7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11-10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98-12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99-1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3-6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h.Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits.UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.

  View details for DOI 10.1016/S0140-6736(14)60584-5

  View details for PubMedID 25106063

• Transcranial Laser Therapy in Acute Stroke Treatment Results of Neurothera Effectiveness and Safety Trial 3, a Phase III Clinical End Point Device Trial STROKE Hacke, W., Schellinger, P. D., Albers, G. W., Bornstein, N. M., Dahlof, B. L., Fulton, R., Kasner, S. E., Shuaib, A., Richieri, S. P., Dilly, S. G., Zivin, J., Lees, K. R. 2014; 45 (11): 3187-3193

  Abstract

  On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke.We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ≤24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included.The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0-2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705-1.488).Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset.http://www.clinicaltrials.gov. Unique identifier: NCT01120301.

  View details for DOI 10.1161/STROKEAHA.114.005795

  View details for Web of Science ID 000344351500020

• Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial INTERNATIONAL JOURNAL OF STROKE Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R. A., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 9 (7): 860-865

  Abstract

  DEFUSE 2 demonstrated that patients with magnetic resonance imaging mismatch had a favorable clinical response to tissue reperfusion assessed by magnetic resonance imaging. This study reports the endovascular results and correlates angiographic reperfusion with clinical and imaging outcomes.Prospectively enrolled ischemic stroke patients underwent baseline magnetic resonance imaging and started endovascular therapy within 12 h of onset. Patients were classified as either target mismatch or no target mismatch using magnetic resonance imaging. The pre- and postprocedure angiogram was evaluated to determine thrombolysis in cerebral infarction scores. Favorable clinical response was determined at day 30, and good functional outcome was defined as a modified Rankin Scale 0-2 at day 90.One-hundred patients had attempted endovascular treatment. At procedure end, 23% were thrombolysis in cerebral infarction 0-1, 31% thrombolysis in cerebral infarction 2A, 28% thrombolysis in cerebral infarction 2B, and 18% thrombolysis in cerebral infarction 3. More favorable thrombolysis in cerebral infarction-reperfusion scores were associated with greater magnetic resonance imaging reperfusion (P<0·001). thrombolysis in cerebral infarction scores correlated with 30-day favorable clinical response (P=0·041) and 90-day modified Rankin Scale 0-2 (P=0·008). These correlations were significant for target mismatch patients at 30 days (P=0·034) and 90 days (P=0·003). Infarct growth was strongly associated with poorer thrombolysis in cerebral infarction scores in target mismatch patients (P<0·001). Patients with thrombolysis in cerebral infarctionnfarction 2A reperfusion had less magnetic resonance imaging reperfusion (P=0·004) and poorer clinical outcome at 90 days (P=0·01) compared with thrombolysis in cerebral infarction 2B-3 patients.Thrombolysis in cerebral infarction reperfusion following endovascular therapy for ischemic stroke is highly correlated with magnetic resonance imaging reperfusion, infarct growth, and clinical outcome.

  View details for DOI 10.1111/ijs.12271

  View details for Web of Science ID 000342581900013

  View details for PubMedCentralID PMC4411961

• Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial. International journal of stroke Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R. A., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 9 (7): 860-865

  Abstract

  DEFUSE 2 demonstrated that patients with magnetic resonance imaging mismatch had a favorable clinical response to tissue reperfusion assessed by magnetic resonance imaging. This study reports the endovascular results and correlates angiographic reperfusion with clinical and imaging outcomes.Prospectively enrolled ischemic stroke patients underwent baseline magnetic resonance imaging and started endovascular therapy within 12 h of onset. Patients were classified as either target mismatch or no target mismatch using magnetic resonance imaging. The pre- and postprocedure angiogram was evaluated to determine thrombolysis in cerebral infarction scores. Favorable clinical response was determined at day 30, and good functional outcome was defined as a modified Rankin Scale 0-2 at day 90.One-hundred patients had attempted endovascular treatment. At procedure end, 23% were thrombolysis in cerebral infarction 0-1, 31% thrombolysis in cerebral infarction 2A, 28% thrombolysis in cerebral infarction 2B, and 18% thrombolysis in cerebral infarction 3. More favorable thrombolysis in cerebral infarction-reperfusion scores were associated with greater magnetic resonance imaging reperfusion (P<0·001). thrombolysis in cerebral infarction scores correlated with 30-day favorable clinical response (P=0·041) and 90-day modified Rankin Scale 0-2 (P=0·008). These correlations were significant for target mismatch patients at 30 days (P=0·034) and 90 days (P=0·003). Infarct growth was strongly associated with poorer thrombolysis in cerebral infarction scores in target mismatch patients (P<0·001). Patients with thrombolysis in cerebral infarctionnfarction 2A reperfusion had less magnetic resonance imaging reperfusion (P=0·004) and poorer clinical outcome at 90 days (P=0·01) compared with thrombolysis in cerebral infarction 2B-3 patients.Thrombolysis in cerebral infarction reperfusion following endovascular therapy for ischemic stroke is highly correlated with magnetic resonance imaging reperfusion, infarct growth, and clinical outcome.

  View details for DOI 10.1111/ijs.12271

  View details for PubMedID 24684804

• NeuroThera® Efficacy and Safety Trial-3 (NEST-3): a double-blind, randomized, sham-controlled, parallel group, multicenter, pivotal study to assess the safety and efficacy of transcranial laser therapy with the NeuroThera® Laser System for the treatment of acute ischemic stroke within 24?h of stroke onset. International journal of stroke Zivin, J. A., Sehra, R., Shoshoo, A., Albers, G. W., Bornstein, N. M., Dahlof, B., Kasner, S. E., Howard, G., Shuaib, A., Streeter, J., Richieri, S. P., Hacke, W. 2014; 9 (7): 950-955

  Abstract

  Transcranial laser therapy is undergoing clinical trials in patients with acute ischemic stroke. The NeuroThera® Efficacy and Safety Trial-1 was strongly positive for 90-day functional benefit with transcranial laser therapy, and post hoc analyses of the subsequent NeuroThera® Efficacy and Safety Trial-2 trial suggested a meaningful beneficial effect in patients with moderate to moderately severe ischemic stroke within 24 h of onset. These served as the basis for the NeuroThera® Efficacy and Safety Trial-3 randomized controlled trial.The purpose of this pivotal study was to demonstrate safety and efficacy of transcranial laser therapy with the NeuroThera® Laser System in the treatment of subjects diagnosed with acute ischemic stroke.NeuroThera® Efficacy and Safety Trial-3 is a double-blind, randomized, sham-controlled, parallel group, multicenter, pivotal study that will enroll 1000 subjects at up to 50 sites. All subjects will receive standard medical management based on the American Stroke Association and European Stroke Organization Guidelines. In addition to standard medical management, both groups will undergo the transcranial laser therapy procedure between 4·5 and 24 h of stroke onset. The study population will be randomized into two arms: the sham control group will receive a sham transcranial laser therapy procedure and the transcranial laser therapy group will receive an active transcranial laser therapy procedure. The randomization ratio will be 1:1 and will be stratified to ensure a balanced subject distribution between study arms.The primary efficacy end point is disability at 90 days (or the last rating), as assessed on the modified Rankin Scale, dichotomized as a success (a score of 0-2) or a failure (a score of 3 to 6).

  View details for DOI 10.1111/j.1747-4949.2012.00896.x

  View details for PubMedID 23013107

• Fatal acanthamoeba encephalitis in a patient with a total artificial heart (syncardia) device. Open forum infectious diseases Tan, S. K., Gajurel, K., Tung, C., Albers, G., Deresinski, S., Montoya, J. G., Sheikh, A. Y., Banerjee, D., Ha, R. 2014; 1 (2): ofu057-?

  Abstract

  Acanthamoeba encephalitis is an uncommon but often fatal infection complication. Here we report the first case of Acanthamoeba encephalitis in a patient with a Total Artificial Heart device.

  View details for DOI 10.1093/ofid/ofu057

  View details for PubMedID 25734127

• Exploratory Analysis of Glyburide as a Novel Therapy for Preventing Brain Swelling NEUROCRITICAL CARE Sheth, K. N., Kimberly, W. T., Elm, J. J., Kent, T. A., Yoo, A. J., Thomalla, G., Campbell, B., Donnan, G. A., Davis, S. M., Albers, G. W., Jacobson, S., del Zoppo, G., Simard, J. M., Stern, B. J., Mandava, P. 2014; 21 (1): 43-51

  Abstract

  Malignant infarction is characterized by the formation of cerebral edema, and medical treatment is limited. Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. We previously reported feasibility of the GAMES-Pilot study, a two-center prospective, open label, phase IIa trial of 10 subjects at high risk for malignant infarction based on diffusion weighted imaging (DWI) threshold of 82 cm(3) treated with RP-1127 (glyburide for injection). In this secondary analysis, we tested the hypothesis that RP-1127 may be efficacious in preventing poor outcome when compared to controls.Controls suffering large hemispheric infarction were obtained from the EPITHET and MMI-MRI studies. We first screened subjects for controls with the same DWI threshold used for enrollment into GAMES-Pilot, 82 cm(3). Next, to address imbalances, we applied a weighted Euclidean matching. Ninety day mRS 0-4, rate of decompressive craniectomy, and mortality were the primary clinical outcomes of interest.The mean age of the GAMES cohort was 51 years and initial DWI volume was 102 ± 23 cm(3). After Euclidean matching, GAMES subjects showed similar NIHSS, higher DWI volume, younger age and had mRS 0-4-90% versus 50% in controls p = 0.049; with a similar trend in mRS 0-3 (40 vs. 25%; p = 0.43) and trend toward lower mortality (10 vs. 35%; p = 0.21).In this pilot study, RP-1127-treated subjects showed better clinical outcomes when compared to historical controls. An adequately powered and randomized phase II trial of patients at risk for malignant infarction is needed to evaluate the potential efficacy of RP-1127.

  View details for DOI 10.1007/s12028-014-9970-2

  View details for Web of Science ID 000339350500007

  View details for PubMedID 24671831

• Pittsburgh outcomes after stroke thrombectomy score predicts outcomes after endovascular therapy for anterior circulation large vessel occlusions. Stroke; a journal of cerebral circulation Rangaraju, S., Liggins, J. T., Aghaebrahim, A., Streib, C., Sun, C., Gupta, R., Nogueira, R., Frankel, M., Mlynash, M., Lansberg, M., Albers, G., Jadhav, A., Jovin, T. G. 2014; 45 (8): 2298-2304

  Abstract

  Prognostication tools that predict good outcome in patients with anterior circulation large vessel occlusions after endovascular therapy are lacking. We aim to develop a tool that incorporates clinical and imaging data to predict outcomes after endovascular therapy.In a derivation cohort of anterior circulation large vessel occlusion stroke patients treated with endovascular therapy within 8 hours from time last seen well (n=247), we performed logistic regression to identify independent predictors of good outcome (90-day modified Rankin Scale, 0-2). Factors were weighted based on β-coefficients to derive the Pittsburgh Outcomes After Stroke Thrombectomy (POST) score. POST was validated in an institutional endovascular database (University of Pittsburgh Medical Center, n=393) and the Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) data set (n=105), as well as in patients treated beyond 8 hours (n=194) and in octogenarians (n=111).In the derivation cohort, independent predictors (P<0.1) of good outcome included 24- to 72-hour final infarct volume (in cm(3), P<0.001), age (years, P<0.001), and parenchymal hematoma types 1 and 2 (H, P=0.01). POST was calculated as age+0.5×final infarct volume+15×H. Patients with POST score <60 had a 91% chance of good outcome compared with 4% with POST score ≥120. POST accurately predicted good outcomes in the derivation (area under the curve [AUC]=0.85) and validation cohorts (University of Pittsburgh Medical Center, AUC=0.81; DEFUSE-2, AUC=0.86), as well as in patients treated beyond 8 hours (AUC, 0.85) and octogenarians (AUC=0.76). POST had better predictive accuracy for good and poor outcome than the ischemic stroke predictive risk score (iSCORE).POST score is a validated predictor of outcome in patients with anterior circulation large vessel occlusions after endovascular therapy.

  View details for DOI 10.1161/STROKEAHA.114.005595

  View details for PubMedID 25005445

• Predictors of Functional Dependence Despite Successful Revascularization in Large-Vessel Occlusion Strokes STROKE Shi, Z., Liebeskind, D. S., Xiang, B., Ge, S. G., Feng, L., Albers, G. W., Budzik, R., Devlin, T., Gupta, R., Jansen, O., Jovin, T. G., Killer-Oberpfalzer, M., Lutsep, H. L., Macho, J., Nogueira, R. G., Rymer, M., Smith, W. S., Wahlgren, N., Duckwiler, G. R. 2014; 45 (7): 1977-1984

  View details for DOI 10.1161/STROKEAHA.114.005603

  View details for Web of Science ID 000338129400023

• O-034 Carotid Artery Angioplasty versus Stenting in Acute Ischemic Stroke. Journal of neurointerventional surgery Choudhri, O., Gupta, M., Feroze, A., Albers, G., Lansberg, M., Do, H., Dodd, R., Marcellus, M., Marks, M. 2014; 6: A18-9

  Abstract

  Acute ischemic stroke secondary to cervical carotid artery occlusion can lead to significant morbidity and mortality. Acute carotid occlusion may be managed by carotid angioplasty, stenting, or both. The use of carotid stents requires patients to be placed on dual antiplatelet agents, which may contribute to increased haemorrhage risk. We undertook this study to evaluate outcomes for angioplasty alone versus stenting in the setting of acute carotid occlusion.All patients treated from 2008 to 2013 with acute cervical internal carotid artery occlusions that had intervention within eight hours of symptom onset were included. NIHSS were recorded preceding intervention, and clinical outcomes were assessed using mRS at 90 days. All imaging and angiographic data were reviewed for pre-procedural ASPECT scores, pre- and post- TICI reperfusion scores, and intracranial haemorrhage as defined by PH grading score for haemorrhage. Demographic and treatment factors were correlated with good functional outcome (mRS < 2 at 90 days and a comparison was made for patients undergoing angioplasty alone versus stenting. All patients who underwent carotid stent were placed on dual antiplatelet agents while angioplasty patients received aspirin only.Twenty-four patients (15 males, 9 females; mean age, 67 years) satisfied the inclusion criteria. Seventeen patients underwent placement of carotid stent and 7 patients had angioplasty alone. Patients in both subgroups were comparable across characteristics including comorbidities, time for onset to recanalization, ASPECTS, and IV tPA use. 35% of patients who underwent stenting had good functional outcomes, versus 71% of patients treated with angioplasty alone, although these differences were not statistically significant. No differences were seen for the two treatment groups comparing time from onset to recanalization, baseline ASPECTS, and IV tPA use. Additionally, increased age (p = 0.049) and post-treatment parenchymal haemorrhage- PH1 or PH2 (p = 0.016) correlated with poor outcomes (mRS > 2). All parenchymal haemorrhages (6/17) and deaths (5/17) fell within the stenting subgroup (35.3% and 29.4%, respectively).This data suggest that patients undergoing angioplasty alone in the setting of acute internal carotid artery occlusion may have improved functional outcome at 90-day compared to those undergoing stenting. This study was limited by a small sample size and a larger study would be needed to confirm these findings.angioplasty, stenting, acute ischemic stroke, carotid occlusion.O. Choudhri: None. M. Gupta: None. A. Feroze: None. G. Albers: None. M. Lansberg: None. H. Do: None. R. Dodd: None. M. Marcellus: None. M. Marks: None.

  View details for DOI 10.1136/neurintsurg-2014-011343.34

  View details for PubMedID 25064877

• Endovascular treatment for stroke: when does the window for good outcome close? The Lancet. Neurology Albers, G. W. 2014; 13 (6): 529-31

  View details for DOI 10.1016/S1474-4422(14)70086-9

  View details for PubMedID 24784551

• Comparison of magnetic resonance imaging mismatch criteria to select patients for endovascular stroke therapy. Stroke; a journal of cerebral circulation Mishra, N. K., Albers, G. W., Christensen, S., Marks, M., Hamilton, S., Straka, M., Liggins, J. T., Kemp, S., Mlynash, M., Bammer, R., Lansberg, M. G. 2014; 45 (5): 1369-1374

  Abstract

  The Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study has shown that clinical response to endovascular reperfusion differs between patients with and without perfusion-diffusion (perfusion-weighted imaging-diffusion-weighted imaging, PWI-DWI) mismatch: patients with mismatch have a favorable clinical response to reperfusion, whereas patients without mismatch do not. This study examined whether alternative mismatch criteria can also differentiate patients according to their response to reperfusion.Patients from the DEFUSE 2 study were categorized according to vessel occlusion on magnetic resonance angiography (MRA) and DWI lesion volume criteria (MRA-DWI mismatch) and symptom severity and DWI criteria (clinical-DWI mismatch). Favorable clinical response was defined as an improvement of ≥8 points on the National Institutes of Health Stroke Scale (NIHSS) by day 30 or an NIHSS score of ≤1 at day 30. We assessed, for each set of criteria, whether the association between reperfusion and favorable clinical response differed according to mismatch status.A differential response to reperfusion was observed between patients with and without MRA-DWI mismatch defined as an internal carotid artery or M1 occlusion and a DWI lesion <50 mL. Reperfusion was associated with good functional outcome in patients who met these MRA-DWI mismatch criteria (odds ratio [OR], 8.5; 95% confidence interval [CI], 2.3-31.3), whereas no association was observed in patients who did not meet these criteria (OR, 0.5; 95% CI, 0.08-3.1; P for difference between the odds, 0.01). No differential response to reperfusion was observed with other variations of the MRA-DWI or clinical-DWI mismatch criteria.The MRA-DWI mismatch is a promising alternative to DEFUSE 2's PWI-DWI mismatch for patient selection in endovascular stroke trials.

  View details for DOI 10.1161/STROKEAHA.114.004772

  View details for PubMedID 24699054

• Aortic arch atheroma: a plaque of a different color or more of the same? Stroke; a journal of cerebral circulation George, P. M., Albers, G. W. 2014; 45 (5): 1239-1240

  View details for DOI 10.1161/STROKEAHA.114.004827

  View details for PubMedID 24699053

• Effect of collateral blood flow on patients undergoing endovascular therapy for acute ischemic stroke. Stroke; a journal of cerebral circulation Marks, M. P., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Kemp, S., McTaggart, R., Inoue, M., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 45 (4): 1035-1039

  Abstract

  Our aim was to determine the relationships between angiographic collaterals and diffusion/perfusion findings, subsequent infarct growth, and clinical outcome in patients undergoing endovascular therapy for ischemic stroke.Sixty patients with a thrombolysis in cerebral infarction (TICI) score of 0 or 1 and internal carotid artery/M1 occlusion at baseline were evaluated. A blinded reader assigned a collateral score using a previous 5-point scale, from 0 (no collateral flow) to 4 (complete/rapid collaterals to the entire ischemic territory). The analysis was dichotomized to poor flow (0-2) versus good flow (3-4). Collateral score was correlated with baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging volume, perfusion-weighted imaging volume (Tmax ≥6 seconds), TICI reperfusion, infarct growth, and modified Rankin Scale score at day 90.Collateral score correlated with baseline National Institutes of Health Stroke Scale (P=0.002) and median volume of tissue at Tmax ≥6 seconds (P=0.009). Twenty-nine percent of patients with poor collateral flow had TICI 2B-3 reperfusion versus 65.5% with good flow (P=0.009). Patients with poor collaterals who reperfused (TICI 2B-3) were more likely to have a good functional outcome (modified Rankin Scale score 0-2 at 90 days) compared with patients who did not reperfuse (odds ratio, 12; 95% confidence interval, 1.6-98). There was no difference in the rate of good functional outcome after reperfusion in patients with poor collaterals versus good collaterals (P=1.0). Patients with poor reperfusion (TICI 0-2a) showed a trend toward greater infarct growth if they had poor collaterals versus good collaterals (P=0.06).Collaterals correlate with baseline National Institutes of Health Stroke Scale, perfusion-weighted imaging volume, and good reperfusion. However, target mismatch patients who reperfuse seem to have favorable outcomes at a similar rate, irrespective of the collateral score.http://www.clinicaltrials.gov. Unique identifier: NCT01349946.

  View details for DOI 10.1161/STROKEAHA.113.004085

  View details for PubMedID 24569816

• Early diffusion-weighted imaging reversal after endovascular reperfusion is typically transient in patients imaged 3 to 6 hours after onset. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Christensen, S., Wheeler, H. M., Straka, M., Tipirneni, A., Kemp, S. M., Zaharchuk, G., Olivot, J., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1024-1028

  Abstract

  The aim of this study was to assess the frequency and extent of early diffusion-weighted imaging (DWI) lesion reversal after endovascular therapy and to determine whether early reversal is sustained or transient.MRI with DWI perfusion imaging was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular treatment; follow-up MRI was obtained on day 5. Both DWIs were coregistered to follow-up MRI. Early DWI reversal was defined as the volume of the DWI 1 lesion that was not superimposed on the DWI 2 lesion. Permanent reversal was the volume of the DWI 1 lesion not superimposed on the day 5 infarct volume. Associations between early DWI reversal and clinical outcomes in patients with and without reperfusion were assessed.A total of 110 patients had technically adequate DWI before endovascular therapy (performed median [interquartile range], 4.5 [2.8-6.2] hours after onset); 60 were eligible for this study. Thirty-two percent had early DWI reversal >10 mL; 17% had sustained reversal. The median volume of permanent reversal at 5 days was 3 mL (interquartile range, 1.7-7.0). Only 2 patients (3%) had a final infarct volume that was smaller than their baseline DWI lesion. Early DWI reversal was not an independent predictor of clinical outcome and was not associated with early reperfusion.Early DWI reversal occurred in about one third of patients after endovascular therapy; however, reversal was often transient and was not associated with a significant volume of tissue salvage or favorable clinical outcome.

  View details for DOI 10.1161/STROKEAHA.113.002135

  View details for PubMedID 24558095

• Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort. Stroke; a journal of cerebral circulation Olivot, J. M., Mlynash, M., Inoue, M., Marks, M. P., Wheeler, H. M., Kemp, S., Straka, M., Zaharchuk, G., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1018-1023

  Abstract

  We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2).Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days.Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014.HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

  View details for DOI 10.1161/STROKEAHA.113.003857

  View details for PubMedID 24595591

• Patients with single distal MCA perfusion lesions have a high rate of good outcome with or without reperfusion INTERNATIONAL JOURNAL OF STROKE Lemmens, R., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Marks, M. P., Davis, S. M., Donnan, G. A., Albers, G. W., Lansberg, M. G. 2014; 9 (2): 156-159

  Abstract

  Reperfusion is associated with good functional outcome after stroke. However, minimal data are available regarding the effect of reperfusion on clinical outcome and infarct growth in patients with distal MCA branch occlusions.The aim of this study was to evaluate this association and to determine the impact of the perfusion-diffusion mismatch.Individual patient data from three stroke studies (EPITHET, DEFUSE and DEFUSE 2) with baseline MRI profiles and reperfusion status were pooled. Patients were included if they had a single cortical perfusion lesion on their baseline MRI that was consistent with a distal MCA branch occlusion. Good functional outcome was defined as a score of 0-2 on the modified Rankin Scale at day 90 and infarct growth was defined as change in lesion volume between the baseline DWI and the final T2/FLAIR.Thirty patients met inclusion criteria. Eighteen (60%) had a good functional outcome and twenty (67%) had reperfusion. Reperfusion was not associated with good functional outcome in the overall cohort (OR: 1·0, 95% CI 0·2-4·7) and also not in the subset of patients with a PWI-DWI mismatch (n = 17; OR: 0·7, 95% CI 0·1-5·5). Median infarct growth was modest and not significantly different between patients with (0 ml) and without reperfusion (6 ml); P = 0·2.The overall high rate of good outcomes in patients with distal MCA perfusion lesions might obscure a potential benefit from reperfusion in this population. A larger pooled analysis evaluating the effect of reperfusion in patients with distal MCA branch occlusions is warranted as confirmation of our results could have implications for the design of future stroke trials.

  View details for DOI 10.1111/ijs.12230

  View details for PubMedID 24373557

• Secondary prevention of atherothrombotic or cryptogenic stroke. Circulation Tai, W. A., Albers, G. W. 2014; 129 (4): 527-531

  View details for DOI 10.1161/CIRCULATIONAHA.112.000658

  View details for PubMedID 24470474

• Radiological examinations of transient ischemic attack. Frontiers of neurology and neuroscience Tung, C. E., Olivot, J. M., Albers, G. W. 2014; 33: 115-122

  Abstract

  Neuroimaging is critical in the evaluation of patients with TIA. CT and MRI are the two available options for imaging. Head CT is more widely available and commonly used. Diffusion MRI is the recommended modality to image an ischemic lesion. The presence of a diffusion lesion in a patient with transient neurological symptoms is an indicator of a high risk of recurrent stroke. Perfusion imaging with perfusion MRI or CT perfusion may improve the detection of ischemic lesions. Noninvasive vessel imaging may detect a symptomatic vessel lesion associated with an increased risk of stroke.

  View details for DOI 10.1159/000351913

  View details for PubMedID 24157560

• Lipoprotein phospholipase A2 mass and activity are not associated with the diagnosis of acute brain ischemia. Cerebrovascular diseases Tai, W., Garcia, M., Mlynash, M., Kemp, S., Albers, G. W., Olivot, J. 2014; 38 (5): 324-327

  Abstract

  Elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with both coronary artery and cerebrovascular diseases. The clinical diagnosis of neurovascular events, specifically transient ischemic attack can be challenging, although there is disagreement among vascular trained neurologists regarding this. Currently, there is no single accurate biomarker for the diagnosis of acute brain ischemia.We studied the relationship between Lp-PLA2 mass and activity levels and the diagnosis of acute brain ischemia in the acute phase among patients evaluated in the emergency department following transient focal neurological symptoms.Patients evaluated in our academic center for transient neurological symptoms of possible ischemic mechanism were enrolled with informed consent. Lp-PLA2 mass and activity levels were performed by DiaDexus, Inc.100 patients were enrolled: 58 were ischemic (30 stroke, 28 TIA), 10 were unknown, and 28 were non-ischemic. Blood samples were collected after a median delay of 23 h (IQR: 17, 36) after symptom onset. The median levels of Lp-PLA2 activity level for ischemic (stroke and TIA) versus non-ischemic events were 186.5 nmol/ml/min (IQR = 153, 216.3) and 169 nmol/ml/min (IQR = 137, 212.5), respectively. The median levels of Lp-PLA2 mass level for ischemic versus non-ischemic events were 202 ng/ml (IQR = 171.6, 226.1) and 192 ng/ml (167.8, 230). The differences in median Lp-PLA2 mass and activity levels were not statistically significant in the ischemic versus non-ischemic patients. Vessel imaging revealed a symptomatic stenosis in 14 patients (10 intracranial and 4 cervical). The median Lp-PLA2 mass and activity levels among patients with a symptomatic stenosis were not significantly higher than the levels measured in TIA/stroke patients without stenosis.The results of our study do not support the early measurement of Lp-PLA2 mass or activity levels for confirming an ischemic etiology in patients experiencing minor or transient focal neurological events.

  View details for PubMedID 25428761

• Transient global amnesia associated with a unilateral infarction of the fornix: case report and review of the literature. Frontiers in neurology Gupta, M., Kantor, M. A., Tung, C. E., Zhang, N., Albers, G. W. 2014; 5: 291-?

  Abstract

  Stroke is an extremely uncommon cause of transient global amnesia (TGA). Unilateral lesions of the fornix rarely cause amnesia and have not previously been reported to be associated with the distinctive amnesic picture of TGA. We describe the case of a 60-year-old woman who presented with acute onset, recent retrograde, and anterograde amnesia characteristic of TGA. Serial magnetic resonance imaging showed a persistent focal infarction of the body and left column of the fornix, without acute lesions in the hippocampus or other structures. Amnesia resolved in 6 h. Infarction of the fornix should thus be included in the differential diagnosis of TGA, as it changes the management of this otherwise self-limited syndrome.

  View details for DOI 10.3389/fneur.2014.00291

  View details for PubMedID 25628601

  View details for PubMedCentralID PMC4290584

• Pilot Study of Intravenous Glyburide in Patients With a Large Ischemic Stroke STROKE Sheth, K. N., Kimberly, W. T., Elm, J. J., Kent, T. A., Mandava, P., Yoo, A. J., Thomalla, G., Campbell, B., Donnan, G. A., Davis, S. M., Albers, G. W., Jacobson, S., Simard, J. M., Stern, B. J. 2014; 45 (1): 281-283

  Abstract

  Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection).We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm3, whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127≤10 hours.Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 102±23 cm3. There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 50±33 cm3. The proportion of 90-day modified Rankin Scale≤4 was 90% (40% modified Rankin Scale, ≤3).RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01268683.

  View details for DOI 10.1161/STROKEAHA.113.003352

  View details for PubMedID 24193798

• THRIVE Score Predicts Outcomes With a Third-Generation Endovascular Stroke Treatment Device in the TREVO-2 Trial. Stroke; a journal of cerebral circulation Flint, A. C., Xiang, B., Gupta, R., Nogueira, R. G., Lutsep, H. L., Jovin, T. G., Albers, G. W., Liebeskind, D. S., Sanossian, N., Smith, W. S. 2013; 44 (12): 3370-3375

  Abstract

  Several outcome prediction scores have been tested in patients receiving acute stroke treatment with previous generations of endovascular stroke treatment devices. The TREVO-2 trial was a randomized controlled trial comparing a novel endovascular stroke treatment device (the Trevo device) to a previous-generation endovascular stroke treatment device (the Merci device).We used data from the TREVO-2 trial to validate the Totaled Health Risks in Vascular Events (THRIVE) score in patients receiving treatment with a third-generation endovascular stroke treatment device and to compare THRIVE to other predictive scores. We used logistic regression to model outcomes and compared score performance with receiver operating characteristic curve analysis.In the TREVO-2 trial, the THRIVE score strongly predicts clinical outcome and mortality. The relationship between THRIVE score and outcome is not influenced by either success of recanalization or the type of device used (Trevo versus Merci). The superiority of the Trevo device to the Merci device is evident particularly among patients with a low-to-moderate THRIVE score (0-5; 53.8% good outcome with Trevo versus 27.5% good outcome with Merci). In receiver operating characteristic curve analysis, the THRIVE score was comparable or superior to several other outcome prediction scores (HIAT, HIAT-2, SPAN-100, and iScore).The THRIVE score strongly predicts clinical outcome and mortality in the TREVO-2 trial. Taken together with THRIVE validation data from patients receiving intravenous tissue-type plasminogen activator or no acute treatment, the THRIVE score has broad predictive power in patients with acute ischemic stroke, which is likely because THRIVE reflects a set of strong nonmodifiable predictors of stroke outcome. A free Web calculator for the THRIVE score is available at http://www.thrivescore.org.

  View details for DOI 10.1161/STROKEAHA.113.002796

  View details for PubMedID 24072003

• Stroke Treatment Academic Industry Roundtable Research Priorities in the Assessment of Neurothrombectomy Devices STROKE Saver, J. L., Jovin, T. G., Smith, W. S., Albers, G. W. 2013; 44 (12): 3596-3601

  Abstract

  The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of stroke therapies. At STAIR VIII, consensus recommendations were developed for clinical trial strategies to demonstrate the benefit of endovascular reperfusion therapies for acute ischemic stroke.Prospects for success with forthcoming endovascular trials are robust, because new neurothrombectomy devices have superior reperfusion efficacy compared with earlier-generation interventions. Specific recommendations are provided for trial designs in 3 populations: (1) patients undergoing intravenous fibrinolysis, (2) early patients ineligible for or having failed intravenous fibrinolysis, and (3) wake-up and other late-presenting patients. Among intravenous fibrinolysis-eligible patients, key principles are that CT or MRI confirmation of target arterial occlusions should precede randomization; endovascular intervention should be pursued with the greatest rapidity possible; and combined intravenous and neurothrombectomy therapy is more promising than neurothrombectomy alone. Among patients ineligible for or having failed intravenous fibrinolysis, scientific equipoise was affirmed and the need to randomize all eligible patients emphasized. Vessel imaging to confirm occlusion is mandatory, and infarct core and penumbral imaging is desirable in later time windows. Additional STAIR VIII recommendations include approaches to test multiple devices in a single trial, utility weighting of disability end points, and adaptive designs to delineate time and tissue injury thresholds at which benefits from intervention no longer accrue.Endovascular research priorities in acute ischemic stroke are to perform trials testing new, highly effective neuro thrombectomy devices rapidly deployed in patients confirmed to have target vessel occlusions.

  View details for DOI 10.1161/STROKEAHA.113.002769

  View details for PubMedID 24193797

• Imaging recommendations for acute stroke and transient ischemic attack patients: A joint statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery. AJNR. American journal of neuroradiology Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J., Derdeyn, C., Hetts, S. W., Johnson, M. H., Kidwell, C., Lev, M. H., Liebeskind, D. S., Rowley, H., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 34 (11): E117-27

  Abstract

  Stroke is a leading cause of death and disability worldwide. Imaging plays a critical role in evaluating patients suspected of acute stroke and transient ischemic attack, especially before initiating treatment. Over the past few decades, major advances have occurred in stroke imaging and treatment, including Food and Drug Administration approval of recanalization therapies for the treatment of acute ischemic stroke. A wide variety of imaging techniques has become available to assess vascular lesions and brain tissue status in acute stroke patients. However, the practical challenge for physicians is to understand the multiple facets of these imaging techniques, including which imaging techniques to implement and how to optimally use them, given available resources at their local institution. Important considerations include constraints of time, cost, access to imaging modalities, preferences of treating physicians, availability of expertise, and availability of endovascular therapy. The choice of which imaging techniques to employ is impacted by both the time urgency for evaluation of patients and the complexity of the literature on acute stroke imaging. Ideally, imaging algorithms should incorporate techniques that provide optimal benefit for improved patient outcomes without delaying treatment.

  View details for DOI 10.3174/ajnr.A3690

  View details for PubMedID 23907247

• Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J. A., Derdeyn, C. P., Hetts, S. W., Johnson, M. H., Kidwell, C. S., Lev, M. H., Liebeskind, D. S., Rowley, H. A., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 10 (11): 828-832

  Abstract

  In the article entitled "Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery", we are proposing a simple, pragmatic approach that will allow the reader to develop an optimal imaging algorithm for stroke patients at their institution.

  View details for DOI 10.1016/j.jacr.2013.06.019

  View details for Web of Science ID 000327418100009

• Reduction in Early Stroke Risk in Carotid Stenosis With Transient Ischemic Attack Associated With Statin Treatment STROKE Merwick, A., Albers, G. W., Arsava, E. M., Ay, H., Calvet, D., Coutts, S. B., Cucchiara, B. L., Demchuk, A. M., Giles, M. F., Mas, J., Olivot, J. M., Purroy, F., Rothwell, P. M., Saver, J. L., Sharma, V. K., Tsivgoulis, G., Kelly, P. J. 2013; 44 (10): 2814-2820

  Abstract

  Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis.We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded.In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8-2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054).In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.

  View details for DOI 10.1161/STROKEAHA.113.001576

  View details for Web of Science ID 000324831900038

  View details for PubMedID 23908061

• Acute Stroke Imaging Research Roadmap II STROKE Wintermark, M., Albers, G. W., Broderick, J. P., Demchuk, A. M., Fiebach, J. B., Fiehler, J., Grotta, J. C., Houser, G., Jovin, T. G., Lees, K. R., Lev, M. H., Liebeskind, D. S., Luby, M., Muir, K. W., Parsons, M. W., von Kummer, R., Wardlaw, J. M., Wu, O., Yoo, A. J., Alexandrov, A. V., Alger, J. R., Aviv, R. I., Bammer, R., Baron, J., Calamante, F., Campbell, B. C., Carpenter, T. C., Christensen, S., Copen, W. A., Derdeyn, C. P., Haley, C., Khatri, P., Kudo, K., Lansberg, M. G., Latour, L. L., Lee, T., Leigh, R., Lin, W., Lyden, P., Mair, G., Menon, B. K., Michel, P., Mikulik, R., Nogueira, R. G., Ostergaard, L., Pedraza, S., Riedel, C. H., Rowley, H. A., Sanelli, P. C., Sasaki, M., Saver, J. L., Schaefer, P. W., Schellinger, P. D., Tsivgoulis, G., Wechsler, L. R., White, P. M., Zaharchuk, G., Zaidat, O. O., Davis, S. M., Donnan, G. A., Furlan, A. J., Hacke, W., Kang, D., Kidwell, C., Thijs, V. N., Thomalla, G., Warach, S. J. 2013; 44 (9): 2628-2639

  View details for DOI 10.1161/STROKEAHA.113.002015

  View details for Web of Science ID 000329982500063

  View details for PubMedID 23860298

• Recommendations on Angiographic Revascularization Grading Standards for Acute Ischemic Stroke A Consensus Statement STROKE Zaidat, O. O., Yoo, A. J., Khatri, P., Tomsick, T. A., von Kummer, R., Saver, J. L., Marks, M. P., Prabhakaran, S., Kallmes, D. F., Fitzsimmons, B. M., Mocco, J., Wardlaw, J. M., Barnwell, S. L., Jovin, T. G., Linfante, I., Siddiqui, A. H., Alexander, M. J., Hirsch, J. A., Wintermark, M., Albers, G., Woo, H. H., Heck, D. V., Lev, M., Aviv, R., Hacke, W., Warach, S., Broderick, J., Derdeyn, C. P., Furlan, A., Nogueira, R. G., Yavagal, D. R., Goyal, M., Demchuk, A. M., Bendszus, M., Liebeskind, D. S. 2013; 44 (9): 2650-2663

  View details for DOI 10.1161/STROKEAHA.113.001972

  View details for Web of Science ID 000329982500066

  View details for PubMedID 23920012

• Comparison of the response to endovascular reperfusion in relation to site of arterial occlusion. Neurology Lemmens, R., Mlynash, M., Straka, M., Kemp, S., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2013; 81 (7): 614-618

  Abstract

  We explored the relationship between the site of vascular occlusion and the response to endovascular treatment in patients with acute ischemic stroke and also considered the impact of mismatch profile.DEFUSE-2 was a prospective cohort study of patients treated with endovascular therapy. Patients with internal carotid artery (ICA) and middle cerebral artery (MCA) involvement were included in this substudy. Mismatch and reperfusion status was assessed on MRI. Favorable clinical response was defined as an improvement of at least 8 points on the NIH Stroke Scale.Reperfusion rates were comparable in both groups (61% for ICA and 59% for MCA). In the setting of reperfusion, percentages of favorable clinical response were similar between patients with stroke due to ICA (65%) and MCA (63%) occlusions. When reperfusion was not achieved, favorable outcomes were less frequent with obstructions of the ICA (9%) than the MCA (52%). Among target mismatch patients, the adjusted odds ratio for favorable clinical response associated with reperfusion was 39.7 (95% confidence interval 1.4-1,132.8) for ICA occlusions vs 5.1 (95% confidence interval 1.4-19.3) for MCA occlusions.Endovascular reperfusion is associated with favorable clinical response regardless of the location of the arterial occlusion. This association is strongest for target mismatch patients with ICA occlusions. Target mismatch patients with either ICA or MCA occlusions appear to be good candidates for endovascular reperfusion therapy.

  View details for DOI 10.1212/WNL.0b013e3182a08f07

  View details for PubMedID 23851962

• Impact of diffusion-weighted imaging lesion volume on the success of endovascular reperfusion therapy. Stroke; a journal of cerebral circulation Olivot, J., Mosimann, P. J., Labreuche, J., Inoue, M., Meseguer, E., Desilles, J., Rouchaud, A., Klein, I. F., Straka, M., Bammer, R., Mlynash, M., Amarenco, P., Albers, G. W., Mazighi, M. 2013; 44 (8): 2205-2211

  Abstract

  BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization. METHODS: We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days. RESULTS: A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5-43) after a median onset time to imaging of 110 minutes (interquartile range, 77-178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31-0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206-285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90-13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles (P<0.005). CONCLUSIONS: Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.

  View details for DOI 10.1161/STROKEAHA.113.000911

  View details for PubMedID 23760215

• Validating Imaging Biomarkers of Cerebral Edema in Patients With Severe Ischemic Stroke JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Yoo, A. J., Sheth, K. N., Kimberly, W. T., Chaudhry, Z. A., Elm, J. J., Jacobson, S., Davis, S. M., Donnan, G. A., Albers, G. W., Stern, B. J., Gonzalez, R. G. 2013; 22 (6): 742-749

  Abstract

  There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether magnetic resonance imaging (MRI)-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints.Serial MRI studies from patients in the Echoplanar Imaging Thrombolytic Evaluation Trial with initial diffusion-weighted imaging (DWI) lesion volume >82 cm(3) were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and days 3 to 5. We assessed interrater agreement, volume change between scans, and the association of volume change with early neurologic deterioration (National Institutes of Health Stroke Scale score worsening of ≥ 4 points), a 90-day modified Rankin scale (mRS) score of 0 to 4, and mortality.Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm(3) and 234 cm(3), respectively. The mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2 ± 8.3% (P < .0001), and the mean percent ventricle volume decrease was 45.6 ± 16.9% (P < .001). Percent hemisphere growth predicted early neurologic deterioration (area under the curve [AUC] 0.92; P = .0005) and 90-day mRS 0 to 4 (AUC 0.80; P = .02).In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2012.01.002

  View details for Web of Science ID 000323497700008

  View details for PubMedID 22325573

  View details for PubMedCentralID PMC3529850

• Clinical outcomes strongly associated with the degree of reperfusion achieved in target mismatch patients: pooled data from the diffusion and perfusion imaging evaluation for understanding stroke evolution studies. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Straka, M., Kemp, S., Jovin, T. G., Tipirneni, A., Hamilton, S. A., Marks, M. P., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (7): 1885-1890

  Abstract

  BACKGROUND AND PURPOSE: To investigate relationships between the degree of early reperfusion achieved on perfusion-weighted imaging and clinical outcomes in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. We hypothesized that there would be a strong correlation between the degree of reperfusion achieved and clinical outcomes in target mismatch (TMM) patients. METHODS: The degree of reperfusion was calculated on the basis of the difference in perfusion-weighted imaging volumes (time to maximum of tissue residue function [Tmax]>6 s) between the baseline MRI and the early post-treatment follow-up scan. Patients were grouped into quartiles, on the basis of degree of reperfusion achieved, and the association between the degree of reperfusion and clinical outcomes in TMM and no TMM patients was assessed. Favorable clinical response was determined at day 30 on the basis of the National Institutes of Health Stroke Scale and good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. RESULTS: This study included 121 patients; 98 of these had TMM. The median degree of reperfusion achieved was not different in TMM patients (60%) versus No TMM patients (64%; P=0.604). The degree of reperfusion was strongly correlated with both favorable clinical response (P<0.001) and good functional outcome (P=0.001) in TMM patients; no correlation was present in no TMM. The frequency of achieving favorable clinical response or good functional outcome was significantly higher in TMM patients in the highest reperfusion quartile versus the lower 3 quartiles (88% versus 41% as odds ratio, 10.3; 95% confidence interval, 2.8-37.5; and 75% versus 34% as odds ratio, 5.9; 95% confidence interval, 2.1-16.7, respectively). A receiver operating characteristic curve analysis identified 90% as the optimal reperfusion threshold for predicting good functional outcomes. CONCLUSIONS: The degree of reperfusion documented on perfusion-weighted imaging after reperfusion therapies corresponds closely with clinical outcomes in TMM patients. Reperfusion of ≥90% of the perfusion lesion is an appropriate goal for reperfusion therapies to aspire to.

  View details for DOI 10.1161/STROKEAHA.111.000371

  View details for PubMedID 23704106

• MR RESCUE Is the Glass Half-Full or Half-Empty? STROKE Parsons, M. W., Albers, G. W. 2013; 44 (7): 2055-2057

  View details for DOI 10.1161/STROKEAHA.113.001443

  View details for Web of Science ID 000330527500058

  View details for PubMedID 23760218

• Impact of Recanalization, Reperfusion, and Collateral Flow on Clinical Efficacy 28th Princeton Conference Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2013: S11–S12

  View details for DOI 10.1161/STROKEAHA.111.000258

  View details for Web of Science ID 000319459000005

  View details for PubMedID 23709700

• Details of a prospective protocol for a collaborative meta-analysis of individual participant data from all randomized trials of intravenous rt-PA vs. control: statistical analysis plan for the Stroke Thrombolysis Trialists' Collaborative meta-analysis INTERNATIONAL JOURNAL OF STROKE Emberson, J., Lees, K. R., Howard, G., Bluhmki, E., Tilley, B., Albers, G., Baigent, C., Blackwell, L., Davis, S., Donnan, G., Grotta, J., Hacke, W., Kaste, M., von Kummer, R., Lansberg, M., Lindley, R., Lyden, P., Sandercock, P., Toni, D., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J. 2013; 8 (4): 278-283

  View details for DOI 10.1111/ijs.12040

  View details for Web of Science ID 000319398900023

• Imaging-based selection for intra-arterial stroke therapies. Journal of neurointerventional surgery Morais, L. T., Leslie-Mazwi, T. M., Lev, M. H., Albers, G. W., Yoo, A. J. 2013; 5: i13-20

  View details for DOI 10.1136/neurintsurg-2013-010733

  View details for PubMedID 23572461

• Advanced imaging improves prediction of hemorrhage after stroke thrombolysis ANNALS OF NEUROLOGY Campbell, B. C., Christensen, S., Parsons, M. W., Churilov, L., Desmond, P. M., Barber, P. A., Butcher, K. S., Levi, C. R., De Silva, D. A., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2013; 73 (4): 510-519

  Abstract

  OBJECTIVE: Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion. METHODS: The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume<2.5th percentile of brain contralateral to the infarct. Parenchymal hematoma (PH) was defined using European Cooperative Acute Stroke Study criteria. Reperfusion was assessed using subacute perfusion MRI coregistered to baseline imaging. RESULTS: In DEFUSE, 69 patients were analyzed, including 9 who developed PH. The >2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p<0.001) and tPA (p=0.02) predicted PH independent of clinical factors better than models using diffusion or time to maximum>8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis. INTERPRETATION: VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion. ANN NEUROL 2013;

  View details for DOI 10.1002/ana.23837

  View details for Web of Science ID 000319523800012

  View details for PubMedCentralID PMC3665631

• Selection of patients for intra-arterial therapy--authors' reply. Lancet neurology Lansberg, M. G., Albers, G. W. 2013; 12 (3): 225-226

  View details for DOI 10.1016/S1474-4422(13)70019-X

  View details for PubMedID 23415563

• Early Diffusion-Weighted Imaging and Perfusion-Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2 STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirneni, A., Liggins, J., Zaharchuk, G., Straka, M., Kemp, S., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (3): 681-685

  Abstract

  It is hypothesized that early diffusion-weighted imaging (DWI) lesions accurately estimate the size of the irreversibly injured core and thresholded perfusion-weighted imaging (PWI) lesions (time to maximum of tissue residue function [Tmax] >6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and posttreatment PWI is hypothesized to predict infarct volume.This is a substudy of Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2); all patients with technically adequate MRI scans at 3 time points were included. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program. Final infarct volumes were assessed with 5-day fluid-attenuated inversion recovery and were corrected for edema. Reperfusion was defined on the basis of the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes.Seventy-three patients were eligible. Twenty-six patients with >90% reperfusion show a high correlation between early DWI volume and final infarct volume (r=0.95; P<0.001). Nine patients with <10% reperfusion have a high correlation between baseline PWI (Tmax >6 seconds) volume and final infarct volume (r=0.86; P=0.002). Using all 73 patients, the union of baseline DWI and early follow-up PWI is highly correlated with final infarct volume (r=0.94; P<0.001). The median absolute difference between observed and predicted final volumes is 15 mL (interquartile range, 5.5-30.2).Baseline DWI and early follow-up PWI (Tmax >6 seconds) volumes provide a reasonable approximation of final infarct volume after endovascular therapy.

  View details for DOI 10.1161/STROKEAHA.111.000135

  View details for Web of Science ID 000315447400024

  View details for PubMedID 23390119

  View details for PubMedCentralID PMC3625664

• The Effects of Alteplase 3 to 6 Hours After Stroke in the EPITHET-DEFUSE Combined Dataset Post Hoc Case-Control Study STROKE Ogata, T., Christensen, S., Nagakane, Y., Ma, H., Campbell, B. C., Churilov, L., Lansberg, M. G., Straka, M., De Silva, D. A., Mlynash, M., Bammer, R., Olivot, J., Desmond, P. M., Albers, G. W., Davis, S. M., Donnan, G. A. 2013; 44 (1): 87-93

  Abstract

  Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques.The EPITHET-DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay >6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures.From 165 patients with adequate MR scans in the EPITHET-DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo (P=0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P=0.003). Mortality and clinical outcomes were not different between groups.The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging.

  View details for DOI 10.1161/STROKEAHA.112.668301

  View details for Web of Science ID 000312883800016

  View details for PubMedID 23250996

• Advanced Imaging to Extend the Therapeutic Time Window of Acute Ischemic Stroke ANNALS OF NEUROLOGY Fisher, M., Albers, G. W. 2013; 73 (1): 4-9

  Abstract

  Reperfusion therapy for acute stroke has evolved from the initial use of intravenous tissue plasminogen activator (tPA) within 3 hours of symptom onset to more recent guideline-recommended use up to 4.5 hours. In addition, endovascular therapy is increasingly utilized for stroke treatment and is typically initiated up to 8 hours after onset. Recent studies demonstrate that imaging of the ischemic penumbra with diffusion/perfusion magnetic resonance imaging (MRI) can identify subgroups of patients who are likely to improve following successful reperfusion (Target Mismatch profile) and others who are at increased risk for hemorrhage and poor clinical outcomes (Malignant profile). New data indicate that stent retriever devices provide better recanalization efficacy and clinical outcomes than the previously available mechanical thrombectomy devices. Going forward, we believe that the use of penumbral imaging with validated MRI techniques, as well as the currently less well-validated computed tomography (CT) perfusion approach, will maximize benefit and reduce the risk of adverse events and poor outcomes when used both early after stroke onset and at later time points. New trials that feature diffusion/perfusion MRI or CT perfusion-based patient selection for treatment with intravenous tPA and or endovascular therapies versus nonreperfused control groups are planned or in progress. We predict that these trials will confirm the hypothesis that penumbral imaging can enhance patient selection and extend the therapeutic time window for acute ischemic stroke.

  View details for DOI 10.1002/ana.23744

  View details for Web of Science ID 000314660800005

  View details for PubMedID 23378323

• Oral Antithrombotic Agents for the Prevention of Stroke in Nonvalvular Atrial Fibrillation A Science Advisory for Healthcare Professionals From the American Heart Association/American Stroke Association STROKE Furie, K. L., Goldstein, L. B., Albers, G. W., Khatri, P., Neyens, R., Turakhia, M. P., Turan, T. N., Wood, K. A. 2012; 43 (12): 3442-3453

  View details for Web of Science ID 000311497600063

  View details for PubMedID 22858728

• Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial LANCET Nogueira, R. G., Lutsep, H. L., Gupta, R., Jovin, T. G., Albers, G. W., Walker, G. A., Liebeskind, D. S., Smith, W. S. 2012; 380 (9849): 1231-1240

  Abstract

  Present mechanical devices are unable to achieve recanalisation in up to 20-40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever.In this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18-85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8-29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69-85 years) and NIHSS scores (≤18 vs 19-29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01270867.Between Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92-9·69; p(superiority)<0·0001). Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0·1826).Patients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever.Stryker Neurovascular.

  View details for DOI 10.1016/S0140-6736(12)61299-9

  View details for Web of Science ID 000309817500030

  View details for PubMedID 22932714

• MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study LANCET NEUROLOGY Lansberg, M. G., Straka, M., Kemp, S., Mlynash, M., Wechsler, L. R., Jovin, T. G., Wilder, M. J., Lutsep, H. L., Czartoski, T. J., Bernstein, R. A., Chang, C. W., Warach, S., Fazekas, F., Inoue, M., Tipirneni, A., Hamilton, S. A., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2012; 11 (10): 860-867

  Abstract

  Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion.In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data.138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8·8 (95% CI 2·7-29·0) in the target mismatch group and 0·2 (0·0-1·6) in the no target mismatch group (p=0·003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4·0, 95% CI 1·3-12·2) in the target mismatch group, but not in the no target mismatch group (1·9, 0·2-18·7).Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted.National Institute for Neurological Disorders and Stroke.

  View details for DOI 10.1016/S1474-4422(12)70203-X

  View details for PubMedID 22954705

• The Desmoteplase in Acute Ischemic Stroke (DIAS) clinical trial program INTERNATIONAL JOURNAL OF STROKE von Kummer, R., Albers, G. W., Mori, E. 2012; 7 (7): 589-596

  Abstract

  Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in phase III of clinical development. In comparison to alteplase, it has high fibrin selectivity, is associated with minimal or no neurotoxicity, and has no apparent negative effect on the blood-brain barrier. The safety and efficacy of desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind, placebo-controlled, phase III trials are ongoing at >200 sites worldwide (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo-controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in Acute Ischemic Stroke-Japan, n = 48; DIAS-J).The objective of DIAS-3 and DIAS-4 is to evaluate the safety and efficacy of a single IV bolus injection of 90 μg/kg desmoteplase given three- to nine-hours after onset of ischemic stroke (National Institutes of Health Stroke Scale 4-24, age 18-85 years). The objective of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70 and 90 μg/kg three- to nine-hours after ischemic stroke onset in Japanese patients.Patients are included with occlusion or high-grade stenosis (thrombolysis in myocardial infarction 0-1) in proximal cerebral arteries on magnetic resonance or computed tomography angiography but excluded with extended ischemic edema on computed tomography or diffusion-weighted imaging.Desmoteplase is the only thrombolytic agent in late-stage development for acute ischemic stroke that is now tested in patients with proven stroke pathology. The results of the Desmoteplase in Acute Ischemic Stroke clinical trial program will show whether patients with major artery occlusions but not extended ischemic brain damage can be safely and effectively treated up to nine-hours after onset.

  View details for DOI 10.1111/j.1747-4949.2012.00910.x

  View details for Web of Science ID 000308968100021

  View details for PubMedID 22989394

• Patients With the Malignant Profile Within 3 Hours of Symptom Onset Have Very Poor Outcomes After Intravenous Tissue-Type Plasminogen Activator Therapy STROKE Inoue, M., Mlynash, M., Straka, M., Lansberg, M. G., Zaharchuk, G., Bammer, R., Albers, G. W. 2012; 43 (9): 2494-2496

  Abstract

  The malignant profile has been associated with poor outcomes after reperfusion in the 3- to 6-hour time window. The aim of this study was to estimate the incidence and prognostic implications of the malignant profile, as identified by CT perfusion, in intravenous tissue-type plasminogen activator-treated patients who were imaged <3 hours from stroke onset.The incidence of the malignant profile, based on the previously published optimal perfusion-weighted imaging definition, was assessed in consecutive patients using a fully automated software program (RApid processing of Perfusion and Diffusion [RAPID]). A receiver operating characteristic curve analysis was done to identify time to maximum and core volume thresholds that optimally identify patients with poor outcome (modified Rankin Scale 5-6).Forty-two patients had an interpretable CT perfusion performed within 3 hours of symptom onset. Mean age was 74±14 years and median (interquartile range) National Institutes of Stroke Scale score was 13 (6-19). Four patients (9.5%) met the prespecified criteria for the malignant profile and all 4 had poor outcome. Receiver operating characteristic analysis determined that the best CT perfusion measure to identify patients with poor outcome was a cerebral blood flow based infarct core >53 mL (100% specificity and 67% sensitivity). This criterion identified 5 patients as malignant (12%). The poor outcome rate in these patients was 100% versus 7.1% in the 37 nonmalignant patients (P<0.001).The incidence of the malignant profile on CT perfusion is approximately 10% in tissue-type plasminogen activator-eligible patients imaged within 3 hours of symptom onset. The clinical outcome of these patients is very poor despite intravenous tissue-type plasminogen activator therapy.

  View details for DOI 10.1161/STROKEAHA.112.653329

  View details for Web of Science ID 000308416300050

  View details for PubMedID 22811464

• Clinical Assessment of Standard and Generalized Autocalibrating Partially Parallel Acquisition Diffusion Imaging: Effects of Reduction Factor and Spatial Resolution AMERICAN JOURNAL OF NEURORADIOLOGY Andre, J. B., Zaharchuk, G., Fischbein, N. J., Augustin, M., Skare, S., Straka, M., Rosenberg, J., Lansberg, M. G., Kemp, S., Wijman, C. A., Albers, G. W., Schwartz, N. E., Bammer, R. 2012; 33 (7): 1337-1342

  Abstract

  PI improves routine EPI-based DWI by enabling higher spatial resolution and reducing geometric distortion, though it remains unclear which of these is most important. We evaluated the relative contribution of these factors and assessed their ability to increase lesion conspicuity and diagnostic confidence by using a GRAPPA technique.Four separate DWI scans were obtained at 1.5T in 48 patients with independent variation of in-plane spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1 versus R = 3). A neuroradiologist with access to clinical history and additional imaging sequences provided a reference standard diagnosis for each case. Three blinded neuroradiologists assessed scans for abnormalities and also evaluated multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic regression was used to determine the impact of each factor on subjective image quality and confidence.Reference standard diagnoses in the patient cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n = 5). While readers preferred both a higher reduction factor and a higher spatial resolution, the largest effect was due to an increased reduction factor (odds ratio, 47 ± 16). Small lesions were more confidently discriminated from artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward the reference standard reading and exclusively for posterior fossa lesions.PI improves DWI primarily by reducing geometric distortion rather than by increasing spatial resolution. This outcome leads to a more accurate and confident diagnosis of small lesions.

  View details for DOI 10.3174/ajnr.A2980

  View details for Web of Science ID 000307628200025

  View details for PubMedID 22403781

• Combined spin- and gradient-echo perfusion-weighted imaging MAGNETIC RESONANCE IN MEDICINE Schmiedeskamp, H., Straka, M., Newbould, R. D., Zaharchuk, G., Andre, J. B., Olivot, J., Moseley, M. E., Albers, G. W., Bammer, R. 2012; 68 (1): 30-40

  Abstract

  In this study, a spin- and gradient-echo echo-planar imaging (SAGE EPI) MRI pulse sequence is presented that allows simultaneous measurements of gradient-echo and spin-echo dynamic susceptibility-contrast perfusion-weighted imaging data. Following signal excitation, five readout trains were acquired using spin- and gradient-echo echo-planar imaging, all of them with echo times of less than 100 ms. Contrast agent concentrations in brain tissue were determined based on absolute R2* and R(2) estimates rather than relative changes in the signals of individual echo trains, producing T(1)-independent dynamic susceptibility-contrast perfusion-weighted imaging data. Moreover, this acquisition technique enabled vessel size imaging through the simultaneous quantification of R2* and R(2), without an increase in acquisition time. In this work, the concepts of SAGE EPI pulse sequence and results in stroke and tumor imaging are presented. Overall, SAGE EPI combined the advantages of higher sensitivity to contrast agent passage of gradient-echo perfusion-weighted imaging with better microvascular selectivity of spin-echo perfusion-weighted imaging.

  View details for DOI 10.1002/mrm.23195

  View details for Web of Science ID 000305119100004

  View details for PubMedID 22114040

  View details for PubMedCentralID PMC3374915

• Comparison of Arterial Spin Labeling and Bolus Perfusion-Weighted Imaging for Detecting Mismatch in Acute Stroke STROKE Zaharchuk, G., El Mogy, I. S., Fischbein, N. J., Albers, G. W. 2012; 43 (7): 1843-1848

  Abstract

  The perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch paradigm is widely used in stroke imaging studies. Arterial spin labeling (ASL) is an alternative perfusion method that does not require contrast. This study compares the agreement of ASL-DWI and PWI-DWI mismatch classification in patients with stroke.This was a retrospective study drawn from all 1.5-T MRI studies performed in 2010 at a single institution. Inclusion criteria were: symptom onset<5 days, DWI lesion>10 mL, and acquisition of both PWI and ASL. DWI and PWI time to maximum>6 seconds lesion volumes were determined using automated software. Patients were classified into reperfused, matched, or mismatch groups. Two radiologists classified ASL-DWI qualitatively into the same categories blinded to DWI-PWI. Agreement between both individual readers and methods was assessed.Fifty-one studies met the inclusion criteria. Seven cases were excluded (1 due to PWI susceptibility artifact, 2 due to motion, and 4 due to severe ASL border zone sign), resulting in 44 studies for comparison. Interrater agreement for ASL-DWI mismatch status was high (κ=0.92; 95% CI, 0.80-1.00). ASL-DWI and PWI-DWI mismatch categories agreed in 25 of 44 cases (57%). In the 16 of 19 discrepant cases (84%), ASL overestimated the PWI lesion size. In 34 of 44 cases (77%), they agreed regarding the presence of mismatch versus no mismatch.Mismatch classification based on ASL and PWI agrees frequently but not perfectly. ASL tends to overestimate the PWI time to maximum lesion volume. Improved ASL methodologies and/or higher field strength are necessary before ASL can be recommended for routine use in acute stroke.

  View details for DOI 10.1161/STROKEAHA.111.639773

  View details for Web of Science ID 000305882000030

  View details for PubMedID 22539548

  View details for PubMedCentralID PMC3383868

• Automated Perfusion Imaging for the Evaluation of Transient Ischemic Attack STROKE Kleinman, J. T., Zaharchuk, G., Mlynash, M., Ogdie, A. A., Straka, M., Lansberg, M. G., Schwartz, N. E., Kemp, S., Bammer, R., Albers, G. W., Olivot, J. 2012; 43 (6): 1556-1560

  Abstract

  Diffusion-weighted imaging (DWI) is recommended for the evaluation of transient ischemic attack. Perfusion imaging can increase the yield of MRI in transient ischemic attack. We evaluated automated bolus perfusion (the time when the residue function reaches its maximum [TMax] and mean transit time [MTT]) and arterial spin labeling (ASL) sequences for the detection of ischemic lesions in patients with transient ischemic attack.We enrolled consecutive patients evaluated for suspicion of acute transient ischemic attack by multimodal MRI within 36 hours of symptom onset. Two independent raters assessed the presence and location of ischemic lesions blinded to the clinical presentation. The prevalence of ischemic lesions and the interrater agreement were 1,410 assessed.From January 2010 to 2011, 93 patients were enrolled and 90 underwent perfusion imaging (69 bolus perfusion and 76 ASL). Overall, 25 of 93 patients (27%) were DWI-positive and 14 (15%) were perfusion-positive but DWI-negative (ASL n=9; TMax n=9; MTT n=2). MTT revealed an ischemic lesion in fewer patients than TMax (7 versus 20, P=0.004). Raters agreed on 89% of diffusion-weighted imaging cases, 89% of TMax, 87% o10f010 MTT, and 90% of ASL cases. The interrater agreement was good for DWI, TMax, and ASL (κ=0.73, 0.72, and 0.74, respectively) and fair for MTT (κ=0.43). Diffusion and/or perfusion were positive in 39 of 69 (57%) patients with a discharge diagnosis of possible ischemic event.Our results suggest that in patients referred for suspicion of transient ischemic attack, automated TMax is more sensitive than MTT, and both ASL and TMax increase the yield of MRI for the detection of ischemic lesions.

  View details for DOI 10.1161/STROKEAHA.111.644971

  View details for Web of Science ID 000304523800025

  View details for PubMedID 22474058

• Hemisphere Volume Is Associated with Neurological Deterioration and Outcome after Malignant Infarction 64th Annual Meeting of the American-Academy-of-Neurology (AAN) Sheth, K., Yoo, A., Gonzalez, R., Kimberly, W., Chaudhry, Z., Elm, J., Jacobson, S., Davis, S., Donnan, G., Albers, G., Stern, B. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000303204804024

• Closure or Medical Therapy for Cryptogenic Stroke with Patent Foramen Ovale NEW ENGLAND JOURNAL OF MEDICINE Furlan, A. J., Reisman, M., Massaro, J., Mauri, L., Adams, H., Albers, G. W., Felberg, R., Herrmann, H., Kar, S., Landzberg, M., Raizner, A., Wechsler, L. 2012; 366 (11): 991-999

  Abstract

  The prevalence of patent foramen ovale among patients with cryptogenic stroke is higher than that in the general population. Closure with a percutaneous device is often recommended in such patients, but it is not known whether this intervention reduces the risk of recurrent stroke.We conducted a multicenter, randomized, open-label trial of closure with a percutaneous device, as compared with medical therapy alone, in patients between 18 and 60 years of age who presented with a cryptogenic stroke or transient ischemic attack (TIA) and had a patent foramen ovale. The primary end point was a composite of stroke or transient ischemic attack during 2 years of follow-up, death from any cause during the first 30 days, or death from neurologic causes between 31 days and 2 years.A total of 909 patients were enrolled in the trial. The cumulative incidence (Kaplan-Meier estimate) of the primary end point was 5.5% in the closure group (447 patients) as compared with 6.8% in the medical-therapy group (462 patients) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P=0.37). The respective rates were 2.9% and 3.1% for stroke (P=0.79) and 3.1% and 4.1% for TIA (P=0.44). No deaths occurred by 30 days in either group, and there were no deaths from neurologic causes during the 2-year follow-up period. A cause other than paradoxical embolism was usually apparent in patients with recurrent neurologic events.In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA. (Funded by NMT Medical; ClinicalTrials.gov number, NCT00201461.).

  View details for Web of Science ID 000301482800002

  View details for PubMedID 22417252

• Arterial Spin Labeling Imaging Findings in Transient Ischemic Attack Patients: Comparison with Diffusion- and Bolus Perfusion-Weighted Imaging CEREBROVASCULAR DISEASES Zaharchuk, G., Olivot, J., Fischbein, N. J., Bammer, R., Straka, M., Kleinman, J. T., Albers, G. W. 2012; 34 (3): 221-228

  Abstract

  Since transient ischemic attacks (TIAs) can predict future stroke, it is important to distinguish true vascular events from non-vascular etiologies. Arterial spin labeling (ASL) is a non-contrast magnetic resonance (MR) method that is sensitive to cerebral perfusion and arterial arrival delays. Due to its high sensitivity to minor perfusion alterations, we hypothesized that ASL abnormalities would be identified frequently in TIA patients, and could therefore help increase clinicians' confidence in the diagnosis.We acquired diffusion-weighted imaging (DWI), intracranial MR angiography (MRA), and ASL in a prospective cohort of TIA patients. A subset of these patients also received bolus contrast perfusion-weighted imaging (PWI). Two neuroradiologists evaluated the images in a blinded fashion to determine the frequency of abnormalities on each imaging sequence. Kappa (ĸ) statistics were used to assess agreement, and the χ(2) test was used to detect differences in the proportions of abnormal studies.76 patients met the inclusion criteria, 48 (63%) of whom received PWI. ASL was abnormal in 62%, a much higher frequency compared with DWI (24%) and intracranial MRA (13%). ASL significantly increased the MR imaging yield above the combined DWI and MRA yield (62 vs. 32%, p < 0.05). Arterial transit artifact in vascular borderzones was the most common ASL abnormality (present in 51%); other abnormalities included focal high or low ASL signal (11%). PWI was abnormal in 31% of patients, and in these, ASL was abnormal in 14 out of 15 cases (93%). In hemispheric TIA patients, both PWI and ASL findings were more common in the symptomatic hemisphere. Agreement between neuroradiologists regarding abnormal studies was good for ASL and PWI [ĸ = 0.69 (95% CI 0.53-0.86) and ĸ = 0.66 (95% CI 0.43-0.89), respectively].In TIA patients, perfusion-related alterations on ASL were more frequently detected compared with PWI or intracranial MRA and were most frequently associated with the symptomatic hemisphere. Almost all cases with a PWI lesion also had an ASL lesion. These results suggest that ASL may aid in the workup and triage of TIA patients, particularly those who cannot undergo a contrast study.

  View details for DOI 10.1159/000339682

  View details for Web of Science ID 000313654100007

  View details for PubMedID 23006669

• The infarct core is well represented by the acute diffusion lesion: sustained reversal is infrequent JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Campbell, B. C., Purushotham, A., Christensen, S., Desmond, P. M., Nagakane, Y., Parsons, M. W., Lansberg, M. G., Mlynash, M., Straka, M., De Silva, D. A., Olivot, J., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2012; 32 (1): 50-56

  Abstract

  Diffusion-weighted imaging (DWI) is commonly used to assess irreversibly infarcted tissue but its accuracy is challenged by reports of diffusion lesion reversal (DLR). We investigated the frequency and implications for mismatch classification of DLR using imaging from the EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial) and DEFUSE (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) studies. In 119 patients (83 treated with IV tissue plasminogen activator), follow-up images were coregistered to acute diffusion images and the lesions manually outlined to their maximal visual extent in diffusion space. Diffusion lesion reversal was defined as voxels of acute diffusion lesion that corresponded to normal brain at follow-up (i.e., final infarct, leukoaraiosis, and cerebrospinal fluid (CSF) voxels were excluded from consideration). The appearance of DLR was visually checked for artifacts, the volume calculated, and the impact of adjusting baseline diffusion lesion volume for DLR volume on perfusion-diffusion mismatch analyzed. Median DLR volume reduced from 4.4 to 1.5 mL after excluding CSF/leukoaraiosis. Visual inspection verified 8/119 (6.7%) with true DLR, median volume 2.33 mL. Subtracting DLR from acute diffusion volume altered perfusion-diffusion mismatch (T(max)>6 seconds, ratio>1.2) in 3/119 (2.5%) patients. Diffusion lesion reversal between baseline and 3 to 6 hours DWI was also uncommon (7/65, 11%) and often transient. Clinically relevant DLR is uncommon and rarely alters perfusion-diffusion mismatch. The acute diffusion lesion is generally a reliable signature of the infarct core.

  View details for DOI 10.1038/jcbfm.2011.102

  View details for Web of Science ID 000299010000008

  View details for PubMedID 21772309

  View details for PubMedCentralID PMC3323290

• MRI guides diagnostic approach for ischaemic stroke JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Kumar, M. A., Vangala, H., Tong, D. C., Campbell, D. M., Balgude, A., Eyngorn, I., Beraud, A. S., Olivot, J. M., Hsia, A. W., Bernstein, R. A., Wijman, C. A., Lansberg, M. G., Mlynash, M., Hamilton, S., Moseley, M. E., Albers, G. W. 2011; 82 (11): 1201-1205

  Abstract

  Identification of ischaemic stroke subtype currently relies on clinical evaluation supported by various diagnostic studies. The authors sought to determine whether specific diffusion-weighted MRI (DWI) patterns could reliably guide the subsequent work-up for patients presenting with acute ischaemic stroke symptoms.273 consecutive patients with acute ischaemic stroke symptoms were enrolled in this prospective, observational, single-centre NIH-sponsored study. Electrocardiogram, non-contrast head CT, brain MRI, head and neck magnetic resonance angiography (MRA) and transoesophageal echocardiography were performed in this prespecified order. Stroke neurologists determined TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification on admission and on discharge. Initial TOAST stroke subtypes were compared with the final TOAST subtype. If the final subtype differed from the initial assessment, the diagnostic test deemed the principal determinant of change was recorded. These principal determinants of change were compared between a CT-based and an MRI-based classification schema.Among patients with a thromboembolic DWI pattern, transoesophageal echocardiography was the principal determinant of diagnostic change in 8.8% versus 0% for the small vessel group and 1.7% for the other group (p<0.01). Among patients with the combination of a thromboembolic pattern on MRI and a negative cervical MRA, transoesophageal echocardiography led to a change in diagnosis in 12.1%. There was no significant difference between groups using a CT-based scheme.DWI patterns appear to predict stroke aetiologies better than conventional methods. The study data suggest an MRI-based diagnostic algorithm that can potentially obviate the need for echocardiography in one-third of stroke patients and may limit the number of secondary extracranial vascular imaging studies to approximately 10%.

  View details for DOI 10.1136/jnnp.2010.237941

  View details for Web of Science ID 000295920000006

  View details for PubMedID 21551473

• Greater Effect of Stroke Thrombolysis in the Presence of Arterial Obstruction ANNALS OF NEUROLOGY De Silva, D. A., Churilov, L., Olivot, J., Christensen, S., Lansberg, M. G., Mlynash, M., Campbell, B. C., Desmond, P., Straka, M., Bammer, R., Albers, G. W., Davis, S. M., Donnan, G. A. 2011; 70 (4): 601-605

  Abstract

  Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p < 0.001).The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis.

  View details for DOI 10.1002/ana.22444

  View details for Web of Science ID 000296396700013

  View details for PubMedID 22028220

  View details for PubMedCentralID PMC3205432

• Heterogeneity in the penumbra JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM del Zoppo, G. J., Sharp, F. R., Heiss, W., Albers, G. W. 2011; 31 (9): 1836-1851

  Abstract

  Original experimental studies in nonhuman primate models of focal ischemia showed flow-related changes in evoked potentials that suggested a circumferential zone of low regional cerebral blood flow with normal K(+) homeostasis, around a core of permanent injury in the striatum or the cortex. This became the basis for the definition of the ischemic penumbra. Imaging techniques of the time suggested a homogeneous core of injury, while positing a surrounding 'penumbral' region that could be salvaged. However, both molecular studies and observations of vascular integrity indicate a more complex and dynamic situation in the ischemic core that also changes with time. The microvascular, cellular, and molecular events in the acute setting are compatible with heterogeneity of the injury within the injury center, which at early time points can be described as multiple 'mini-cores' associated with multiple 'mini-penumbras'. These observations suggest the progression of injury from many small foci to a homogeneous defect over time after the onset of ischemia. Recent observations with updated imaging techniques and data processing support these dynamic changes within the core and the penumbra in humans following focal ischemia.

  View details for DOI 10.1038/jcbfm.2011.93

  View details for Web of Science ID 000294524300003

  View details for PubMedID 21731034

• Stroke Treatment Academic Industry Roundtable (STAIR) Recommendations for Maximizing the Use of Intravenous Thrombolytics and Expanding Treatment Options With Intra-arterial and Neuroprotective Therapies STROKE Albers, G. W., Goldstein, L. B., Hess, D. C., Wechsler, L. R., Furie, K. L., Gorelick, P. B., Hurn, P., Liebeskind, D. S., Nogueira, R. G., Saver, J. L. 2011; 42 (9): 2645-2650

  Abstract

  The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of acute and restorative stroke therapies. Summary of Review- At the STAIR VII recommendations for strategies to maximize the use of intravenous thrombolytics through targeting public education, and the refinement of current treatment exclusion criteria were proposed. Increased utilization of mechanical devices for intra-arterial recanalization can be achieved by obtaining more definitive evidence of efficacy in randomized clinical trials, identification of patient characteristics associated with treatment efficacy, optimization of technical approaches, clarification of effective time windows, and development of approaches to limit complications. Neuroprotective strategies remain viable; recommendations for further study of these agents include an emphasis on rapid administration, consideration of the systemic effects of ischemic stroke, prevention of complications associated with early reperfusion, a focus on agents with multiple mechanisms of action, and consideration of possible interactions between neuroprotective and thrombolytic therapies.Extending intravenous thrombolysis to a broader patient population, clarifying the risk and benefits of intra-arterial reperfusion therapies, and further development of neuroprotective therapies were the key recommendations from STAIR VII.

  View details for DOI 10.1161/STROKEAHA.111.618850

  View details for Web of Science ID 000294342800061

  View details for PubMedID 21852620

• Improving the Accuracy of Perfusion Imaging in Acute Ischemic Stroke ANNALS OF NEUROLOGY Albers, G. W., Fisher, M. 2011; 70 (3): 347-349

  View details for DOI 10.1002/ana.22524

  View details for Web of Science ID 000294816800007

  View details for PubMedID 21905076

• Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA A multicenter study NEUROLOGY Giles, M. F., Albers, G. W., Amarenco, P., Arsava, E. M., Asimos, A. W., Ay, H., Calvet, D., Coutts, S. B., Cucchiara, B. L., Demchuk, A. M., Johnston, S. C., Kelly, P. J., Kim, A. S., Labreuche, J., Lavallee, P. C., Mas, J., Merwick, A., Olivot, J. M., Purroy, F., Rosamond, W. D., Sciolla, R., Rothwell, P. M. 2011; 77 (13): 1222-1228

  Abstract

  Stroke risk immediately after TIA defined by time-based criteria is high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist management. The American Stroke Association has proposed changing the criteria for the distinction between TIA and stroke from time-based to tissue-based. Research using these definitions is lacking. In a multicenter observational cohort study, we have investigated prognosis and performance of the ABCD2 score in TIA, subcategorized as tissue-positive or tissue-negative on diffusion-weighted imaging (DWI) or CT imaging according to the newly proposed criteria.Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging, and follow-up in cohorts of patients with TIA diagnosed by time-based criteria. Stroke rates at 7 and 90 days were studied in relation to tissue-positive or tissue-negative subcategorization, according to the presence or absence of brain infarction. The predictive power of the ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses.A total of 4,574 patients were included. Among DWI patients (n = 3,206), recurrent stroke rates at 7 days were 7.1%(95% confidence interval 5.5-9.1) after tissue-positive and 0.4% (0.2-0.7) after tissue-negative events (p diff < 0.0001). Corresponding rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.2), respectively (p diff < 0.0001). The ABCD2 score had predictive value in tissue-positive and tissue-negative events (AUC = 0.68 [95% confidence interval 0.63-0.73] and 0.73 [0.67-0.80], respectively; p sig < 0.0001 for both results, p diff = 0.17). Tissue-positive events with low ABCD2 scores and tissue-negative events with high ABCD2 scores had similar stroke risks, especially after a 90-day follow-up.Our findings support the concept of a tissue-based definition of TIA and stroke, at least on prognostic grounds.

  View details for DOI 10.1212/WNL.0b013e3182309f91

  View details for Web of Science ID 000295253800008

  View details for PubMedID 21865578

  View details for PubMedCentralID PMC3179650

• Systemic augmentation of alpha B-crystallin provides therapeutic benefit twelve hours post-stroke onset via immune modulation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Arac, A., Brownell, S. E., Rothbard, J. B., Chen, C., Ko, R. M., Pereira, M. P., Albers, G. W., Steinman, L., Steinberg, G. K. 2011; 108 (32): 13287-13292

  Abstract

  Tissue plasminogen activator is the only treatment option for stroke victims; however, it has to be administered within 4.5 h after symptom onset, making its use very limited. This report describes a unique target for effective treatment of stroke, even 12 h after onset, by the administration of αB-crystallin (Cryab), an endogenous immunomodulatory neuroprotectant. In Cryab(-/-) mice, there was increased lesion size and diminished neurologic function after stroke compared with wild-type mice. Increased plasma Cryab was detected after experimental stroke in mice and after stroke in human patients. Administration of Cryab even 12 h after experimental stroke reduced both stroke volume and inflammatory cytokines associated with stroke pathology. Cryab is an endogenous anti-inflammatory and neuroprotectant molecule produced after stroke, whose beneficial properties can be augmented when administered therapeutically after stroke.

  View details for DOI 10.1073/pnas.1107368108

  View details for Web of Science ID 000293691400065

  View details for PubMedID 21828004

  View details for PubMedCentralID PMC3156222

• TWO ACES Transient Ischemic Attack Work-Up as Outpatient Assessment of Clinical Evaluation and Safety STROKE Olivot, J., Wolford, C., Castle, J., Mlynash, M., Schwartz, N. E., Lansberg, M. G., Kemp, S., Albers, G. W. 2011; 42 (7): 1839-1843

  Abstract

  To evaluate a novel emergency department-based TIA triage system.We developed an approach to TIA triage and management based on risk assessment using the ABCD(2) score in combination with early cervical and intracranial vessel imaging. It was anticipated that this triage system would avoid hospitalization for the majority of TIA patients and result in a low rate of recurrent stroke. We hypothesized that the subsequent stroke rate among consecutively encountered patients managed with this approach would be lower than predicted based on their ABCD2 scores.From June 2007 to December 2009, 224 consecutive patients evaluated in the Stanford emergency department for a possible TIA were enrolled in the study. One hundred fifty-seven were discharged to complete their evaluation at the outpatient TIA clinic; 67 patients were hospitalized. One hundred sixteen patients had a final diagnosis of TIA/minor stroke or possible TIA. The stroke rates at 7, 30, and 90 days were 0.6% (0.1%-3.5%) for patients referred to the TIA clinic and 1.5% (0.3%-8.0%) for the hospitalized patients. Combining both groups, the overall stroke rate was 0.9% (0.3%-3.2%), which is significantly less than expected based on ABCD2 scores (P=0.034 at 7 days and P=0.001 at 90 days).This emergency department-based inpatient versus outpatient TIA triage system led to a low rate of hospitalization (30%). Recurrent stroke rates were low for both the hospitalized and outpatient subgroups.

  View details for DOI 10.1161/STROKEAHA.110.608380

  View details for Web of Science ID 000292090900019

  View details for PubMedID 21617143

• RAPID Automated Patient Selection for Reperfusion Therapy A Pooled Analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study STROKE Lansberg, M. G., Lee, J., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Davis, S. M., Donnan, G. A., Albers, G. W. 2011; 42 (6): 1608-1614

  Abstract

  The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome.Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE; n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥ 8-point improvement on the National Institutes of Health Stroke Scale score at Day 90.In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6; 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10 ± 23 mL with reperfusion versus 40 ± 44 mL without reperfusion; P<0.001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74; 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85 ± 74 mL with reperfusion versus 95 ± 79 mL without reperfusion; P=0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05; 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10 ± 15 mL with reperfusion versus 17 ± 30 mL without reperfusion; P=0.9) in No Mismatch patients.MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.

  View details for DOI 10.1161/STROKEAHA.110.609008

  View details for PubMedID 21493916

• A Topographic Study of the Evolution of the MR DWI/PWI Mismatch Pattern and Its Clinical Impact A Study by the EPITHET and DEFUSE Investigators STROKE Ogata, T., Nagakane, Y., Christensen, S., Ma, H., Campbell, B. C., Churilov, L., Olivot, J., Desmond, P. M., Albers, G. W., Davis, S. M., Donnan, G. A. 2011; 42 (6): 1596-1601

  Abstract

  The ischemic penumbra may be classical, with complete annular configuration around the infarct core, or nonclassical with a more fragmented pattern. We tested the hypotheses that these penumbral patterns may: be associated with specific predictive factors, influence infarct growth and clinical outcome, and influence the effect of tissue plasminogen activator (t-PA).Using the EPITHET/DEFUSE data set, in which patients received alteplase or placebo 3 to 6 hours poststroke, perfusion-weighted imaging and diffusion-weighted imaging images were analyzed. These mismatch patterns were defined as "classical" or "nonclassical." Multivariate analysis was used to identify variables associated with mismatch patterns, the effect of t-PA, as well as the relationship between mismatch patterns, infarct growth, and clinical outcomes.We included 158 patients (median age, 74 years; median National Institute of Health Stroke Scale score, 12). Multivariate analysis indicated that the factors associated with classical mismatch pattern type were large mismatch volume (P<0.001) and cortical infarct location (P=0.036). Infarct growth, clinical outcome, and the efficacy of t-PA were not statistically different between patterns.Coregistered mismatch volume and cortical location of infarction were the important factors associated with presence of the classical mismatch pattern. The lack of effect of the type of mismatch patterns on infarct growth, clinical outcomes, or the benefit of t-PA would suggest that mismatch topography is less important during the hyperacute phase of ischemic stroke than during subacute phase.

  View details for DOI 10.1161/STROKEAHA.110.609016

  View details for Web of Science ID 000291032700036

  View details for PubMedID 21512174

• Refining the Definition of the Malignant Profile Insights From the DEFUSE-EPITHET Pooled Data Set STROKE Mlynash, M., Lansberg, M. G., De Silva, D. A., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Donnan, G. A., Davis, S. M., Albers, G. W. 2011; 42 (5): 1270-1275

  Abstract

  To refine the definition of the malignant magnetic resonance imaging profile in acute stroke patients using baseline diffusion-weighted magnetic resonance imaging (DWI) and perfusion-weighted magnetic resonance imaging (PWI) findings from the pooled DEFUSE/EPITHET database.Patients presenting with acute stroke within 3 to 6 hours from symptom onset were treated with tissue plasminogen activator or placebo. Baseline and follow-up DWI and PWI images from both studies were reprocessed using the same software program. A receiver operating characteristic curve analysis was used to identify Tmax and DWI volumes that optimally predicted poor outcomes (modified Rankin Scale 5-6) at 90 days in patients who achieved reperfusion.Sixty-five patients achieved reperfusion and 46 did not reperfuse. Receiver operating characteristic analysis identified a PWI (Tmax>8 s) volume of >85 mL as the optimal definition of the malignant profile. Eighty-nine percent of malignant profile patients had poor outcome with reperfusion versus 39% of patients without reperfusion (P=0.02). Parenchymal hematomas occurred more frequently in malignant profile patients who experienced reperfusion versus no reperfusion (67% versus 11%, P<0.01). DWI analysis identified a volume of 80 mL as the best DWI threshold, but this definition was less sensitive than were PWI-based definitions.Stroke patients likely to suffer parenchymal hemorrhages and poor outcomes following reperfusion can be identified from baseline magnetic resonance imaging findings. The current analysis demonstrates that a PWI threshold (Tmax>8 s) of approximately 100 mL is appropriate for identifying these patients. Exclusion of malignant profile patients from reperfusion therapies may substantially improve the efficacy and safety of reperfusion therapies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00238537.

  View details for DOI 10.1161/STROKEAHA.110.601609

  View details for Web of Science ID 000289835900023

  View details for PubMedID 21474799

  View details for PubMedCentralID PMC3248048

• Role of Diffusion and Perfusion MRI in Selecting Patients for Reperfusion Therapies NEUROIMAGING CLINICS OF NORTH AMERICA Grigoryan, M., Tung, C. E., Albers, G. W. 2011; 21 (2): 247-?

  Abstract

  After onset of ischemic stroke, potentially viable tissue at risk (ischemic penumbra) may be salvageable. Currently, intravenous alteplase is approved for up to 4.5 hours after symptom onset of acute ischemic stroke. Increasing this time window may allow many more patients to be treated. The ability to use MRI to help define the irreversibly damaged brain (infarct core) and the reversible ischemic penumbra shows great promise for stroke treatment. Recent advances in penumbral imaging technology may enable a phase III trial of an intravenous thrombolytic to be performed beyond 4.5 hours using techniques to select patients with penumbral tissue.

  View details for DOI 10.1016/j.nic.2011.01.002

  View details for Web of Science ID 000292007900006

  View details for PubMedID 21640298

• National Stroke Association Recommendations for Systems of Care for Transient Ischemic Attack ANNALS OF NEUROLOGY Johnston, S. C., Albers, G. W., Gorelick, P. B., Cumbler, E., Klingman, J., Ross, M. A., Briggs, M., Carlton, J., Sloan, E. P., Vaince, U. 2011; 69 (5): 872-877

  Abstract

  Transient ischemic attacks (TIAs) are common and portend a high short-term risk of stroke. Evidence-based recommendations for the urgent evaluation and treatment of patients with TIA have been published. However, implementation of these recommendations reliably and consistently will require changes in the systems of care established for TIA. The National Stroke Association convened a multidisciplinary panel of experts to develop recommendations for the essential components of systems of care at hospitals to improve the quality of care provided to patients with TIA. The panel recommends that hospitals establish standardized protocols to assure rapid and complete evaluation and treatment for patients with TIA, with particular attention to urgency and close observation in patients at high risk of stroke.

  View details for DOI 10.1002/ana.22332

  View details for Web of Science ID 000290156300014

  View details for PubMedID 21391236

• A 5-Item Scale to Predict Stroke Outcome After Cortical Middle Cerebral Artery Territory Infarction Validation From Results of the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study STROKE Vora, N. A., Shook, S. J., Schumacher, H. C., Tievsky, A. L., Albers, G. W., Wechsler, L. R., Gupta, R. 2011; 42 (3): 645-649

  Abstract

  Various clinical, laboratory, and radiographic parameters have been identified as predictors of outcome for ischemic stroke. The purpose of this study was to combine these parameters into a validated scale for outcome prognostication in patients with a middle cerebral artery territory infarction.We retrospectively reviewed 129 patients over a 2-year period and considered demographic, clinical, laboratory, and radiographic parameters as potential predictors of outcome. Inclusion criteria were unilateral hemispheric infarcts within the middle cerebral artery territory >15 mm in diameter. Our primary outcome measure was a favorable recovery defined as a modified Rankin Score was ≤2 at 30 days. A multivariable model was used to determine independent predictors of outcome and weighted to create a 5-item scale to predict stroke recovery. External validation of this model was done using data from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study.The 5 independent predictors of outcome were as follows: age (OR, 1.09; 95% CI, 1.03 to 1.14; P=0.001), National Institutes of Health Stroke Scale score (OR, 1.17; 95% CI, 1.06 to 1.30; P=0.003), infarct volume (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.03), admission white blood cell count (8.5×10(3)/mm(3); OR, 1.16; 95% CI, 1.03 to 1.27; P=0.04), and presence of hyperglycemia (OR, 4.2; 95% CI, 1.1 to 16.4; P=0.04). Combining these variables into a point scale significantly improved prediction over the individual variables accounted alone as evidenced by the area underneath the receiver operating curve (OR, 0.91; 95% CI, 0.87 to 0.96; P=0.0001). When applied to the DEFUSE study population for validation, the model achieved a sensitivity of 83% and specificity of 86%.With validation from a prospective study of similar patients, this model serves as a useful clinical and research tool to predict stroke recovery after cortical middle cerebral artery territory infarction.

  View details for DOI 10.1161/STROKEAHA.110.596312

  View details for Web of Science ID 000287479401453

  View details for PubMedID 21273564

• TIA Clinic Triage Strategy Reduces the Cost of TIA Evaluation International Stroke Conference Mlynash, M., Castle, J., Olivot, J., Wolford, C., Schwartz, N. E., Lansberg, M. G., Edwards, G., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E250–E250

  View details for Web of Science ID 000287479401072

• Worse Stroke Outcome In Atrial Fibrillation Links To More Severe Hypoperfusion International Stroke Conference Tu, H. T., Campbell, B. C., Christensen, S., De Silva, D. A., Parsons, M. W., Churilov, L., Olivot, J., Lansberg, M. G., Mlynash, M., Straka, M., Bammer, R., Albers, G. W., Desmond, P. M., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2011: E119–E119

  View details for Web of Science ID 000287479400248

• The Combination Of Reperfusion And Recanalization Predicts Favorable Outcome Better Than Reperfusion Or Recanalization Alone In Target Mismatch Patients International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., De Silva, D. A., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E66–E67

  View details for Web of Science ID 000287479400088

• Higher rCBV Values In The PWI/DWI Mismatch Area Predict Favorable Clinical Outcome In Acute Ischemic Stroke International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., Straka, M., Bammer, R., Olivot, J., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E112–E112

  View details for Web of Science ID 000287479400228

• Mri Based Tia Triage Study International Stroke Conference Wolford, C., Mlynash, M., Schwartz, N. E., Purushotham, A., Lansberg, M., Kemp, S., Albers, G. W., Olivot, J. LIPPINCOTT WILLIAMS & WILKINS. 2011: E210–E210

  View details for Web of Science ID 000287479400572

• The Acute Diffusion Lesion Reliably Represents Infarct Core: Clinically Relevant Reversibility Is Rare International Stroke Conference Campbell, B. C., Purushotham, A., Christensen, S., Desmond, P. M., Nagakane, Y., Parsons, M. W., Lansberg, M. G., Mlynash, M., Straka, M., De Silva, D. A., Olivot, J., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2011: E71–E71

  View details for Web of Science ID 000287479400102

• Postthrombolysis hemorrhage risk is affected by stroke assessment bias between hemispheres NEUROLOGY Audebert, H. J., Singer, O. C., Gotzler, B., Vatankhah, B., Boy, S., Fiehler, J., Lansberg, M. G., Albers, G. W., Kastrup, A., Rovira, A., Gass, A., Rosso, C., Derex, L., Kim, J. S., Heuschmann, P. 2011; 76 (7): 629-636

  Abstract

  Stroke symptoms in right hemispheric stroke tend to be underestimated in clinical assessment scales, resulting in greater infarct volumes in right as compared to left hemispheric strokes despite similar clinical stroke severity. We hypothesized that patients with right hemispheric nonlacunar stroke are at higher risk for secondary intracerebral hemorrhage after thrombolysis despite similar stroke severity.We analyzed data of 2 stroke cohorts with CT-based and MRI-based imaging before thrombolysis. Initial stroke severity was measured with the NIH Stroke Scale (NIHSS). Lacunar strokes were excluded through either the presence of cortical symptoms (CT cohort) or restriction to patients with prestroke diffusion-weighted imaging (DWI) lesion size >3.75 mL (MRI cohort). Probabilities of having a parenchymal hematoma were determined using multivariate logistic regression.A total of 392 patients in the CT cohort and 400 patients in the MRI cohort were evaluated. Although NIHSS scores were similar in strokes of both hemispheres (median NIHSS: CT: 15 vs 13, MRI: 14 vs 16), the frequencies of parenchymal hematoma were higher in right hemispheric compared to left hemispheric strokes (CT: 12.4% vs 5.7%, MRI: 10.4% vs 6.8%). After adjustment for potential confounders (but not pretreatment lesion volume), the probability of parenchymal hematoma was higher in right hemispheric nonlacunar strokes (CT: odds ratio [OR] 2.3; 95% confidence interval [CI] 1.08-4.89; p = 0.032) and showed a borderline significant effect in the MRI cohort (OR 2.1; 95% CI 0.98-4.49; p = 0.057). Adjustment for pretreatment DWI lesion size eliminated hemispheric differences in hemorrhage risk.Higher hemorrhage rates in right hemispheric nonlacunar strokes despite similar stroke severity may be caused by clinical underestimation of the proportion of tissue at bleeding risk.

  View details for DOI 10.1212/WNL.0b013e31820ce505

  View details for Web of Science ID 000287363800010

  View details for PubMedID 21248275

  View details for PubMedCentralID PMC3053338

• Diffusion-perfusion MRI for triaging transient ischemic attack and acute cerebrovascular syndromes CURRENT OPINION IN NEUROLOGY Olivot, J., Albers, G. W. 2011; 24 (1): 44-49

  Abstract

  Time from symptom onset to treatment is considered to be the key variable that influences the indication of recanalization therapy for treatment of acute brain infarction. Symptom duration less than 24 h defines transient ischemic attack (TIA). The evolution of multimodal brain MRI demonstrates that neuroimaging findings of tissue injury may be more important predictors of clinical outcomes than arbitrary time thresholds.Preliminaries studies suggest that stroke victims with a significant penumbra estimated by the diffusion/perfusion mismatch on MRI benefit from thrombolysis beyond the currently recommended time window of 4.5 h. New software programs can automatically produce reliable perfusion and diffusion maps for use in clinical practice. Combined diffusion and perfusion MRI reveals an acute ischemic lesion in about 60% of TIA patients. Patients with transient symptoms and a restricted diffusion lesion on MRI are considered by the American Heart Association (AHA) scientific committee to have suffered a brain infarction and have a very high risk of early stroke recurrence.Multimodal MRI provides critical real-time information about ongoing tissue injury as well as the risk of additional ischemic damage. It is becoming an essential tool for the diagnosis, management and triage of acute TIA and brain infarction.

  View details for DOI 10.1097/WCO.0b013e328341f8a5

  View details for Web of Science ID 000285742400008

  View details for PubMedID 21157338

• Fluid-Attenuated Inversion Recovery Hyperintensity in Acute Ischemic Stroke May Not Predict Hemorrhagic Transformation CEREBROVASCULAR DISEASES Campbell, B. C., Costello, C., Christensen, S., Ebinger, M., Parsons, M. W., Desmond, P. M., Barber, P. A., Butcher, K. S., Levi, C. R., De Silva, D. A., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2011; 32 (4): 401-405

  Abstract

  Fluid-attenuated inversion recovery (FLAIR) hyperintensity within an acute cerebral infarct may reflect delayed onset time and increased risk of hemorrhage after thrombolysis. Given the important implications for clinical practice, we examined the prevalence of FLAIR hyperintensity in patients 3-6 h from stroke onset and its relationship to parenchymal hematoma (PH).Baseline DWI and FLAIR imaging with subsequent hemorrhage detection (ECASS criteria) were prospectively obtained in patients 3-6 h after stroke onset from the pooled EPITHET and DEFUSE trials. FLAIR hyperintensity within the region of the acute DWI lesion was rated qualitatively (dichotomized as visually obvious or subtle (i.e. only visible after careful windowing)) and quantitatively (using relative signal intensity (RSI)). The association of FLAIR hyperintensity with hemorrhage was then tested alongside established predictors (very low cerebral blood volume (VLCBV) and diffusion (DWI) lesion volume) in logistic regression analysis.There were 49 patients with pre-treatment FLAIR imaging (38 received tissue plasminogen activator (tPA), 5 developed PH). FLAIR hyperintensity within the region of acute DWI lesion occurred in 48/49 (98%) patients, was obvious in 18/49 (37%) and subtle in 30/49 (61%). Inter-rater agreement was 92% (κ = 0.82). The prevalence of obvious FLAIR hyperintensity did not differ between studies obtained in the 3-4.5 h and 4.5-6 h time periods (40% vs. 33%, p = 0.77). PH was poorly predicted by obvious FLAIR hyperintensity (sensitivity 40%, specificity 64%, positive predictive value 11%). In univariate logistic regression, VLCBV (p = 0.02) and DWI lesion volume (p = 0.03) predicted PH but FLAIR lesion volume (p = 0.87) and RSI (p = 0.11) did not. In ordinal logistic regression for hemorrhage grade adjusted for age and baseline stroke severity (NIHSS), increased VLCBV (p = 0.002) and DWI lesion volume (p = 0.003) were associated with hemorrhage but FLAIR lesion volume (p = 0.66) and RSI (p = 0.35) were not.Visible FLAIR hyperintensity is almost universal 3-6 h after stroke onset and did not predict subsequent hemorrhage in this dataset. Our findings question the value of excluding patients with FLAIR hyperintensity from reperfusion therapies. Larger studies are required to clarify what implications FLAIR-positive lesions have for patient selection.

  View details for DOI 10.1159/000331467

  View details for Web of Science ID 000299642300014

  View details for PubMedID 21986096

  View details for PubMedCentralID PMC3214893

• Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association STROKE Furie, K. L., Kasner, S. E., Adams, R. J., Albers, G. W., Bush, R. L., Fagan, S. C., Halperin, J. L., Johnston, S. C., Katzan, I., Kernan, W. N., Mitchell, P. H., Ovbiagele, B., Palesch, Y. Y., Sacco, R. L., Schwamm, L. H., Wassertheil-Smoller, S., Turan, T. N., Wentworth, D. 2011; 42 (1): 227-276

  Abstract

  The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.

  View details for DOI 10.1161/STR.0b013e3181f7d043

  View details for Web of Science ID 000285636400046

  View details for PubMedID 20966421

• Study Design of the CLOSURE I Trial A Prospective, Multicenter, Randomized, Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With Stroke or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale STROKE Furlan, A. J., Reisman, M., Massaro, J., Mauri, L., Adams, H., Albers, G. W., Felberg, R., Herrmann, H., Kar, S., Landzberg, M., Raizner, A., Wechsler, L. 2010; 41 (12): 2872-2883

  Abstract

  Some strokes of unknown etiology may be the result of a paradoxical embolism traversing through a nonfused foramen ovale (patent foramen ovale [PFO]). The utility of percutaneously placed devices for treatment of patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO is unknown. In addition, there are no clear data about the utility of medical interventions or other surgical procedures in this situation. Despite limited data, many patients are being treated with PFO closure devices. Thus, there is a strong need for clinical trials that test the potential efficacy of PFO occlusive devices in this situation. To address this gap in medical knowledge, we designed the CLOSURE I trial, a randomized, clinical trial comparing the use of a percutaneously placed PFO occlusive device and best medical therapy versus best medical therapy alone for prevention of recurrent ischemic neurologic symptoms among persons with TIA or ischemic stroke.This prospective, multicenter, randomized, controlled trial has finished enrollment. Two-year follow-up for all 910 patients is required. The primary end point is the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurologic mortality from ≥ 31 days of follow-up, as adjudicated by a panel of physicians who are unaware of treatment allocation. This article describes the rationale and study design of CLOSURE I.This trial should provide information as to whether the STARFlex septal closure system is safe and more effective than best medical therapy alone in preventing recurrent stroke/TIA and mortality in patients with PFO and whether the STARFlex septal closure device can demonstrate superiority compared with best medical therapy alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00201461.

  View details for DOI 10.1161/STROKEAHA.110.593376

  View details for Web of Science ID 000284685600032

  View details for PubMedID 21051670

• MRI Profile of the Perihematomal Region in Acute Intracerebral Hemorrhage STROKE Olivot, J., Mlynash, M., Kleinman, J. T., Straka, M., Venkatasubramanian, C., Bammer, R., Moseley, M. E., Albers, G. W., Wijman, C. A. 2010; 41 (11): 2681-2683

  Abstract

  The pathophysiology of the presumed perihematomal edema immediately surrounding an acute intracerebral hemorrhage is poorly understood, and its composition may influence clinical outcome. Method-Twenty-three patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were prospectively enrolled and studied with MRI. Perfusion-weighted imaging, diffusion-weighted imaging, and fluid-attenuated inversion recovery sequences were coregistered. TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient values in the presumed perihematomal edema regions of interest were compared with contralateral mirror and remote ipsilateral hemispheric regions of interest.Compared with mirror and ipsilateral hemispheric regions of interest, TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient were consistently increased in the presumed perihematomal edema. Two thirds of the patients also exhibited patchy regions of restricted diffusion in the presumed perihematomal edema.The MRI profile of the presumed perihematomal edema in acute intracerebral hemorrhage exhibits delayed perfusion and increased diffusivity mixed with areas of reduced diffusion.

  View details for DOI 10.1161/STROKEAHA.110.590638

  View details for PubMedID 20947849

• Real-Time Diffusion-Perfusion Mismatch Analysis in Acute Stroke JOURNAL OF MAGNETIC RESONANCE IMAGING Straka, M., Albers, G. W., Bammer, R. 2010; 32 (5): 1024-1037

  Abstract

  Diffusion-perfusion mismatch can be used to identify acute stroke patients that could benefit from reperfusion therapies. Early assessment of the mismatch facilitates necessary diagnosis and treatment decisions in acute stroke. We developed the RApid processing of PerfusIon and Diffusion (RAPID) for unsupervised, fully automated processing of perfusion and diffusion data for the purpose of expedited routine clinical assessment. The RAPID system computes quantitative perfusion maps (cerebral blood volume, CBV; cerebral blood flow, CBF; mean transit time, MTT; and the time until the residue function reaches its peak, T(max)) using deconvolution of tissue and arterial signals. Diffusion-weighted imaging/perfusion-weighted imaging (DWI/PWI) mismatch is automatically determined using infarct core segmentation of ADC maps and perfusion deficits segmented from T(max) maps. The performance of RAPID was evaluated on 63 acute stroke cases, in which diffusion and perfusion lesion volumes were outlined by both a human reader and the RAPID system. The correlation of outlined lesion volumes obtained from both methods was r(2) = 0.99 for DWI and r(2) = 0.96 for PWI. For mismatch identification, RAPID showed 100% sensitivity and 91% specificity. The mismatch information is made available on the hospital's PACS within 5-7 min. Results indicate that the automated system is sufficiently accurate and fast enough to be used for routine care as well as in clinical trials.

  View details for DOI 10.1002/jmri.22338

  View details for Web of Science ID 000284190200002

  View details for PubMedID 21031505

  View details for PubMedCentralID PMC2975404

• Addition of brain and carotid imaging to the ABCD(2) score to identify patients at early risk of stroke after transient ischaemic attack: a multicentre observational study LANCET NEUROLOGY Merwick, A., Albers, G. W., Amarenco, P., Arsava, E. M., Ay, H., Calvet, D., Coutts, S. B., Cucchiara, B. L., Demchuk, A. M., Furie, K. L., Giles, M. F., Labreuche, J., Lavallee, P. C., Mas, J., Olivot, J. M., Purroy, F., Rothwell, P. M., Saver, J. L., Sheehan, O. C., Stack, J. P., Walsh, C., Kelly, P. J. 2010; 9 (11): 1060-1069

  Abstract

  The ABCD² score improves stratification of patients with transient ischaemic attack by early stroke risk. We aimed to develop two new versions of the score: one that was based on preclinical information and one that was based on imaging and other secondary care assessments.We analysed pooled data from patients with clinically defined transient ischaemic attack who were investigated while in secondary care. Items that contribute to the ABCD² score (age, blood pressure, clinical weakness, duration, and diabetes), other clinical variables, carotid stenosis, and abnormal acute diffusion-weighted imaging (DWI) were recorded and were included in multivariate logistic regression analysis of stroke occurrence at early time intervals after onset of transient ischaemic attack. Scores based on the findings of this analysis were validated in patients with transient ischaemic attack from two independent population-based cohorts.3886 patients were included in the study: 2654 in the derivation sample and 1232 in the validation sample. We derived the ABCD³ score (range 0-9 points) by assigning 2 points for dual transient ischaemic attack (an earlier transient ischaemic attack within 7 days of the index event). C statistics (which indicate discrimination better than chance at >0·5) for the ABCD³ score were 0·78 at 2 days, 0·80 at 7 days, 0·79 at 28 days, and 0·77 at 90 days, compared with C statistics for the ABCD² score of 0·71 at 2 days (p=0·083), 0·71 at 7 days (p=0·012), 0·71 at 28 days (p=0·021), and 0·69 at 90 days (p=0·018). We included stenosis of at least 50% on carotid imaging (2 points) and abnormal DWI (2 points) in the ABCD³-imaging (ABCD³-I) score (0-13 points). C statistics for the ABCD³-I score were 0·90 at 2 days (compared with ABCD² score p=0·035), 0·92 at 7 days (p=0·001), 0·85 at 28 days (p=0·028), and 0·79 at 90 days (p=0·073). The 90-day net reclassification improvement compared with ABCD² was 29·1% for ABCD³ (p=0·0003) and 39·4% for ABCD³-I (p=0·034). In the validation sample, the ABCD³ and ABCD³-I scores predicted early stroke at 7, 28, and 90 days. However, discrimination and net reclassification of patients with early stroke were similar with ABCD³ compared with ABCD².The ABCD³-I score can improve risk stratification after transient ischaemic attack in secondary care settings. However, use of ABCD³ cannot be recommended without further validation.Health Research Board of Ireland, Irish Heart Foundation, and Irish National Lottery.

  View details for DOI 10.1016/S1474-4422(10)70240-4

  View details for Web of Science ID 000284246800014

  View details for PubMedID 20934388

• Capsular warning syndrome caused by middle cerebral artery stenosis JOURNAL OF THE NEUROLOGICAL SCIENCES Lee, J., Albers, G. W., Marks, M. P., Lansberg, M. G. 2010; 296 (1-2): 115-120

  Abstract

  The capsular warning syndrome is a term used to describe recurrent stereotyped lacunar transient ischemic attacks (TIAs). This syndrome is associated with a high risk of developing a completed stroke. The presumed mechanism for this syndrome is angiopathy of a lenticulostriate artery. We describe the case of a 33-year-old man who presented with the capsular warning syndrome who was successfully treated with angioplasty. The patient's capsular warning syndrome manifested as recurrent episodes of transient left hemiparesis. Symptoms recurred one to three times daily despite treatment with antithrombotics. Cerebral angiography demonstrated stenosis of the right middle cerebral artery (MCA) with decreased flow to a dominant lenticulostriate artery. Angioplasty of the right middle cerebral artery increased flow to the lenticulostriate artery and the TIAs resolved following the procedure. In select cases intracranial angioplasty, may be an effective treatment for patients with capsular warning syndrome.

  View details for DOI 10.1016/j.jns.2010.06.003

  View details for PubMedID 20619422

• Addition of Brain Infarction to the ABCD(2) Score (ABCD(2)I) A Collaborative Analysis of Unpublished Data on 4574 Patients STROKE Giles, M. F., Albers, G. W., Amarenco, P., Arsava, M. M., Asimos, A., Ay, H., Calvet, D., Coutts, S., Cucchiara, B. L., Demchuk, A. M., Johnston, S. C., Kelly, P. J., Kim, A. S., Labreuche, J., Lavallee, P. C., Mas, J., Merwick, A., Olivot, J. M., Purroy, F., Rosamond, W. D., Sciolla, R., Rothwell, P. M. 2010; 41 (9): 1907-1913

  Abstract

  The ABCD system was developed to predict early stroke risk after transient ischemic attack. Incorporation of brain imaging findings has been suggested, but reports have used inconsistent methods and been underpowered. We therefore performed an international, multicenter collaborative study of the prognostic performance of the ABCD(2) score and brain infarction on imaging to determine the optimal weighting of infarction in the score (ABCD(2)I).Twelve centers provided unpublished data on ABCD(2) scores, presence of brain infarction on either diffusion-weighted imaging or CT, and follow-up in cohorts of patients with transient ischemic attack diagnosed by World Health Organization criteria. Optimal weighting of infarction in the ABCD(2)I score was determined using area under the receiver operating characteristic curve analyses and random effects meta-analysis.Among 4574 patients with TIA, acute infarction was present in 884 (27.6%) of 3206 imaged with diffusion-weighted imaging and new or old infarction was present in 327 (23.9%) of 1368 imaged with CT. ABCD(2) score and presence of infarction on diffusion-weighted imaging or CT were both independently predictive of stroke (n=145) at 7 days (after adjustment for ABCD(2) score, OR for infarction=6.2, 95% CI=4.2 to 9.0, overall; 14.9, 7.4 to 30.2, for diffusion-weighted imaging; 4.2, 2.6 to 6.9, for CT; all P<0.001). Incorporation of infarction in the ABCD(2)I score improved predictive power with an optimal weighting of 3 points for infarction on CT or diffusion-weighted imaging. Pooled areas under the curve increased from 0.66 (0.53 to 0.78) for the ABCD(2) score to 0.78 (0.72 to 0.85) for the ABCD(2)I score.In secondary care, incorporation of brain infarction into the ABCD system (ABCD(2)I score) improves prediction of stroke in the acute phase after transient ischemic attack.

  View details for DOI 10.1161/STROKEAHA.110.578971

  View details for Web of Science ID 000281503000011

  View details for PubMedID 20634480

• Agreement Regarding Diagnosis of Transient Ischemic Attack Fairly Low Among Stroke-Trained Neurologists STROKE Castle, J., Mlynash, M., Lee, K., Caulfield, A. F., Wolford, C., Kemp, S., Hamilton, S., Albers, G. W., Olivot, J. 2010; 41 (7): 1367-1370

  Abstract

  Agreement between physicians to define the likelihood of a transient ischemic attack (TIA) remains poor. Several studies have compared neurologists with nonneurologists, and neurologists among themselves, but not between fellowship-trained stroke neurologists. We investigated the diagnostic agreement in 55 patients with suspected TIA.The history and physical examination findings of 55 patients referred to the Stanford TIA clinic from the Stanford emergency room were blindly reviewed by 3 fellowship-trained stroke neurologists who had no knowledge of any test results or patient outcomes. Each patient's presentation was rated as to the likelihood that the presentation was consistent with TIA. We used 3 different scales (2-, 3-, and 4-point scales) to define TIA likelihood. We assessed global agreement between the raters and evaluated the biases related to individual raters and scale type.The agreement between fellowship-trained stroke neurologists remained poor regardless of the rating system used and the statistical test used to measure it. Difference in rating bias among all raters was significant for each scale: P=0.001, 0.012, and <0.001. In addition, for each reviewer, the rate of labeling an event an "unlikely TIA" progressively decreased with the number of points that composed the scale.TIA remains a highly subjective diagnosis, even among stroke subspecialists. The use of confirmatory testing beyond clinical judgment is needed to help solidify the diagnosis. Caution should be used when diagnosing an event as a possible TIA.

  View details for DOI 10.1161/STROKEAHA.109.577650

  View details for Web of Science ID 000279272200013

  View details for PubMedID 20508192

• Combined Arterial Spin Label and Dynamic Susceptibility Contrast Measurement of Cerebral Blood Flow MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Straka, M., Marks, M. P., Albers, G. W., Moseley, M. E., Bammer, R. 2010; 63 (6): 1548-1556

  Abstract

  Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC-CBF quantitation is challenging due to many uncertainties, including partial- volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patient-specific correction factor, the ratio of ASL- and DSC-CBF, calculated only in short-arrival-time regions (as determined by the DSC-based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold-standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI-based CBF to xenon CT CBF (coefficient of variation) was 90 +/- 30% (33%) for combined ASL and DSC CBF, 43 +/- 21% (47%) for DSC, and 91 +/- 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease.

  View details for DOI 10.1002/mrm.22329

  View details for PubMedID 20512858

• Using advanced MRI techniques for patient selection before acute stroke therapy. Current treatment options in cardiovascular medicine Olivot, J., Albers, G. W. 2010; 12 (3): 230-239

  Abstract

  OPINION STATEMENT: Results of acute MRI studies may help guide the management of acute stroke. Patients with a malignant MRI pattern may be poor candidates for reperfusion therapies yet may benefit from hemicraniectomy. Preliminary data suggest that patients with a carefully identified diffusion weighted imaging (DWI)/perfusion weighted imaging (PWI) mismatch may benefit from intravenous recombinant tissue plasminogen activator in a 3- to 6-hour time window; however, confirmatory studies with larger sample sizes are required before clinical use of this strategy can be generally recommended. Post hoc analyses of recent studies suggest that PWI techniques that use a threshold to exclude benign oligemia from penumbra and DWI techniques that use apparent diffusion coefficient thresholds to exclude reversible DWI lesions to distinguish the ischemic core from penumbra appear to provide more accurate determinations of the volume of salvageable tissue. New automated software programs are now implementing these techniques to generate quantitative PWI and DWI maps within minutes. Prospective trials are in progress to investigate these new techniques. The results of these studies will further refine the application of MRI to select patients for acute recanalization therapies.

  View details for DOI 10.1007/s11936-010-0072-y

  View details for PubMedID 20842546

• Dabigatran Challenges Warfarin's Superiority for Stroke Prevention in Atrial Fibrillation STROKE Schwartz, N. E., Albers, G. W. 2010; 41 (6): 1307-1309

  View details for DOI 10.1161/STROKEAHA.110.584557

  View details for Web of Science ID 000278019400041

  View details for PubMedID 20395603

• Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials LANCET Lees, K. R., Bluhmki, E., von Kummer, R., Brott, T. G., Toni, D., Grotta, J. C., Albers, G. W., Kaste, M., Marler, J. R., Hamilton, S. A., Tilley, B. C., Davis, S. M., Donnan, G. A., Hacke, W., Ninds, E. A. 2010; 375 (9727): 1695-1703

  Abstract

  Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis.We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis.Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min.Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit.None.

  View details for Web of Science ID 000277890200031

  View details for PubMedID 20472172

• Validation of the Malignant Profile in the DEFUSE-EPITHET Pooled Database International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., De Silva, D. A., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E258–E258

  View details for Web of Science ID 000276106100270

• Factors Predicting the Presence of Acute Ischemic Lesions on Diffusion Weighted in the Stanford TIA Study (Two Aces) International Stroke Conference Olivot, J. M., Wolford, C., Mlynash, M., Castle, J., Lansberg, M., Schwartz, N., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E273–E273

  View details for Web of Science ID 000276106100329

• Diagnostic Accuracy of MRI in Spontaneous Intra-cerebral Hemorrhage (DASH): Initial Results International Stroke Conference Wijman, C. A., Snider, R. W., Venkatasubramanian, C., Caulfield, A. F., Buckwalter, M., Eyngorn, I., Fischbein, N., Gean, A., Schwartz, N., Lansberg, M., Mlynash, M., Kemp, S., Thai, D., Narayana, R. K., Marks, M., Bammer, R., Moseley, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E210–E211

  View details for Web of Science ID 000276106100102

• Large and Severe Baseline PWI Volumes Predict Poor Response to Intravenous tPA vs. Placebo in the Pooled DEFUSE-EPITHET Database International Stroke Conference De Silva, D. A., Mlynash, M., Lansberg, M. G., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J. M., Donnan, G. A., Davis, S. M., Albers, G. A. LIPPINCOTT WILLIAMS & WILKINS. 2010: E208–E208

  View details for Web of Science ID 000276106100092

• Symptomatic Intracranial Hemorrhage Rates With IV tPA Treatment by Stroke Subtype International Stroke Conference De Silva, D. A., Thomalla, G., Oppenheim, C., Albers, G. W., Lansberg, M. G., Kang, D., Hjort, N., Liebeskind, D. S., Hao, Q., Neumann-Haefelin, T., Singer, O. C., Nighoghossian, N., Derex, L., Shara, N., Donnan, G. A., Davis, S. M., Kidwell, C. S. LIPPINCOTT WILLIAMS & WILKINS. 2010: E363–E363

  View details for Web of Science ID 000276106100673

• DEFUSE and EPITHET: Two Different Studies With One Consistent Message International Stroke Conference Lansberg, M. G., Lee, J., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Davis, S. M., Donnan, G. A., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E295–E295

  View details for Web of Science ID 000276106100410

• Optimal Perfusion Thresholds for Prediction of Tissue Destined for Infarction in the Combined EPITHET and DEFUSE Dataset International Stroke Conference Christensen, S., Campbell, B. C., de la Ossa, N. P., Lansberg, M., Straka, M., De Silva, D. A., Nagakane, Y., Ogata, T., Mlynash, M., Bammer, R., Olivot, J., Desmond, P., Albers, G. W., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2010: E297–E297

  View details for Web of Science ID 000276106100416

• Optimal Definition of the Malignant Profile in the DEFUSE-EPITHET Pooled Database International Stroke Conference Mlynash, M., De Silva, D. A., Lansberg, M. G., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E207–E207

  View details for Web of Science ID 000276106100088

• Does Presence of Arterial Obstruction Influence the Treatment Effect of Intravenous tPA Over Placebo in the 3-6 Hour Time Window? International Stroke Conference De Silva, D. A., Churilov, L., Olivot, J. M., Christensen, S., Lansberg, M. G., Mlynash, M., Straka, M., Campbell, B. C., Bammer, R., Albers, G. W., Davis, S. M., Donnan, G. A. LIPPINCOTT WILLIAMS & WILKINS. 2010: E207–E208

  View details for Web of Science ID 000276106100091

• Mismatch-Based Delayed Thrombolysis A Meta-Analysis STROKE Mishra, N. K., Albers, G. W., Davis, S. M., Donnan, G. A., Furlan, A. J., Hacke, W., Lees, K. R. 2010; 41 (1): E25-E33

  Abstract

  Clinical benefit from thrombolysis is reduced as stroke onset to treatment time increases. The use of "mismatch" imaging to identify patients for delayed treatment has face validity and has been used in case series and clinical trials. We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria.We collated outcome data for patients who were enrolled after 3 hours of stroke onset in thrombolysis trials and had mismatch on pretreatment imaging. We selected the trials on the basis of a systematic search of the Web of Knowledge. We compared favorable outcome, reperfusion and/or recanalization, mortality, and symptomatic intracerebral hemorrhage between the thrombolyzed and nonthrombolyzed groups of patients and the probability of a favorable outcome among patients with successful reperfusion and clinical findings for 3 to 6 versus 6 to 9 hours from poststroke onset. Results are expressed as adjusted odds ratios (a-ORs) with 95% CIs. Heterogeneity was explored by test statistics for clinical heterogeneity, I(2) (inconsistency), and L'Abbé plot.We identified articles describing the DIAS, DIAS II, DEDAS, DEFUSE, and EPITHET trials, giving a total of 502 mismatch patients thrombolyzed beyond 3 hours. The combined a-ORs for favorable outcomes were greater for patients who had successful reperfusion (a-OR=5.2; 95% CI, 3 to 9; I(2)=0%). Favorable clinical outcome was not significantly improved by thrombolysis (a-OR=1.3; 95% CI, 0.8 to 2.0; I(2)=20.9%). Odds for reperfusion/recanalization were increased among patients who received thrombolytic therapy (a-OR=3.0; 95% CI, 1.6 to 5.8; I(2)=25.7%). The combined data showed a significant increase in mortality after thrombolysis (a-OR=2.4; 95% CI, 1.2 to 4.9; I(2)=0%), but this was not confirmed when we excluded data from desmoteplase doses that were abandoned in clinical development (a-OR=1.6; 95% CI, 0.7 to 3.7; I(2)=0%). Symptomatic intracerebral hemorrhage was significantly increased after thrombolysis (a-OR=6.5; 95% CI, 1.2 to 35.4; I(2)=0%) but not significant after exclusion of abandoned doses of desmoteplase (a-OR=5.4; 95% CI, 0.9 to 31.8; I(2)=0%).Delayed thrombolysis amongst patients selected according to mismatch imaging is associated with increased reperfusion/recanalization. Recanalization/reperfusion is associated with improved outcomes. However, delayed thrombolysis in mismatch patients was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible. Thrombolysis carries a significant risk of symptomatic intracerebral hemorrhage and possibly increased mortality. Criteria to diagnose mismatch are still evolving. Validation of the mismatch selection paradigm is required with a phase III trial. Pending these results, delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care.

  View details for DOI 10.1161/STROKEAHA.109.566869

  View details for Web of Science ID 000273093400041

  View details for PubMedID 19926836

• Stroke: more protection for patients with atrial fibrillation LANCET NEUROLOGY Albers, G. W. 2010; 9 (1): 2-4

  View details for Web of Science ID 000273199700002

  View details for PubMedID 20083021

• Challenges in childhood arterial ischaemic stroke LANCET NEUROLOGY Massicotte, M. P., Bauman, M. E., Albers, G. W. 2009; 8 (12): 1079-1081

  View details for DOI 10.1016/S1474-4422(09)70269-8

  View details for Web of Science ID 000272106100005

  View details for PubMedID 19801205

• Neurological Outcomes in Patients With Ischemic Stroke Receiving Enoxaparin or Heparin for Venous Thromboembolism Prophylaxis Subanalysis of the Prevention of VTE After Acute Ischemic Stroke With LMWH (PREVAIL) Study STROKE Kase, C. S., Albers, G. W., Bladin, C., Fieschi, C., Gabbai, A. A., O'Riordan, W., Pineo, G. F. 2009; 40 (11): 3532-3540

  Abstract

  The Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study demonstrated that enoxaparin was superior to unfractionated heparin (UFH) in preventing venous thromboembolism in patients with ischemic stroke and was associated with a small but statistically significant increase in extracranial hemorrhage rates. In this PREVAIL subanalysis, we evaluate the long-term neurological outcomes associated with the use of enoxaparin compared with UFH. We also determine predictors of stroke progression.Acute ischemic stroke patients aged >or=18 years, who could not walk unassisted, were randomized to receive enoxaparin (40 mg once daily) or UFH (5000 U every 12 hours) for 10 days. Patients were stratified according to baseline stroke severity using the National Institutes of Health Stroke Scale score. End points for this analysis included stroke progression (>or=4-point increase in National Institutes of Health Stroke Scale score), neurological outcomes up to 3 months postrandomization (assessed using National Institutes of Health Stroke Scale score and modified Rankin Scale score), and incidence of intracranial hemorrhage.Stroke progression occurred in 45 of 877 (5.1%) patients in the enoxaparin group and 42 of 872 (4.8%) of those receiving UFH. Similar improvements in National Institutes of Health Stroke Scale and modified Rankin Scale scores were observed in both groups over the 90-day follow-up period. Incidence of intracranial hemorrhage was comparable between groups (20 of 877 [2.3%] and 22 of 872 [2.5%] in enoxaparin and UFH groups, respectively). Baseline National Institutes of Health Stroke Scale score, hyperlipidemia, and Hispanic ethnicity were independent predictors of stroke progression.The clinical benefits associated with use of enoxaparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke are not associated with poorer long-term neurological outcomes or increased rates of symptomatic intracranial hemorrhage compared with UFH.

  View details for DOI 10.1161/STROKEAHA.109.555003

  View details for Web of Science ID 000271160300021

  View details for PubMedID 19696423

• Clinical and Radiographic Natural History of Cervical Artery Dissections JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Schwartz, N. E., Vertinsky, A. T., Hirsch, K. G., Albers, G. W. 2009; 18 (6): 416-423

  Abstract

  Cervical artery dissection (CADsx) is a common cause of stroke in young patients, but long-term clinical and radiographic follow-up from a large population is lacking.Epidemiologic data, treatment, recurrence, and other features were extracted from the records of all patients seen at our stroke center with confirmed CAD during a 15-year period. A subset of cases was examined to provide detailed information about vessel status.In all, 177 patients (mean age 44.0 +/- 11.1 years) were identified, with the male patients being older than the female patients. Almost 60% of dissections were spontaneous, whereas the remainder involved some degree of head and/or neck trauma. More than 70% of patients were treated with anticoagulation. During follow-up (mean 18.2 months; 0-220 months) there were 15 cases (8.5%) of recurrent ischemic events, and two cases (1.1%) of a recurrent dissection. About half of recurrent stroke/transient ischemic attack events occurred within 2 weeks of presentation. There was no clear association between the choice of antithrombotic agent and recurrent ischemic events. Detailed analysis of imaging findings was performed in 51 cases. Some degree of recanalization was seen in 58.8% of patients overall, and was more frequent in women. The average time to total or near-total recanalization was 4.7 +/- 2.5 months. Patients with complete occlusions at presentation tended not to recanalize.This large series from a single institution highlights many of the features of CAD. A relatively benign course with low recurrence rate is supported, independent of the type and duration of antithrombotic therapy.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.11.016

  View details for Web of Science ID 000272114400002

  View details for PubMedID 19900642

• Improving Dynamic Susceptibility Contrast MRI Measurement of Quantitative Cerebral Blood Flow using Corrections for Partial Volume and Nonlinear Contrast Relaxivity: A Xenon Computed Tomographic Comparative Study JOURNAL OF MAGNETIC RESONANCE IMAGING Zaharchuk, G., Bammer, R., Straka, M., Newbould, R. D., Rosenberg, J., Olivot, J., Mlynash, M., Lansberg, M. G., Schwartz, N. E., Marks, M. M., Albers, G. W., Moseley, M. E. 2009; 30 (4): 743-752

  Abstract

  To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold-standard CBF method, xenon computed tomography (xeCT).Eighteen patients with cerebrovascular disease underwent xeCT and MRI within 36 h. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed.Mean xeCT CBF was 43.3 +/- 13.7 mL/100g/min (mean +/- SD). BB correction decreased CBF by a factor of 4.7 +/- 0.4, but did not affect precision. The least-biased CBF measurement was with BB but without PV correction (45.8 +/- 17.2 mL/100 g/min, coefficient of variation [COV] = 32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3 +/- 10.8 mL/100 g/min, COV = 27%). Between patients correlation was moderate even with both corrections (R = 0.53).Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI-based CBF maps. However, there remain challenges given the moderate between-patient correlation, which limit diagnostic confidence of such measurements in individual patients.

  View details for DOI 10.1002/jmri.21908

  View details for PubMedID 19787719

• Geography, Structure, and Evolution of Diffusion and Perfusion Lesions in Diffusion and Perfusion Imaging Evaluation For Understanding Stroke Evolution (DEFUSE) STROKE Olivot, J., Mlynash, M., Thijs, V. N., Purushotham, A., Kemp, S., Lansberg, M. G., Wechsler, L., Gold, G. E., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (10): 3245-3251

  Abstract

  The classical representation of acute ischemic lesions on MRI is a central diffusion-weighted imaging (DWI) lesion embedded in a perfusion-weighted imaging (PWI) lesion. We investigated spatial relationships between final infarcts and early DWI/PWI lesions before and after intravenous thrombolysis in the Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study.Baseline and follow-up DWI and PWI lesions and 30-day fluid-attenuated inversion recovery scans of 32 patients were coregistered. Lesion geography was defined by the proportion of the DWI lesion superimposed by a Tmax (time when the residue function reaches its maximum) >4 seconds PWI lesion; Type 1: >50% overlap and Type 2: < or = 50% overlap. Three-dimensional structure was dichotomized into a single lesion (one DWI and one PWI lesion) versus multiple lesions. Lesion reversal was defined by the percentage of the baseline DWI or PWI lesion not superimposed by the early follow-up DWI or PWI lesion. Final infarct prediction was estimated by the proportion of the final infarct superimposed on the union of the DWI and PWI lesions.Single lesion structure with Type 1 geography was present in only 9 patients (28%) at baseline and 4 (12%) on early follow-up. In these patients, PWI and DWI lesions were more likely to correspond with the final infarcts. DWI reversal was greater among patients with Type 2 geography at baseline. Patients with multiple lesions and Type 2 geography at early follow-up were more likely to have early reperfusion.Before thrombolytic therapy in the 3- to 6-hour time window, Type 2 geography is predominant and is associated with DWI reversal. After thrombolysis, both Type 2 geography and multiple lesion structure are associated with reperfusion.

  View details for DOI 10.1161/STROKEAHA.109.558635

  View details for PubMedID 19679845

• Stroke Therapy Academic Industry Roundtable (STAIR) Recommendations for Extended Window Acute Stroke Therapy Trials STROKE Saver, J. L., Albers, G. W., Dunn, B., Johnston, K. C., Fisher, M. 2009; 40 (7): 2594-2600

  Abstract

  The Stroke Therapy Academic Industry Roundtable (STAIR) meetings focus on helping to advance the development of acute stroke therapies. Further extending the time window for acute stroke therapies is an important endeavor for increasing the number of stroke patients who might benefit from treatment. The STAIR group recommends that future extended time window trials initially should focus on selected patient groups most likely to respond to investigational therapies and that penumbral imaging is one tool that may identify such patients. The control group in these trials should receive best locally available medical care; if regulatory approval for intravenous (i.v.) tPA is extended to 4.5 hours, then tPA will become the most appropriate comparator in trials conducted within this time window. In future well-designed extended window clinical trials randomization is appropriate and should not be precluded by using unproven treatment with intraarterial (i.a.) thrombolysis or mechanical devices. For proof of concept, extended time window, phase II trials of i.v. thrombolysis, or mechanical devices in which early recanalization/reperfusion is the primary end point, rescue therapy/bailout treatment with i.a. thrombolysis or devices may be acceptable. Statistical considerations and definitions of successful recanalization/reperfusion are suggested for these trials.

  View details for DOI 10.1161/STROKEAHA.109.552554

  View details for Web of Science ID 000267467900056

  View details for PubMedID 19478212

  View details for PubMedCentralID PMC2761073

• Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation NEW ENGLAND JOURNAL OF MEDICINE Connolly, S. J., Yusuf, S., Camm, J., Chrolavicius, S., Commerford, P., Flather, M., Hart, R. G., Hohnloser, S. H., Joyner, C., Pfeffer, M., Gaudin, C., Blumenthal, M., Marchese, C., Pogue, J., Hart, R., Hohnloser, S., Anand, I., Arthur, H., Avezum, A., BUDAJ, A., CEREMUZYNSKI, L., De Caterina, R., Diaz, R., Dorian, P., Flaker, G., Fox, K. A., Franzosi, M. G., Goldhaber, S., Golitsyn, S., Granger, C., Halon, D., Hermosillo, A., HUNT, D., Jansky, P., Karatzas, N., Keltai, M., Kozan, O., Lanas, F., Lau, P., Le Heuzey, J. Y., Lewis, B. S., Morais, J., Morillo, C., PAOLASSO, E., Peters, R. J., Pfisterer, M., Piegas, L., PIPILIS, A., Sitkei, E., Swedberg, K., Talajic, M., Valentin, V., Van Mieghem, W., Varigos, J., Ameriso, S., Atra, M., Avezum, A., Berwanger, O., Bonilla, C., Bornstein, N., BUDAJ, A., Chamiec, T., Chan, Y. K., Cottin, Y., Csiba, L., Cybulski, J., Czepiel, A., De Raedt, H., Diaz, R., Dvorakova, H., Eikelboom, J., Ergene, O., Fodor, G., Galli, M., Gardinale, E., Golitsyn, S., Granger, C., Gross, B., Goodfield, P., Halon, D., Happola, O., Healey, J., Himbert, D., HUNT, D., Jacobsson, F., Jansky, P., Kalvach, P., Karatzas, N., Keltai, M., Kies, B., Laine, M., Lam, A., Le Heuzey, J. Y., Lewis, B. S., Lewis, S., Leys, D., Maggioni, A. P., Massaro, A., Mayosi, B. M., Norrving, B., Okay, T., Olah, L., Osende, J. O., Oto, A., Peeters, A., Penicka, M., Perakis, A., Piegas, L., PIPILIS, A., Pizzolato, G., RAFTI, F., Renkin, J., Siva, A., Steg, P. G., STOCKINS, B., Strozynska, E., Swedberg, K., Turazza, F., VANDERHOVEN, L., Vizel, S., Widimsky, P., Zaborski, J., Albers, G., Hankey, G., Norrving, B., Shuaib, A., Silva, J., Wyse, D. G., Cairns, J. A., Gent, M., Hirsh, J., Marler, J., Pritchett, E., Wittes, J., Beresh, H., Floyd, L., Gasic, Z., Holadyk-Gris, I., Lawrence, M., Moro, I., Perry, S., Roberts, J., Rodrigues, T., Robinson, L., Stevens, C., WORTHY, L., Yuan, F., Guerrero, R. A., Allall, O., Amuchastegui, L. M., Boskis, M., Labarta, M. H., Castellanos, C. R., Chiale, P., CUNEO, C. A., Czcczuo, A., Gabito, A. J., Garrido, M., GUZMAN, L. A., Hasban, E. G., Hershson, A. R., Hominal, M. A., Krauss, J. G., Luciardi, H. L., Marzetti, E. M., Montana, O. R., Rabinovich, R. F., Ramos, H. R., Sanchez, A. S., Schygiel, P. O., Sumay, G. M., Vogel, D. R., Zaidman, C. J., Aroney, G. M., Ashby, D. T., Barlow, M. A., Cooke, P., Cross, D. B., Fitzpatrick, M. A., Garrahy, P., Karrasch, J., Nelson, G. I., Rees, D., Roger, S. D., Rogers, J., Singh, B. B., STICKLAND, J. F., WAITES, J. H., Walsh, W. F., Eichinger, J., Huber, K., Leisch, F., Boland, J., Conraads, V. M., Cools, F. J., De Roy, L., El Allaf, D., Mairesse, G. H., Vankelecom, B., Abrantes, J., Armaganijan, D., Atie, J., Blacher, C., Bodanese, L. C., Braga, J. C., Braile, M. V., Chaves, H., Coelho, O. R., CUNHA, C. L., De Lima, G. G., de Paola, A. A., Esteves, J. P., Francischetti, A., Francischetti, A. E., Lorga-Filho, A. M., Maia, L. N., Marcussi, D. M., Marin-Neto, J. A., Meneghelo, Z. M., Rocha, R. M., Nogueira, P. R., Oigman, W., Paiva, M., Precoma, D. B., Rabelo, W., Rabelo, A., Rassi, S., Rassi, A., Reis, G., Rossi, P. R., Neto, J. M., Saraiva, J. K., Sobral-Filho, D. C., Zimmermann, S. L., Ashton, T. A., Bhargava, R., Carroll, S., Chehayeb, R., Connors, S. P., Constance, C., Costi, P., Coutu, B., Crystal, E., Douketis, J. D., Fortin, C., Fox, B. A., Gupta, M. K., Krahn, A. D., Kuritzky, R., Kwok, K., Leader, R., Ma, P., Mangat, I., MARANDA, C. R., MATANGI, M. F., Moddel, G., Mukherjee, A., Nawaz, S., PALAIC, M., Pandey, A. S., Rebane, T. M., Ruel, M., Sapp, J. L., Senaratne, M. P., St-Hilaire, R., Talbot, P., To, T. B., Vakani, M., WEIGEL, M. A., Wulffhart, Z., Yao, L., Zaniol, D., Conejeros, C. R., Corbalan, R., DUSSAILLANT, G. R., ESCOBAR, E., Hassi, M. E., Parra, C. A., STOCKINS, B. A., Varleta, P. E., Berka, L., Dedek, V., Florian, J., Hejhal, O., Herold, M., Klimsa, Z., Kotik, I., Simon, J., Smetana, K., Spinar, J., Spinarova, L., Tousek, F., Husted, S., Nielsen, T., Pehrson, S., Tuxen, C., Harjola, V. P., Huikuri, H. V., Kettunen, R. V., Melin, J. H., Peuhkurinen, K., Carlioz, R., Coisne, D., Decoulx, E., Defaye, P., DEMARCQ, J. M., Gacem, K., Galley, D. L., Lardoux, H. M., Mabo, P., Mansour, M., Olive, T. G., Poulard, J. E., Pruvot, C. F., Rey, J. L., Bauer, W. R., Baumann, G., Berghoefer, G., Boehm, G., Borggrefe, M. M., Bruecker, G., Darius, H., Duray, G. Z., Felix, S. B., Fink, P., Fritz, H., Haberl, R., Hoffmann, S., Horacek, T., Kalusche, D. W., Kasper, W., Katus, H. A., KLEPZIG, H. H., Loos, U., Merher, R., Munzel, T., Neuzner, J., Ochs, H. R., Pieske, B., POLLOCK, B. W., Schmidt, A., Schumacher, M., Seidl, K., Speier, U., Spitzer, S. G., STENZEL, G., Volkmann, H., Wunderlich, J., Zacharzowsky, U., Antonakoudis, H., Georgakopoulos, N., Goudevenos, J. A., Iliopoulos, T. A., Kallikazaros, I., Pyrgakis, V. N., Skoufas, P., Chan, W. K., Chan, H. W., Fung, J. W., Li, S. K., Wong, K. S., Forster, T., Karpati, P., Keltai, K., Kovacs, A., Kurta, G., Laszlo, Z., RAPI, J., Regos, L., ROSTAS, L., Szakal, I., Tomcsanyi, J., Toth, C., Bloch, L., Khader, N., Klainman, E., Koukoui, D., Lotan, C., Marmor, A., Omary, M. Z., Reisin, L. H., Vered, Z., Zeltser, D., Zimlichman, R., Bianconi, L., Bicego, D., Cosmi, D., Filigheddu, F., Garini, A., Lunati, M., Moretti, L., Mos, L., Pontiroli, A. E., Renda, G., Ricci, S., Rossi, P., Santonastaso, M., Scioli, G. A., Stramba-Badiale, M., Terrosu, P., Omar, R., Ong, T. K., Ahmad, W. A., ALVARADO, R., Calvo, C., Cordero-Cabra, J. A., HERNANDEZ, I., Jerjes-Sanchez, C., Lara, S., Lopez Rosas, E., Molina, L., Morales, E., Petersen-Aranguren, F., Picos Bovio, E. M., Pozas, G., Robles Torres, F. J., HOLWERDA, K., Lok, D. J., Nierop, R., PIETERSE, M. G., van der Heijden, R., Van Kempen, L., OIE, B. K., Omland, T. M., Otterstad, J., von Brandis, C., Bronisz, M., Chizynski, K., Czerski, T., Dluzniewski, M., Gessek, J., Gieroba, A., Gniot, J. R., Gorny, J., Halaczuiewicz, H., Janik, K., Janion, M., Jerzykowska, O., Kawka-Urbanek, T., Kincel, K., KOCON, S., Kopaczewski, J., Krasowski, W., Makuch, M., Malinowski, S., Miastkowski, Z., Mickiewicz-Pawlowska, M., Miekus, P., Obrebska-Tabaczka, E., Ogorek, M., Piasecka-Krysiak, E., Piepiorka, A. W., Piotrowski, W., Pluta, W., Puzio, E., Rekosz, J., Sinkiewicz, W., Stopinski, M., Szelemej, R., Tendera, M., Trusz-Gluza, M., Wilkoszynski, M., Zalska, B., Antunes, E., CARRAGETA, M. O., de Sousa, J., Martins, L., Mendonca, M. I., Silvestre, I., Akatova, E. V., Aleksandrov, V., Antuch, E. A., Arutyunov, G., Bart, B., Belousov, Y. B., Chernichka, I. I., Dovgalevsky, P., Gratsiansky, N., Ivleva, A. Y., Kislyak, O. A., Mareyev, V. Y., Maykov, E. B., Milyagin, V., Novikova, T. N., Panchenko, E. P., Reshetko, O., Semernin, E., Sidorenko, B. A., Sinopalnikov, A., Skvortsova, V., Solomatin, A., Sukhinina, T. S., Suslina, Z. A., Titkov, Y., Tsyrline, V., Chan, B., Foo, D., Omar, A. R., Teo, W. S., Brown, B. G., Ebrahim, I. O., Gibson, G. J., Klug, E., Marx, J. D., Mntla, P. S., Okreglicki, A., Pretorius, M., ROOS, J. S., Snyders, F., Van, L. J., Cano, L., Garcia-Puig, J., Hernandez-Madrid, A., Mostaza, J. M., Orriach, M. D., Sabate, X., Vinolas, X., Blomstrom, P., Jacobsson, F., Johansson, L., Klintberg, L., LYCKSELL, M., Nilsson, O., Rasmanis, G., Nilehn, K. E., Ulvenstam, G., Baumgartner, R. W., Francois, M., Gallino, A., MOCCETTI, T., Tettenborn, B. E., Chou, H., Kuo, J., Lai, W., Lin, J. L., Lin, L., Ueng, K. C., Yeih, D., Bakar, M., Ilerigelen, B., Kumral, E., Nisanci, Y., Savas, Z. I., Adgey, Y., Brack, M. J., Cleland, J., Davey, P. P., DAVIES, J., Glen, S. K., Jennings, K., Levy, T., Lip, G. Y., MORIARTY, A. J., Pearson, C., PURVIS, J. A., Pye, M. P., Savelieva, I., Senior, R., Trouton, T. G., Ahmed, I. S., Amin, M., Anderson, J. L., BAUERNFEIND, R. A., Belew, K., Bilazarian, S. D., Black, R. A., Burton, M. E., Cebe, J. E., Chandrashekhar, Y. S., Chen, C., Das, D., Denny, D. M., Desai, V., FAHMY, R. N., Fishbein, G. J., GELERNT, M. D., Gerber, J., Goldberg, M. C., Grena, P. G., HONAN, M. B., Hunter, J. J., Jacobson, J., Jarmukli, N. F., Klancke, K., KOBAYASHI, J. F., Lewis, S. J., Little, T., Mallis, I., Marani, A. M., Marshall, J. J., MELTZER, P., Menapace, F. J., O'Neill, P. G., Pearce, D. J., Quick, A., Ravipudi, S., Rivera, E., Sackett, M., Salerno, D. M., Schussheim, A., Sheikh, K., Shettigar, U. R., Treasure, C. B., Vidaillet, H., Vijay, N., Wagner, D., Walker, J. L., Winters, S. L., Young, D. R., Zoble, R. G. 2009; 360 (20): 2066-2078

  View details for DOI 10.1056/NEJMoa0901301

  View details for Web of Science ID 000266011200005

• Hyperfibrinogenemia and Functional Outcome From Acute Ischemic Stroke 80th Annual Scientific Session of the American-Heart-Association (AHA) del Zoppo, G. J., Levy, D. E., Wasiewski, W. W., Pancioli, A. M., Demchuk, A. M., Trammel, J., Demaerschalk, B. M., Kaste, M., Albers, G. W., Ringelstein, E. B. LIPPINCOTT WILLIAMS & WILKINS. 2009: 1687–91

  Abstract

  Epidemiological studies have found strong correlations between elevated plasma fibrinogen levels and both ischemic stroke incidence and stroke mortality. Little is known about the influence of fibrinogen levels on functional stroke outcome.Placebo data from the Stroke Treatment with Ancrod Trial (STAT) and European Stroke Treatment with Ancrod Trial (ESTAT) were analyzed. Fibrinogen levels were determined within 3 hours (STAT) or 6 hours (ESTAT) of stroke onset and at preset intervals throughout 5 days of intravenous infusions. Barthel Index scores at 90 days quantified functional outcomes. The association between initial fibrinogen levels and functional outcomes was evaluated using a multiple logistic regression analysis.Fibrinogen levels increased gradually over the first 24 hours from a pretreatment median value of 340 mg/dL to a 24-hour median value of 376 mg/dL. In a univariate analysis, the proportion of patients with good functional outcome decreased with increasing quartiles of initial fibrinogen levels in both STAT (36.0% to 26.2%) and ESTAT (53.8% to 24.8%). In a multifactorial analysis, the same trend was observed. Patients with initial fibrinogen levels <450 mg/dL had better outcomes in both studies; the difference (42.0% versus 21.6%) was significant in ESTAT (P=0.0006), even when corrected for age and initial stroke severity.The independent association of higher initial fibrinogen levels with poor outcome needs to be verified using a larger acute stroke dataset. Even in the present small populations, the apparent association of these 2 variables suggests that treatments designed to reduce fibrinogen levels could potentially be important in treating acute ischemic stroke.

  View details for DOI 10.1161/STROKEAHA.108.527804

  View details for Web of Science ID 000265579800026

  View details for PubMedID 19299642

  View details for PubMedCentralID PMC2774454

• Relationships Between Cerebral Perfusion and Reversibility of Acute Diffusion Lesions in DEFUSE Insights from RADAR STROKE Olivot, J., Mlynash, M., Thijs, V. N., Purushotham, A., Kemp, S., Lansberg, M. G., Wechsler, L., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (5): 1692-1697

  Abstract

  Acute ischemic lesions with restricted diffusion can resolve after early recanalization. The impact of superimposed perfusion abnormalities on the fate of acute diffusion lesions is unclear.Data were obtained from DEFUSE, a prospective multicenter study of patients treated with IV tPA 3 to 6 hours after stroke onset. Thirty-two patients with baseline diffusion and perfusion lesions and 30 day FLAIR scans were coregistered. The acute diffusion lesion was divided into 3 regions according to the Tmax delay of the superimposed perfusion lesion: normal baseline perfusion; mild-moderately hypoperfused (2 s8 s). The reversal rate was calculated as the percentage of the acute diffusion lesion that did not overlap with the final infarct on 30-day FLAIR. Diffusion reversal rates were compared based on whether a favorable clinical response occurred and whether early recanalization was achieved.On average, 54% of the acute diffusion lesion volume had normal perfusion. Diffusion reversal rates were significantly increased among cases with favorable clinical response and in patients with early recanalization, especially in regions with normal baseline perfusion. The portion of the diffusion lesion with normal perfusion had significantly higher mean apparent diffusion coefficient values and reversal rates.Acute ischemic lesions with restricted diffusion are most likely to recover if reperfusion occurs within 6 hours of symptom onset, and reversibility is associated with early recanalization and favorable clinical outcome. We propose the term RADAR (Reversible Acute Diffusion lesion Already Reperfused) to describe regions of acute restricted diffusion with normal perfusion.

  View details for DOI 10.1161/STROKEAHA.108.538082

  View details for PubMedID 19299632

• Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke STROKE Zivin, J. A., Albers, G. W., Bornstein, N., Chippendale, T., Dahlof, B., Devlin, T., Fisher, M., Hacke, W., Holt, W., Ilic, S., Kasner, S., Lew, R., Nash, M., Perez, J., Rymer, M., Schellinger, P., Schneider, D., Schwab, S., Veltkamp, R., Walker, M., Streeter, J. 2009; 40 (4): 1359-1364

  Abstract

  We hypothesized that transcranial laser therapy (TLT) can use near-infrared laser technology to treat acute ischemic stroke. The NeuroThera Effectiveness and Safety Trial-2 (NEST-2) tested the safety and efficacy of TLT in acute ischemic stroke.This double-blind, randomized study compared TLT treatment to sham control. Patients receiving tissue plasminogen activator and patients with evidence of hemorrhagic infarct were excluded. The primary efficacy end point was a favorable 90-day score of 0 to 2 assessed by the modified Rankin Scale. Other 90-day end points included the overall shift in modified Rankin Scale and assessments of change in the National Institutes of Health Stroke Scale score.We randomized 660 patients: 331 received TLT and 327 received sham; 120 (36.3%) in the TLT group achieved favorable outcome versus 101 (30.9%), in the sham group (P=0.094), odds ratio 1.38 (95% CI, 0.95 to 2.00). Comparable results were seen for the other outcome measures. Although no prespecified test achieved significance, a post hoc analysis of patients with a baseline National Institutes of Health Stroke Scale score of <16 showed a favorable outcome at 90 days on the primary end point (P<0.044). Mortality rates and serious adverse events did not differ between groups with 17.5% and 17.4% mortality, 37.8% and 41.8% serious adverse events for TLT and sham, respectively.TLT within 24 hours from stroke onset demonstrated safety but did not meet formal statistical significance for efficacy. However, all predefined analyses showed a favorable trend, consistent with the previous clinical trial (NEST-1). Both studies indicate that mortality and adverse event rates were not adversely affected by TLT. A definitive trial with refined baseline National Institutes of Health Stroke Scale exclusion criteria is planned.

  View details for DOI 10.1161/STROKEAHA.109.547547

  View details for Web of Science ID 000264709500052

  View details for PubMedID 19233936

• SENSE Diffusion-weighted Imaging Improves Diagnostic Sensitivity in Acute Ischemic Stroke American-Association-International-Stroke Conference 2009 Schwartz, N. E., Newbould, R. D., Skare, S., Zaharchuk, G., Mlynash, M., Olivot, J., Lansberg, M. G., Eyngorn, I., Thai, D., Albers, G. W., Bammer, R. LIPPINCOTT WILLIAMS & WILKINS. 2009: E115–E115

  View details for Web of Science ID 000264709500133

• Prognostic Value of Brain Diffusion-Weighted Imaging after Cardiac Arrest ANNALS OF NEUROLOGY Wijman, C. A., Mlynash, M., Caulfield, A. F., Hsia, A. W., Eyngorn, I., Bammer, R., Fischbein, N., Albers, G. W., Moseley, M. 2009; 65 (4): 394-402

  Abstract

  Outcome prediction is challenging in comatose postcardiac arrest survivors. We assessed the feasibility and prognostic utility of brain diffusion-weighted magnetic resonance imaging (DWI) during the first week.Consecutive comatose postcardiac arrest patients were prospectively enrolled. AWI data of patients who met predefined specific prognostic criteria were used to determine distinguishing apparent diffusion coefficient (ADC) thresholds. Group 1 criteria were death at 6 months and absent motor response or absent pupillary reflexes or bilateral absent cortical responses at 72 hours or vegetative at 1 month. Group 2 criterion was survival at 6 months with a Glasgow Outcome Scale score of 4 or 5 (group 2A) or 3 (group 2B). The percentage of voxels below different ADC thresholds was calculated at 50 x 10(-6) mm(2)/sec intervals.Overall, 86% of patients underwent DWI. Fifty-one patients with 62 brain DWIs were included. Forty patients met the specific prognostic criteria. The percentage of brain volume with an ADC value less than 650 to 700 x 10(-6)mm(2)/sec best differentiated between Group 1 and Groups 2A and 2B combined (p < 0.001), whereas the 400 to 450 x 10(-6)mm(2)/sec threshold best differentiated between Groups 2A and 2B (p = 0.003). The ideal time window for prognostication using DWI was between 49 and 108 hours after the arrest. When comparing DWI in this time window with the 72-hour neurological examination, DWI improved the sensitivity for predicting poor outcome by 38% while maintaining 100% specificity (p = 0.021).Quantitative DWI in comatose postcardiac arrest survivors holds promise as a prognostic adjunct.

  View details for DOI 10.1002/ana.21632

  View details for Web of Science ID 000265656200008

  View details for PubMedID 19399889

  View details for PubMedCentralID PMC2677115

• Perfusion MRI (Tmax and MTT) correlation with xenon CT cerebral blood flow in stroke patients NEUROLOGY Olivot, J., Mlynash, M., Zaharchuk, G., Straka, M., Bammer, R., Schwartz, N., Lansberg, M. G., Moseley, M. E., Albers, G. W. 2009; 72 (13): 1140-1145

  Abstract

  While stable xenon CT (Xe-CT) cerebral blood flow (CBF) is an accepted standard for quantitative assessment of cerebral hemodynamics, the accuracy of magnetic resonance perfusion-weighted imaging (PWI-MRI) is unclear. The Improved PWI Methodology in Acute Clinical Stroke Study compares PWI findings with Xe-CT CBF values in patients experiencing symptomatic severe cerebral hypoperfusion.We compared mean transit time (MTT) and Tmax PWI-MRI with the corresponding Xe-CT CBF values in 25 coregistered regions of interest (ROIs) of multiple sizes and locations in nine subacute stroke patients. Comparisons were performed with Pearson correlation coefficients (R). We performed receiver operating characteristic (ROC) curve analyses to define the threshold of Tmax and absolute MTT that could best predict a Xe-CT CBF <20 mL/100 g/minute.The subjects' mean (SD) age was 50 (15) years, the median (interquartile range [IQR]) NIH Stroke Scale score was 2 (2-6), and the median (IQR) time between MRI and Xe-CT was 12 (-7-19) hours. The total number of ROIs was 225, and the median (IQR) ROI size was 550 (360-960) pixels. Tmax correlation with Xe-CT CBF (R = 0.63, p < 0.001) was stronger than absolute MTT (R = 0.55, p < 0.001), p = 0.049. ROC curve analysis found that Tmax >4 seconds had 68% sensitivity, 80% specificity, and 77% accuracy and MTT >10 seconds had 68% sensitivity, 77% specificity, and 75% accuracy for predicting ROIs with Xe-CT CBF <20 mL/100 g/minute.Our results suggest that in subacute ischemic stroke patients, Tmax correlates better than absolute mean transit time (MTT) with xenon CT cerebral blood flow (Xe-CT CBF) and that both Tmax >4 seconds and MTT >10 seconds are strongly associated with Xe-CT CBF <20 mL/100 g/minute. CBF = cerebral blood flow; DBP = diastolic blood pressure; DEFUSE = Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution; DWI = diffusion-weighted imaging; EPITHET = Echoplanar Imaging Thrombolytic Evaluation Trial; FOV = field of view; ICA = internal carotid artery; IQR = interquartile range; MCA = middle cerebral artery; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; PWI-MRI = magnetic resonance perfusion-weighted imaging; ROC = receiver operating characteristic; ROI = region of interest; SBP = systolic blood pressure; SVD = singular value decomposition; Xe-CT = xenon CT.

  View details for DOI 10.1212/01.wnl.0000345372.49233.e3

  View details for Web of Science ID 000264709000007

  View details for PubMedID 19332690

  View details for PubMedCentralID PMC2680065

• Yield of combined perfusion and diffusion MR imaging in hemispheric TIA NEUROLOGY Mlynash, M., Olivot, J., Tong, D. C., Lansberg, M. G., Eyngorn, I., Kemp, S., Moseley, M. E., Albers, G. W. 2009; 72 (13): 1127-1133

  Abstract

  Transient ischemic attacks (TIA) predict future stroke. However, there are no sensitive and specific diagnostic criteria for TIA and interobserver agreement regarding the diagnosis is poor. Diffusion-weighted MRI (DWI) demonstrates acute ischemic lesions in approximately 30% of TIA patients; the yield of perfusion-weighted MRI (PWI) is unclear.We prospectively performed both DWI and PWI within 48 hours of symptom onset in consecutive patients admitted with suspected hemispheric TIAs of <24 hours symptom duration. Two independent raters, blinded to clinical features, assessed the presence and location of acute DWI and PWI lesions. Lesions were correlated with suspected clinical localization and baseline characteristics. Clinical features predictive of a PWI lesion were assessed.Forty-three patients met the inclusion criteria. Thirty-three percent had a PWI lesion and 35% had a DWI lesion. Seven patients (16%) had both PWI and DWI lesions and 7 (16%) had only PWI lesions. The combined yield for identification of either a PWI or a DWI was 51%. DWI lesions occurred in the clinically suspected hemisphere in 93% of patients; PWI lesions in 86%. PWI lesions occurred more frequently when the MRI was performed within 12 hours of symptom resolution, in patients with symptoms of speech impairment, and among individuals younger than 60 years.The combination of early diffusion-weighted MRI and perfusion-weighted MRI can document the presence of a cerebral ischemic lesion in approximately half of all patients who present with a suspected hemispheric transient ischemic attack (TIA). MRI has the potential to improve the accuracy of TIA diagnosis. ACA = anterior cerebral artery; CI = confidence interval; DWI = diffusion-weighted MRI; ICA = internal carotid artery; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; OR = odds ratios; PCA = posterior cerebral artery; PWI = perfusion-weighted MRI; RR = risk ratios; TIA = transient ischemic attacks; TOAST = Trial of Org 10172 in Acute Stroke Treatment.

  View details for DOI 10.1212/01.wnl.0000340983.00152.69

  View details for Web of Science ID 000264709000005

  View details for PubMedID 19092109

  View details for PubMedCentralID PMC2680066

• Optimal Tmax Threshold for Predicting Penumbral Tissue in Acute Stroke STROKE Olivot, J., Mlynash, M., Thijs, V. N., Kemp, S., Lansberg, M. G., Wechsler, L., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (2): 469-475

  Abstract

  We sought to assess whether the volume of the ischemic penumbra can be estimated more accurately by altering the threshold selected for defining perfusion-weighting imaging (PWI) lesions.DEFUSE is a multicenter study in which consecutive acute stroke patients were treated with intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset. Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Baseline and posttreatment PWI volumes were defined according to increasing Tmax delay thresholds (>2, >4, >6, and >8 seconds). Penumbra salvage was defined as the difference between the baseline PWI lesion and the final infarct volume (30-day fluid-attenuated inversion recovery sequence). We hypothesized that the optimal PWI threshold would provide the strongest correlations between penumbra salvage volumes and various clinical and imaging-based outcomes.Thirty-three patients met the inclusion criteria. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by Tmax >6 seconds versus Tmax >2 seconds, as was the difference in median penumbra salvage volume in patients with a favorable versus an unfavorable clinical response. Among patients who did not experience early reperfusion, the Tmax >4 seconds threshold provided a more accurate prediction of final infarct volume than the >2 seconds threshold.Defining PWI lesions based on a stricter Tmax threshold than the standard >2 seconds delay appears to provide more a reliable estimate of the volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours after symptom onset. A threshold between 4 and 6 seconds appears optimal for early identification of critically hypoperfused tissue.

  View details for DOI 10.1161/STROKEAHA.108.526954

  View details for PubMedID 19109547

• Use of MRI to Estimate the Therapeutic Window in Acute Stroke Is Perfusion-Weighted Imaging/Diffusion-Weighted Imaging Mismatch an EPITHET for Salvageable Ischemic Brain Tissue? STROKE Toth, G., Albers, G. W. 2009; 40 (1): 333-335

  View details for DOI 10.1161/STROKEAHA.108.525683

  View details for Web of Science ID 000262059400057

  View details for PubMedID 18845795

• Risk of Symptomatic Intracerebral Hemorrhage in Patients Treated with Intra-Arterial Thrombolysis CEREBROVASCULAR DISEASES Singer, O. C., Berkefeld, J., Lorenz, M. W., Fiehler, J., Albers, G. W., Lansberg, M. G., Kastrup, A., Rovira, A., Liebeskind, D. S., Gass, A., Rosso, C., Derex, L., Kim, J. S., Neumann-Haefelin, T. 2009; 27 (4): 368-374

  Abstract

  In intra-arterial (IA) thrombolysis trials, higher rates of symptomatic intracerebral haemorrhage (sICH) were found than in trials with intravenous (IV) recombinant tissue plasminogen activator (tPA); this observation could have been due to the inclusion of more severely affected patients in IA thrombolysis trials. In the present study, we investigated the rate of sICH in IA and combined IV + IA thrombolysis versus IV thrombolysis after adjusting for differences in clinical and MRI parameters.In this multicenter study, we systematically analyzed data from 645 patients with anterior-circulation strokes treated with either IV or IA thrombolysis within 6 h following symptom onset. Thrombolytic regimens included (1) IV tPA treatment (n = 536) and (2) IA treatment with either tPA or urokinase (n = 74) or (3) combined IV + IA treatment with either tPA or urokinase (n = 35).44 (6.8%) patients developed sICH. sICH patients had significantly higher scores on the National Institutes of Health Stroke Scale (NIHSS) at admission and pretreatment DWI lesions. The sICH risk was 5.2% (n = 28) in IV thrombolysis, which is significantly lower than in IA (12.5%, n = 9) or IV + IA thrombolysis (20%, n = 7). In a binary logistic regression analysis including age, NIHSS score, time to thrombolysis, initial diffusion weighted imaging lesion size, mode of thrombolytic treatment and thrombolytic agent, the mode of thrombolytic treatment remained an independent predictor for sICH. The odds ratio for IA or IV + IA versus IV treatment was 3.466 (1.19-10.01, 95% CI, p < 0.05).In this series, IA and IV + IA thrombolysis is associated with an increased sICH risk as compared to IV thrombolysis, and this risk is independent of differences in baseline parameters such as age, initial NIHSS score or pretreatment lesion size.

  View details for DOI 10.1159/000202427

  View details for Web of Science ID 000264862500010

  View details for PubMedID 19218803

  View details for PubMedCentralID PMC2715450

• Antithrombotic agents for stroke prevention. Handbook of clinical neurology Schwartz, N. E., Diener, H., Albers, G. W. 2009; 94: 1277-1294

  View details for DOI 10.1016/S0072-9752(08)94064-1

  View details for PubMedID 18793901

• Acute strokes in the setting of a persistent primitive trigeminal artery. BMJ case reports Schwartz, N. E., Albers, G. W. 2009; 2009: bcr2006111773-?

  View details for DOI 10.1136/bcr.2006.111773

  View details for PubMedID 21687235

  View details for PubMedCentralID PMC3105872

• Patients with Acute Stroke Treated with Intravenous tPA 3-6 Hours after Stroke Onset: Correlations between MR Angiography Findings and Perfusion- and Diffusion-weighted Imaging in the DEFUSE Study RADIOLOGY Marks, M. P., Olivot, J., Kemp, S., Lansberg, M. G., Bammer, R., Wechsler, L. R., Albers, G. W., Thijs, V. 2008; 249 (2): 614-623

  Abstract

  To study magnetic resonance (MR) angiography findings in patients with acute stroke treated with intravenous tissue plasminogen activator (tPA) in relationship to perfusion- and diffusion-weighted imaging changes and clinical outcome.Patients treated with intravenous tPA 3-6 hours after stroke onset (with informed consent) were evaluated in a HIPAA-compliant multicenter prospective study approved by all institutional review boards. MR imaging and MR angiography studies were performed before and 3-6 hours after treatment. MR angiography studies that were technically adequate at both time points were evaluated for occlusion, decreased flow, any early recanalization, and degree of recanalization. These results were compared with favorable clinical response (an improvement in National Institutes of Health Stroke Scale score of >or=8 points at 30 days or a modified Rankin scale score of 0 or 1 at 30 days) in patients with and those without mismatch between perfusion- and diffusion-weighted imaging at baseline.Seventy-four patients were enrolled in the initial investigation; pre- and posttreatment MR angiography studies were both technically adequate in 62 patients. MR angiography demonstrated occlusion or decreased flow in 46 patients. Patients with isolated middle cerebral artery (MCA) occlusion and early recanalization at MR angiography had higher rates of favorable clinical response than those with tandem internal carotid artery-MCA occlusion and early recanalization (P = .05). Any early recanalization was not associated with favorable clinical response, but degree of recanalization did correlate with favorable clinical response (P = .048). Favorable clinical response was more frequently seen in patients with mismatch between perfusion- and diffusion-weighted imaging findings at baseline who experienced early recanalization than in those who did not have early recanalization (odds ratio = 6.2; 95% confidence interval: 1.3, 30.2; P = .021). No relationship between early recanalization and favorable clinical response was seen in patients without mismatch.Early recanalization seen at MR angiography before and after treatment coupled with diffusion- and perfusion-weighted imaging data may predict clinical outcome in patients with stroke treated with tPA 3-6 hours after symptom onset.

  View details for DOI 10.1148/radiol.2492071751

  View details for PubMedID 18936316

• Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study LANCET NEUROLOGY Dienert, H., Saccot, R. L., Yusuft, S., Cotton, D., Ounpuu, S., Lawton, W. A., Palesch, Y., Martin, R. H., Albers, G. W., Bath, P., Bornstein, N., Chan, B. P., Chen, S., Cunha, L., Dahlof, B., De Keyser, J., Donnan, G. A., Estol, C., Gorelick, P., Gu, V., Hermansson, K., Hilbrich, L., Kaste, M., Lu, C., Machnig, T., Pais, P., Roberts, R., Skvortsova, V., Teal, P., Toni, D., VanderMaelen, C., Voigt, T., Weber, M., Yoon, B. 2008; 7 (10): 875-884

  Abstract

  The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062.20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups.Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.

  View details for DOI 10.1016/S1474-4422(08)70198-4

  View details for Web of Science ID 000259725700011

  View details for PubMedID 18757238

• Comparison of Multidetector CT Angiography and MR Imaging of Cervical Artery Dissection AMERICAN JOURNAL OF NEURORADIOLOGY Vertinsky, A. T., Schwartz, N. E., Fischbein, N. J., Rosenberg, J., Albers, G. W., Zaharchuk, G. 2008; 29 (9): 1753-1760

  Abstract

  Conventional angiography has been historically considered the gold standard for the diagnosis of cervical artery dissection, but MR imaging/MR angiography (MRA) and CT/CT angiography (CTA) are commonly used noninvasive alternatives. The goal of this study was to compare the ability of multidetector CT/CTA and MR imaging/MRA to detect common imaging findings of dissection.Patients in the data base of our Stroke Center between 2003 and 2007 with dissections who had CT/CTA and MR imaging/MRA on initial work-up were reviewed retrospectively. Two neuroradiologists evaluated the images for associated findings of dissection, including acute ischemic stroke, luminal narrowing, vessel irregularity, wall thickening/hematoma, pseudoaneurysm, and intimal flap. The readers also subjectively rated each vessel on the basis of whether the imaging findings were more clearly displayed with CT/CTA or MR imaging/MRA or were equally apparent.Eighteen patients with 25 dissected vessels (15 internal carotid arteries [ICA] and 10 vertebral arteries [VA]) met the inclusion criteria. CT/CTA identified more intimal flaps, pseudoaneurysms, and high-grade stenoses than MR imaging/MRA. CT/CTA was preferred for diagnosis in 13 vessels (5 ICA, 8 VA), whereas MR imaging/MRA was preferred in 1 vessel (ICA). The 2 techniques were deemed equal in the remaining 11 vessels (9 ICA, 2 VA). A significant preference for CT/CTA was noted for VA dissections (P < .05), but not for ICA dissections.Multidetector CT/CTA visualized more features of cervical artery dissection than MR imaging/MRA. CT/CTA was subjectively favored for vertebral dissection, whereas there was no technique preference for ICA dissection. In many cases, MR imaging/MRA provided complementary or confirmatory information, particularly given its better depiction of ischemic complications.

  View details for DOI 10.3174/ajnr.A1189

  View details for Web of Science ID 000260023800029

  View details for PubMedID 18635617

• Telmisartan to prevent recurrent stroke and cardiovascular events NEW ENGLAND JOURNAL OF MEDICINE Yusuf, S., Diener, H., Sacco, R. L., Cotton, D., Ounpuu, S., Lawton, W. A., Palesch, Y., Martin, R. H., Albers, G. W., Bath, P., Bornstein, N., Chan, B. P., Chen, S., Cunha, L., Dahlof, B., De Keyser, J., Donnan, G. A., Estol, C., Gorelick, P., Gu, V., Hermansson, K., Hilbrich, L., Kaste, M., Lu, C., Machnig, T., Pais, P., Roberts, R., Skvortsova, V., Teal, P., Toni, D., VanderMaelen, C., Voigt, T., Weber, M., Yoon, B. 2008; 359 (12): 1225-1237

  Abstract

  Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes.The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10).Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)

  View details for Web of Science ID 000259259900006

  View details for PubMedID 18753639

• Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke NEW ENGLAND JOURNAL OF MEDICINE Sacco, R. L., Diener, H., Yusuf, S., Cotton, D., Ounpuu, S., Lawton, W. A., Palesch, Y., Martin, R. H., Albers, G. W., Bath, P., Bornstein, N., Chan, B. P., Chen, S., Cunha, L., Dahlof, B., De Keyser, J., Donnan, G. A., Estol, C., Gorelick, P., Gu, V., Hermansson, K., Hilbrich, L., Kaste, M., Lu, C., Machnig, T., Pais, P., Roberts, R., Skvortsova, V., Teal, P., Toni, D., VanderMaelen, C., Voigt, T., Weber, M., Yoon, B. 2008; 359 (12): 1238-1251

  Abstract

  Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel.In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

  View details for Web of Science ID 000259259900007

  View details for PubMedID 18753638

• The MRA-DWI mismatch identifies patients with stroke who are likely to benefit from reperfusion STROKE Lansberg, M. G., Thijs, V. N., Bammer, R., Olivot, J., Marks, M. P., Wechsler, L. R., Kemp, S., Albers, G. W. 2008; 39 (9): 2491-2496

  Abstract

  The aim of this exploratory analysis was to evaluate if a combination of MR angiography (MRA) and diffusion-weighted imaging (DWI) selection criteria can be used to identify patients with acute stroke who are likely to benefit from early reperfusion.Data from DEFUSE, a study of 74 patients with stroke who received intravenous tissue plasminogen activator in the 3- to 6-hour time window and underwent MRIs before and approximately 4 hours after treatment were analyzed. The MRA-DWI mismatch model was defined as (1) a DWI lesion volume less than 25 mL in patients with a proximal vessel occlusion; or (2) a DWI lesion volume less than 15 mL in patients with proximal vessel stenosis or an abnormal finding of a distal vessel. Favorable clinical response was defined as an improvement on the National Institutes of Health Stroke Scale score of at least 8 points between baseline and 30 days or a National Institutes of Health Stroke Scale score

  View details for DOI 10.1161/STROKEAHA.107.508572

  View details for Web of Science ID 000258727000015

  View details for PubMedID 18635861

• Relationships between infarct growth, clinical outcome, and early recanalization in Diffusion and perfusion imaging For Understanding Stroke Evolution (DEFUSE) STROKE Olivot, J., Mlynash, M., Thijs, V. N., Kemp, S., Lansberg, M. G., Wechsler, L., Schlaug, G., Bammer, R., Marks, M. P., Albers, G. W. 2008; 39 (8): 2257-2263

  Abstract

  The purpose of this study was to determine the relationships between ischemic lesion growth, recanalization, and clinical response in stroke patients with and without a perfusion/diffusion mismatch.DEFUSE is an open label multicenter study in which 74 consecutive acute stroke patients were treated with intravenous tPA 3 to 6 hours after stroke onset. Magnetic resonance imaging (MRI) scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Lesion growth was defined as the difference between the final infarct volume (30 day FLAIR) and the baseline diffusion lesion. Baseline MRI profiles were used to categorize 44 patients into Mismatch versus Absence of Mismatch subgroups. Early recanalization was assessed in 28 patients with an initial vessel lesion on magnetic resonance angiography. Infarct growth was compared based on whether a favorable clinical response (FCR) occurred and whether early recanalization was achieved.In the Mismatch subgroup, FCR was associated with less infarct growth P=0.03 and early recanalization was predictive of both FCR (odds ratio: 22, P=0.047) and reduced infarct growth P=0.024. There was no significant relationship between recanalization, infarct growth, and clinical outcome in the Absence of Mismatch subgroup. A threshold of <7 cc of growth had the highest sensitivity and specificity for predicting a FCR in Mismatch patients (odds ratio: 65, P=0.015, sensitivity 82%, specificity 75%).In contrast to Absence of Mismatch patients, significant associations between recanalization, reduced infarct growth, and favorable clinical response were documented in patients with a perfusion/diffusion mismatch who were treated with tPA within 3 to 6 hours after stroke onset. These findings support the Mismatch hypothesis but require validation in a larger study.

  View details for DOI 10.1161/STROKEAHA.107.511535

  View details for PubMedID 18566302

• Optimal outcome measures for detecting clinical benefits of early reperfusion: insights from the DEFUSE Study. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Kakuda, W., Hamilton, S., Thijs, V. N., Lansberg, M. G., Kemp, S., Skalabrin, E., Albers, G. W. 2008; 17 (4): 235-240

  Abstract

  There is no consensus regarding which clinical outcome scales are the most sensitive indicators of early reperfusion in patients with acute stroke.Patients with acute stroke enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study with a perfusion-/diffusion-weighted imaging mismatch at baseline magnetic resonance imaging were studied. Prespecified secondary outcome measures were evaluated at both 30 and 90 days after treatment with intravenous tissue plasminogen activator. A nonparametric recursive partitioning algorithm was also used to identify the optimal dichotomous splits for differentiating patients who experienced early reperfusion from those who did not.In all, 34 of the 74 patients enrolled in DEFUSE met the inclusion criteria for this study. Statistically significant benefits of reperfusion were documented on multiple outcome measures. The most powerful predefined outcome measure was improvement in the National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 11 points between baseline and day 90 and/or a day-90 NIHSS score of 0 to 1 (odds ratio 22.5, P = .0021). The recursive partitioning algorithm analysis identified an improvement of greater than or equal to 10 on the NIHSS score between baseline and 30 days and an NIHSS score of less than or equal to 2 at 30 days as optimal end points.For patients with stroke and a perfusion-/diffusion-weighted imaging mismatch treated with intravenous tissue plasminogen activator at 3 to 6 hours, a substantial change in the baseline NIHSS score (> or =10 points) is a potent discriminator of patients who experience early reperfusion from those who do not. In addition, an NIHSS score of less than or equal to 2 appears to be an excellent end point for phase II studies of reperfusion therapies.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.03.001

  View details for PubMedID 18589345

• Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schünemann, H. J., American College of Chest Physician 2008; 133 (6): 110S-112S

  Abstract

  Since publication of the seventh American College of Chest Physicians (ACCP) supplement on antithrombotic and thrombolytic therapy, the results of clinical trials have provided important new information on the management of thromboembolic disorders, and the science of developing recommendations has advanced. In the accompanying supplement, we provide the new and updated recommendations and review several important changes that we have made in our guideline development process. We again made a conscious effort to increase the participation of female authors and contributors from outside North America, the latter reflecting the widespread use and dissemination of these guidelines internationally. The grading system for the recommendations was adopted in 2006 by the ACCP for all its guidelines, is similar to the increasingly widely used Grades of Recommendation, Assessment, Development, and Evaluation approach, and is described in detail in one of the introductory chapters. While most of the evidence on which recommendations are made remains low quality in fields of pediatric thrombosis, thrombosis in pregnancy, and thrombosis in valvular heart disease, rigorous studies in other fields have resulted in new and strong evidence-based recommendations for many indications.

  View details for DOI 10.1378/chest.08-0652

  View details for PubMedID 18574260

• Antithrombotic and thrombolytic therapy CHEST Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schunemann, H. J. 2008; 133 (6): 110S-112S

  Abstract

  Since publication of the seventh American College of Chest Physicians (ACCP) supplement on antithrombotic and thrombolytic therapy, the results of clinical trials have provided important new information on the management of thromboembolic disorders, and the science of developing recommendations has advanced. In the accompanying supplement, we provide the new and updated recommendations and review several important changes that we have made in our guideline development process. We again made a conscious effort to increase the participation of female authors and contributors from outside North America, the latter reflecting the widespread use and dissemination of these guidelines internationally. The grading system for the recommendations was adopted in 2006 by the ACCP for all its guidelines, is similar to the increasingly widely used Grades of Recommendation, Assessment, Development, and Evaluation approach, and is described in detail in one of the introductory chapters. While most of the evidence on which recommendations are made remains low quality in fields of pediatric thrombosis, thrombosis in pregnancy, and thrombosis in valvular heart disease, rigorous studies in other fields have resulted in new and strong evidence-based recommendations for many indications.

  View details for DOI 10.1378/chest.08-0652

  View details for Web of Science ID 000257151800002

• American College of Chest Physicians evidence-based clinical practice guidelines (8th edition) CHEST Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schunemann, H. J. 2008; 133 (6): 71S-109S

  View details for DOI 10.1378/chest.08-0693

  View details for Web of Science ID 000257151800001

• Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation STROKE Hart, R. G., Pearce, L. A., Halperin, J. L., Hylek, E. M., Albers, G. W., Anderson, D. C., Connolly, S. J., Friday, G. H., Gage, B. F., Go, A. S., Goldstein, L. B., Gronseth, G., Lip, G. Y., Sherman, D. G., Singer, D. E., van Walraven, C. 2008; 39 (6): 1901-1910

  Abstract

  More than a dozen schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation have been published. Differences among these schemes lead to inconsistent stroke risk estimates for many atrial fibrillation patients, resulting in confusion among clinicians and nonuniform use of anticoagulation.Twelve published schemes stratifying stroke risk in patients with nonvalvular atrial fibrillation are analyzed, and observed stroke rates in independent test cohorts are compared with predicted risk status.Seven schemes were based directly on event-rate analyses, whereas 5 resulted from expert consensus. Four considered only clinical features, whereas 7 schemes included echocardiographic variables. The number of variables per scheme ranged from 4 to 8 (median, 6). The most frequently included features were previous stroke/TIA (100% of schemes), patient age (83%), hypertension (83%), and diabetes (83%), and 8 additional variables were included in >/=1 schemes. Based on published test cohorts, all 8 tested schemes stratified stroke risk, but the absolute stroke rates varied widely. Observed rates for those categorized as low risk ranged from 0% to 2.3% per year and those categorized as high risk ranged from 2.5% to 7.9% per year. When applied to the same cohorts, the fractions of patients categorized by the different schemes as low risk varied from 9% to 49% and those categorized by the different schemes as high-risk varied from 11% to 77%.There are substantial, clinically relevant differences among published schemes designed to stratify stroke risk in patients with atrial fibrillation. Additional research to identify an optimum scheme for primary prevention and subsequent standardization of recommendations may lead to more uniform selection of patients for anticoagulant prophylaxsis.

  View details for DOI 10.1161/STROKEAHA.107.501825

  View details for Web of Science ID 000256162600046

  View details for PubMedID 18420954

• Executive summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schünemann, H. J. 2008; 133 (6): 71S-109S

  View details for DOI 10.1378/chest.08-0693

  View details for PubMedID 18574259

• Antithrombotic and thrombolytic therapy for ischemic stroke CHEST Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. 2008; 133 (6): 630S-669S

  Abstract

  This article about treatment and prevention of stroke is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading, see the "Grades of Recommendations" chapter by Guyatt et al, CHEST 2008; 133:123S-131S). Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke, we recommend administration of IV tissue plasminogen activator (tPA) if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with acute ischemic stroke of > 3 h but < 4.5 h, we suggest clinicians do not use IV tPA (Grade 2A). For patients with acute stroke onset of > 4.5 h, we recommend against the use of IV tPA (Grade 1A). For patients with acute ischemic stroke who are not receiving thrombolysis, we recommend early aspirin therapy (Grade 1A). For acute ischemic stroke patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low-molecular-weight heparins (Grade 1A). For long-term stroke prevention in patients with noncardioembolic stroke or transient ischemic attack (TIA) [ie, atherothrombotic, lacunar, or cryptogenic], we recommend treatment with an antiplatelet agent (Grade 1A), including aspirin (recommended dose, 50-100 mg/d), the combination of aspirin and extended-release dipyridamole (25 mg/200 mg bid), or clopidogrel (75 mg qd). In these patients, we recommend use of the combination of aspirin and extended-release dipyridamole (25/200 mg bid) over aspirin (Grade 1A) and suggest clopidogrel over aspirin (Grade 2B), and recommend avoiding long-term use of the combination of aspirin and clopidogrel (Grade 1B). For patients who are allergic to aspirin, we recommend clopidogrel (Grade 1A). In patients with atrial fibrillation and a recent stroke or TIA, we recommend long-term oral anticoagulation (target international normalized ratio, 2.5; range, 2.0 to 3.0) [Grade 1A]. In patients with venous sinus thrombosis, we recommend unfractionated heparin (Grade 1B) or low-molecular-weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase.

  View details for DOI 10.1378/chest.08-0720

  View details for Web of Science ID 000257151800017

  View details for PubMedID 18574275

• Antithrombotic therapy in atrial fibrillation CHEST Singer, D. E., Albers, G. W., Dalen, J. E., Fang, M. C., Go, A. S., Halperin, J. L., Lip, G. Y., Manning, W. J. 2008; 133 (6): 546S-592S

  Abstract

  This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the American College of Chest Physicians Evidence-Based Guidelines Clinical Practice Guidelines (8th Edition). Grade 1 recommendations indicate that most patients would make the same choice and Grade 2 suggests that individual patient's values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range 2.0-3.0, unless otherwise noted). In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, transient ischemic attack (TIA), or systemic embolism, we recommend long-term anticoagulation with an oral VKA, such as warfarin, because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A). In patients with AF, including those with paroxysmal AF, who have two or more of the risk factors for future ischemic stroke listed immediately below, we recommend long-term anticoagulation with an oral VKA (Grade 1A). Two or more of the following risk factors apply: age >75 years, history of hypertension, diabetes mellitus, moderately or severely impaired left ventricular systolic function and/or heart failure. In patients with AF, including those with paroxysmal AF, with only one of the risk factors listed immediately above, we recommend long-term antithrombotic therapy (Grade 1A), either as anticoagulation with an oral VKA, such as warfarin (Grade 1A), or as aspirin, at a dose of 75-325 mg/d (Grade 1B). In these patients at intermediate risk of ischemic stroke we suggest a VKA rather than aspirin (Grade 2A). In patients with AF, including those with paroxysmal AF, age < or =75 years and with none of the other risk factors listed above, we recommend long-term aspirin therapy at a dose of 75-325 mg/d (Grade 1B), because of their low risk of ischemic stroke. For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C). For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA (Grade 1B). For patients with AF and prosthetic heart valves we recommend long-term anticoagulation with an oral VKA at an intensity appropriate for the specific type of prosthesis (Grade 1B). See CHEST 2008; 133(suppl):593S-629S. For patients with AF of > or =48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA, such as warfarin, for 3 weeks before elective cardioversion and for at least 4 weeks after sinus rhythm has been maintained (Grade 1C). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacological or electrical cardioversion, we also recommend either immediate anticoagulation with unfractionated IV heparin, or low-molecular-weight heparin (LMWH), or at least 5 days of warfarin by the time of cardioversion (achieving an INR of 2.0-3.0) as well as a screening multiplane transesophageal echocardiography (TEE). If no thrombus is seen, cardioversion is successful, and sinus rhythm is maintained, we recommend anticoagulation for at least 4 weeks. If a thrombus is seen on TEE, then cardioversion should be postponed and anticoagulation should be continued indefinitely. We recommend obtaining a repeat TEE before attempting later cardioversion (Grade 1B addressing the equivalence of TEE-guided vs non-TEE-guided cardioversion). For patients with AF of known duration <48 h, we suggest cardioversion without prolonged anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or LMWH at presentation (Grade 2C).

  View details for DOI 10.1378/chest.08-0678

  View details for Web of Science ID 000257151800015

  View details for PubMedID 18574273

• Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Kakuda, W., Lansberg, M. G., Thijs, V. N., Kemp, S. M., Bammer, R., Wechsler, L. R., Moseley, M. E., Parks, M. P., Albers, G. W. 2008; 28 (5): 887-891

  Abstract

  Although the perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch model has been proposed to identify acute stroke patients who benefit from reperfusion therapy, the optimal definition of a mismatch is uncertain. We evaluated the odds ratio for a favorable clinical response in mismatch patients with reperfusion compared with no reperfusion for various mismatch ratio thresholds in patients enrolled in the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. A mismatch ratio of 2.6 provided the highest sensitivity (90%) and specificity (83%) for identifying patients in whom reperfusion was associated with a favorable response. Defining mismatch with a larger PWI/DWI ratio may provide greater power for detecting beneficial effects of reperfusion.

  View details for DOI 10.1038/sj.jcbfm.9600604

  View details for Web of Science ID 000255261300003

  View details for PubMedID 18183031

• Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack STROKE Adams, R. J., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Sacco, R. L., Schwamm, L. H. 2008; 39 (5): 1647-1652

  View details for DOI 10.1161/STROKEAHA.107.189063

  View details for Web of Science ID 000255393100046

  View details for PubMedID 18322260

• Acute stroke imaging research roadmap. AJNR. American journal of neuroradiology Wintermark, M., Albers, G. W., Alexandrov, A. V., Alger, J. R., Bammer, R., Baron, J., Davis, S., Demaerschalk, B. M., Derdeyn, C. P., Donnan, G. A., Eastwood, J. D., Fiebach, J. B., Fisher, M., Furie, K. L., Goldmakher, G. V., Hacke, W., Kidwell, C. S., Kloska, S. P., Köhrmann, M., Koroshetz, W., Lee, T., Lees, K. R., Lev, M. H., Liebeskind, D. S., Ostergaard, L., Powers, W. J., Provenzale, J., Schellinger, P., Silbergleit, R., Sorensen, A. G., Wardlaw, J., Wu, O., Warach, S. 2008; 29 (5): e23-30

  Abstract

  The recent "Advanced Neuroimaging for Acute Stroke Treatment" meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them.

  View details for PubMedID 18477656

• Effect of ximelagatran and warfarin on Stroke subtypes in atrial fibrillation CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES Teitelbaum, J. S., von Kummer, R., Gjesdal, K., Kristinsson, A., Gahn, G., Albers, G. W. 2008; 35 (2): 160-165

  Abstract

  The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke.7329 patients with AF and > or = 1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0--3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype.The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant.In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.

  View details for Web of Science ID 000256184600009

  View details for PubMedID 18574928

• Rapid assessment and intervention at specialist outpatient clinics - time for a new standard in TIA care? NATURE CLINICAL PRACTICE NEUROLOGY Albers, G. W. 2008; 4 (4): 184-185

  View details for DOI 10.1038/ncpneuro0733

  View details for Web of Science ID 000254581200004

  View details for PubMedID 18227824

• Yield of transesophageal echocardiography in ischemic stroke patients by age and lesion pattern on diffusion-weighted MRI 33rd International Stroke Conference Campbell, D. M., Beraud, A., Mlynash, M., Schnittger, I., Eyngorn, I., Kumar, M. A., Tong, D. C., Moseley, M., Albers, G. W., Wijman, C. A. LIPPINCOTT WILLIAMS & WILKINS. 2008: 575–76

  View details for Web of Science ID 000252726100246

• MRI-based diagnostic evaluation has substantial impact on final stroke diagnosis 33rd International Stroke Conference Kumar, M. A., Campbell, D. M., Vangala, H. L., Eyngorn, I., Olivot, J. M., Beraud, A. S., Belgude, A., Lansberg, M. G., Schnittger, I., Wijman, C. A., Tong, D. C., Mlynash, M., Albers, G. W., Moseley, M. LIPPINCOTT WILLIAMS & WILKINS. 2008: 569–69

  View details for Web of Science ID 000252726100222

• Use of antiplatelet agents to prevent stroke: What is the role for combinations of medications? CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS Schwartz, N. E., Albers, G. W. 2008; 8 (1): 29-34

  Abstract

  Antiplatelet agents are the medications of choice for preventing non-cardioembolic strokes. The diverse pathways involved in platelet function suggest the possibility of synergistic effects by combining various agents. In heart disease and in the setting of coronary artery stents, antiplatelet therapy with clopidogrel and aspirin has established benefits. Although it is tempting to extrapolate the benefits of this combination for stroke prevention, recent clinical trials have not borne this out. Unacceptable bleeding risks without additional efficacy weigh against the routine use of clopidogrel with aspirin for stroke prophylaxis. The combination of aspirin and extended-release dipyridamole has demonstrated superiority over aspirin in two large secondary stroke prevention trials.

  View details for Web of Science ID 000256319000004

  View details for PubMedID 18367036

• Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging ANNALS OF NEUROLOGY Singer, O. C., Humpich, M. C., Fiehler, J., Albers, G. W., Lansberg, M. G., Kastrup, A., Rovira, A., Liebeskind, D. S., Gass, A., Rosso, C., Derex, L., Kim, J. S., Neumann-Haefelin, T. 2008; 63 (1): 52-60

  Abstract

  The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion-weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis.In this retrospective multicenter study, prospectively collected data from 645 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours (<3 hours: n = 320) after symptom onset were pooled. Patients were categorized according to the pretreatment DWI lesion size into three prespecified groups: small (< or =10 ml; n = 218), moderate (10-100 ml; n = 371), and large (>100 ml; n = 56) DWI lesions.In total, 44 (6.8%) patients experienced development of sICH. The sICH rate was significantly different between subgroups: 2.8, 7.8, and 16.1% in patients with small, moderate, and large DWI lesions, respectively (p < 0.05). This translates to a 5.8 (2.8)-fold greater sICH risk for patients with large DWI lesions as compared with patients with small (or moderate) DWI lesions. The results were similar in the large subgroup (n = 536) of patients treated with intravenous tissue plasminogen activator. DWI lesion size remained an independent risk factor when including National Institutes of Health Stroke Scale, age, time to thrombolysis, and leukoariosis in a logistic regression analysis.This multicenter study provides estimates of sICH risk in potential candidates for thrombolysis. The sICH risk increases gradually with increasing DWI lesion size, indicating that the potential benefit of therapy needs to be balanced carefully against the risk for sICH, especially in patients with large DWI lesions.

  View details for DOI 10.1002/ana.21222

  View details for Web of Science ID 000253008700008

  View details for PubMedID 17880020

• Is there a role for combinations of antiplatelet agents in stroke prevention? Current treatment options in neurology Schwartz, N. E., Albers, G. W. 2007; 9 (6): 442-450

  Abstract

  Antiplatelet medications are the agents of choice for secondary prevention of noncardioembolic ischemic strokes. Multiple clinical trials have proven their reliable albeit modest clinical benefits and relatively good safety profile. The most commonly recommended antiplatelet agents for secondary stroke prevention in North America and Europe are aspirin, clopidogrel, and the combination of aspirin and extended-release dipyridamole. Because of the multiple pharmacologic mechanisms available for platelet inhibition, combination antiplatelet agents have the potential for synergistic effects. However, combinations of antithrombotic agents do not necessarily improve clinical efficacy and are typically associated with increased toxicity. Clopidogrel and aspirin have been used in combination in patients with diverse arterial vascular diseases. Combination antiplatelet therapy with clopidogrel and aspirin has established clinical benefits, particularly in coronary disease and in patients who have undergone coronary stenting. Although it is tempting to extrapolate the benefits of clopidogrel and aspirin to the setting of secondary stroke prevention, recent clinical trials have failed to document significant clinical benefits in cerebrovascular patients. This failure has occurred because of a lack of significant efficacy for prevention of vascular events and a substantial increase in bleeding risk. Therefore, the clopidogrel and aspirin combination is not recommended for recurrent stroke prevention. In general, when clopidogrel is used for cerebrovascular patients, the addition of aspirin should be avoided unless there is a specific cardiac indication such as recent acute coronary syndrome or a coronary stent. The combination of aspirin and extended-release dipyridamole is supported by Class I data from two large studies demonstrating superiority over aspirin alone for recurrent stroke prevention. Although dual antiplatelet therapy with clopidogrel and aspirin has never been directly compared with the combination of aspirin and extended-release dipyridamole, clinical trial results favor the latter for secondary stroke prevention. Currently, there are no data for primary stroke prevention with dual antiplatelet agents regarding aspirin and extended-release dipyridamole. Limited data from the recent Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization Management and Avoidance (CHARISMA) trial indicate that the combination of clopidogrel and aspirin may be harmful, compared with aspirin alone.

  View details for PubMedID 18173943

• Bleeding Risk Analysis in Stroke Imaging before ThromboLysis (BRASIL) - Pooled analysis of t2*-weighted magnetic resonance imaging data from 570 patients STROKE Fiehler, J., Albers, G. W., Boulanger, J., Derex, L., Gass, A., Hjort, N., Kim, J. S., Liebeskind, D. S., Neumann-Haefelin, T., Pedraza, S., Rother, J., Rothwell, P., Rovira, A., Schellinger, P. D., Trenkler, J. 2007; 38 (10): 2738-2744

  Abstract

  There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients.We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by >or=4 points, temporally related to a parenchymal hematoma on follow-up-imaging.A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CMBs ranged from 1 to 77 in the individual patient, with >or=5 CMBs in 6 of 570 patients (1.1%). Proportions of patients with SICH were 5.8% (95% CI, 1.9 to 13.0) in the presence of CMBs and 2.7% (95% CI, 1.4 to 4.5) in patients without CMBs (P=0.170, Fisher's exact test), resulting in no significant absolute increase in the risk of SICH of 3.1% (95% CI, -2.0 to 8.3).The data suggest that if there is any increased risk of SICH attributable to CMBs, it is likely to be small and unlikely to exceed the benefits of thrombolytic therapy. No reliable conclusion regarding risk in the rare patient with multiple CMBs can be reached.

  View details for DOI 10.1161/STROKEAHA.106.480848

  View details for Web of Science ID 000249694900021

  View details for PubMedID 17717319

• Warfarin prevails for stroke prevention in atrial fibrillation-even in octogenarians LANCET NEUROLOGY Albers, G. W. 2007; 6 (10): 844-846

  View details for Web of Science ID 000250035600005

  View details for PubMedID 17884669

• Independent predictors of stroke in patients with atrial fibrillation - A systematic review NEUROLOGY Hart, R. G., Pearce, L. A., Albers, G. W., Connolly, S. J., Friday, G. H., Gage, B. F., Go, A. S., Goldstein, L. B., Gronseth, G., Halperin, J. L., Hylek, E. M., Lip, G. Y., Sherman, D. G., Singer, D. E., van Walraven, C. 2007; 69 (6): 546-554

  Abstract

  Absolute stroke rates vary widely among patients with nonvalvular atrial fibrillation. To balance the benefits and risks of chronic antithrombotic prophylaxis, it is important to estimate the absolute risk of stroke for individual patients.Systematic review of studies using multivariate regression techniques to identify independent risk factors for stroke in patients with atrial fibrillation was conducted, and reports of absolute stroke rates in subgroups of patients with these risk factors collected. A summary estimate of the relative risk associated with each independent risk factor was calculated using maximum likelihood methods.Seven studies (including six entirely independent cohorts) were identified. Prior stroke/TIA (relative risk 2.5, 95% CI 1.8 to 3.5), increasing age (relative risk 1.5 per decade, 95% CI 1.3 to 1.7), a history of hypertension (relative risk 2.0, 95% CI 1.6 to 2.5), and diabetes mellitus (relative risk 1.7, 95% CI 1.4 to 2.0) were the strongest, most consistent independent risk factors. Observed absolute stroke rates for nonanticoagulated patients with single independent risk factors were in the range of 6 to 9% per year for prior stroke/TIA, 1.5 to 3% per year for history of hypertension, 1.5 to 3% per year for age >75, and 2.0 to 3.5% per year for diabetes. Female sex was inconsistently associated with stroke risk, whereas the evidence was inconclusive that either heart failure or coronary artery disease is independently predictive of stroke.Four clinical features (prior stroke/TIA, advancing age, hypertension, diabetes) are consistent independent risk factors for stroke in atrial fibrillation patients. Prior stroke/TIA is the most powerful risk factor and reliably confers a high stroke risk (>5% per year, averaging 10% per year). Absolute stroke rates associated with other individual risk factors are difficult to precisely estimate from available data.

  View details for Web of Science ID 000248573000007

  View details for PubMedID 17679673

• Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke STROKE Lansberg, M. G., Thijs, V. N., Bammer, R., Kemp, S., Wijman, C. A., Marks, M. P., Albers, G. W. 2007; 38 (8): 2275-2278

  Abstract

  Studies evaluating predictors of tPA-associated symptomatic intracerebral hemorrhage (SICH) have typically focused on clinical and CT-based variables. MRI-based variables have generally not been included in predictive models, and little is known about the influence of reperfusion on SICH risk.Seventy-four patients were prospectively enrolled in an open-label study of intravenous tPA administered between 3 and 6 hours after symptom onset. An MRI was obtained before and 3 to 6 hours after tPA administration. The association between several clinical and MRI-based variables and tPA-associated SICH was determined using multivariate logistic regression analysis. SICH was defined as a > or = 2 point change in National Institutes of Health Stroke Scale Score (NIHSSS) associated with any degree of hemorrhage on CT or MRI. Reperfusion was defined as a decrease in PWI lesion volume of at least 30% between baseline and the early follow-up MRI.SICH occurred in 7 of 74 (9.5%) patients. In univariate analysis, NIHSSS, DWI lesion volume, PWI lesion volume, and reperfusion status were associated with an increased risk of SICH (P<0.05). In multivariate analysis, DWI lesion volume was the single independent baseline predictor of SICH (odds ratio 1.42; 95% CI 1.13 to 1.78 per 10 mL increase in DWI lesion volume). When early reperfusion status was included in the predictive model, the interaction between DWI lesion volume and reperfusion status was the only independent predictor of SICH (odds ratio 1.77; 95% CI 1.25 to 2.50 per 10 mL increase in DWI lesion volume).Patients with large baseline DWI lesion volumes who achieve early reperfusion appear to be at greatest risk of SICH after tPA therapy.

  View details for DOI 10.1161/STROKEAHA.106.480475

  View details for PubMedID 17569874

• Neurological picture. Acute strokes in the setting of a persistent primitive trigeminal artery. Journal of neurology, neurosurgery, and psychiatry Schwartz, N. E., Albers, G. W. 2007; 78 (7): 745-?

  View details for PubMedID 17575019

• Perfusion mapping with multiecho multishot parallel imaging EPI MAGNETIC RESONANCE IN MEDICINE Newbould, R. D., Skare, S. T., Jochimsen, T. H., Alley, M. T., Moseley, M. E., Albers, G. W., Bammer, R. 2007; 58 (1): 70-81

  Abstract

  Echo-planar imaging (EPI) is the standard technique for dynamic susceptibility-contrast (DSC) perfusion MRI. However, EPI suffers from well-known geometric distortions, which can be reduced by increasing the k-space phase velocity. Moreover, the long echo times (TEs) used in DSC lead to signal saturation of the arterial input signal, and hence to severe quantitation errors in the hemodynamic information. Here, through the use of interleaved shot acquisition and parallel imaging (PI), rapid volumetric EPI is performed using pseudo-single-shot (ss)EPI with the effective T(*)(2) blur and susceptibility distortions of a multishot EPI sequence. The reduced readout lengths permit multiple echoes to be acquired with temporal resolution and spatial coverage similar to those obtained with a single-echo method. Multiecho readouts allow for unbiased R(*)(2) mapping to avoid incorrect estimation of tracer concentration due to signal saturation or T(1) shortening effects. Multiecho perfusion measurement also mitigates the signal-to-noise ratio (SNR) reduction that results from utilizing PI. Results from both volunteers and clinical stroke patients are presented. This acquisition scheme can aid most rapid time-series acquisitions. The use of this method for DSC addresses the problem of signal saturation and T(1) contamination while it improves image quality, and is a logical step toward better quantitative MR PWI.

  View details for DOI 10.1002/mrm.21255

  View details for Web of Science ID 000248488400009

  View details for PubMedID 17659630

• Identifying systematic errors in quantitative dynamic-susceptibility contrast perfusion imaging by high-resolution multi-echo parallel EPI NMR IN BIOMEDICINE Jochimsen, T. H., Newbould, R. D., Skare, S. T., Clayton, D. B., Albers, G. W., Moseley, M. E., Bammer, R. 2007; 20 (4): 429-438

  Abstract

  Several obstacles usually confound a straightforward perfusion analysis using dynamic-susceptibility contrast-based magnetic resonance imaging (DSC-MRI). In this work, it became possible to eliminate some of these sources of error by combining a multiple gradient-echo technique with parallel imaging (PI): first, the large dynamic range of tracer concentrations could be covered satisfactorily with multiple echo times (TE) which would otherwise result in overestimation of image magnitude in the presence of noise. Second, any bias from T(1) relaxation could be avoided by fitting to the signal magnitude of multiple TEs. Finally, with PI, a good tradeoff can be achieved between number of echoes, brain coverage, temporal resolution and spatial resolution. The latter reduces partial voluming, which could distort calculation of the arterial input function. Having ruled out these sources of error, a 4-fold overestimation of cerebral blood volume and flow remained, which was most likely due to the completely different relaxation mechanisms that are effective in arterial voxels compared with tissue. Hence, the uniform tissue-independent linear dependency of relaxation rate upon tracer concentration, which is usually assumed, must be questioned. Therefore, DSC-MRI requires knowledge of the exact dependency of transverse relaxation rate upon tracer concentration in order to calculate truly quantitative perfusion maps.

  View details for DOI 10.1002/nbm.1107

  View details for Web of Science ID 000246767000004

  View details for PubMedID 17044140

• Evaluation of the clinical-diffusion and perfusion-diffusion mismatch models in DEFUSE STROKE Lansberg, M. G., Thijs, V. N., Hamilton, S., Schlaug, G., Bammer, R., Kemp, S., Albers, G. W. 2007; 38 (6): 1826-1830

  Abstract

  The perfusion-diffusion mismatch (PDM) model has been proposed as a tool to select acute stroke patients who are most likely to benefit from reperfusion therapy. The clinical-diffusion mismatch (CDM) model is an alternative method that is technically less challenging because it does not require perfusion-weighted imaging. This study is an evaluation of these 2 models in the DEFUSE dataset.DEFUSE is an open-label multicenter study in which acute stroke patients were treated with intravenous tPA between 3 and 6 hours after symptoms onset and an MRI was obtained before and 3 to 6 hours after treatment. Presence of PDM and CDM was determined for each patient.Based on conventional predefined mismatch criteria, PDM was present in 54% of the DEFUSE population and CDM in 62%. There was no agreement beyond chance between the 2 mismatch models (kappa 0.07). The presence of PDM was associated with an increased chance of favorable clinical response after reperfusion (OR, 5.4; P=0.039). Reperfusion was not associated with a significant increase in the rate of favorable clinical response in patients with CDM (OR, 2.2; P=0.34). Using optimized mismatch criteria, determined retrospectively based on DEFUSE data, the OR for favorable clinical response was 70 (P=0.001) for PDM and 5.1 (P=0.066) for CDM.The PDM model appears to be more accurate than the CDM model for selecting patients who are likely to benefit from reperfusion therapy in the 3- to 6-hour time window.

  View details for DOI 10.1161/STROKEA.HA.106.480145

  View details for Web of Science ID 000246827100026

  View details for PubMedID 17495217

• Transient isolated vertigo secondary to an acute stroke of the cerebellar nodulus ARCHIVES OF NEUROLOGY Schwartz, N. E., Venkat, C., Albers, G. W. 2007; 64 (6): 897-898

  View details for Web of Science ID 000247143500018

  View details for PubMedID 17562941

• Clinical multishot DW-EPI through parallel imaging with considerations of susceptibility, motion, and noise MAGNETIC RESONANCE IN MEDICINE Skare, S., Newbould, R. D., Clayton, D. B., Albers, G. W., Nagle, S., Bammer, R. 2007; 57 (5): 881-890

  Abstract

  Geometric distortions and poor image resolution are well known shortcomings of single-shot echo-planar imaging (ss-EPI). Yet, due to the motion immunity of ss-EPI, it remains the most common sequence for diffusion-weighted imaging (DWI). Moreover, both navigated DW interleaved EPI (iEPI) and parallel imaging (PI) methods, such as sensitivity encoding (SENSE) and generalized autocalibrating parallel acquisitions (GRAPPA), can improve the image quality in EPI. In this work, DW-EPI accelerated by PI is proposed as a self-calibrated and unnavigated form of interleaved acquisition. The PI calibration is performed on the b = 0 s/mm2 data and applied to each shot in the rest of the DW data set, followed by magnitude averaging. Central in this study is the comparison of GRAPPA and SENSE in the presence of off-resonances and motion. The results show that GRAPPA is more robust than SENSE against both off-resonance and motion-related artifacts. The SNR efficiency was also investigated, and it is shown that the SNR/scan time ratio is equally high for one- to three-shot high-resolution diffusion scans due to the shortened EPI readout train length. The image quality improvements without SNR efficiency loss, together with motion tolerance, make the GRAPPA-driven DW-EPI sequence clinically attractive.

  View details for DOI 10.1002/mrm.21176

  View details for Web of Science ID 000246052800010

  View details for PubMedID 17457876

• The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venousthromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison LANCET Sherman, D. G., Albers, G. W., Bladin, C., Fieschi, C., Gabbai, A. A., Kase, C. S., O'Riordan, W., Pineo, G. F. 2007; 369 (9570): 1347-1355

  Abstract

  Venous thromboembolism prophylaxis with low molecular weight heparin or unfractionated heparin is recommended in acute ischaemic stroke, but which regimen provides optimum treatment is uncertain. We aimed to compare the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with stroke.1762 patients with acute ischaemic stroke who were unable to walk unassisted were randomly assigned within 48 h of symptoms to receive either enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14, less severe stroke <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary safety endpoints were symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality. This study is registered with ClinicalTrials.gov, number NCT00077805.In the efficacy population (ie, one or more dose received, presence of deep vein thrombosis or pulmonary embolism, or assessment for venous thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%] vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The occurrence of any bleeding was similar with enoxaparin (69 [8%]) or unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%]; p=0.23). We noted no difference for symptomatic intracranial haemorrhage between groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs 0; p=0.015).Our results suggest that for patients with acute ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration.

  View details for Web of Science ID 000245856100027

  View details for PubMedID 17448820

• Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation - Pooled analysis of SPORTIF III and V clinical trials 14th European Stroke Conference Akins, P. T., Feldman, H. A., Zoble, R. G., Newman, D., Spitzer, S. G., Diener, H., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2007: 874–80

  Abstract

  Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA.We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin < or =100 mg/d.Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events.Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

  View details for DOI 10.1161/01.STR.0000258004.64840.0b

  View details for Web of Science ID 000244482500017

  View details for PubMedID 17255547

• Can the ESPRIT results end the antiplatelet battle between neurologists and cardiologists? NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE Albers, G. W. 2007; 4 (3): 118-119

  View details for DOI 10.1038/ncpcardio0803

  View details for Web of Science ID 000244378000002

  View details for PubMedID 17330124

• Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control - Results from SPORTIF III and IV ARCHIVES OF INTERNAL MEDICINE White, H. D., Gruber, M., Feyzi, J., Kaatz, S., Tse, H., Husted, S., Albers, G. W. 2007; 167 (3): 239-245

  Abstract

  Warfarin sodium reduces stroke risk in patients with atrial fibrillation, but international normalized ratio (INR) monitoring is required. Target INRs are frequently not achieved, and the risk of death, bleeding, myocardial infarction (MI), and stroke or systemic embolism event (SEE) may be related to INR control.We analyzed the relationship between INR control and the rates of death, bleeding, MI, and stroke or SEE among 3587 patients with atrial fibrillation randomized to receive warfarin treatment in the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation) III and V trials. The mean+/-SD follow-up was 16.6 +/- 6.3 months. Patients were divided into 3 equal groups (those with good control [>75%], those with moderate control [60%-75%], or those with poor control [<60%]) according to the percentage time with an INR of 2.0 to 3.0. Outcomes were compared according to INR control. The main outcome measures were death, bleeding, MI, and stroke or SEE.The poor control group had higher rates of annual mortality (4.20%) and major bleeding (3.85%) compared with the moderate control group (1.84% and 1.96%, respectively) and the good control group (1.69% and 1.58%, respectively) (P<.01 for all). Compared with the good control group, the poor control group had higher rates of MI (1.38% vs 0.62%, P = .04) and of stroke or SEE (2.10% vs 1.07%, P = .02).In patients with atrial fibrillation taking warfarin, the risks of death, MI, major bleeding, and stroke or SEE are related to INR control. Good INR control is important to improve patient outcomes.

  View details for Web of Science ID 000244163200003

  View details for PubMedID 17296878

• A multicenter pooled, patient-level data analysis of diffusion-weighted MRI in TIA patients 32nd International Stroke Conference Shah, S. H., Saver, J. L., Kidwell, C. S., Albers, G., Rothwell, P., Ay, H., Koroshetz, W. J., Inatomi, Y., Uchino, M., Demchuk, A. M., Coutts, S. B., Purroy, F., Alvarez-Sabin, J., Sander, K., Sander, D., Restrepo, L., Wityk, R. J., Marx, J. J., Easton, J. D. LIPPINCOTT WILLIAMS & WILKINS. 2007: 463–63

  View details for Web of Science ID 000244122600103

• Clinical and radiographic history of cervical artery dissections 32nd International Stroke Conference Hirsch, K., Vertinsky, T., Albers, G. W., Schwartz, N. E. LIPPINCOTT WILLIAMS & WILKINS. 2007: 587–87

  View details for Web of Science ID 000244122600671

• Intravenous alteplase for ischaemic stroke LANCET Albers, G. W., Olivot, J. 2007; 369 (9558): 249-250

  View details for Web of Science ID 000243912000004

  View details for PubMedID 17258646

• Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: A review of the risk factors CEREBROVASCULAR DISEASES Lansberg, M. G., Albers, G. W., Wijman, C. A. 2007; 24 (1): 1-10

  Abstract

  Symptomatic intracerebral hemorrhage (SICH) following thrombolytic therapy for acute ischemic stroke is associated with a high rate of morbidity and mortality. Knowledge of the risk factors associated with SICH following thrombolyitc therapy may provide insight into the pathophysiological mechanisms underlying the development of SICH, lead to the development of treatments that reduce the risk of SICH and have implications for the design of future stroke trials.Relevant studies were identified through a search in Pubmed. Included studies used multivariate analyses to identify independent risk factors for SICH following thrombolytic therapy. For each variable that was found to have a significant association with SICH, a secondary literature search was conducted to identify additional reports on the specific relationship between that variable and SICH.Twelve studies met inclusion criteria for the systematic review. Extent of hypoattenuated brain parenchyma on pretreatment CT and elevated serum glucose or history of diabetes were independent risk factors for thrombolysis-associated SICH in six of the twelve studies. Symptom severity was an independent risk factor in three of the studies and advanced age, increased time to treatment, high systolic blood pressure, low platelets, history of congestive heart failure and low plasminogen activator inhibitor levels were found to be independent risk factors for SICH in a single study. Although these data should not alter the current guidelines for the use of rt-PA in acute stroke, they may help develop future strategies aimed at reducing the rate of thrombolysis-associated SICH.

  View details for DOI 10.1159/000103110

  View details for Web of Science ID 000247435300001

  View details for PubMedID 17519538

• Safety and tolerability of arundic acid in acute ischemic stroke JOURNAL OF THE NEUROLOGICAL SCIENCES Pettigrew, L. C., Kasner, S. E., Albers, G. W., Gorman, M., Grotta, J. C., Sherman, D. G., Funakoshi, Y., Ishibashi, H. 2006; 251 (1-2): 50-56

  Abstract

  Arundic acid (AA; ONO-2506), a novel modulator of astrocyte activation, may improve neuronal survival after stroke. We conducted a multicenter, dose-escalating, randomized, double-blind Phase I trial of AA in acute ischemic stroke. Subjects were randomized to treatment with AA or placebo in sequential dose tiers of 2-12 mg/kg/h (10-16 patients/group) within 24 h of stroke onset. Study drug was infused for 1 h daily over 7 days, and follow-up terminated at 40 days. Neurological and functional outcomes were evaluated through Day 40 as exploratory endpoints. A total of 92 subjects were enrolled with no dose-related pattern of serious adverse events (AEs). Premature terminations caused by AEs occurred in four (8.2%) patients treated with AA and five (11.6%) treated with placebo. Two subjects treated with AA (4.1%) and four given placebo (9.3%) died. Exploratory efficacy analysis showed a trend toward improvement in the change from baseline National Institutes of Health Stroke Scale (NIHSS) in the 8 mg/kg/h AA group on Days 3 (p=0.023 vs. placebo), 7 (p=0.002), 10 (p=0.003), and 40 (p=0.018). A dose of 8 mg/kg/h AA produced a favorable trend in reduction of NIHSS that should be confirmed in a future clinical trial.

  View details for DOI 10.1016/j.jns.2006.09.001

  View details for Web of Science ID 000243059000009

  View details for PubMedID 17095018

• Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study ANNALS OF NEUROLOGY Albers, G. W., Thijs, V. N., Wechsle, L., Kemp, S., Schlaug, G., Skalabrin, E., Bammer, R., Kakuda, W., Lansberg, M. G., Shuaib, A., Coplin, W., Hamilton, S., Moseley, M., Marks, M. P. 2006; 60 (5): 508-517

  Abstract

  To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset.We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved.Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile.For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

  View details for DOI 10.1002/ana.20976

  View details for PubMedID 17066483

• Acute cerebrovascular syndrome: time for new terminology for acute brain ischemia NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE Albers, G. W. 2006; 3 (10): 521-521

  View details for DOI 10.1038/ncpcardio0679

  View details for Web of Science ID 000240850900001

  View details for PubMedID 16990832

• Proof-of-principle phase II MRI studies in stroke - Sample size estimates from dichotomous and continuous data STROKE Donnan, G. A., Davis, S. M., Phan, T. G., Ludbrook, J., Byrnes, G., Parsons, M., Barber, A. P., Reutens, D. C., Rose, S. E., Chalk, J., Demchuk, A. M., Coutts, S. B., Simon, J. E., Tomanek, A., Roether, J., Weiller, C., Fiehler, J., Thomalla, G., Kucinski, T., Schellinger, P. D., Hacke, W., Gass, A., Szabo, K., Hennerici, M., Siebler, M., Villringer, A., Junge-Huelsing, G. J., Pedraza, S., Davalos, A., Castillo, J., Albers, G. W., Lansberg, M. G., Thijs, V. N., Bammer, R., Moseley, M. E., Marks, M., Warach, S., Baird, A., Kidwell, C., Saver, J., Sorensen, G., Fisher, M., Nighoghossian, N., Muir, K. 2006; 37 (10): 2521-2525

  Abstract

  Since the failure of a number of phase III trials of neuroprotection in ischemic stroke, the need for smaller phase II studies with MRI surrogates has emerged. There is, however, little information available about sample size requirements for such phase II trials and rarely enough patients in single studies to make robust estimates. We have formed an international collaborative group to assemble larger datasets and from these have generated sample size tables for MRI-based infarct expansion as the outcome measure.Twelve centers from Australia, Europe, and North America contributed data from patients with hemispheric ischemic stroke. Infarct expansion was defined from initial diffusion-weighted images and later fluid-attenuated inversion recover or T2 images. Sample size estimates were calculated from data on infarct expansion ratios treated as dichotomous or continuous variables. A nonparametric approach was used because the distribution of infarct expansion was resistant to all forms of transformation.As an example, a 20% absolute reduction in infarct expansion ratio (< or = 1), 80% power, and alpha = 0.05 requires 99 patients in each arm. To achieve an equivalent effect size with a continuous approach requires 61 patients.These tables will be useful in planning phase II trials of therapy with the use of MRI outcome measures. For positive studies, biologically plausible surrogates such as these may provide a rationale for proceeding to phase III trials.

  View details for DOI 10.1161/01.STR.0000239696.61545.4b

  View details for Web of Science ID 000240938700021

  View details for PubMedID 16931782

• Trials and tribulations of noninferiority: The ximelagatran experience JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Albers, G. W., Diener, H., Frison, L., Grind, M., Horrow, J., Nevinson, M., Olsson, S. B., Partridge, S., Petersen, P., Vahanian, A., Halperin, J. L. 2006; 48 (5): 1058-1058

  View details for DOI 10.1016/j.jacc.2006.06.004

  View details for Web of Science ID 000240324500025

  View details for PubMedID 16949503

• National stroke association guidelines for the management of transient ischemic attacks ANNALS OF NEUROLOGY Johnston, S. C., Nguyen-Huynh, M. N., Schwarz, M. E., Fuller, K., Williams, C. E., Josephson, S. A. 2006; 60 (3): 301-313

  Abstract

  Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks.Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest.Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management.The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

  View details for DOI 10.1002/ana.20942

  View details for Web of Science ID 000241007600007

  View details for PubMedID 16912978

• Dose escalation of desmoteplase for acute ischemic stroke (DEDAS) - Evidence of safety and efficacy 3 to 9 hours after stroke onset STROKE Furlan, A. J., Eyding, D., Albers, G. W., Al-Rawi, Y., Lees, K. R., Rowley, H. A., Sachara, C., Soehngen, M., Warach, S., Hacke, W. 2006; 37 (5): 1227-1231

  Abstract

  Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke.DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 microg/kg and 125 microg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined.Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg: n=14; 125 microg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 microg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 microg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 microg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 microg/kg desmoteplase (P=0.022).Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 microg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).

  View details for DOI 10.1161/01.STR.0000217403.66996.6d

  View details for Web of Science ID 000237053900028

  View details for PubMedID 16574922

• MRI characteristics of cerebral air embolism from a venous source NEUROLOGY Caulfield, A. F., Lansberg, M. G., Marks, M. P., Albers, G. W., Wijman, C. A. 2006; 66 (6): 945-946

  View details for Web of Science ID 000236292300037

  View details for PubMedID 16567722

• Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack - A statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke - Co-sponsored by the Council on Cardiovascular Radiology and Intervention - The American Academy of Neurology affirms the value of this guideline. CIRCULATION Sacco, R. L., Adams, R., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Schwamm, L. H., Tomsick, T. 2006; 113 (10): E409-E449

  Abstract

  The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.

  View details for Web of Science ID 000235971600025

  View details for PubMedID 16534023

• Mechanical thrombectomy following intravenous thrombolysis in the treatment of acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Fields, J. D., Albers, G. W., Jayaraman, M. V., Do, H. M., Marks, M. P. 2005; 62 (11): 1763-1765

  Abstract

  The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment.To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study.Case studies at a university hospital.Patients treated with intravenous thrombolytics within 3 hours of symptom onset subsequently underwent computed tomographic angiography. If an occlusion of a proximal cerebral vessel was shown by a computed tomographic angiogram, mechanical thrombectomy was performed. Patients were observed for 1 month after treatment.National Institutes of Health Stroke Scale (NIHSS) score.The computed tomographic angiography of 2 patients showed complete occlusion of the M1 branch of the middle cerebral artery following administration of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases, blood flow through the occluded artery was restored with mechanical thrombectomy and dramatic neurologic improvement occurred. There were no complications. The NIHSS scores were 0 and 2 at 1-month follow-up.Treatment with intravenous thrombolytics followed by mechanical thrombectomy may improve outcomes in acute stroke patients and a pilot safety trial is warranted.

  View details for PubMedID 16286552

• Clinical importance of microbleeds in patients receiving IV thrombolysis NEUROLOGY Kakuda, W., Thijs, V. N., Lansberg, M. G., Bammer, R., Wechsler, L., Kemp, S., Moseley, M. E., Marks, M. P., Albers, G. W. 2005; 65 (8): 1175-1178

  Abstract

  Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA).The authors prospectively evaluated patients with acute ischemic stroke treated with IV tPA between 3 and 6 hours of symptom onset. MRI scans, including GRE imaging, were performed prior to tPA treatment, 3 to 6 hours after treatment and at day 30. The authors compared the frequency of hemorrhagic complications after thrombolysis in patients with and without MBs on their baseline GRE imaging.Seventy consecutive patients (mean age, 71 +/- 29 years; 31 men, 39 women) were included. MBs were identified in 11 patients (15.7%) on baseline GRE imaging. There was no significant difference in the frequency of either symptomatic or asymptomatic hemorrhagic complications after thrombolysis between patients with and without MBs at baseline. None of the 11 patients with MBs (0%) at baseline had a symptomatic intracerebral hemorrhage compared with 7 of 59 patients who did not have baseline MBs (11.9%). In addition, no patients with baseline MBs had asymptomatic hemorrhagic transformation observed at the site of any pre-treatment MB.The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset.

  View details for Web of Science ID 000232813600008

  View details for PubMedID 16247042

• Enhancing the development and approval of acute stroke therapies - Stroke Therapy Academic Industry Roundtable STROKE Fisher, M. 2005; 36 (8): 1808-1813

  Abstract

  Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval.The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed.The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.

  View details for DOI 10.1161/01.STR.0000173403.60553.27

  View details for Web of Science ID 000230817600033

  View details for PubMedID 16020764

• Mechanical thrombectomy for acute stroke AMERICAN JOURNAL OF NEURORADIOLOGY Versnick, E. J., Do, H. M., Albers, G. W., Tong, D. C., Marks, M. P. 2005; 26 (4): 875-879

  Abstract

  We evaluated a mechanical thrombectomy protocol to treat acute stroke and report the angiographic results and clinical outcomes.Patients with anterior circulation strokes <8 hours and posterior circulation strokes <12 hours were treated at a single center over 10 months. Patients were excluded if they were candidates for intravenous tissue plasminogen activator (tPA). Treatment involved one of two mechanical thrombectomy devices. Retrieval was augmented by low-dose intra-arterial tPA if needed. Outcome was measured by using the Modified Rankin score.Ten patients were treated: five with anterior circulation strokes, four with posterior circulation strokes, and one with embolic strokes involving both circulations. Mean National Institutes of Health Stroke Scale score at presentation was 24.6 +/- 10.9. In eight patients (80%), revascularization was successful (Thrombolysis in Acute Myocardial Infarction score, 3). Mean time from symptom onset to initiation of the procedure was 6 hours (5.3 hours for anterior circulation and 7.0 hours for posterior circulation). Mean time for recanalization from the start of the procedure was 1.17 +/- 0.58 hours for the six anterior circulation strokes and 2.75 +/- 1.34 hours in the two posterior circulation strokes. Five patients died within 48 hours; all had posterior circulation strokes. Mean Modified Rankin score at 90 days was 1.4.In this small series, mechanical thrombectomy of acute stroke appeared to improve recanalization rates compared with intra-arterial thrombolysis. No hemorrhagic complications occurred. Further study is required to determine the role of these techniques.

  View details for PubMedID 15814937

• Intracranial Angioplasty without stenting for symptomatic atherosclerotic stenosis: Long-term follow-up AMERICAN JOURNAL OF NEURORADIOLOGY Marks, M. P., Marcellus, M. L., Do, H. M., Schraedley-Desmond, P. K., Steinberg, G. K., Tong, D. C., Albers, G. W. 2005; 26 (3): 525-530

  Abstract

  Angioplasty and stent placement have been reported for the treatment of intracranial stenosis. This study was undertaken to assess the efficacy and long-term clinical outcome of angioplasty without stent placement for patients with symptomatic intracranial stenosis.A retrospective study was done to evaluate 36 patients with 37 symptomatic atherosclerotic intracranial stenosis who underwent primary balloon angioplasty. All patients had symptoms despite medical therapy. Thirty-four patients were available for follow-up ranging from 6 to 128 months. Mean follow-up was 52.9 months.Mean pretreatment stenosis was 84.2% before angioplasty and 43.3% after angioplasty. The periprocedural death and stroke rate was 8.3% (two deaths and one minor stroke). Two patients had strokes in the territory of angioplasty at 2 and 37 months after angioplasty. The annual stroke rate in the territory appropriate to the site of angioplasty was 3.36%, and for those patients with a residual stenosis of > or =50% it was 4.5%. Patients with iatrogenic dissection (n=11) did not have transient ischemic attacks or strokes after treatment.Results of long-term follow-up suggest that intracranial angioplasty without stent placement reduces the risk of further stroke in symptomatic patients.

  View details for PubMedID 15760860

• Oral antiplatelet therapy JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Bernstein, R. A., Albers, G. W. 2005; 293 (7): 793-794

  View details for Web of Science ID 000226984600012

  View details for PubMedID 15713763

• Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation - A Randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Albers, G. W., Diener, H. C., Frison, L., Grind, M., Nevinson, M., Partridge, S., Halperin, J. L., Horrow, J., Olsson, S. B., Petersen, P., Vahanian, A. 2005; 293 (6): 690-698

  Abstract

  In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use.To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism.Double-blind, randomized, multicenter trial (2000-2001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors.Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily.The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model.During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the predefined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P = .86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred.The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.

  View details for Web of Science ID 000226842200022

  View details for PubMedID 15701910

• Who is most likely to benefit from tPA? The perfusion-diffusion and clinical-diffusion mismatch models disagree 30th International Stroke Conference Lansberg, M. G., Thijs, V. N., Bammer, R., Wechsler, L. R., O'Donnell, M. J., Olshen, R. A., Wijman, C. A., Kemp, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2005: 437–37

  View details for Web of Science ID 000227523800098

• The Desmoteplase In Acute Ischemic Stroke Trial (DIAS) - A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase STROKE Hacke, W., Albers, G., Al-Rawi, Y., Bogousslavsky, J., Davalos, A., Eliasziw, M., Fischer, M., Furlan, A., Kaste, M., Lees, K. R., Soehngen, M., Warach, S. 2005; 36 (1): 66-73

  Abstract

  Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI.DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 microg/kg, 90 microg/kg, and 125 microg/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days.Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 microg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 microg/kg; P=0.757) and 60.0% (125 microg/kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion.Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 microg/kg.

  View details for DOI 10.1161/01.STR.0000149938.08731.2c

  View details for Web of Science ID 000225944800018

  View details for PubMedID 15569863

• Optimizing oral anticoagulation in managed care AMERICAN JOURNAL OF MANAGED CARE Schaecher, K., Albers, G. W., Caro, J. J. 2004; 10 (14): S474-S477

  View details for Web of Science ID 000226142200006

  View details for PubMedID 15696911

• Stroke prevention in atrial fibrillation: Pooled analysis of SPORTIF III and V trials 5th World Stroke Congress Albers, G. W. MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC. 2004: S462–S469

  Abstract

  This article will review 2 clinical trials that recently compared the safety and efficacy of the oral direct thrombin inhibitor ximelagatran (fixed dose, 36 mg twice daily) with warfarin (adjusted dose, target international normalized ratio [INR] 2.0-3.0) in patients with nonvalvular atrial fibrillation and at least 1 risk factor for stroke. These noninferiority trials involved 7329 patients and a mean exposure to study drug of 18.5 months. The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III (open-label, N = 3407) and V trials (double-blind, N = 3922) were designed for pooled analysis, and the data showed the efficacy of ximelagatran therapy was comparable (noninferior) with extremely well-controlled warfarin therapy in preventing stroke and systemic embolic events; the primary event rates were 1.65% per year and 1.62% per year in the warfarin and ximelagatran groups, respectively (P = .941). In patients with a history of stroke or transient ischemic attack (about 20% of the SPORTIF population), the event rates were 3.27% per year and 2.83% per year in the warfarin and ximelagatran groups, respectively (P = .625). The distribution of stroke subtypes was similar in the 2 treatment groups. Intracranial hemorrhage occurred at a rate of 0.20% per year with warfarin and 0.11% per year with ximelagatran. Combined rates of minor and major bleeding were significantly lower with ximelagatran than with warfarin (32% per year vs 39% per year; P < .0001). The myocardial infarction rates were the same in the pooled database (no difference between agents). The aspirin data will be the subject of two substudy papers. Oral ximelagatran administered without coagulation monitoring or dose adjustment was as effective as well-controlled, adjusted-dose warfarin for prevention of stroke and systemic embolic events and was associated with significantly less total bleeding. This oral direct thrombin inhibitor is a potentially promising treatment option for the prevention of thromboembolism.

  View details for Web of Science ID 000226142200004

  View details for PubMedID 15696910

• Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. 2004; 126 (3): 483S-512S

  Abstract

  This chapter about treatment and prevention of stroke is part of the 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al). Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke (AIS), we recommend administration of i.v. tissue plasminogen activator (tPA), if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with extensive and clearly identifiable hypodensity on CT, we recommend against thrombolytic therapy (Grade 1B). For unselected patients with AIS of > 3 h but < 6 h, we suggest clinicians not use i.v. tPA (Grade 2A). For patients with AIS, we recommend against streptokinase (Grade 1A) and suggest clinicians not use full-dose anticoagulation with i.v. or subcutaneous heparins or heparinoids (Grade 2B). For patients with AIS who are not receiving thrombolysis, we recommend early aspirin therapy, 160 to 325 mg qd (Grade 1A). For AIS patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low molecular weight heparins or heparinoids (Grade 1A); and for patients who have contraindications to anticoagulants, we recommend use of intermittent pneumatic compression devices or elastic stockings (Grade 1C). In patients with acute intracerebral hematoma, we recommend the initial use of intermittent pneumatic compression (Grade 1C+). In patients with noncardioembolic stroke or transient ischemic attack (TIA) [ie, atherothrombotic, lacunar or cryptogenic], we recommend treatment with an antiplatelet agent (Grade 1A) including aspirin, 50 to 325 mg qd; the combination of aspirin and extended-release dipyridamole, 25 mg/200 mg bid; or clopidogrel, 75 mg qd. In these patients, we suggest use of the combination of aspirin and extended-release dipyridamole, 25/200 mg bid, over aspirin (Grade 2A) and clopidogrel over aspirin (Grade 2B). For patients who are allergic to aspirin, we recommend clopidogrel (Grade 1C+). In patients with atrial fibrillation and a recent stroke or TIA, we recommend long-term oral anticoagulation (target international normalized ratio, 2.5; range, 2.0 to 3.0) [Grade 1A]. In patients with venous sinus thrombosis, we recommend unfractionated heparin (Grade 1B) or low molecular weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase.

  View details for PubMedID 15383482

• Antithrombotic and thrombolytic therapy for ischemic stroke CHEST Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. 2004; 126 (3): 483S-512S

  View details for Web of Science ID 000224298900014

• Antithrombotic therapy in atrial fibrillation CHEST Singer, D. E., Albers, G. W., Dalen, J. E., Go, A. S., Halperin, J. L., Manning, W. J. 2004; 126 (3): 429S-456S

  View details for Web of Science ID 000224298900012

• Diffusion-weighted MR imaging in acute ischemia: Value of apparent diffusion coefficient and signal intensity thresholds in predicting tissue at risk and final infarct size AMERICAN JOURNAL OF NEURORADIOLOGY Na, D. G., Thijs, V. N., Albers, G. W., Moseley, M. E., Marks, M. P. 2004; 25 (8): 1331-1336

  Abstract

  Identifying tissue at risk for infarction is an important goal of stroke imaging. This study was performed to determine whether pixel-based apparent diffusion coefficient (ADC) and signal intensity ratio are helpful diffusion-weighted (DW) imaging metrics to predict tissue at risk for infarction.Twelve patients presenting with acute hemispheric strokes underwent DW imaging within 7 hours of symptom onset. Region of interest (ROI), pixel-based ADC, and signal intensity analyses were performed at initial DW imaging to assess area of infarct growth, final infarct area, and normal tissue.Pixel-based analysis was less accurate than ROI-based analysis for evaluating infarct growth or final infarct with ADC, ADC ratio, and signal intensity ratios. In pixel-based analysis, signal intensity ratios were better than ADCs or ADC ratios for identifying tissue at risk (accuracy, 67.4%) and for predicting final infarct (accuracy, 79.9%). Linear regression analysis demonstrated a strong correlation between lesion volume on quantitative DW images or ADC maps and final infarct volume (P < .001). When receiver operating characteristic (ROC) curves were used to determine optimal cutoffs for ADC and DW image values, the region of infarct growth was significantly correlated with only the mismatch between initial qualitative DW image and quantitative DW image signal intensity ratio (cutoff value, 1.19; R = 0.652; P = .022).Pixel-based thresholds applied to ADC or DW image signal intensity maps were not accurate prognostic measures of tissue at risk. Quantitative DW images or ADC maps may provide added information not obtained by visual inspection of the qualitative DW image map.

  View details for PubMedID 15466327

• Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest Singer, D. E., Albers, G. W., Dalen, J. E., Go, A. S., Halperin, J. L., Manning, W. J. 2004; 126 (3): 429S-456S

  Abstract

  This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range, 2.0 to 3.0): In patients with persistent or paroxysmal AF (PAF) [intermittent AF] at high risk of stroke (ie, having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, age > 75 years, moderately or severely impaired left ventricular systolic function and/or congestive heart failure, history of hypertension, or diabetes mellitus), we recommend anticoagulation with an oral VKA, such as warfarin (Grade 1A). In patients with persistent AF or PAF, age 65 to 75 years, in the absence of other risk factors, we recommend antithrombotic therapy with either an oral VKA or aspirin, 325 mg/d, in this group of patients who are at intermediate risk of stroke (Grade 1A). In patients with persistent AF or PAF < 65 years old and with no other risk factors, we recommend aspirin, 325 mg/d (Grade 1B). For patients with AF and mitral stenosis, we recommend anticoagulation with an oral VKA (Grade 1C+). For patients with AF and prosthetic heart valves, we recommend anticoagulation with an oral VKA (Grade 1C+); the target INR may be increased and aspirin added depending on valve type and position, and on patient factors. For patients with AF of > or = 48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA for 3 weeks before and for at least 4 weeks after successful cardioversion (Grade 1C+). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacologic or electrical cardioversion, an alternative strategy is anticoagulation and screening multiplane transesophageal echocardiography (Grade 1B). If no thrombus is seen and cardioversion is successful, we recommend anticoagulation for at least 4 weeks (Grade 1B). For patients with AF of known duration < 48 h, we suggest cardioversion without anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or low molecular weight heparin at presentation (Grade 2C).

  View details for PubMedID 15383480

• Proceedings of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: evidence-based guidelines. Chest 2004; 126 (3): 172S-696S

  Abstract

  Since the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy, the results of clinical trials have provided important new information on the management of thromboembolic disorders, and the science of developing recommendations has advanced. In the accompanying supplement, we provide the new and previously existing recommendations and review several important changes that we have made in our guideline development process. We made a conscious effort to increase the participation of female authors and of contributors from outside North America, with the latter reflecting the widespread use and dissemination of these guidelines internationally. The change in the title from a conference emphasizing consensus to "ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines" reflects the evidence-based approach to making recommendations. The recommendations follow the grading system described in the 2001 recommendations. If the guideline developers are very certain that benefits do, or do not, outweigh risks, burdens, and costs, they will make a strong recommendation (in our formulation, Grade 1). If they are less certain of the magnitude of the benefits and the risks, burdens, and costs, and thus of their relative impact, they make a weaker Grade 2 recommendation. Consistent results from RCTs generate Grade A recommendations, observational studies with very strong effects or secure generalizations from randomized clinical trials (RCTs) generate Grade C+ recommendations, inconsistent results from RCTs generate Grade B recommendations, and observational studies generate Grade C recommendations. We now use the language "we recommend" for strong recommendations (ie, Grades 1A, 1C+, 1B, and 1C) and "we suggest" for weaker recommendations (ie, Grades 2A, 2C+, 2B, and 2C). While evidence on which recommendation are made remains weak in the fields of pediatric thrombosis, thrombosis in pregnancy, and thrombosis in valvular heart disease, rigorous studies in other fields have resulted in new and strong evidence-based recommendations for many indications.

  View details for PubMedID 15383469

• A review of published TIA treatment recommendations NEUROLOGY Albers, G. W. 2004; 62 (8): S26-S28

  View details for Web of Science ID 000221202700008

  View details for PubMedID 15111654

• Discussion: Reconsideration of TIA terminology and definitions. Neurology Easton, J. D., Albers, G. W., Caplan, L. R., Saver, J. L., Sherman, D. G. 2004; 62 (8): S29-34

  View details for PubMedID 15111655

• Comparing the guidelines: Anticoagulation therapy to optimize stroke prevention in patients with atrial fibrillation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Rockson, S. G., Albers, G. W. 2004; 43 (6): 929-935

  Abstract

  Atrial fibrillation (AF) is an important risk factor for stroke. According to a pooled analysis of controlled clinical trials with warfarin, anticoagulation therapy reduces stroke risk by 62%. However, clinicians must decide whether the benefit of long-term anticoagulation therapy with available agents outweighs the risk of bleeding for individual patients. Guidelines issued by the American College of Chest Physicians and by the joint American College of Cardiology, American Heart Association, and the European Society of Cardiology task force recommend antithrombotic therapy to protect AF patients from stroke based on risk-stratification algorithms. Risk factors for stroke AF patients include age > or =75 years; hypertension; thyrotoxicosis; diabetes; cardiovascular disease; congestive heart failure; and history of stroke, transient ischemic attack, or thromboembolism. Patients at high risk for stroke experience greater absolute benefit from anticoagulation therapy than patients at low risk. The guidelines are consistent in recommendations for high-risk patients (warfarin therapy, international normalized ratio 2.0 to 3.0) and low-risk patients (aspirin 325 mg), but differ for intermediate-risk patients with diabetes or heart disease. The guidelines continue to evolve, and future guidelines are likely to incorporate new clinical data, including the CHADS(2) algorithm for determining risk and the results of the Atrial Fibrillation Follow-up Investigation of Rhythm Management trial, the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study, and the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation II to V trials.

  View details for DOI 10.1016/j.jacc.2003.11.028

  View details for PubMedID 15028346

• Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials LANCET Hacke, W., Donnan, G., Fieschi, C., Kaste, M., von Kummer, R., Broderick, J. P., Brott, T., Frankel, M., Grotta, J. C., Haley, E. C., Kwiatkowski, T., Levine, S. R., Lewandowski, C., Lu, M., Lyden, P., Marler, J. R., Patel, S., Tilley, B. C., Albers, G., Brott, T., Grotta, J., Bluhmki, P. E., Wilhelm, M., Hamilton, S. 2004; 363 (9411): 768-774

  Abstract

  Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment.We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage.Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002).The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks.

  View details for Web of Science ID 000220092000007

  View details for PubMedID 15016487

• Influence of arterial input function on hypoperfusion volumes measured with perfusion-weighted imaging STROKE Thijs, V. N., Somford, D. M., Bammer, R., Robberecht, W., Moseley, M. E., Albers, G. W. 2004; 35 (1): 94-98

  Abstract

  The arterial input function (AIF) is critical in determining hemodynamic parameters quantitatively with bolus-tracking MRI. We studied the effect of varying the location of measurement of AIF on the volume of hypoperfusion. We compared the volumes of hypoperfusion obtained with different AIFs with the final ischemic lesion volume.We included 13 patients with acute cerebral ischemia in the anterior circulation who underwent diffusion- (DWI) and perfusion (PWI)-weighted imaging within 8 hours after symptom onset and exhibited DWI lesion expansion between baseline and follow-up. AIF was measured at 4 locations: near both middle cerebral arteries (MCAs), in MCA branches adjacent to the largest DWI abnormality, and at the same level on the opposite hemisphere. Hypoperfusion lesion volumes were compared with the DWI volume at follow-up.Large variations in PWI lesion size were found with different AIF locations. The largest PWI lesions were found when AIF was measured at the contralateral MCA. Smaller PWI lesions were found when AIF was measured in the other locations. There was no significant difference between PWI lesion area at baseline and follow-up DWI lesion when AIF was measured at the contralateral MCA. The other PWI lesions significantly underestimated follow-up DWI lesion size.AIF is an important determinant of the size of hypoperfusion lesions measured with PWI. PWI lesion volumes determined with AIF from the contralateral MCA are associated with follow-up lesion volume.

  View details for DOI 10.1161/01.STR.0000106136.15163.73

  View details for Web of Science ID 000187630500020

  View details for PubMedID 14671249

• Safety and tolerability of ONO-2506 in acute ischemic stroke. 29th International Stroke Conference Pettigrew, L. C., Kasner, S. E., Kwiatkowski, T., Albers, G. W., Gorman, M., Grotta, J. C., Sherman, D., Funakoshi, Y. LIPPINCOTT WILLIAMS & WILKINS. 2004: 293–93

  View details for Web of Science ID 000187630500343

• Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial LANCET Albers, G. W., Diener, H. C., Grind, M., Halperin, J. L., Horrow, J., Olsson, S. B., Petersen, P., Vahanian, A., Frison, L., Nevinson, M., Partridge, S. 2003; 362 (9397): 1691-1698

  Abstract

  Warfarin prevents ischaemic stroke in patients with non-valvular atrial fibrillation, but dose adjustment, coagulation monitoring, and bleeding risk limit its use. The oral direct thrombin inhibitor ximelagatran represents a potential alternative. We aimed to establish whether ximelagatran is non-inferior to warfarin, within a margin of 2% per year, for prevention of stroke and systemic embolism.We randomised 3410 patients with atrial fibrillation and one or more stroke risk factors to open-label warfarin (adjusted-dose, international normalised ratio [INR] 2.0-3.0) or ximelagatran (fixed-dose, 36 mg twice daily); patients were recruited from 259 hospitals, doctor's offices, or health-care clinics. Primary analysis was based on masked event assessment and was by intention to treat. Primary endpoint was stroke or systemic embolism.During 4941 patient-years of exposure (mean 17.4 months, SD 4.1), 96 patients had primary events (56 in the warfarin group vs 40 in the ximelagatran group). The primary event rate by intention to treat was 2.3% per year with warfarin and 1.6% per year with ximelagatran (absolute risk reduction 0.7% [95% CI -0.1 to 1.4], p=0.10; relative risk reduction 29% [95% CI -6.5 to 52]). Rates of disabling or fatal stroke, mortality, and major bleeding were similar between groups, but combined minor and major haemorrhages were lower with ximelagatran than with warfarin (29.8% vs 25.8% per year; relative risk reduction 14% [4 to 22]; p=0.007). Raised serum alanine aminotransferase was more common with ximelagatran.In high-risk patients with atrial fibrillation, fixed-dose oral ximelagatran was at least as effective as well-controlled warfarin for prevention of stroke and systemic embolism.

  View details for Web of Science ID 000186767700006

  View details for PubMedID 14643116

• Spinal manipulative therapy is an independent risk factor for vertebral artery dissection NEUROLOGY Smith, W. S., Johnston, S. C., Skalabrin, E. J., Weaver, M., Azari, P., Albers, G. W., Gress, D. R. 2003; 60 (9): 1424-1428

  Abstract

  To determine whether spinal manipulative therapy (SMT) is an independent risk factor for cervical artery dissection.Using a nested case-control design, the authors reviewed all patients under age 60 with cervical arterial dissection (n = 151) and ischemic stroke or TIA from between 1995 and 2000 at two academic stroke centers. Controls (n = 306) were selected to match cases by sex and within age strata. Cases and controls were solicited by mail, and respondents were interviewed using a structured questionnaire. The medical records of interviewed patients were reviewed by two blinded neurologists to confirm that the patient had stroke or TIA and to determine whether there was evidence of arterial dissection.After interview and blinded chart review, 51 patients with dissection (mean age 41 +/- 10 years; 59% female) and 100 control patients (44 +/- 9 years; 58% female) were studied. In univariate analysis, patients with dissection were more likely to have had SMT within 30 days (14% vs 3%, p = 0.032), to have had neck or head pain preceding stroke or TIA (76% vs 40%, p < 0.001), and to be current consumers of alcohol (76% vs 57%, p = 0.021). In multivariate analysis, vertebral artery dissections were independently associated with SMT within 30 days (OR 6.62, 95% CI 1.4 to 30) and pain before stroke/TIA (OR 3.76, 95% CI 1.3 to 11).This case-controlled study of the influence of SMT and cervical arterial dissection shows that SMT is independently associated with vertebral arterial dissection, even after controlling for neck pain. Patients undergoing SMT should be consented for risk of stroke or vascular injury from the procedure. A significant increase in neck pain following spinal manipulative therapy warrants immediate medical evaluation.

  View details for Web of Science ID 000182754100007

  View details for PubMedID 12743225

• Spinal manipulative therapy is an independent risk factor for vertebral artery dissection 28th International Stroke Conference Smith, W. S., Johnston, S. C., Skalabrin, E. J., Weaver, M., Albers, G. W., Gress, D. R. LIPPINCOTT WILLIAMS & WILKINS. 2003: 296–96

  View details for Web of Science ID 000180251100368

• Transient ischemic attack - Proposal for a new definition. NEW ENGLAND JOURNAL OF MEDICINE Albers, G. W., Caplan, L. R., Easton, J. D., Fayad, P. B., Mohr, J. P., Saver, J. L., Sherman, D. G. 2002; 347 (21): 1713-1716

  View details for Web of Science ID 000179339900015

  View details for PubMedID 12444191

• Telephone assessment of functioning and well-being following stroke: is it feasible? Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Goldstein, L. B., Lyden, P., Mathias, S. D., Colman, S. S., Pasta, D. J., Albers, G., Atkinson, R., Kelley, G., Ng, K., Rylander, A. 2002; 11 (2): 80-87

  Abstract

  Stroke can affect the physical, emotional, and social aspects of patients' lives. The purpose of this study was to assess the feasibility and psychometric properties of a telephone-administered version of the Health Utilities Index Mark 2 and 3 (HUI2/3). Subjects included patients who had had an ischemic stroke within the prior 12 months and their unpaid caregivers (n = 76 pairs) and an additional 33 unpaid caregivers of patients who were generally aphasic or severely affected. Complete response rates, test-retest reliability, and convergent, divergent, and known-groups validity were determined. For patient-caregiver pairs, 27% had no complete Health Utilities Index Mark 2 (HUI2) responses (i.e., had missing responses for at least 1 item of each assessment), 51% had partial responses (i.e., had complete responses for at least 1, but not all of the assessments), and 22% had complete responses. For the Health Utilities Mark 3 (HUI3), the percentages were 19%, 52%, and 29%. Test-retest reliability for patients intraclass correlation coefficient (ICC = 0.76 for HUI2; 0.75 for HUI3) and caregivers (ICC = 0.91 and 0.89, respectively) were excellent. There were generally high levels of both convergent and divergent validity. There was limited known-groups validity (mild v moderately and mild v severely affected patients reported different overall HUI2 and HUI3 scores; there was no difference between those with moderate and severe disabilities). The same pattern was found for caregivers. We conclude that the telephone-administered HUI2/3 appears to be reliable and have at least limited validity. However, the proportions of missing data for patient/caregivers administered the HUI2/3 were surprisingly high. This high proportion of missing data would limit the use of the telephone-administered HUI2/3 in the context of stroke trials.

  View details for PubMedID 17903861

• Patient safety in trials of therapy for acute ischemic stroke JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Goldstein, L. B., Albers, G. W. 2002; 287 (8): 987-987

  View details for Web of Science ID 000174052100020

  View details for PubMedID 11866641

• ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. Stroke Albers, G. W., Clark, W. M., Madden, K. P., Hamilton, S. A. 2002; 33 (2): 493-495

  Abstract

  Only a single study has demonstrated beneficial effects of intravenous tissue plasminogen activator (tPA) in stroke patients.We evaluated the clinical outcomes of the 61 patients enrolled in the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study who were randomized to receive intravenous tPA or placebo within 3 hours of symptom onset.Despite a significant increase in the rate of symptomatic intracranial hemorrhage, tPA-treated patients were more likely to have a very favorable outcome (score of < or = 1) on the National Institutes of Health Stroke Scale at 90 days (P=0.01).These data support current recommendations to administer intravenous tPA to eligible ischemic stroke patients who can be treated within 3 hours of symptom onset.

  View details for PubMedID 11823658

• ATLANTIS trial - Results for patients treated within 3 hours of stroke onset STROKE Albers, G. W., Clark, W. M., Madden, K. P., Hamilton, S. A. 2002; 33 (2): 493-495

  View details for Web of Science ID 000173644900013

• Clinical and radiological correlates of reduced cerebral blood flow measured using magnetic resonance Imaging ARCHIVES OF NEUROLOGY Thijs, V. N., Adami, A., Neumann-Haefelin, T., Moseley, M. E., Albers, G. W. 2002; 59 (2): 233-238

  Abstract

  Methods for determining cerebral blood flow (CBF) using bolus-tracking magnetic resonance imaging (MRI) have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional CBF in animal stroke models.To determine the clinical and radiological features of patients with severe reductions in CBF on MRI and to analyze the relationship between reduced CBF and ADCs in acute ischemic stroke.Case series.Referral center.We studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within 7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We compared patients with ischemic lesions that had CBF of less than 50% relative to the contralateral hemisphere with patients with lesions that had relative CBF greater than 50%. Characteristics analyzed included age, time to MRI, baseline National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion volumes, and 1-month Barthel Index score.Patients with low CBF (n = 5) had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs. 69.3 cm(3); P =.01), and more severe baseline National Institutes of Health Stroke Scale scores (median, 15 vs. 9; P =.02).Ischemic lesions with severe CBF reductions, measured using bolus-tracking MRI, are associated with lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of Health Stroke Scale scores.

  View details for Web of Science ID 000173799900008

  View details for PubMedID 11843694

• Aptiganel hydrochloride in acute ischemic stroke - A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Albers, G. V., Goldstein, L. B., Hall, D., Lesko, L. M. 2001; 286 (21): 2673-2682

  Abstract

  Tissue plasminogen activator is the only thrombolytic agent approved in the United States for treatment of acute ischemic stroke, and has limitations. Aptiganel hydrochloride is a novel and selective ligand for the ion-channel site of the N-methyl-D-aspartate receptor-channel complex and a promising neuroprotective agent in animal models of focal brain ischemia.To determine whether aptiganel improves the clinical outcome for acute ischemic stroke patients.Nested phase 2/phase 3 randomized controlled trial conducted between July 1996 and September 1997.One hundred fifty-six medical centers in the United States, Canada, Australia, South Africa, England, and Scotland.A total of 628 patients with hemispheric ischemic stroke (50.3% male; mean age, 71.5 years).Patients were randomly assigned within 6 hours of stroke to receive 1 of 3 treatment regimens: high-dose aptiganel (5-mg bolus followed by 0.75 mg/h for 12 hours; n = 214); low-dose aptiganel (3-mg bolus followed by 0.5 mg/h for 12 hours; n = 200); or placebo (n = 214).The primary efficacy end point was the Modified Rankin Scale score at 90 days after stroke onset. Secondary end points included mortality and change in National Institutes of Health (NIH) Stroke Scale score at 7 days after stroke.The trial was suspended by the sponsor and the independent data and safety monitoring board because of both a lack of efficacy and a potential imbalance in mortality. There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31). At 7 days, placebo-treated patients exhibited slightly greater neurological improvement on the NIH Stroke Scale than high-dose aptiganel patients (mean improvement for placebo group, -0.8 points vs for high-dose aptiganel, 0.9 points; P =.04). The mortality rate at 120 days in patients treated with high-dose aptiganel was higher than that in patients who received placebo (26.3% vs 19.2%; P =.06). Mortality in the low-dose aptiganel group was 22.5% (P =.39 vs placebo).Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful. The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.

  View details for Web of Science ID 000172488300026

  View details for PubMedID 11730442

• Combination therapy with clopidogrel and aspirin - Can the CURE results be extrapolated to cerebrovascular patients? STROKE Albers, G. W., Amarenco, P. 2001; 32 (12): 2948-2949

  View details for Web of Science ID 000172599500046

  View details for PubMedID 11740003

• A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke NEW ENGLAND JOURNAL OF MEDICINE Mohr, J. P., Thompson, J. L., Lazar, R. M., Levin, B., Sacco, R. L., Furie, K. L., Kistler, J. P., Albers, G. W., Pettigrew, L. C., Adams, H. P., Jackson, C. M., Pullicino, P. 2001; 345 (20): 1444-1451

  Abstract

  Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke.In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years.The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke (1237 patients had had previous small-vessel or lacunar infarcts, 576 had had cryptogenic infarcts, and 259 had had infarcts designated as due to severe stenosis or occlusion of a large artery).Over two years, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives.

  View details for Web of Science ID 000172132700002

  View details for PubMedID 11794192

• Use of anti-ICAM-1 therapy in ischemic stroke - Results of the Enlimomab Acute Stroke Trial NEUROLOGY Sherman, D. G., Bes, A., Easton, J. D., Hacke, W., Kaste, M., Polmar, S. H., Zivin, J. A., Fieschi, C., Miller, P., Schoenfeld, D., Street, J., Albers, G., Atkinson, R., Biller, J., Bruno, A., Carpenter, D., Clark, W., DeGraba, T., Driscoll, P., Ellis, J., Greenlee, R., Hess, D., Horowitz, D. R., Davenport, J., Hsu, C., Starkman, S., Madden, K., Pettigrew, C., Rosenbaum, D., Schim, J., Tietjen, G., Mansbach, H., Edwards, K., Webb, R., Crisostomo, E., Wilterdink, J., Rothrock, J., Zweifler, R., Dexter, J., Horowitz, S., Futrell, N., Alter, M., Schneider, D., Ferbert, A., Hacke, W., Prange, H., Wiersbitzky, M., Buttner, T., Schwartz, A., Busse, O., Klingelhofer, J., Kaste, M., Erila, T., Sivenius, J., Sotaniemi, K., Liukkonen, J., Hedman, C., Muuronen, A., Rissanen, A., Bes, A., Feve, J. R., Mahagne, M. H., Rancurel, G., Trouillas, P., Weber, M., Thomassen, L., Johnsen, H. J., Kjallman, L., Petersson, J., Ferrari, G., Lagi, A., Mamoli, A., Re, G. 2001; 57 (8): 1428-1434

  Abstract

  There has been recent interest in the possible role of reperfusion-induced inflammation with neuronal injury after stroke. Enlimomab, a murine intercellular adhesion molecule-1 (ICAM-1) antibody, reduces leukocyte adhesion and infarct size in experimental stroke studies. The purpose of the current clinical trial was to evaluate the use of enlimomab after ischemic stroke.A total of 625 patients with ischemic stroke were randomized to receive either enlimomab (n = 317) or placebo (n = 308) within 6 hours of stroke onset. Treatment was given over 5 days. Patients were evaluated at baseline and on days 5 and 90 after initiation of treatment; long-term assessments were carried out after 6 and 12 months. The primary efficacy endpoint was the response to therapy at 90 days on the Modified Rankin Scale; other endpoints included Barthel Index (BI) and NIH Stroke Scale and survival.At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever. Patients experiencing fever were more likely to have a poor outcome or die.The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.

  View details for Web of Science ID 000171681500015

  View details for PubMedID 11673584

• Relationship between severity of MR perfusion deficit and DWI lesion evolution NEUROLOGY Thijs, V. N., Adami, A., Neumann-Haefelin, T., Moseley, M. E., Marks, M. P., Albers, G. W. 2001; 57 (7): 1205-1211

  Abstract

  To assess whether a quantitative analysis of the severity of the early perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that can distinguish between critical and noncritical hypoperfusion.Patients with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom onset and again after 4 to 7 days. Patients with early important decreases in points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were created. These hemodynamic parameters were correlated with the degree of recruitment of the baseline PWI lesion by the DWI lesion.Twelve patients had an initial PWI > DWI mismatch of >20%. A linear relationship was observed between the initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted final infarct size.Among patients who have had an acute stroke with PWI > DWI, who do not have dramatic early clinical improvement, the degree of expansion of the initial DWI lesion correlates with the severity of the initial perfusion deficit as measured by the mean transit time and the cerebral blood volume.

  View details for Web of Science ID 000171415400010

  View details for PubMedID 11591836

• Potential utility of diffusion-weighted imaging in venous infarction ARCHIVES OF NEUROLOGY Bernstein, R., Albers, G. W. 2001; 58 (10): 1538-1539

  View details for Web of Science ID 000171444400001

  View details for PubMedID 11594909

• Advances in intravenous thrombolytic therapy for treatment of acute stroke NEUROLOGY Albers, G. W. 2001; 57 (5): S77-S81

  Abstract

  Intravenous tissue plasminogen activator (tPA) is an effective therapy for treatment of acute ischemic stroke when administered within 3 hours of symptom onset. Three large randomized clinical trials that have attempted to extend the time window for tPA treatment beyond 3 hours have failed to demonstrate convincing evidence of efficacy. A recently published prospective, monitored, multicenter study of 389 patients, who were treated with tPA for ischemic stroke at 57 medical centers (24 academic, 33 community) across the United States, demonstrated favorable outcomes and low rates of symptomatic intracerebral hemorrhage. Recent advances in neuroimaging, including diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI), have the potential to differentiate salvageable ischemic brain tissue from irreversibly injured tissue. Preliminary data suggest that acute stroke patients who present with a PWI lesion that is considerably larger than the initial DWI lesion may be good candidates for intravenous thrombolysis, even beyond 3 hours after symptom onset. Additional research is required to clarify the optimal use of these diagnostic techniques and their cost-effectiveness.

  View details for Web of Science ID 000170938000015

  View details for PubMedID 11552060

• Antithrombotic therapy for prevention and treatment of ischemic stroke 6th National Conference on Anticoagulant Therapy Albers, G. W. SPRINGER. 2001: 19–22

  Abstract

  Atherosclerosis involving the cervical vessels, intracranial vessels, or the aorta is the most common cause of ischemic stroke. Occlusive lesions of small penetrating brain arteries cause small "lacunar" strokes, which account for about 20% of ischemic strokes. Emboli from a variety of cardiac sources, particularly atrial fibrillation, account for about 25%. Efforts to prevent and treat ischemic stroke are complicated by the variety of etiologies underlying it and the selection of antithrombotic or thrombolytic therapy appropriate to the particular etiology.

  View details for Web of Science ID 000172168500003

  View details for PubMedID 11711684

• Hyperperfusion syndrome with hemorrhage after angioplasty for middle cerebral artery stenosis AMERICAN JOURNAL OF NEURORADIOLOGY Liu, A. Y., Do, H. M., Albers, G. W., Lopez, J. R., Steinberg, G. K., Marks, M. P. 2001; 22 (8): 1597-1601

  Abstract

  Hyperperfusion syndrome is a well-documented complication of carotid endarterectomy, as well as internal carotid artery angioplasty and stent placement. We report a similar complication after distal intracranial (middle cerebral artery [MCA] M2 segment) angioplasty. To our knowledge, this is the first report of hyperperfusion syndrome after intracranial angioplasty of a distal MCA branch.

  View details for PubMedID 11559514

• Recommendations for clinical trial evaluation of acute stroke therapies - Stroke Therapy Academic Industry Roundtable II (STAIR-II) STROKE Albers, G. W., Bogousslavsky, J., Bozik, M. A., Brass, L. M., Broderick, J. P., Fisher, M., Goldstein, L. B., Salazar-Grueso, E., Akitsuki, S., Aranko, K., Ashwood, T., Atkinson, R. P., Bell, R. D., Brott, T. G., Cady, W. J., Caplan, L. R., Coggins, S., Cramer, S., Cyrus, P., Dayno, J., Easton, J. D., Elliott, P. J., Finklestein, S. P., Furlan, A. J., Gamzu, E., Glasky, M. S., Gordon, K., Gorelick, P. B., Greenwood, D. T., Grotta, J. C., Gunn, K., Hachinski, V., Hacke, W., Hall, E. D., Hsu, C. Y., Humphreys, D. M., Ishikawa, H., Jacobs, A. J., Kaste, M., Koroshetz, W. J., Krams, M., Lauritano, A. A., Leclerc, J., Lees, K. R., Lesko, L., Levine, S. R., Levy, D. E., Li, F. H., Lyden, P. D., Masayasu, H., McDermott, J., Meibach, R. C., Meya, U., Miyairi, K., Niidome, T., Oeda, J., Poole, R. M., Ron, E. S., Sacco, R. L., Saltarelli, M. D., Shimizu, K., Shook, B. J., Soehngen, M., Soehngen, W., Stamler, D. A., Styren, S. D., Teal, P. A., Tilley, B. C., Traystman, R. J., Walker, M. D., Wallin, B. A., Warach, S., Ward, D. P., Wessel, T. C., Wettstein, J. 2001; 32 (7): 1598-1606

  View details for Web of Science ID 000169724900022

• Evolution of cerebral infarct volume assessed by diffusion-weighted magnetic resonance imaging ARCHIVES OF NEUROLOGY Lansberg, M. G., O'Brien, M. W., Tong, D. C., Moseley, M. E., Albers, G. W. 2001; 58 (4): 613-617

  Abstract

  Knowledge of the natural evolution of ischemic brain lesions may be a crucial aspect in the assessment of future stroke therapies.To establish daily changes of ischemic cerebral lesion volume using diffusion-weighted magnetic resonance imaging.Prospective cohort study.Referral center.Serial magnetic resonance imaging scans were performed in consecutive untreated stroke patients. The baseline scan was obtained within 48 hours after symptom onset; subsequent scans, 12 to 48 hours, 3 to 4 days, 5 to 7 days, and 30 days after baseline. Lesion volumes were measured on each scan by 2 independent observers.Daily change in lesion volume.A total of 112 magnetic resonance imaging scans were obtained in 24 patients. An early increase in lesion volume was seen in all patients. Maximum lesion volume was reached at a mean of 74 hours. Lesion volumes increased by a mean (+/- SEM) of 21% +/- 12% during day 2 and 10% +/- 12% during day 3. No significant change occurred during day 4. During days 5, 6, and 7, statistically significant mean (+/- SEM) decreases of 6% +/- 8%, 3% +/- 4%, and 4% +/- 5%, respectively, were observed.Ischemic lesions follow a relatively consistent pattern of growth during the first 3 days and subsequent decrease in size. These data in conjunction with data regarding the evolution of lesion volume during the first 24 hours after symptom onset may be useful in the design of pilot studies of therapies for acute stroke.

  View details for Web of Science ID 000167935900011

  View details for PubMedID 11295992

• Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke AMERICAN JOURNAL OF NEURORADIOLOGY Lansberg, M. G., Thijs, V. N., O'Brien, M. W., Ali, J. O., de Crespigny, A. J., Tong, D. C., Moseley, M. E., Albers, G. W. 2001; 22 (4): 637-644

  Abstract

  Serial study of such MR parameters as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to establish the natural evolution of MR signal intensity characteristics of acute ischemic lesions and to assess the potential of using specific MR parameters to estimate lesion age.Five serial echo-planar DWI studies with and without an inversion recovery pulse were performed in 27 patients with acute stroke. The following lesion characteristics were studied: 1) conventional ADC (ADC(CONV)); 2) ADC(FLAIR); 3) DWI signal intensity (SI(DWI)); 4) T2-weighted signal intensity (SI(T2)), and 5) FLAIR signal intensity (SI(FLAIR)).The lesion ADC(CONV) gradually increased from low values during the first week to pseudonormal during the second week to supranormal thereafter. The lesion ADC(FLAIR) showed the same pattern of evolution but with lower absolute values. A low ADC value indicated, with good sensitivity (88%) and specificity (90%), that a lesion was less than 10 days old. All signal intensities remained high throughout follow-up. SI(DWI) showed no significant change during the first week but decreased thereafter. SI(T2) initially increased, decreased slightly during week 2, and again increased after 14 days. SI(FLAIR) showed the same initial increase as the SI(T2) but remained relatively stable thereafter.Our findings further clarify the time course of stroke evolution on MR parameters and indicate that the ADC map may be useful for estimating lesion age. Application of an inversion recovery pulse results in lower, potentially more accurate, absolute ADC values.

  View details for PubMedID 11290470

• Antithrombotic therapy in atrial fibrillation CHEST Albers, G. W., Dalen, J. E., Laupacis, A., Manning, W. J., Petersen, P., Singer, D. E. 2001; 119 (1): 194S-206S

  View details for Web of Science ID 000166812000012

  View details for PubMedID 11157649

• Recent clinical trials of neuroprotective agents and thrombolytic therapy for acute stroke 21st Princeton Conference on Cerebrovascular Disease Albers, G. W. FUTURA PUBL CO INC. 2001: 419–428

  View details for Web of Science ID 000172045100029

• Antithrombotic and thrombolytic therapy for ischemic stroke CHEST Albers, C. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. 2001; 119 (1): 300S-320S

  View details for Web of Science ID 000166812000019

  View details for PubMedID 11157656

• Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis STROKE Thijs, V. N., Lansberg, M. G., Beaulieu, C., Marks, M. P., Moseley, M. E., Albers, G. W. 2000; 31 (11): 2597-2602

  Abstract

  The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome.We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score >/=85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis.Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score >/=85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI.DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.

  View details for PubMedID 11062281

• Advantages of adding diffusion-weighted magnetic resonance imaging to conventional magnetic resonance imaging for evaluating acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Norbash, A. M., Marks, M. P., Tong, D. C., Moseley, M. E., Albers, G. W. 2000; 57 (9): 1311-1316

  Abstract

  Accurate localization of acute ischemic lesions in patients with an acute stroke may aid in understanding the etiology of their stroke and may improve the management of these patients.To determine the yield of adding diffusion-weighted magnetic resonance imaging (DWI) to a conventional magnetic resonance imaging (MRI) protocol for acute stroke.A prospective cohort study.A referral center.Fifty-two patients with a clinical diagnosis of acute stroke who presented within 48 hours after symptom onset were included. An MRI scan was obtained within 48 hours after symptom onset. A neuroradiologist (A.M.N.) and a stroke neurologist (G.W.A.) independently identified suspected acute ischemic lesions on MRI sequences in the following order: (1) T2-weighted and proton density-weighted images, (2) fluid-attenuated inversion recovery images, and (3) diffusion-weighted images and apparent diffusion coefficient maps.Diagnostic yield and interrater reliability for the identification of acute lesions, and confidence and conspicuity ratings of acute lesions for different MRI sequences.Conventional MRI correctly identified at least one acute lesion in 71% (34/48) to 80% (39/49) of patients who had an acute stroke; with the addition of DWI, this percentage increased to 94% (46/49) (P<.001). Conventional MRI showed only moderate sensitivity (50%-60%) and specificity (49%-69%) compared with a "criterion standard." Based on the diffusion-weighted sequence, interrater reliability for identifying acute lesions was moderate for conventional MRI (kappa = 0.5-0.6) and good for DWI (kappa = 0.8). The observers' confidence with which lesions were rated as acute and the lesion conspicuity was significantly (P<.01) higher for DWI than for conventional MRI.During the first 48 hours after symptom onset, the addition of DWI to conventional MRI improves the accuracy of identifying acute ischemic brain lesions in patients who experienced a stroke.

  View details for Web of Science ID 000089283000010

  View details for PubMedID 10987898

• Symptomatic intracranial atherosclerosis - Outcome of patients who fail antithrombotic therapy NEUROLOGY Thijs, V. N., Albers, G. W. 2000; 55 (4): 490-497

  Abstract

  To determine the prognosis of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy.The outcome of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy is unknown. These patients may represent the target group for investigation of more aggressive therapies such as intracranial angioplasty.The authors performed a chart review and telephone interview of patients with symptomatic intracranial atherosclerosis identified in the Stanford Stroke Center clinical database. A Cox regression model was created to identify factors predictive of failure of antithrombotic therapy. The authors generated Kaplan-Meier survival curves to determine the timing of recurrent TIA, stroke, or death after failure of antithrombotic therapy.Fifty-two patients had symptomatic intracranial atherosclerosis and fulfilled entry criteria. Twenty-nine of the 52 patients (55.8%) had cerebral ischemic events while receiving an antithrombotic agent (antiplatelet agents [55%], warfarin [31%], or heparin [14%]). In a Cox regression model, older age was an independent predictor of failure of antithrombotic therapy, and warfarin use was associated with a decrease in risk. Recurrent TIA (n = 7), nonfatal/fatal stroke (n = 6/1), or death (n = 1) occurred in 15 of 29 (51.7%) of the patients who failed antithrombotic therapy. The median time to recurrent TIA, stroke, or death was 36 days (95% CI 13 to 59).Patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy have extremely high rates of recurrent TIA/stroke or death. Recurrent ischemic events typically occur within a few months after failure of standard medical therapy. The high recurrence risk observed warrants testing of alternative treatment strategies such as intracranial angioplasty.

  View details for Web of Science ID 000088855000007

  View details for PubMedID 10953179

• Clinical problem-solving. Eyes wide open. New England journal of medicine Morton-Bours, E. C., Jacobs, M. B., Albers, G. W. 2000; 343 (1): 50-55

  View details for PubMedID 10882769

• New magnetic resonance imaging methods for cerebrovascular disease: Emerging clinical applications ANNALS OF NEUROLOGY Neumann-Haefelin, T., Moseley, M. E., Albers, G. W. 2000; 47 (5): 559-570

  Abstract

  During the 1990s, novel magnetic resonance imaging (MRI) techniques have emerged that allow the noninvasive and rapid assessment of normal brain functioning and cerebral pathophysiology. Some of these techniques, including diffusion-weighted imaging and perfusion-weighted imaging, have already been used extensively in specialized centers for the evaluation of patients with cerebrovascular disease. Evidence is now rapidly accumulating that both diffusion- and perfusion-weighted imaging, particularly when used in combination with high-speed MR angiography, will lead to improvements in the clinical management of acute stroke patients. Other novel MR techniques, such as spectroscopic imaging, diffusion tensor imaging, and blood oxygenation level-dependent functional MRI, have not yet assumed a definitive role in the diagnostic evaluation of cerebrovascular disease. However, they are promising research tools that provide noninvasive data about infarct evolution as well as mechanisms of stroke recovery. In this article, we review the basic principles underlying these novel MRI techniques and outline their current and anticipated future impact on the diagnosis and management of patients with cerebrovascular disease.

  View details for Web of Science ID 000086731000002

  View details for PubMedID 10805325

• Recent advances in stroke management. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Albers, G. W., Alberts, M. J., Broderick, J. P., Lyden, P. D., Sacco, R. L. 2000; 9 (3): 95-105

  Abstract

  Major advances in stroke treatment and prevention have, occurred over the last several years. Recent studies have documented that appropriate modification of stroke risk factors can lead to, a substantial reduction in stroke incidence. In addition, a variety of new risk factors, such as elevated plasma homocysteine levels, antiphospholipid antibodies, and specific genetic factors, are being recognized. The most significant advance in acute stroke therapy is the use of intravenous tissue plasminogen activator, (t-PA) for treatment of patients with ischemic stroke within 3 hours of symptom onset. T-PA is currently the only stroke treatment approved by the Federal Drug Administration. There continues to be uncertainty and misunder-standing regarding the risks and benefits of this therapy. A variety of neuroprotective agents have been highly successful for reducing ischemic brain injury in animal stroke models. Recent clinical trials with these agents, however, have not produced beneficial effects in humans. Newer neuroprotective agents with more favorable safety profiles and improvements in clinical trial design may lead to therapeutic successes in the near future. It is apparent that both thrombolytic and neuroprotective treatments for acute stroke must be administered very rapidly, after stroke onset. Therefore, acute stroke teams are being developed to facilitate rapid diagnostic evaluation and treatment of stroke patients.

  View details for PubMedID 17895205

• Comparison of diffusion-weighted MRI and CT in acute stroke NEUROLOGY Lansberg, M. G., Albers, G. W., Beaulieu, C., Marks, M. P. 2000; 54 (8): 1557-1561

  Abstract

  To compare diffusion-weighted MRI (DWI) and CT with respect to accuracy of localizing acute cerebral infarction; sensitivity, specificity, and interrater reliability for identifying more than one-third middle cerebral artery (MCA) territory involvement; and correlation of acute lesion volume with final infarct volume.Nineteen consecutive stroke patients underwent CT and DWI within 7 hours of stroke onset and a follow-up DWI examination 36 hours after symptom onset, which served as the "gold standard" for lesion location and extent of MCA involvement. Each scan was evaluated for acute ischemic lesions by two experienced observers. After 30 days, T2-weighted MRI was obtained for assessment of the final infarct volume.The acute CT and DWI scans were obtained on average 2.6 and 5.1 hours after symptom onset. On DWI the acute lesion was identified correctly in all instances and on CT it was identified correctly in 42 to 63% of patients. Sensitivity for detection of more than 33% MCA involvement was better for DWI (57 to 86%) than for CT (14 to 43%), whereas specificity was excellent for both. Interrater reliability was moderately good for both (kappa, 0.6 for DWI; 0.5 for CT). A positive correlation (r = 0.79; p = 0.001) existed between lesion volume on acute DWI and final infarct volume, whereas no correlation was found between CT volume and final infarct volume.When compared with CT, DWI was more accurate for identifying acute infarction and more sensitive for detection of more than 33% MCA involvement. In addition, lesion volume on acute DWI, but not on acute CT, correlated strongly with final infarct volume. Additional studies are required to demonstrate whether these advantages of DWI are clinically relevant in the management of patients with acute stroke.

  View details for Web of Science ID 000086642000006

  View details for PubMedID 10762493

• Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients NEUROLOGY Albers, G. W., Lansberg, M. G., Norbash, A. M., Tong, D. C., O'Brien, M. W., Woolfenden, A. R., Marks, M. P., Moseley, M. E. 2000; 54 (8): 1562-1567

  Abstract

  To determine whether diffusion-weighted imaging (DWI) could identify potentially clinically relevant findings in patients presenting more than 6 hours after stroke onset when compared with conventional MRI.MRI with both conventional (T2 and proton density images) and echoplanar imaging (DWI and apparent diffusion coefficient maps) was performed 6 to 48 hours after symptom onset (mean, 27 hours) in 40 consecutive patients with acute stroke. All acute lesions were identified first on conventional images, then on DWI, by a neuroradiologist who was provided with the suspected lesion location, based on a neurologist's examination before imaging. Abnormalities were rated as potentially clinically relevant if they were detected only on DWI and 1) confirmed the acute symptomatic lesion to be in a different vascular territory than suspected clinically, 2) revealed multiple lesions in different vascular territories suggestive of a proximal source of embolism, or 3) clarified that a lesion, thought to be acute on conventional imaging, was not acute.The initial clinical impression of lesion localization was incorrect in 12 patients (30%). Clinically significant findings were detected by DWI alone in 19 patients (48%). DWI demonstrated the symptomatic lesion in a different vascular territory than suspected clinically or by conventional MRI in 7 patients (18%) and showed acute lesions in multiple vascular distributions in 5 patients (13%). In 8 patients (20%), DWI clarified that lesions thought to be acute on conventional MRI were actually old.In patients imaged 6 to 48 hours after stroke onset, DWI frequently provided potentially clinically relevant findings that were not apparent on conventional MRI.

  View details for Web of Science ID 000086642000007

  View details for PubMedID 10762494

• Supplement to the AHA guidelines for the management of transient ischemic attacks Stroke; a journal of cerebral circulation Hughes, R. L., Albers, G. W., Hart, R. G., Lutsep, H. L., Newell, D. W., Sacco, R. L. 2000; 31 (4): 983-91

  View details for PubMedID 10754011

• Addendum to the supplement to the guidelines for the management of transient ischemic attacks Stroke Albers, Hart, Lutsep, NEWELL, Sacco 2000; 31 (4): 1001-?

  View details for PubMedID 10754016

• The rtPA (Alteplase) 0-to 6-hour acute stroke trial, part A (A0276g) - Results of a double-blind, placebo-controlled, multicenter study STROKE Clark, W. M., Albers, G. W., Madden, K. P., Hamilton, S. 2000; 31 (4): 811-816

  Abstract

  The Thrombolytic Therapy in Acute Ischemic Stroke Study, which started in August of 1991, was designed to assess the efficacy and safety of intravenous rtPA (alteplase) in patients with acute (0 to 6 hours) ischemic stroke. In October 1993 enrollment was halted because of Safety Committee (DMSB) concerns. In December 1993 the time window was changed to 0 to 5 hours, and it was decided to restart enrollment as a separate study (part B). We report here the results of the original study (part A), focusing on evaluating the safety and efficacy of rtPA given between 0 and 6 hours after stroke onset.This investigation was a phase II, placebo-controlled, double-blind, randomized study utilizing 0.9 mg/kg IV rtPA or placebo over 1 hour, which was conducted at university and community sites in North America. Except for time to treatment, enrollment criteria were very similar to those of the NINDS rtPA stroke study. Primary efficacy end points were the number of patients with a decrease of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) at 24 hours and day 30, along with infarct volume at day 30. Secondary end points included mortality and functional recoveries on the Barthel Index and Modified Rankin scale at days 30 and 90.A total of 142 patients were enrolled at 42 sites in North America, including 22 <3 hours (15%) and 46 between 5 and 6 hours (32%). The groups were well matched on baseline characteristics, including NIHSS (mean of 13 for both). For the primary end points, a higher percentage of rtPA patients had a 4-point improvement at 24 hours (placebo 21%, rtPA 40%; P=0.02); however, this early effect was reversed by 30 days, with more placebo patients having a 4-point improvement (75%) than patients treated with rtPA (60%, P=0.05). Treatment with rtPA significantly increased the rate of symptomatic intracerebral hemorrhage within 10 days (11% versus 0%, P<0.01) and mortality at 90 days (23% versus 7%, P<0.01).This study found no significant rtPA benefit on any of the planned efficacy end points at 30 and 90 days in patients treated between 0 and 6 hours after stroke onset. These negative results apply to patients treated after 3 hours, because only 15% of the patients were enrolled before 3 hours. The risk of symptomatic intracerebral hemorrhage was increased with rtPA treatment, particularly in patients treated between 5 and 6 hours after onset. These results do not support the use of intravenous rtPA for stroke treatment >3 hours after onset.

  View details for PubMedID 10753980

• Choice of endpoints in antiplatelet trials - Which outcomes are most relevant to stroke patients? NEUROLOGY Albers, G. W. 2000; 54 (5): 1022-1028

  Abstract

  The relative efficacies of different antiplatelet agents for stroke prevention are unclear because of differences in clinical trial design, a lack of direct comparisons between individual agents, and differences in the choice of primary endpoints. Individual endpoints in a clinical trial are often combined into a single primary endpoint cluster. Theoretically, a combined endpoint may reduce the sample size required to demonstrate significant benefits of an effective therapy. However, unless all components of a composite endpoint are affected in the same direction and to a similar degree, their inclusion may not provide the anticipated increase in statistical power. In fact, the use of a combined endpoint may lead to an underestimate of therapeutic benefits when patients at high risk for one particular endpoint are studied. For patients with stroke or TIA, the single outcome of stroke is particularly important because these patients have a higher risk of recurrent stroke than any other vascular outcome during the initial years after a stroke. Because of the low incidence of myocardial infarction (MI) in stroke trials, the inclusion of MI in the primary endpoint will usually have minimal influence on trial outcome, and antiplatelet therapy has not been shown to be beneficial in preventing nonvascular death. Chance variations in the incidence of MI or death may detract from the benefit of the agent for stroke prevention when it is included in a combined endpoint. The benefit of antiplatelet therapies for patients with recent cerebrovascular events is determined most accurately if stroke alone is chosen as the primary endpoint.

  View details for Web of Science ID 000085785700005

  View details for PubMedID 10720269

• Intravenous tissue-type plasminogen activator for treatment of acute stroke - The standard treatment with alteplase to reverse stroke (STARS) study JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Albers, G. W., Bates, V. E., Clark, W. M., Bell, R., Verro, P., Hamilton, S. A. 2000; 283 (9): 1145-1150

  Abstract

  Tissue-type plasminogen activator (tPA) is the only therapy for acute ischemic stroke approved by the Food and Drug Administration.To assess the safety profile and to document clinical outcomes and adverse events in patients treated with intravenous tPA for acute stroke in clinical practice.Prospective, multicenter study of consecutive patients enrolled between February 1997 and December 1998 at 57 medical centers in the United States (24 academic and 33 community).Intravenous tPA (recombinant alteplase).Three hundred eighty-nine patients with a mean age of 69 years (range, 28-100 years); 55% were men.Time intervals between stroke symptom onset, hospital arrival, and treatment with tPA; pretreatment computed tomographic scan results, intracerebral hemorrhage, and major systemic bleeding. The modified Rankin Scale score was used to assess clinical outcomes at 30 days.Median time from stroke onset to treatment was 2 hours 44 minutes, and the median baseline National Institutes of Health Stroke Scale score was 13. The 30-day mortality rate was 13%. At 30 days after treatment, 35% of patients had very favorable outcomes (modified Rankin score, 0-1) and 43% were functionally independent (modified Rankin score, 0-2). Thirteen patients (3.3%) experienced symptomatic intracerebral hemorrhage, including 7 who died. Twenty-eight patients (8.2%) had asymptomatic intracerebral hemorrhage within 3 days of treatment with tPA. Protocol violations were reported for 127 patients (32.6%), and included treatment with tPA more than 3 hours after symptom onset in 13.4%, treatment with anticoagulants within 24 hours of tPA administration in 9.3%, and tPA administration despite systolic blood pressure exceeding 185 mm Hg in 6.7%. A multivariate analysis found predictors of favorable outcome to be a less severe baseline National Institutes of Health Stroke Scale score, absence of specific abnormalities (effacement or hypodensity of >33% of the middle cerebral artery territory or a hyperdense middle cerebral artery) on the baseline computed tomographic scan, an age of 85 years or younger, and a lower mean arterial pressure at baseline.This study, conducted at multiple institutions throughout the United States, suggests that favorable clinical outcomes and low rates of symptomatic intracerebral hemorrhage can be achieved using tPA for stroke treatment.

  View details for Web of Science ID 000085424100023

  View details for PubMedID 10703776

• Basilar artery stenosis: clinical and neuroradiographic features. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Woolfenden, A. R., Tong, D. C., Norbash, A. M., Ali, A. O., Marks, M. P., O'Brien, M. W., Albers, G. W. 2000; 9 (2): 57-63

  Abstract

  Although basilar artery stenosis (BAS) is an important cause of posterior circulation stroke, few reports detail the clinical and neuroradiological features of patients with BAS.A retrospective review of symptomatic BAS patients who were evaluated by our Stroke Center.Twenty-eight patients were followed-up for a median of 16 months. Transient ischemic attacks (TIAs) specific for posterior circulation involvement were common (12/19 patients with TIA), were often multiple, and frequently preceded a posterior circulation stroke. The proximal (13/28) and mid (10/28) basilar arteries were the most common sites of stenosis. Brain infarction most often affected the pons, but also frequently involved the cerebellum and thalamus. Concomitant vertebral artery disease was prevalent (12/18 patients who underwent conventional cerebral angiography). Stroke mechanisms included artery to artery embolus, basilar branch disease, and hypoperfusion. The same-territory recurrent stroke rate was 8.2% per year. Most patients in the series were treated with warfarin. No patients suffered a recurrent stroke while on a therapeutic dose of warfarin (international normalized ratio [INR], 2.0 to 3.0). Angioplasty was performed in 6 patients.The same-territory stroke recurrence rate was 8.2% per year. Warfarin (INR, 2.0 to 3.0) appeared to be effective in preventing recurrent strokes. Angioplasty of the basilar artery was technically feasible. Symptomatic BAS typically affected the proximal and mid-basilar artery and most often caused infarction in the pons. The mechanisms for stroke were heterogeneous. TIAs frequently preceded a posterior circulation stroke.

  View details for PubMedID 17895197

• Selfotel in acute ischemic stroke - Possible neurotoxic effects of an NMDA antagonist STROKE Davis, S. M., Lees, K. R., Albers, G. W., Diener, H. C., Markabi, S., Karlsson, G., Norris, J. 2000; 31 (2): 347-354

  Abstract

  Based on neuroprotective efficacy in animal models, we evaluated the N-methyl D-aspartate antagonist Selfotel in patients with ischemic stroke, after doses up to 1.5 mg/kg were shown to be safe in phase 1 and phase 2a studies.Two pivotal phase 3 ischemic stroke trials tested the hypothesis, by double-blind, randomized, placebo-controlled parallel design, that a single intravenous 1.5 mg/kg dose of Selfotel, administered within 6 hours of stroke onset, would improve functional outcome at 90 days, defined as the proportion of patients achieving a Barthel Index score of >/=60. The trials were performed in patients aged 40 to 85 years with acute ischemic hemispheric stroke and a motor deficit.The 2 trials were suspended on advice of the independent Data Safety Monitoring Board because of an imbalance in mortality after a total enrollment of 567 patients. The groups were well matched for initial stroke severity and time from stroke onset to therapy. There was no difference in the 90-day mortality rate, with 62 deaths (22%) in the Selfotel group and 49 (17%) in the placebo-treated group (RR=1.3; 95% CI 0.92 to 1.83; P=0.15). However, early mortality was higher in the Selfotel-treated patients (day 30: 54 of 280 versus 37 of 286; P=0.05). In patients with severe stroke, mortality imbalance was significant throughout the trial (P=0.05).Selfotel was not an effective treatment for acute ischemic stroke. Furthermore, a trend toward increased mortality, particularly within the first 30 days and in patients with severe stroke, suggests that the drug might have a neurotoxic effect in brain ischemia.

  View details for Web of Science ID 000085039900001

  View details for PubMedID 10657404

• Phase II studies of the glycine antagonist GV150526 in acute stroke - The North American experience 23rd International Joint Conference on Stroke and Cerebral Circulation Babikian, V., Licata-Gehr, E., Joseph, L. N., Bailey, P., Boyle, R., MacDougall, A., MacLean, G., Wheelock, W. B., Kolyvas, G., Banas, T., Wissman, M. A., Heckaman, J. D., Porter, M. A., Bhat, M. H., Later, P. E., Wissmann, S. D., Ottinger, C. J., Stevens, J. C., Plant, R., CHANG, F. L., Beatty, J., Beatty, T. W., Cohen, S. B., Vasquez, A. B., Schmidt, D. W., Allen, T., Bellavance, A., Hebert, L., Berger, L., Filatrault, R., Nasredding, Z., Trottier, A. G., Duplessis, M., Maison, F. G., Ninkovic, S., Berman, B., Yipelkonen, M., Miskin, B. M., Shaivitz, S. A., Benavente, O., Bruce, G., Solomen, D., Sherman, D., Hart, R., Kanter-Carolin, M., Lalonde, D. R., Rogers, D., Bruce, G., Leonard, A., Brott, T., Spilker, J., Broderick, J., Kothari, R., Panicoli, A., Sauerbeck, L., Miller, R., Clark, W. M., Deely, S. M., Fisher, S., Lutsep, H., Quinn, J., Crawford, J., EGAN, R., Nesbit, G., Al-Azzaz, A., Earley, C., Herr, M., Michel, H., Dike, G., Maragakis, N., Polydefkis, M., Wagner, K., Wang, M., Rusa, R., Jones, C., Kerr, D., Moo, L., Pardo, C., Silverman, I., Hoffman, J., Diebert, E., Jinnah, H., York, J., Hoke, A., Vega-Bermudez, F., Comi, A., HILLIS, A., Rich, J., Ervin, J., Bryan, C., Allen, A. A., Kelley, G. B., Perll, M. F., Box, M. S., Robles, L. H., Zwibelman, J. S., Hopewell, D. K., Ryan, M. E., Wendland, R. T., Feinberg, W., Coull, B., Rose-Taylor, D., Ahern, G., Anderson, L. R., Keim, S., Sherman, S., Rose-Taylor, D., Haley, E. C., Morris, A., Ahern, K., Johnston, K., Solenski, N., Nathan, B., Bleck, T., Worrall, B., Leszczyszyn, D., Hemstreet, M., Kiely, J., Burns, T., Klein, C., Cail, W., Huff, S., Quinn, J., Armstrong, R., Provencio, J., Snider, R., Van Gerpen, J., Hsu, C., Duke, L., Banet, G., Choi, J., Lee, J. M., Lowenkopf, T., Innes, G., Metcalf, C., Huang, P., Rumball, C., Miller, B., Haegert, J., Holmes, A., Oldring, B., Macnab, J., Grosch, R., Deady, B., Street, R., O'Brien, R., Vertesi, L., Erhardt, G., Finkler, J., Tessler, C., Glazer, S., Noseworthy, R., Knazen, M., Macdonald, P., Smyth, A., Karp, J., Phillips, B., Spiegel, A., Bowman, S. C., Hampsey, J. P., Habib, M. W., Schroeder, T., Stopnytsky, K., Kertecz, A., Piotrowski, S., Cooper, P., Lyden, P., Rapp, K., Jackson, C., Ellis, R., Noack, H., Sabbagh, M., Galasko, D., Rapp, K., Kelly, N., WERNER, J., Chang, C. L., Morris, D. T., Pusek, S., Hinn, A., Ma, J., Bernard, E., Phillips, S., Reidy, Y., Gubitz, G., Tanha, F., Leckey, R., Ansell, J., Darvesh, S., Aguilar, E., Pullicino, P., Starr, S., Munschauer, F. E., Ross, D. B., Norris, D., Steinberg, J., Zaret, B., Maniar, M., Sacco, R. L., Boden-Albala, B., Jimenez, M., Mohr, J. P., Kargman, D., Marshall, R., Elkind, M. S., Roberts, K., Gan, R., Shipley, N., Aboumatar, S., Greene, R., Shuaib, A., Kadribasic, E., Keegan, M., Stewart, B., Khaan, K., Shuaib, A., Dean, T. R., Richardson, P., Moussavian, M., Faloriji, W., Johnson, M., Levin, Z., Silliman, S., Fuqua, P. S., Berger, A., Najjar, S., Schwartz, R., Solomon, D. H., Limon, L., Hart, R. G., Sherman, D. G., Carolin, M. C., Lalonde, D. R., Benavente, O., Starkman, S., Schubert, G. B., Dobkin, B., Saver, J., Vespa, P., Alger, J., Teitelbaum, J., Lachance, N., Robillard, A., Lachapelle, J., Boileau, J., Rousseau, S., Roy, L., Laplante, P., Thurston, S., McGee, J. R., Lutz, M. A., McGee, F. E., Harris, J. K., White, R. J., O'Bannon, J. M., Brush, J. J., Cohen, R. J., SMITH, T. A., Mathe, S. A., Karner, S. F., Worthington, A. K., Deel, J. G., Tong, D., Hock, N., Albers, G., O'Brien, M., Woofenden, A., Yenari, M., Freyberg, S., Guro, G., Hock, N., Tuhrim, S., Augustine, S., Weinberger, J., Horowitz, D., Sheinart, K., Schonewille, W., Atlas, S., Veloso, F., REID, M., Adaikari, K., Gebhardt, V., Nair, C. P., Wang, D., Vrabel, D., McLean, J., Kumar, J., Garwacki, D., Roda, M., Hui, E., Coyner, J., Vrabel, D., Honings, D., Rose, J., Sladana, R., Wechsler, L., Yasko, L., Knepper, L., Massaro, L., Graham, S., Larkin, G., Ulicny, T., Yonas, H., Barch, C., Lin, H., Brader, E., Berkey, K., Ludovici, J., Kaufmann, A., De Cesare, S., Hodgdon, A., MacLeod, B., Thompson, D., Piatkowski, S., O'Toole, K., Yasko, L., Ilkhanipour, K., Maenza, R., Mathias, S., Thulborn, K., Jungreis, C., Cockley, P., Corsello, G., Ammon, C., Rasheed, A., Weston, L., Bourque, G., Silverberg, D., Harper, B., Robinson, D., MacEachern, M., Williams, A. D., Roth, R., Rice, M., Hogan, J., Pellegrino, T. R., Holland, M. T., Lanoue, R. J., Redding, A., Handler, J., Haley, E. C., Alves, W. M., Elder, L., Davenport, K., McClure, K., Knowlton, S., Cuccia, E., Maupin, K., Lotts, M., Hund, M., Shelleck, K., Szewc, T., Cail, W., Wagner, G., Gates, K., Earley, C., Haley, E. C., Johnston, K. C., Sacco, R. L., Schuaib, A., Snipes, R., Wang, D. Z., Brass, L. M., Clark, W. R., Grotta, J. C., Harrison, M., McIntyre, N., Zimmerman, H., Wellcome, G., Snipes, R., Watson, D., Ordronneau, P., Hoke, F., Ko, W. J., Clayton, L., EnneyO' Mara, L., Johnson, J., Orander, C., Card, B., Green, S. LIPPINCOTT WILLIAMS & WILKINS. 2000: 358–65

  View details for Web of Science ID 000085039900003

• Diffusion and perfusion magnetic resonance imaging for the evaluation of acute stroke: potential use in guiding thrombolytic therapy CURRENT OPINION IN NEUROLOGY Tong, D. C., Albers, G. W. 2000; 13 (1): 45-50

  Abstract

  Recent data indicate that diffusion/perfusion weighted imaging could eventually play a significant role in acute stroke management, particularly in determining the suitability of acute stroke patients for thrombolytic therapy. The evidence supporting these uses is reviewed, and the future role of diffusion and perfusion weighted imaging in acute stroke management is discussed.

  View details for Web of Science ID 000168284400009

  View details for PubMedID 10719649

• Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: Frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies CEREBROVASCULAR DISEASES Hart, R. G., Pearce, L. A., Miller, V. T., Anderson, D. C., Rothrock, J. F., Albers, G. W., Nasco, E. 2000; 10 (1): 39-43

  Abstract

  While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic.To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies.On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I-III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy.Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05).Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin.

  View details for Web of Science ID 000085008100007

  View details for PubMedID 10629345

• Impact of diffusion weighted MRI (DWI) on patient management: Is it of practical value? Tong, D. C., Skalabrin, E., Chan, B. P., Moseley, M. E., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2000: 286–86

  View details for Web of Science ID 000084589100113

• The ATLANTIS T-PA acute stroke trial: Results for patients treated within three hours of stroke onset Albers, G. W., Clark, W. M., Madden, K. P., Hamilton, S. A. LIPPINCOTT WILLIAMS & WILKINS. 2000: 307–

  View details for Web of Science ID 000084589100221

• Recanalization rates in cervical carotid and vertebral dissection Skalabrin, E. J., Smith, W. S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2000: 335–35

  View details for Web of Science ID 000084589100354

• Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset - The ATLANTIS study: A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Clark, W. M., Wissman, S., Albers, G. W., Jhamandas, J. H., Madden, K. P., Hamilton, S. 1999; 282 (21): 2019-2026

  Abstract

  Recombinant tissue-type plasminogen activator (rt-PA) improves outcomes for patients with acute ischemic stroke, but current approved use is limited to within 3 hours of symptom onset. This restricts the number of patients who can be treated, since most stroke patients present more than 3 hours after symptom onset.To test the efficacy and safety of rt-PA in patients with acute ischemic stroke when administered between 3 and 5 hours after symptom onset.The Alteplase ThromboLysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study is a phase 3, placebo-controlled, double-blind randomized study conducted between December 1993 and July 1998, with up to 90 days of follow-up.One hundred forty university and community hospitals in North America.An intent-to-treat population of 613 acute ischemic stroke patients was enrolled, with 547 of these treated as assigned within 3 to 5 hours of symptom onset. A total of 39 others were treated within 3 hours of symptom onset, 24 were treated more than 5 hours after symptom onset, and 3 never received any study drug.Administration of 0.9 mg/kg of rt-PA (n = 272) or placebo (n = 275) intravenously over 1 hour.Primary efficacy was an excellent neurologic recovery at day 90 (National Institutes of Health Stroke Scale [NIHSS] score of < or =1); secondary end points included excellent recovery on functional outcome measures (Barthel index, modified Rankin scale, and Glasgow Outcome Scale) at days 30 and 90. Serious adverse events were also assessed.In the target population, 32% of the placebo and 34% of rt-PA patients had an excellent recovery at 90 days (P = .65). There were no differences on any of the secondary functional outcome measures. In the first 10 days treatment with rt-PA significantly increased the rate of symptomatic intracerebral hemorrhage (ICH) (1.1% vs 7.0% [P<.001]), a symptomatic ICH (4.7% vs 11.4% [P = .004]), and fatal ICH (0.3% vs 3.0% [P<.001]). Mortality at 90 days was 6.9% with placebo and 11.0% with rt-PA (P = .09). Results in the intent-to-treat population were similar.This study found no significant rt-PA benefit on the 90-day efficacy end points in patients treated between 3 and 5 hours. The risk of symptomatic ICH increased with rt-PA treatment. These results do not support the use of intravenous rt-PA for stroke treatment beyond 3 hours.

  View details for PubMedID 10591384

• Recommendations for standards regarding preclinical neuroprotective and restorative drug development STROKE Feinklestein, S. P., Fisher, M., Furland, A. J., Goldstein, L. B., Gorelick, P. B., Kaste, M., Lees, K. R., Traystman, R. J., Albers, G. W., Anwer, U. E., Ashwood, T., Barone, F. C., Basta, S. L., Bogousslavsky, J., Buchan, A. M., Cady, W. J., Chan, P. H., Clemens, J. A., Cox, B. F., Craddock, R. E., Cramer, S. C., Del Zoppo, G. J., Dielrich, W. D., Elliott, P., Faden, A. I., Feuerstein, G. Z., Ginsberg, M. D., Gold, M., Greene, W. L., Hall, E. D., Hsu, C. Y., Hunter, A. J., Lai, M., Lesko, L. M., Levy, D. E., Li, F. H., Locke, K. W., LODGE, D., Lowe, D., Marcoux, F. W., McCulloch, J., McDermott, J., Meibach, R., Messersmith, E. K., Moseley, M., Moskowitz, M. A., Mueller, A. L., Munro, F., Nudo, R. J., Oeda, J., Ohlstein, E. H., Parsons, A., Patmore, L., Poole, R. M., Pschorn, U., Pulsinelli, W. A., Sacco, R. L., Saeki, S., Salazar-Grueso, E., Sandage, B. W., Schallert, T., Schielke, G. P., Sharkey, J., Sotak, C. H., Steiger, B., Storall, S., Takahashi, Y., Tumas, D., Van Bruggen, N., Versavel, M., Vornov, J., Walker, M. D., Wallin, B., Wang, J., Warach, S., Wells, D. S., Witcher, J. A. 1999; 30 (12): 2752-2758

  Abstract

  The plethora of failed clinical trials with neuroprotective drugs for acute ischemic stroke have raised justifiable concerns about how best to proceed for the future development of such interventions. Preclinical testing of neuroprotective drugs is an important aspect of assessing their therapeutic potential, but guidelines concerning how to perform preclinical development of purported neuroprotective drugs for acute ischemic stroke are lacking. This conference of academicians and industry representatives was convened to suggest such guidelines for the preclinical evaluation of neuroprotective drugs and to recommend to potential clinical investigators the data they should review to reassure themselves that a particular neuroprotective drug has a reasonable chance to succeed in an appropriately designed clinical trial. Without rigorous, robust, and detailed preclinical evaluation, it is unlikely that novel neuroprotective drugs will prove to be effective when tested in large, time-consuming, and expensive clinical trials. Additionally, similar recommendations are provided for drugs with the potential to enhance recovery after acute ischemic stroke, a burgeoning new field with great potential but little currently available data. The suggestions contained in this document are meant to serve as overall guidelines that must be adapted to the individual characteristics related to particular drugs and their preclinical and clinical development needs.

  View details for Web of Science ID 000083890700044

  View details for PubMedID 10583007

• Antithrombotic management of atrial fibrillation for stroke prevention in older people CLINICS IN GERIATRIC MEDICINE Tong, D. C., Albers, G. W. 1999; 15 (4): 645-?

  Abstract

  Atrial fibrillation (AF) is a common cardiac condition in the elderly population. The primary concern in individuals with AF is the risk of stroke. The management of AF for stroke prevention requires an understanding of the relative risks and benefits of antithrombotic therapy. Numerous randomized clinical trials have improved tremendously our understanding of the relative merits of anticoagulation and aspirin, and indicate that anticoagulation is the appropriate treatment for the majority of individuals with AF. In patients who have contraindications to anticoagulation, aspirin is recommended.

  View details for Web of Science ID 000083539800002

  View details for PubMedID 10499928

• Supplement to the guidelines for the management of transient ischemic attacks - A statement from the Ad Hoc Committee on guidelines for the management of transient ischemic attacks, Stroke Council, American Heart Association STROKE Albers, G. W., Hart, R. G., Lutsep, H. L., Newell, D. W., Sacco, R. L. 1999; 30 (11): 2502-2511

  View details for Web of Science ID 000083434100054

• AHA Scientific Statement. Supplement to the guidelines for the management of transient ischemic attacks: A statement from the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, Stroke Council, American Heart Association. Stroke Albers, G. W., Hart, R. G., Lutsep, H. L., Newell, D. W., Sacco, R. L. 1999; 30 (11): 2502-2511

  View details for PubMedID 10548693

• Expanding the window for thrombolytic therapy in acute stroke - The potential role of acute MRI for patient selection STROKE Albers, G. W. 1999; 30 (10): 2230-2237

  Abstract

  Effective therapy was not available for treatment of acute stroke until 1995, when tissue plasminogen activator (tPA) was shown to improve neurological and functional outcome in stroke patients who were treated within 3 hours of symptom onset.Currently, many patients do not qualify for tPA therapy because they present for evaluation beyond 3 hours after stroke onset. Attempts to expand the treatment window to 6 hours, using CT to select patients, have failed. Use of early MR imaging may provide significant advantages over CT for identification of patients who are likely to benefit from thrombolytic therapy because (1) the early perfusion-weighted imaging (PWI) lesion estimates the region of acute dysfunctional brain tissue, whereas the acute diffusion-weighted imaging (DWI) lesion appears to correspond to the core of the early infarction; (2) the mismatch between the acute PWI lesion and the smaller DWI lesion represents potentially salvageable brain tissue (an estimate of the ischemic penumbra); and (3) in patients with a PWI/DWI mismatch, early reperfusion is often associated with substantial clinical improvement and reversal or reduction of DWI lesion growth.Clinical trials that use new MRI techniques to screen patients may be able to identify a subset of acute stroke patients who are ideal candidates for thrombolytic therapy even beyond 3 hours after stroke onset.

  View details for Web of Science ID 000082983200042

  View details for PubMedID 10512933

• Antiplatelet therapy: New foundations for optimal treatment decisions NEUROLOGY Albers, G. W., Tijssen, J. G. 1999; 53 (7): S25-S31

  Abstract

  Individuals who experience a stroke or a transient ischemic attack require long-term treatment to prevent a subsequent stroke. According to the current guidelines, patients with a first cerebrovascular event due to cardioembolism should be treated with oral anticoagulants, barring any contraindications. Individuals with ischemic cerebral events due to atherothrombosis should typically receive antiplatelet agents. Aspirin is the best-studied antiplatelet agent and has been used in stroke prevention for many years. Trials evaluating aspirin have, over time, enrolled more patients and tested lower aspirin doses. No individual trial conducted in cerebrovascular patients has established the optimal aspirin dose for prevention of vascular events, but meta-analyses of trials at different dose ranges and the two single trials that directly compared different doses strongly suggest that the benefit of aspirin is independent of dose in this patient population. Lower doses (50-325 mg daily) are now recommended because of their more favorable side-effect profiles. Because its value is established, aspirin has been used as a control to evaluate other antiplatelet agents. On the basis of large clinical trials versus aspirin, three other antiplatelet agents (ticlopidine, clopidogrel, and the combination of aspirin plus extended-release dipyridamole) have all been shown to be effective for stroke prevention. Physician opinions regarding the efficacy of these agents in indirect comparisons and the differences in their safety profiles, availability, and cost will influence the choice of agent for the individual patient.

  View details for Web of Science ID 000083207300004

  View details for PubMedID 10532645

• Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: Evolution of lesion volume and correlation with clinical outcome ANNALS OF NEUROLOGY Beaulieu, C., de Crespigny, A., Tong, D. C., Moseley, M. E., Albers, G. W., Marks, M. P. 1999; 46 (4): 568-578

  Abstract

  A prospective longitudinal diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI/PWI) study of stroke patients (n = 21) at five distinct time points was performed to evaluate lesion evolution and to assess whether DWI and PWI can accurately and objectively demonstrate the degree of ischemia-induced deficits within hours after stroke onset. Patients were scanned first within 7 hours of symptom onset and then subsequently at 3 to 6 hours, 24 to 36 hours, 5 to 7 days, and 30 days after the initial scan. Lesion evolution was dynamic during the first month after stroke. Most patients (18 of 19, 95%) showed increased lesion volume over the first week and then decreased at 1 month relative to 1 week (12 of 14, 86%). Overall, lesion growth appeared to depend on the degree of mismatch between diffusion and perfusion at the initial scan. Abnormal volumes on the acute DWI and PWI (<7 hours) correlated well with initial National Institutes of Health (NIH) stroke scale scores, outcome NIH stroke scale scores, and final lesion volume. DWI and PWI can provide an early measure of metabolic and hemodynamic insufficiency, and thus can improve our understanding of the evolution and outcome after acute ischemic stroke.

  View details for PubMedID 10514093

• A standardized MRI stroke protocol: Comparison with CT in hyperacute intracerebral hemorrhage STROKE Tong, D. C., Albers, G. W., Yenari, M. A., Marks, M. P. 1999; 30 (9): 1974-1975

  View details for Web of Science ID 000082278400047

  View details for PubMedID 10471453

• Emerging evidence for inflammation in conditions frequently affecting older adults: Report of a symposium Annual American-College-of-Physicians Meeting Hamerman, D., Berman, J. W., Albers, G. W., Brown, D. L., Silver, D. WILEY-BLACKWELL PUBLISHING, INC. 1999: 1016–25

  View details for Web of Science ID 000081880800015

  View details for PubMedID 10443865

• Cerebral amyloid angiopathy with unilateral hemorrhages, mass effect, and meningeal enhancement NEUROLOGY Morton-Bours, E. C., Skalabrin, E. J., Albers, G. W. 1999; 53 (1): 233-234

  View details for Web of Science ID 000081354000049

  View details for PubMedID 10408572

• Applications of diffusion-perfusion magnetic resonance imaging in acute ischemic stroke NEUROLOGY Fisher, M., Albers, G. W. 1999; 52 (9): 1750-1756

  Abstract

  Diffusion-weighted imaging (DWI) and perfusion imaging (PI) are two new magnetic resonance technologies that are becoming increasingly available for evaluation of acute ischemic stroke patients. DWI provides information about the location of acute focal ischemic brain injury at early time points and PI can document the presence of disturbances in microcirculatory perfusion. DWI and PI are now being used in clinical practice and in clinical trials of potential acute stroke therapies to assess their utility. In the future, DWI and PI may aid in the development of effective acute stroke therapies and help identify which stroke patients are most likely to benefit from specific agents.

  View details for Web of Science ID 000080758500008

  View details for PubMedID 10371519

• Evaluation of early reperfusion and IV tPA therapy using diffusion- and perfusion-weighted MRI NEUROLOGY Marks, M. P., Tong, D. C., Beaulieu, C., Albers, G. W., de Crespigny, A., Moseley, M. E. 1999; 52 (9): 1792-1798

  Abstract

  To characterize the effects of recombinant tissue plasminogen activator (rt-PA) therapy and early reperfusion on diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) changes observed following acute ischemic injury.Twelve patients were evaluated prospectively using echo planar DWI and bolus tracking PWI. Six patients received i.v. rt-PA 0.9 mg/kg and were compared with six patients who did not. Patients receiving rt-PA were initially imaged (T1) 3 to 5 hours postictus (mean, 4 hours 20 minutes) whereas those not treated with tissue plasminogen activator (tPA) were imaged 4 to 7 hours postictus (mean, 5 hours, 25 minutes). Follow-up imaging was performed 3 to 6 hours (T2), 24 to 36 hours (T3), 5 to 7 days (T4), and 30 days (T5) after the first scan in all patients. Lesion volumes were measured on both DWI and time-to-peak maps constructed from PW images.PWI was performed successfully at T1 and T3 in 11 of 12 patients. In the group that received i.v. tPA, initial PWI volumes were less than DWI volumes in five of six patients (83%), whereas only one of five patients (20%) not receiving tPA had PWI < DWI volume (p = 0.08). PWI normalized by 24 to 36 hours (T3) in 6 of 11 patients (early reperfusers), with 5 of 6 of these early reperfusers having received tPA. The aggregate apparent diffusion coefficient (ADC) values for the early reperfusers were consistently higher at T2 (p = 0.04), T3 (p = 0.002), and T4 (p = 0.0005). Five of six patients with early reperfusion demonstrated regions of elevated ADC within the ischemic zone (mean ipsilateral ADC/contralateral ADC, 1.46 +/- 0.19) by 24 to 36 hours, whereas none of the nonearly reperfusers showed these regions of elevated ADC (p = 0.015).Early reperfusion is seen more frequently with i.v. tPA therapy. In addition, the study showed that ADC may undergo early increases that are tied closely to reperfusion, and marked ADC heterogeneity may exist within the same lesion. Early reperfusion is seen more frequently with i.v. tPA therapy.

  View details for Web of Science ID 000080758500014

  View details for PubMedID 10371525

• Acute Ischemic Stroke. Current treatment options in neurology Chan, Albers 1999; 1 (2): 83-96

  Abstract

  Patients with acute ischemic stroke should be immediately transported to the nearest hospital for rapid evaluation and treatment. Intravenous t-PA within 3 hours of symptom onset is the recommended treatment for patients who meet the National Institute of Neurological Disorders and Stroke (NINDS) study eligibility criteria. Patients should be informed of the risk of symptomatic cerebral hemorrhage, and strict adherence to the NINDS study protocol is strongly recommended to optimize the risk-benefit ratio. Ischemic stroke patients who are not eligible for t-PA therapy should usually be started on aspirin. Intravenous heparin is not recommended as a standard treatment but may be considered for specific patient subgroups. Low-dose subcutaneous heparin is recommended for prophylaxis of deep vein thrombosis in immobilized patients. Management of stroke patients by a designated stroke team is recommended to facilitate prompt diagnosis and treatment and early initiation of rehabilitation therapy. We also recommend that physicians who manage patients with acute stroke maintain contact with local or regional stroke centers to facilitate referral of appropriate patients for intensive care or specialized diagnostic tests or therapies.

  View details for PubMedID 11096699

• Outcome of angioplasty for atherosclerotic intracranial stenosis STROKE Marks, M. P., Marcellus, M., Norbash, A. M., Steinberg, G. K., Tong, D., Albers, G. W. 1999; 30 (5): 1065-1069

  Abstract

  We sought to assess the long-term outcome and efficacy of percutaneous transluminal angioplasty in the treatment of symptomatic intracranial atherosclerotic stenoses.Twenty-three patients with fixed symptomatic intracranial stenoses were treated over a 5-year period with percutaneous transluminal angioplasty. Patients who underwent successful angioplasty were followed up for 16 to 74 months (mean, 35.4 months).An angioplasty that resulted in decreased stenosis was performed in 21 of 23 patients (91.3%). In 1 case a stenosis could not be safely crossed, and in another balloon dilatation resulted in vessel rupture. This vessel rupture resulted in the 1 periprocedural death in the series. In follow-up there was 1 stroke in the same vascular territory as the angioplasty and 2 strokes in the series overall. This yielded an annual stroke rate of 3.2% for strokes in the territory appropriate to the site of angioplasty.Intracranial angioplasty can be performed with a high degree of technical success. The long-term clinical follow-up available in this series suggests that it may reduce the risk of future stroke in patients with symptomatic intracranial stenoses.

  View details for PubMedID 10229745

• MRI abnormalities associated with partial status epilepticus NEUROLOGY Lansberg, M. G., O'Brien, M. W., Norbash, A. M., Moseley, M. E., Morrell, M., Albers, G. W. 1999; 52 (5): 1021-1027

  Abstract

  To report neuroimaging findings in patients with complex partial status epilepticus.During status epilepticus, neuroimaging may be used to exclude other neurologic conditions. Therefore, it is important to identify the neuroimaging features that are associated with status epilepticus. In addition, MRI characteristics may provide insight into the pathophysiologic changes during status epilepticus.The history and neuroimaging examination results of three patients with complex partial status epilepticus were reviewed. Studies obtained during status epilepticus included diffusion-weighted MRI (DWI), MR angiography (MRA), postcontrast T1-weighted MRI, T2-weighted MRI, and CT. Follow-up MRI was obtained in two patients, and autopsy results were available for the third.Some of the MRI and CT findings during partial status epilepticus mimicked those of acute ischemic stroke: DWI and T2-weighted MRI showed cortical hyperintensity with a corresponding low apparent diffusion coefficient, and CT showed an area of decreased attenuation with effacement of sulci and loss of gray-white differentiation. However, the lesions did not respect vascular territories, there was increased signal of the ipsilateral middle cerebral artery on MRA, and leptomeningeal enhancement appeared on postcontrast MRI. On follow-up imaging, the abnormalities had resolved, but some cerebral atrophy was present.The radiologic characteristics of status epilepticus resemble those of ischemic stroke but can be differentiated based on lesion location and findings on MRA and postcontrast MRI. The MRI abnormalities indicated the presence of cytotoxic and vasogenic edema, hyperperfusion of the epileptic region, and alteration of the leptomeningeal blood-brain barrier. These changes reversed, but they resulted in some regional brain atrophy.

  View details for Web of Science ID 000079516900022

  View details for PubMedID 10102423

• Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke STROKE Albers, G. W., Clark, W. M., Atkinson, R. P., Madden, K., Data, J. L., Whitehouse, M. J. 1999; 30 (3): 508-513

  Abstract

  Licostinel (ACEA 1021; 5-nitro-6, 7-dichloro-2,3-quinoxalinedione), a competitive antagonist of glycine at the N-methyl-D-aspartate (NMDA) receptor, is an effective neuroprotective agent in animal models of cerebral ischemia. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of licostinel in patients with acute stroke.In this 5-center dose escalation trial, patients were enrolled within 48 hours of an ischemic stroke and treated with ascending doses of a short infusion of licostinel or a placebo. Adverse effects were assessed with clinical and laboratory measurements, and patient outcome was determined with the National Institutes of Health Stroke Scale.Sixty-four patients (44 treated with escalating doses of licostinel and 20 who received placebo) were treated. Lower doses of licostinel (0.03 to 0.60 mg/kg) were not associated with any significant adverse effects. Higher doses of licostinel (1.2 to 3.0 mg/kg) were associated with a variety of mild-to-moderate adverse effects including neurological and gastrointestinal complaints. No major psychotomimetic effects or significant safety concerns occurred. At the higher dose levels, peak plasma concentrations of licostinel were substantially higher than those required for neuroprotection in animal stroke models. A similar improvement in National Institutes of Health Stroke Scale scores over time was seen in both the placebo group and the licostinel-treated patients.A short infusion of licostinel in doses up to 3.0 mg/kg is safe and tolerable in acute stroke patients. Licostinel may be a safer and better tolerated neuroprotective agent than many of the previously evaluated NMDA antagonists.

  View details for Web of Science ID 000078913700006

  View details for PubMedID 10066844

• Moyamoya syndrome in children with Alagille syndrome: Additional evidence of a vasculopathy PEDIATRICS Woolfenden, A. R., Albers, G. W., Steinberg, G. K., Hahn, J. S., Johnston, D. C., Farrell, K. 1999; 103 (2): 505-508

  View details for Web of Science ID 000078437800023

  View details for PubMedID 9925853

• Risk factors for stroke and primary prevention of stroke in atrial fibrillation JOURNAL OF THROMBOSIS AND THROMBOLYSIS Laupacis, A., Singer, D., Jacobsen, A., Dunn, M., Dalen, J., Albers, G. 1999; 7 (1): 21-26

  View details for Web of Science ID 000079077700004

  View details for PubMedID 10337356

• Orolingual angioedema complicating Rtpa (Alteplase) for acute ischemic stroke (AIS) Fayad, P. B., Albers, G. W., Frey, J. L., Raps, E. C. LIPPINCOTT WILLIAMS & WILKINS. 1999: 242–42

  View details for Web of Science ID 000077934200116

• Headache with neurological deficits and CSF lymphocytosis: A transient ischemic attack mimic. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lansberg, M. G., Woolfenden, A. R., Norbash, A. M., Smith, D. B., Albers, G. W. 1999; 8 (1): 42-44

  Abstract

  Headache with neurological deficits and cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is a benign condition with a transient ischemic attack (TIA)-like presentation. It is a disease of young adults that is characterized by headache, transient focal neurological symptoms, and lymphocytic pleocytosis. The onset of neurological symptoms after cerebral angiography in patients with this disease has occasionally been reported. The authors present the case of a 28-year-old man with episodes of left-sided numbness and weakness associated with headache. He underwent cerebral angiography as part of his evaluation, after which he experienced an episode of right hemiplegia and aphasia. A subsequent magnetic resonance image (MRI) revealed two small new infarcts in the left parietal cortex. A diagnosis of HaNDL was made based mainly on clinical symptoms and CSF analysis. The symptoms resolved with conservative therapy. HaNDL is a benign condition that can present with symptoms similar to a TIA. Although HaNDL remains a diagnosis of exclusion, caution is required when considering cerebral angiography in the evaluation of patients with a HaNDL-like syndrome, because these patients seem prone to developing neurological symptoms after angiography.

  View details for PubMedID 17895137

• Antithrombotic and thrombolytic therapy for ischemic stroke CHEST Albers, G. W., Easton, J. D., Sacco, R. L., Teal, P. 1998; 114 (5): 683S-698S

  View details for Web of Science ID 000077034200018

  View details for PubMedID 9822071

• Antithrombotic therapy in atrial fibrillation CHEST Laupacis, A., Albers, G., Dalen, J., Dunn, M. I., Jacobson, A. K., Singer, D. E. 1998; 114 (5): 579S-589S

  View details for Web of Science ID 000077034200011

  View details for PubMedID 9822064

• Diffusion-weighted MRI for evaluation of acute stroke NEUROLOGY Albers, G. W. 1998; 51 (3): S47-S49

  Abstract

  Diffusion-weighted imaging (DWI) is a new magnetic resonance imaging technique that detects the tiny random movements of water molecules (diffusion) in tissues. This technique allows a map of the average apparent diffusion coefficient (ADC) to be calculated. Shortly after the onset of an ischemic stroke, the ADC of brain tissue is significantly reduced because of cytotoxic edema. Over several days, the rapid initial drop in ADC is followed by a return to "pseudonormal" values at approximately 1 week. Subsequently, elevated ADC values are seen at chronic time points. DWI is remarkably sensitive in detecting and localizing acute ischemic brain lesions and allows differentiation of acute regions of ischemia from chronic infarcts. Recent studies have shown a high correlation between the volume of early DWI lesions and clinical neurologic outcome. In addition, the volume of the early DWI lesion correlates well with final infarct volume as measured by T2-weighted imaging. Therefore, this technique may facilitate optimal selection of patients for new medical therapies for stroke and may provide a highly sensitive technique for evaluating the efficacy of new treatments.

  View details for Web of Science ID 000075941900013

  View details for PubMedID 9744834

• Ethical standards in phase 1 trials of neuroprotective agents for stroke therapy STROKE Albers, G. W., Zivin, J. A., Choi, D. W. 1998; 29 (8): 1493-1494

  View details for Web of Science ID 000075183000004

  View details for PubMedID 9707181

• Choice of antithrombotic therapy for stroke prevention in atrial fibrillation - Warfarin, aspirin, or both? ARCHIVES OF INTERNAL MEDICINE Albers, G. W. 1998; 158 (14): 1487-1491

  View details for Web of Science ID 000074957200001

  View details for PubMedID 9679788

• Angiographically defined primary angiitis of the CNS - Is it really benign? NEUROLOGY Woolfenden, A. R., Tong, D. C., Marks, M. P., Ali, A. O., Albers, G. W. 1998; 51 (1): 183-188

  Abstract

  Primary angiitis of the CNS (PACNS) is a diagnostically challenging disorder. In patients whose diagnosis is ascertained solely by cerebral angiography without histologic verification, a benign monophasic clinical course with favorable response to a brief course of immunosuppressive therapy is often reported.We performed a retrospective review of patients with PACNS seen at the Stanford Stroke Center.Patients were followed for a median of 27.5 months. Acute focal deficits (9 of 10) and headache (3 of 10) were the most frequent presenting symptoms. Significant recurrent neurologic symptoms occurred in 5 of 10 patients before the initiation of immunosuppressive treatment. Three of six patients had recurrent symptoms during prednisone therapy alone, whereas only one of seven patients had recurrent symptoms while receiving combination immunosuppressive therapy. None had recurrent stroke during immunosuppressive treatment. Dynamic arterial changes were seen in four of five patients who underwent follow-up angiography that often, but not always, correlated with disease activity.Patients with angiographically defined PACNS frequently did not have a benign outcome or monophasic course. Repeat angiography was useful in supporting the diagnosis of PACNS, but did not always correlate with disease activity. A prospective multicenter collaborative effort is required to better define the clinical course and optimal treatment of PACNS.

  View details for PubMedID 9674800

• Progressive facial hemiatrophy: Abnormality of intracranial vasculature NEUROLOGY Woolfenden, A. R., Tong, D. C., Norbash, A. M., Albers, G. W. 1998; 50 (6): 1915-1917

  Abstract

  Progressive facial hemiatrophy (PFH) or Parry-Romberg syndrome is associated with ipsilateral brain lesions and neurologic symptoms. We describe a 35-year-old man with PFH and frequent hemiplegic migraine. On cerebral angiography, reversible vessel caliber changes were seen within the symptomatic hemisphere. An abnormality of the intracranial vasculature may be present in some patients with PFH and neurologic manifestations.

  View details for Web of Science ID 000074226700078

  View details for PubMedID 9633763

• Thrombolysis with reteplase, an unglycosylated plasminogen activator variant, in experimental embolic stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Yenari, M. A., Lee, L. K., Beaulieu, C., Sun, G. H., Kunis, D., Chang, D., Albers, G. W., Moseley, M. E., Steinberg, G. K. 1998; 7 (3): 179-186

  Abstract

  We incorporated diffusion-weighted magnetic resonance imaging (MRI) (DWI) and perfusion-weighted MRI (PWI) to evaluate the efficacy of thrombolysis in experimental embolic stroke using a plasminogen activator, reteplase. Reteplase (rPA) is an unglycosylated plasminogen activator with enhanced fibrinolytic potency. Right internal carotid arteries of 34 rabbits were embolized using aged heterologous thrombi. Baseline DWI and PWI scans 0.5 hours after embolization confirmed successful embolization among 32. Intravenous treatment with rPA (n=11; 1 mg/kg bolus), recombinant tissue plasminogen activator (rt-PA) (n=11; 6 mg/kg bolus over 1 hour), or placebo (n=10) commenced 1 hour after stroke induction. MRIs were performed at 1.75, 3, and 5 hours after embolization. Six hours after embolization, brains were harvested and examined for hemorrhage. Posttreatment areas of diffusion abnormality and perfusion delay were graded using both a semiquantitative scale and percent areas expressed as a ratio of the baseline values. Improved perfusion was seen among the rt-PA, and rPA-treated groups compared with placebo, using a semiquantitative scale (P<.01 rt-PA v controls, P<.05, rPA v controls). DWI scans, however, were not improved with thrombolysis. Cerebral hemorrhage was not increased with thrombolytic treatment, although the incidence of wound site hemorrhage was higher with either rPA or rt-PA. One fatal systemic hemorrhage was observed in each of the thrombolytic-treated groups. Cerebral perfusion was equally improved with either rt-PA or rPA without causing excess cerebral hemorrhage. An advantage of rPA is single-bolus dosing rather than continuous infusion. Use of rPA for stroke treatment should be further explored.

  View details for PubMedID 17895078

• Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute (< 6.5 hour) ischemic stroke NEUROLOGY Tong, D. C., Yenari, M. A., Albers, G. W., O'Brien, M., Marks, M. P., Moseley, M. E. 1998; 50 (4): 864-870

  Abstract

  Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI are powerful new techniques for the assessment of acute cerebral ischemia. However, quantitative data comparing the severity of clinical neurologic deficit with the results of DWI or PWI in the earliest phases of stroke are scarce. Such information is vital if MRI is potentially to be used as an objective adjunctive measure of stroke severity and outcome.The authors compared initial DWI and PWI lesion volumes with subsequent 24-hour neurologic deficit as determined by National Institutes of Health Stroke Scale (NIHSS) score in acute stroke patients. Initial DWI and PWI volumes were also compared with T2W MRI lesion volume at 1 week to assess the accuracy of these MRI techniques for the detection of acute cerebral ischemia.Patients with stroke underwent MRI scanning within 6.5 hours of symptom onset. Lesion volumes on DWI and PWI were measured and compared with 24-hour NIHSS score. Initial DWI and PWI volumes were also compared with T2W lesion size at 1 week.There was a high correlation between 24-hour NIHSS score and lesion volume as determined by PWI (r = 0.96, p < 0.001) or DWI (r = 0.67, p = 0.03). A similar high correlation was seen between T2W stroke size at 7 days and initial DWI and PWI lesion size (r = 0.99, p < 0.00001).Both DWI and PWI are highly correlated with severity of neurologic deficit by 24-hour NIHSS score. These findings may have substantial implications for the use of MRI scanning in the assessment and management of acute stroke patients.

  View details for Web of Science ID 000073187300010

  View details for PubMedID 9566364

• Rationale for early intervention in acute stroke. American journal of cardiology Albers, G. W. 1997; 80 (4C): 4D-10D

  Abstract

  Ischemic stroke occurs after an abrupt reduction in cerebral blood flow, usually related to thrombosis of an intracranial or extracranial artery. The presenting symptoms and signs of stroke vary greatly, depending on the region of the brain involved. Most individuals are unaware of the warning signs or symptoms of stroke and do not seek medical care immediately after stroke onset. Recently, thrombolytic therapy with intravenous tissue plasminogen activator (t-PA) has been shown to be effective for treatment of selected stroke patients if administered <3 hours after stroke onset. This therapy is now approved for stroke treatment, but relatively few stroke patients currently receive t-PA. Neuroprotective agents that improve the intrinsic ability of brain parenchyma to withstand ischemia are currently undergoing intensive clinical evaluation. Their development has been facilitated by significant scientific advances in the understanding of the pathophysiology of acute ischemic neuronal injury. Strategies aimed at interfering with these fundamental processes of ischemic neuronal injury have shown encouraging results in several preliminary clinical trials. However, these agents probably must also be administered within a few hours of stroke onset to be beneficial. Eventually, combined neuroprotective and thrombolytic therapy will likely be used for acute stroke treatment. This strategy's success will depend on increased public and professional education efforts dealing with stroke recognition, evaluation, and treatment.

  View details for PubMedID 9284038

• Etiology of stroke American-Heart-Association Prevention Conference IV: Prevention and Rehabilitation of Stroke Mohr, J. P., Albers, G. W., Amarenco, P., Babikian, V. L., Biller, J., Brey, R. L., Coull, B., Easton, J. D., Gomez, C. R., Helgason, C. M., Kase, C. S., Pullicino, P. M., Turpie, A. G. LIPPINCOTT WILLIAMS & WILKINS. 1997: 1501–6

  View details for Web of Science ID A1997XK48200040

• Clinical characteristics and management of acute stroke in patients with atrial fibrillation admitted to US university hospitals NEUROLOGY Albers, G. W., Bittar, N., Young, L., Hattemer, C. R., Gandhi, A. J., Kemp, S. M., Hall, E. A., Morton, D. J., Yim, J., Vlasses, P. H. 1997; 48 (6): 1598-1604

  Abstract

  The optimal evaluation and management of patients with atrial fibrillation who suffer an acute ischemic stroke remains controversial.Medical records of 171 consecutive patients with atrial fibrillation and acute stroke at six U.S. university hospitals were reviewed. Data collected included the use of antithrombotic therapy, brain and cardiac imaging, bleeding complications, stroke risk factors, and contraindications to anticoagulation.Mean age was 75.4 years. Cardiovascular risk factors associated with increased stroke risk were present in 87%; 35% had at least one contraindication to anticoagulation. Half of the patients with stroke risk factors and no contraindications to anticoagulation were not receiving any antithrombotic therapy at the time of admission. Of the 22 patients who were treated with warfarin, and had INR values on admission, 16 had levels of < 2.0; only six had INR values between 2.0 and 3.0. Transthoracic echocardiography was performed in 107 patients (63%); intracardiac thrombi were visualized in only 5%. Initial brain imaging revealed hemorrhagic transformation in nine. Heparin was used in 93 patients (54%), usually within 48 hours of stroke onset. Patients who received delayed heparin typically did not have repeat brain imaging prior to starting heparin. One patient had a delayed symptomatic cerebral hemorrhage. Of the survivors, 47% were discharged and treated with warfarin (or warfarin plus aspirin), 28% with ASA, 7% with other antithrombotic therapies, and 18% with no antithrombotic therapy.Antithrombotic therapy was underutilized and inadequately monitored in atrial fibrillation patients prior to stroke onset. After hospital admission, a wide range of diagnostic and management strategies, which often did not follow current recommendations, were employed.

  View details for Web of Science ID A1997XE09100023

  View details for PubMedID 9191773

• Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke ANNALS OF NEUROLOGY Lutsep, H. L., Albers, G. W., deCrespigny, A., Kamat, G. N., Marks, M. P., Moseley, M. E. 1997; 41 (5): 574-580

  Abstract

  Diffusion-weighted imaging (DWI) detects small changes in water diffusion that occur in ischemic brain. This study evaluated the clinical usefulness of a phase-navigated spin-echo DWI sequence compared with T2-weighted magnetic resonance imaging (T2W MRI) in patients with cerebral ischemia and assessed apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI) changes over time. ADC values and T2 ratios of image intensity were measured from the region of ischemia and from the corresponding contralateral brain region. The clinical histories of patients with DWI scans obtained over the course of 1 year were reviewed to ascertain whether DWI aided in clinical diagnosis or management. Of 103 scans obtained a mean of 10.4 days after symptom onset, DWI detected six lesions not seen on T2WI and discriminated two new infarcts from old lesions. DWI was most useful within 48 hours of the ictus. The evolution of ADC values and T2 ratios was evaluated in 26 cases with known symptom onset times. ADC values were low at less than 1 week after stroke onset and became elevated at chronic time points. T2 ratios were near normal acutely, increasing thereafter. DWI was superior to T2W MRI in detecting acute stroke, whereas both techniques assisted in determining lesion age.

  View details for Web of Science ID A1997WZ80900004

  View details for PubMedID 9153518

• Improved perfusion with rt-PA and hirulog in a rabbit model of embolic stroke JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Yenari, M. A., deCrespigny, A., Palmer, J. T., Roberts, S., Schrier, S. L., Albers, G. W., Moseley, M. E., Steinberg, G. K. 1997; 17 (4): 401-411

  Abstract

  We conducted a study using diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic resonance imaging (MRI) to evaluate the efficacy of thrombolysis in an embolic stroke model with recombinant tissue plasminogen activator (rt-PA) and hirulog, a novel direct-acting antithrombin. DWI can identify areas of ischemia minutes from stroke onset, while PWI identifies regions of impaired blood flow. Right internal carotid arteries of 36 rabbits were embolized using aged heterologous thrombi. Baseline DWI and PWI scans were obtained to confirm successful embolization. Four animals with no observable DWI lesion on the initial scan were excluded; therefore, a total of 32 animals were randomized to one of three treatment groups: rt-PA (n = 11), rt-PA plus hirulog (n = 11), or placebo (n = 10). Treatment was begun 1 h after stroke induction. Intravenous doses were as follows: rt-PA, 5 mg/kg over 0.5 h with 20% of the total dose given as a bolus; hirulog, 1 mg/kg bolus followed by 5 mg/kg over 1 h. MRI was performed at 2, 3, and 5 h following embolization. Six hours after embolization, brains were harvested, examined for hemorrhage, then prepared for histologic analysis. The rt-PA decreased fibrinogen levels by 73%, and hirulog prolonged the aPTT to four times the control value. Posttreatment areas of diffusion abnormality and perfusion delay were expressed as a ratio of baseline values. Significantly improved perfusion was seen in the rt-PA plus hirulog group compared with placebo (normalized ratios of the perfusion delay areas were as follows: placebo, 1.58, 0.47-3.59; rt-PA, 1.12, 0.04-3.95; rt-PA and hirulog, 0.40, 0.02-1.08; p < 0.05). Comparison of diffusion abnormality ratios measured at 5 h showed trends favoring reduced lesion size in both groups given rt-PA (normalized ratios of diffusion abnormality areas were as follows: placebo, 3.69, 0.39-15.71; rt-PA, 2.57, 0.74-5.00; rt-PA and hirulog, 1.95, 0.33-6.80; p = 0.32). Significant cerebral hemorrhage was observed in one placebo, two rt-PA, and three rt-PA plus hirulog treated animals. One fatal systemic hemorrhage was observed in each of the rt-PA groups. We conclude that rt-PA plus hirulog improves cerebral perfusion but does not necessarily reduce cerebral injury. DWI and PWI are useful methods for monitoring thrombolysis.

  View details for Web of Science ID A1997WW73800005

  View details for PubMedID 9143222

• Management of acute ischemic stroke - An update for primary care physicians WESTERN JOURNAL OF MEDICINE Albers, G. W. 1997; 166 (4): 253-262

  Abstract

  Few areas of medicine have had as many major advances in recent years as the treatment and prevention of ischemic stroke. During the 1990s-"the decade of the brain"-carotid endarterectomy was demonstrated to be effective for preventing stroke in patients with significant carotid stenosis. Large clinical studies have documented the effectiveness of new antiplatelet agents and oral anticoagulant therapy for stroke prevention in specific patients groups, and recently tissue plasminogen activator was approved for the treatment of acute ischemic stroke. Because the use of these new therapies is restricted to specific patient subgroups, the accurate determination of the cause of stroke is now mandatory. Fortunately, advances in diagnostic methods, including cardiac and vascular ultrasonographic techniques and brain imaging, facilitate the determination of the stroke subtype in most patients. Additional advances in stroke treatment and prevention are on the immediate horizon. New therapeutic agents, including neuroprotective medications, and new treatment modalities such as cerebral angioplasty are promising investigational therapies.

  View details for Web of Science ID A1997WZ70200003

  View details for PubMedID 9168683

• The feasibility of a collaborative double-blind study using an anticoagulant CEREBROVASCULAR DISEASES Mohr, J. P., Sacco, R. L., FLEISS, J., Lazar, R. M., Thompson, J. L., Gohs, D., Lynn, L., Burroughs, D., Caputo, A., Coleman, M., Costigan, T., Fields, B., Kann, G., Kim, J. S., King, R., Ma, W., Ruzicka, J. L., Slane, K., Zidel, A., Tilley, B. C., Sciacca, R., Rosner, B., Wende, K., Levin, B., Adams, H. P., Alter, M., Kistler, J. P., Pettigrew, L. C., Pullicino, P., Brey, R. L., Feldmann, E., Kittner, S. J., Babikian, V., Homma, S. H., DiTullio, M., Greenberg, S., Trevisan, M., Fisher, C. M., Barnett, H. J., Wisnant, J. P., Gautier, J. C., Sandercock, P., Karanjia, P., Buonanno, F. S., Albers, G., Nichols, F., Grotta, J., Helgason, C., RAMIREZLASSEPAS, M., Tuhrim, S., Pessin, M., Culebras, A., Sila, C., Chimowitz, M., Weinreb, H., Brass, L., Warach, S., Kase, C., Hamill, R., Rosenbaum, D., Hollander, J., Johnson, C., Gaines, K., Yaseen, M., Mitsias, P., Libman, R., Nafziger, A., Forteza, A., Miller, A., Biller, J., Kirschner, H., Haley, E., Binder, J., Zalewski, M., Jamieson, D., Anderson, D., Dandapani, B., Lennihan, L., Winkelman, M., Hughes, R., Jackson, C., Boop, B., Chaturvedi, S., Rothrock, J., FREY, A. Z., Dyken, M. L., Lowe, A., Marler, J. R., Meissner, I., Sherman, D. G., Taylor, D. W., Walker, M. D. 1997; 7 (2): 100-112

  View details for Web of Science ID A1997WP25900009

• Use of fluid attenuating inversion recovery, MR angiogram, and diffusion-weighted MRI techniques for assessment of pontine infarction in a patient treated with radiation therapy for pituitary neoplasm NEUROLOGY Graef, L. M., Lutsep, H. L., Norbash, A., Albers, G. W. 1997; 48 (2): 540-542

  View details for Web of Science ID A1997WH53500050

  View details for PubMedID 9040759

• Termination of acute stroke studies involving selfotel treatment LANCET Davis, S. M., Albers, G. W., Diener, H. C., Lees, K. R., Norris, J. 1997; 349 (9044): 32-32

  View details for Web of Science ID A1997WA72500023

  View details for PubMedID 8999265

• Intravenous thrombolytic therapy in acute stroke. Vascular medicine Tong, D. C., Yenari, M. A., Albers, G. W. 1997; 2 (1): 51-60

  Abstract

  The article reviews the experimental basis of thrombolytic therapy, and summarizes the results of the recent trials of thrombolysis. Five large clinical trails have evaluated intravenous thrombolytic therapy for the treatment of hyperacute (< 6 h) stroke. Three of these studies were negative, one was equivocal, and one was strongly positive. The failure of demonstrate efficacy definitively in four of these trials may be related to a number of methodological factors, including the type and dose of drug administered, the timing of drug administered, and the method of patient selection for treatment. The NINDS recombinant tissue plasminogen activator (rt-PA) study showed that thrombolytic therapy can be of substantial benefit when administered within 3 h of stroke onset using strict patient selection criteria and rt-PA is now FDA approved for treatment of acute stroke. However, the risk of clinically significant bleeding is elevated. To achieve the favorable risk/benefit ratio demonstrated in the NINDS trial, patients must be screened by experienced clinicians for contraindications to thrombolysis and the acute computerized tomography (CT) brain scan must be carefully evaluated for radiographic features that increase the risk of cerebral hemorrhage. Guidelines for the use of rt-PA are provided, as well as insights into future thrombolytic treatment strategies.

  View details for PubMedID 9546949

• Dose escalation study of the NMDA glycine-site antagonist ACEA 1021 in acute ischemic stroke Albers, G. W., Clark, W. M., Atkinson, R. P., Madden, K., Barbut, D., LECHTENBERG, R., Whitehouse, M. J. LIPPINCOTT WILLIAMS & WILKINS. 1997: 8–8

  View details for Web of Science ID A1997WB81400059

• Anticoagulant therapy monitoring with international normalized ratio at us academic health centers ANNALS OF PHARMACOTHERAPY YIM, J. M., Albers, G. W., Vlasses, P. H. 1996; 30 (12): 1390-1395

  Abstract

  To assess the extent of incorporation of international normalized ratio (INR) reporting in US academic hospitals.Survey of academic hospital clinical laboratories in January 1995.Fifty-eight academic hospital clinical laboratories at institutions that are members of the University Health System Consortium.The methods for monitoring oral anticoagulant therapy at the surveyed laboratories were determined. The extent of reporting of prothrombin time (PT), PT ratio, INR, and INR therapeutic range was determined.All 58 of the responding hospital clinical laboratories reported INR in patients receiving oral anticoagulation. The median length of time that hospitals had been reporting INR was 24 months (range 3-108). A majority of hospitals continued to report PT values (95%) and PT reference ranges (93%) in addition to INR. Therapeutic INR ranges were reported by only 25 of the laboratories (43%). Of those that report INR ranges, many follow the published recommendations by the American College of Chest Physicians and the Food and Drug Administration. A majority of the hospitals (79%) do not confirm the accuracy of the international sensitivity index (ISI) for their own analyzers.Contrary to previous reports, academic hospital clinical laboratories have now adopted the more accurate system of reporting INR values in addition to PT values in patients receiving oral anticoagulation. However, better reporting of INR ranges, use of more sensitive thromboplastins, and confirmation of the accuracy of the ISI for local analyses would further improve the monitoring of oral anticoagulation.

  View details for Web of Science ID A1996VX90400005

  View details for PubMedID 8968449

• Status of antithrombotic therapy for patients with atrial fibrillation in university hospitals ARCHIVES OF INTERNAL MEDICINE Albers, G. W., YIM, J. M., Belew, K. M., Bittar, N., Hattemer, C. R., Phillips, B. G., Kemp, S., Hall, E. A., Morton, D. J., Vlasses, P. H. 1996; 156 (20): 2311-2316

  Abstract

  The risk of stroke in patients with atrial fibrillation can be significantly reduced with antithrombotic therapy. Despite this, many physicians remain hesitant to prescribe warfarin sodium or aspirin therapy for patients with atrial fibrillation.To assess the use of antithrombotic therapy in patients with atrial fibrillation at 6 academic hospitals in the United States.Records were reviewed from consecutive hospital admissions of 309 patients with atrial fibrillation at 6 members of the University Health System Consortium, Oak Brook, III, which is a member driven alliance of 70 academic health centers in the United States. Risk factors for stroke, contraindications to anticoagulant therapy, and use of antithrombotic therapy at admission and discharge were recorded.The mean age of patients was 71.6 years, 54% had chronic, 22% paroxysmal, and 24% new-onset atrial fibrillation. Eighty-two percent of the patients had cardiovascular risk factors that have been associated with increased risk of stroke. At least 1 relative contraindication to anticoagulant therapy was present in 44%. At the time of admission. 32% of the patients with previously diagnosed atrial fibrillation (n = 235) were receiving warfarin (or warfarin plus aspirin), 31% were receiving aspirin alone, and 36% were receiving no antithrombotic therapy. At discharge (n = 230), 41% of these patients were taking warfarin (or warfarin plus aspirin) and 36% were taking aspirin. Forty-four percent of the patients with risk factors for stroke and no contraindications to anticoagulation (n = 134) were discharged on a regimen of warfarin (or warfarin plus aspirin), 34% were discharged on a regimen of aspirin, and 22% received no antithrombotic therapy.About half of the patients with atrial fibrillation admitted to these academic hospitals had clinical risk factors that are associated with increased risk of stroke and no contraindications to anticoagulation. Antithrombotic therapy was underused in these patients.

  View details for Web of Science ID A1996VR60300004

  View details for PubMedID 8911237

• Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke prevention in atrial fibrillation III randomised clinical trial LANCET Blackshear, J. L., Baker, V. S., Rubino, F., Safford, R., Lane, G., Flipse, T., Malouf, J., Thompson, R., Webel, R., Flaker, G. C., Young, L., Hess, D., Friedman, G., Burger, R., McAnulty, J. H., Coull, B. M., Marchant, C., Timberg, J., Janzik, C., Giraud, G., Halperin, B., Kron, J., Wynn, M., Raitt, M., Anderson, D. C., Asinger, R. W., Newburg, S. M., Fifield, J., Bundlie, S. R., Koller, R. L., Tarrel, R. D., Dick, C., Haugland, J. M., Jorgensen, C. R., Leonard, A. D., KANTER, M. C., Solomon, D. H., Zabalgoitia, M., Mego, D., Carter, J. E., Boyd, S. Y., Boop, B. S., Lalonde, D., Modlin, R., LOGAN, W. R., Green, B. J., Hamilton, W. P., Mezei, L., RIGGIO, S., Feldman, G., Hayward, A., Strauss, R., ANDERSON, W., Grover, J., McKenzie, M., HartMcArthur, P., Gramberg, M., Houston, H., Halperin, J. L., Rothauf, E. B., Weinberger, J. M., Goldman, M. E., Laupacis, A., Chan, K. L., Bourque, P., Biggs, J., Ives, A., Feinberg, W. M., Kern, K. B., Pennock, G. D., Fenster, P. E., Huerta, B. J., Ohm, J., Dittrich, H. C., Kerridge, C., Keen, W., Swenson, M., Kopecky, S. L., Litin, S. C., Wiebers, D. O., Holland, A. E., Brown, R. D., Khandheria, B. K., Meissner, I., Tucker, K. R., Rothbart, R., Torelli, J., Schmidt, J., Murray, D., RUZICH, R. S., Loutfi, H., Appleton, C., Ingall, T., Carlson, L., Wilson, D., Dunn, M., Nolte, B., Edwards, C., Dick, A., Price, L. A., Janosik, D. L., Bjerregaard, P., Quattromani, A., Schiller, L., Labovitz, A., Burch, C., Parks, B. J., Thompson, D., BERARDUCCI, L., Carey, S., Vigil, A., Falk, R., Battinelli, N., McNeil, M., Davidoff, R., Bernard, S., Bergethon, P., Fiori, L., Albers, G., Atwood, E., Clark, J., Tong, D., Yenari, M., Froelicker, V., Lutsep, H., Hock, N. H., Quaglietti, S., Kemp, S., Alpert, M. A., Rothrock, J. F., Hupp, C. H., Massey, C. V., Hamilton, W. J., Miller, V. T., Fox, J. 1996; 348 (9028): 633-638

  Abstract

  Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism.1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening < or = 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrollment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled.The mean INR during follow-up of patients taking combination therapy (n = 521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n = 523). During follow-up, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean, follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p < 0.0001), an absolute reduction of 6.0% per year (95% Cl 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p = 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p = 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups.Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.

  View details for Web of Science ID A1996VF60900007

  View details for PubMedID 8782752

• Acute and chronic stroke: Navigated spin-echo diffusion-weighted MR imaging RADIOLOGY Marks, M. P., deCrespigny, A., Lentz, D., Enzmann, D. R., Albers, G. W., Moseley, M. E. 1996; 199 (2): 403-408

  Abstract

  The authors evaluated a phase-navigated spin-echo (SE) motion-correction sequence for use at diffusion-weighted (DW) magnetic resonance (MR) imaging after cerebral infarction.Twenty-nine patients underwent 32 conventional T2-weighted fast SE and SE DW imaging after stroke (n=25), transient ischemic attack (n=3), or reversible ischemic neurologic deficit (n=1). Imaging was performed in a standard head holder with standard padding. Apparent diffusion coefficient (ADC) maps were constructed.DW images depicted high signal intensity compatible with localization of the ischemic symptoms in all cases. Lesions were depicted more clearly on DW than on T2-weighted images. On DW images, acute infarct ADC values were uniformly low (mean, 0.401x10(-5) cm2/sec =+/- 0.143 [standard deviation]) compared with control ADC values (mean, 0.754x10(-5) cm2/sec +/- 0.201). ADC values of chronic infarcts were supranormal (mean, 1.591x10(-5) cm2/sec +/- 0.840) compared with control values (mean, 0.788x10(-5) cm2/sec +/- 0.166). DW imaging did not show a change after transient ischemic attack. with reversible ischemic neurologic deficit, however, hyperintensity on DW images and low ADC resolved after symptoms abated.Clinical phase-navigated SE DW imaging improved early diagnosis of stroke and helped differentiate acute from chronic stroke. Changes on DW images are reversed after symptoms resolve.

  View details for PubMedID 8668785

• MR and cerebrospinal fluid enzymes as sensitive indicators of subclinical cerebral injury after open-heart valve replacement surgery AMERICAN JOURNAL OF NEURORADIOLOGY Steinberg, G. K., Delapaz, R., Mitchell, R. S., Bell, T. E., Albers, G. W. 1996; 17 (2): 205-212

  Abstract

  To evaluate MR imaging and lumbar cerebrospinal fluid enzymes as potential sensitive indicators of cerebral injury after open-heart valve replacement surgery.Thirty-four patients with cardiac valvular disease were prospectively entered into this study and then underwent valve replacement or repair under cardiopulmonary bypass using a membrane oxygenator. In 26 patients, MR head images were obtained 12 to 24 hours before surgery; repeat MR images were obtained between 1 and 2 weeks after surgery. In 18 patients, lumbar puncture cerebrospinal fluid was analyzed 24 to 48 hours after surgery; the analyses included measurement of lactic dehydrogenase, creatine phosphokinase, adenylate kinase, and neuron-specific enolase.After surgery, MR imaging showed new ischemic lesions in 15 (58%) of 26 patients: 7 with deep white matter hyperintense lesions; 5 with brain stem, caudate, cerebellar, or thalamic/basal ganglia infarcts; 1 with intraparenchymal hemorrhage; 1 with a subdural hematoma and cortical infarct; and 1 with a corpus callosum lesion consistent with calcium or air. These new ischemic lesions seen on MR images were associated with a focal neurologic deficit in only 4 (27%) of the 15 patients. Neuron-specific enolase and lactic dehydrogenase were abnormally elevated after surgery in 5 (28%) of 18 patients. Adenylate kinase and creatine phosphokinase (brain isozymes) were elevated in one (67%) of the patients. Two (40%) of the five patients with abnormally high neuron-specific enolase or lactic dehydrogenase after surgery also showed a new focal neurologic deficit.MR imaging is a sensitive measure of subclinical cerebral ischemia after cardiac valve replacement under cardiopulmonary bypass. Cerebrospinal fluid neuron-specific enolase and lactic dehydrogenase are less sensitive than MR imaging for detecting subclinical cerebral ischemia, but these values were elevated after surgery more frequently than was adenylate kinase in our patients.

  View details for Web of Science ID A1996TW23400001

  View details for PubMedID 8938287

• Safety of heparin in acute ischemic stroke NEUROLOGY Hart, R. G., Boop, B. S., Tong, D. C., Yenari, M. A., Albers, G. W. 1996; 46 (2): 589-589

  View details for Web of Science ID A1996TZ71200067

  View details for PubMedID 8614549

• MELAS: Clinical and pathologic correlations with MRI, xenon/CT, and MR spectroscopy NEUROLOGY Clark, J. M., Marks, M. P., Adalsteinsson, E., Spielman, D. M., Shuster, D., Horoupian, D., Albers, G. W. 1996; 46 (1): 223-227

  Abstract

  We describe the clinical, imaging, and pathologic findings in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient experienced her first stroke-like episode at age forty-four. Brain MRI, obtained at symptom onset, at 3 weeks, and at 1 year, revealed migrating T2-weighted hyperintensities in the temporal/parietal and occipital cortices and later revealed atrophy. Abnormal cerebrovascular reserve was evident on xenon/CT four days after the first MRI. MR spectroscopy at 1 year revealed increased lactate in both the occipital and temporal lobes. Histologic sections demonstrated spongy degeneration of the cortex that was most prominent at the crests of the gyri. Electron microscopy of the blood vessels showed increased numbers of abnormal mitochondria within the vascular smooth muscle and in endothelial cells. We hypothesize that the stroke-like episodes in MELAS may be due to impaired autoregulation secondary to the impaired metabolic activity of mitochondria in the endothelial and smooth muscle cells of blood vessels.

  View details for Web of Science ID A1996TR67100045

  View details for PubMedID 8559380

• COST-EFFECTIVENESS OF WARFARIN AND ASPIRIN FOR PROPHYLAXIS OF STROKE IN PATIENTS WITH NONVALVULAR ATRIAL-FIBRILLATION JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Gage, B. F., Cardinalli, A. B., Albers, G. W., Owens, D. K. 1995; 274 (23): 1839-1845

  Abstract

  To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation (NVAF) with or without additional stroke risk factors (a prior stroke or transient ischemic attack, diabetes, hypertension, or heart disease).Decision and cost-effectiveness analyses. The probabilities for stroke, hemorrhage, and death were obtained from published randomized controlled trials. The quality-of-life estimates were obtained by interviewing 74 patients with atrial fibrillation. Costs were estimated from literature review, phone survey, and Medicare reimbursement.In the base case, the patients were 65 years of age and good candidates for warfarin therapy.Treatment with warfarin, aspirin, or no therapy in the decision analytic model.Quality-adjusted survival and marginal cost-effectiveness of warfarin as compared with aspirin or no therapy.For patients with NVAF and additional risk factors for stroke, warfarin therapy led to a greater quality-adjusted survival and to cost savings. For patients with NVAF and one additional risk factor, warfarin therapy cost $8000 per quality-adjusted life-year saved. For 65-year-old patients with NVAF alone, warfarin cost about $370,000 per quality-adjusted life-year saved, as compared with aspirin therapy. However, for 75-year-old patients with NVAF alone, prescribing warfarin cost $110,000 per quality-adjusted life-year saved. For patients who were not prescribed warfarin, aspirin was preferred to no therapy on the basis of both quality-adjusted survival and cost in all patients, regardless of the number of risk factors present.Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke. In 65-year-old patients with NVAF but no other risk factors for stroke, prescribing warfarin instead of aspirin would affect quality-adjusted survival minimally but increase costs significantly.

  View details for Web of Science ID A1995TK14700024

  View details for PubMedID 7500532

• Antithrombotic therapy in atrial fibrillation. Chest Laupacis, A., Albers, G., Dalen, J., Dunn, M., Feinberg, W., Jacobson, A. 1995; 108 (4): 352S-359S

  View details for PubMedID 7555188

• ANTITHROMBOTIC THERAPY IN ATRIAL-FIBRILLATION 4th American-College-of-Chest-Physicians Consensus Conference on Antithrombotic Therapy Laupacis, A., Albers, G., Dalen, J., Dunn, M., Feinberg, W., Jacobson, A. AMER COLL CHEST PHYSICIANS. 1995: S352–S359

  View details for Web of Science ID A1995TC04800012

• TRANSCRANIAL DOPPLER-DETECTED MICROEMBOLI IN PATIENTS WITH ACUTE STROKE STROKE Tong, D. C., Albers, G. W. 1995; 26 (9): 1588-1592

  Abstract

  Transcranial Doppler sonography (TCD) has been used to detect microembolic signals in a variety of clinical situations. We studied the prevalence of TCD-detected microemboli in 38 acute stroke patients.Consecutive patients with acute anterior circulation stroke were stratified into high-risk (group 1), medium-risk (group 2), and low-risk (group 3) groups based on their risk factors for cerebral embolism.Microemboli were detected in 11% of patients. They were present in 17% of group 1, 10% of group 2, and 0% of group 3 patients. Emboli were present in patients with mechanical prosthetic valves, carotid stenosis (> 70%), and mitral valve strands with a patent foramen ovale. Patients with microemboli more frequently had a history of cerebral ischemia compared with patients without microemboli (P < .05). They also more frequently had recent (< 3 months) symptoms compared with patients without microemboli (P < .05). In patients with a cardiac source of embolization, the number of microemboli detected was directly proportional to the acuity of previous symptoms.These data suggest that TCD-detected microemboli are associated with an increased prevalence of prior cerebrovascular ischemia. The presence of TCD-detected microemboli could be a risk factor for cerebrovascular ischemia.

  View details for Web of Science ID A1995RR82600014

  View details for PubMedID 7660403

• VERTICAL GAZE PALSIES FROM MEDIAL THALAMIC INFARCTIONS WITHOUT MIDBRAIN INVOLVEMENT STROKE Clark, J. M., Albers, G. W. 1995; 26 (8): 1467-1470

  Abstract

  Although the supranuclear pathways for vertical gaze control are not well defined, lesions of the mesencephalic reticular formation including the nucleus of Darkschewitsch, the rostral interstitial medial longitudinal fasciculus, the interstitial nucleus of Cajal, and the posterior commissure are known to produce vertical gaze palsies. MRI studies have not previously reported isolated thalamic lesions as the cause of vertical gaze palsies.Three patients with acute paralysis of vertical gaze were imaged with MRI. Sagittal T1 and axial T1, T2, and proton-weighted images were obtained. All three patients had repeated scans performed from 3 days to 6 weeks after the original study. Two patients exhibited unilateral right thalamic infarcts (polar and paramedial territory), and one patient had a bilateral paramedian thalamic infarction. There was no evidence of midbrain involvement on any of the images.Vertical gaze palsies are known to be produced by lesions of the rostral interstitial medial longitudinal fasciculus. This MRI study reveals thalamic infarctions without associated midbrain infarctions in three patients with vertical gaze palsies. This may be explained by interruption of supranuclear inputs.

  View details for Web of Science ID A1995RM16400036

  View details for PubMedID 7631355

• DETECTION OF CAROTID STENOSIS - FROM NASCET RESULTS TO CLINICAL-PRACTICE STROKE Chang, Y. J., Golby, A. J., Albers, G. W. 1995; 26 (8): 1325-1328

  Abstract

  Results from large multicenter studies have shown that carotid endarterectomy, performed with low perioperative morbidity and mortality, is beneficial for patients with symptomatic carotid stenosis > or = 70% as calculated according to strict angiographic criteria. To apply these results in clinical practice, individual institutions should determine whether locally implemented duplex ultrasonography adequately identifies patients with > or = 70% stenosis and whether the degree of stenosis reported by local angiographers correlates with strict angiographic measurements.We compared estimates of carotid stenosis obtained by duplex ultrasonography and the radiologists' reports from conventional cerebral angiography with each other and with results obtained using North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.One hundred seventy-one vessels were available for review. In 155 (91%) of the cases, the reports from the ultrasound and angiogram were in agreement with regard to whether the stenosis was > or = 70% or < 70%. In 11 of the 16 cases where there was a disparity between the studies, the ultrasound was in closer agreement with measurements obtained using NASCET criteria. Nine of the angiography reports overestimated the degree of stenosis compared with NASCET measurements; twice angiography underestimated the stenosis. Twice the ultrasound underestimated the stenosis, and three times it overestimated the stenosis.Duplex ultrasonography was highly sensitive for detecting significant carotid stenosis at our institution; however, angiography reports often graded the degree of stenosis to be more severe than measurements obtained using NASCET criteria. Institutions that evaluate patients for carotid endarterectomy should investigate the correlation between their ultrasound and angiographic studies so that the results of carotid endarterectomy trials can be accurately applied.

  View details for Web of Science ID A1995RM16400002

  View details for PubMedID 7631330

• NEUROLOGIC COMPLICATIONS FOLLOWING CHIROPRACTIC MANIPULATION - A SURVEY OF CALIFORNIA NEUROLOGISTS NEUROLOGY Lee, K. P., CARLINI, W. G., MCCORMICK, G. F., Albers, G. W. 1995; 45 (6): 1213-1215

  Abstract

  To obtain an estimate of how often practicing neurologists in California encounter unexpected strokes, myelopathies, or radiculopathies following chiropractic manipulation, we surveyed each member of the American Academy of Neurology in California and inquired about the number of patients evaluated over the preceding 2 years who suffered a neurologic complication within 24 hours of chiropractic manipulation. Four hundred eighty-six neurologists were surveyed, 177 responded; 55 strokes, 16 myelopathies, and 30 radiculopathies were reported. Patients were between the ages of 21 and 60, and the majority experienced complications following cervical manipulation. Most of the patients continued to have persistent neurologic deficits 3 months after the onset, and about one-half had marked or severe deficits. Nearly all of the strokes involved the posterior circulation and almost one-half were angiographically proven. Patients, physicians, and chiropractors should be aware of the risk of neurologic complications associated with chiropractic manipulation.

  View details for Web of Science ID A1995RC99300032

  View details for PubMedID 7783892

• Antithrombotic agents in cerebral ischemia. American journal of cardiology Albers, G. W. 1995; 75 (6): 34B-38B

  Abstract

  The choice of antithrombotic agent in cerebral ischemia depends on the pathogenesis: thrombosis, embolism, or hemorrhage. Antiplatelet agents are considered most beneficial in thrombotic stroke, anticoagulants are most effective in cardioembolic stroke; antithrombotic agents are generally contraindicated in hemorrhagic stroke. A meta-analysis of 18 trials documented a 23% reduction in stroke risk with antiplatelet agents; aspirin is typically the antiplatelet agent of choice for stroke prevention. There are no definitive data regarding the optimal aspirin dose for stroke prevention and this issue remains controversial. Ticlopidine is the most effective antiplatelet agent, but its adverse effect profile restricts its use. Anticoagulants are highly effective for preventing cardioembolic stroke, but their effectiveness in non-cardioembolic stroke is uncertain because of lack of trial data. Results of the ongoing Warfarin/Aspirin Recurrent Stroke Study (warfarin [INR 1.8-2.8] vs aspirin [325 mg/day]) may clarify this issue. There is renewed interest in thrombolytics because recent data indicate that reperfusion within a few hours of stroke onset appears to be effective in preventing neuronal damage. In addition, when given within 6 hours of stroke onset, thrombolytics appear to be relatively safe. Several direct thrombin inhibitors are being evaluated. Experimentally, hirudin, hirulog, D-Phe-L-Pro-L-Arg-CH2Cl (PPACK), and argatroban are clearly more effective than heparin in inhibiting platelet deposition and thrombus formation, and also show promise in preventing reocclusion after thrombolysis for both experimental thrombotic and embolic stroke. However, the risk of hemorrhage in patients with cerebrovascular disease is unknown for these agents.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 7863971

• SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF THE N-METHYL-D-ASPARTATE ANTAGONIST DEXTRORPHAN IN PATIENTS WITH ACUTE STROKE STROKE Albers, G. W., Atkinson, R. P., Kelley, R. E., Rosenbaum, D. M. 1995; 26 (2): 254-258

  Abstract

  Dextrorphan hydrochloride is a noncompetitive N-methyl-D-aspartate antagonist that is neuroprotective in experimental models of focal brain ischemia. The purpose of this study was to determine the maximum loading dose and maintenance infusion of dextrorphan hydrochloride that are well tolerated in patients with an acute stroke.An intravenous infusion of dextrorphan or placebo was begun within 48 hours of onset of a mild-to-moderate hemispheric stroke. Initially, patients were treated with either placebo (n = 15) or dextrorphan (n = 22) using a 1-hour loading dose (60 to 150 mg) followed by a 23-hour ascending-dose maintenance infusion (maximum total dose, 3310 mg). Subsequently, 29 patients were treated with dextrorphan in an open trial using a 1-hour loading dose (145 to 260 mg) followed by an 11-hour constant rate (30 to 70 mg/h) infusion.Transient and reversible adverse effects, including nystagmus, nausea, vomiting, somnolence, hallucinations, and agitation, commonly occurred in dextrorphan-treated patients. Loading-dose escalation was stopped because of rapid-onset, reversible, symptomatic hypotension in 7 of 21 patients treated with doses of 200 to 260 mg/h. At the highest rates of maintenance infusion (> 90 mg/h), 3 patients developed deep stupor or apnea. The maximum tolerated loading dose was 180 mg/h, and the maximum tolerated maintenance infusion was 70 mg/h. Maximum plasma levels of 750 to 1000 ng/mL were obtained in 9 patients. There was no difference in neurological outcome at 48 hours between the dextrorphan-treated and placebo-treated patients.The highest doses of dextrorphan administered were associated with serious adverse experiences in some patients. Lower doses (loading doses of 145 to 180 mg, maintenance infusions of 50 to 70 mg/h) were better tolerated and rapidly produced potentially neuroprotective plasma concentrations of dextrorphan. These doses were associated with well-defined pharmacological effects compatible with N-methyl-D-aspartate receptor antagonism.

  View details for Web of Science ID A1995QE11000011

  View details for PubMedID 7831698

• ANTICOAGULATION/PLATELET INHIBITION FOR ATRIAL-FIBRILLATION CORONARY ARTERY DISEASE Albers, G. W., Hirsh, J. 1995; 6 (2): 129-135

  View details for Web of Science ID A1995QR28600007

  View details for PubMedID 7780618

• Safety, tolerability and pharmacokinetics of the N-methyl-D-aspartate antagonist Ro-01-6794/706 in patients with acute ischemic stroke 2nd International Conference on Neuroprotective Agents - Clinical and Experimental Aspects Albers, G. W., Atkinson, R., Kelley, R. E., Rosenbaum, D. M., Katz, P., Lesko, L. M., Paul, K., Rae, J., Modi, M., Yoo, K., Pitman, V., Lehr, L., Magni, G. NEW YORK ACAD SCIENCES. 1995: 249–261

  View details for Web of Science ID A1995BE39D00021

• Low yield of clinically significant transesophageal echocardiographic findings in patients with lacunar stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Golby, A. J., Bracci, P. M., Comess, K. A., DeRook, F. A., Albers, G. W. 1995; 5 (1): 39-43

  Abstract

  Transesophageal echocardiography (TEE) is a sensitive technique for the detection of cardioembolic sources of stroke in patients with cryptogenic stroke. However, the yield of clinically significant TEE-detected abnormalities in other stroke subtypes such as lacunar stroke is unknown. We prospectively followed 145 consecutive stroke patients, including 26 patients with typical lacunar syndromes, to determine the relative risk of recurrent brain ischemia associated with TEE findings. The yield of TEE in patients with lacunar stroke syndromes was extremely low, except for a very high rate of atrial septal aneurysm (ASA). Although ASA was associated with a high risk of recurrent stroke or transient ischemic attack in patients with nonlacunar stroke, ASA was not associated with stroke recurrence in patients with lacunar stroke (p = 0.02, Cox's proportional hazard regression model). We conclude that TEE is unlikely to provide clinically relevant information in patients with typical lacunar syndromes.

  View details for DOI 10.1016/S1052-3057(10)80085-0

  View details for PubMedID 26486557

• INCIDENCE OF TRANSCRANIAL DOPPLER-DETECTED CEREBRAL MICROEMBOLI IN PATIENTS REFERRED FOR ECHOCARDIOGRAPHY STROKE Tong, D. C., Bolger, A., Albers, G. W. 1994; 25 (11): 2138-2141

  Abstract

  Transcranial Doppler can detect cerebral microemboli. These emboli may be a risk factor for embolic stroke. We studied the prevalence of microemboli in patients referred for echocardiography.Forty-two patients were evaluated. Patients were studied with continuous monitoring over one middle cerebral artery for 30 minutes, and the number of microemboli was recorded. Patients were divided into three groups, those with prosthetic heart valves (group A, n = 15), atrial fibrillation (group B, n = 14), and no major cardiac risk factor (group C, n = 14).Seventeen percent (7 of 42) of all patients had microemboli. In group A, 5 of 15 (33%) had microemboli. In group B, 2 of 13 (15%) patients had microemboli. Twenty-five percent (7 of 28) of patients in groups A and B combined (A+B) had microemboli. No patients (0 of 14) in group C had microemboli. Groups A and A+B had significantly more emboli than group C (P < .05). Prosthetic heart valve patients with emboli more commonly had a history of prior stroke than valve patients without emboli (3 of 5 versus 2 of 10). The number of emboli seen per 30-minute monitoring session was greater in patients with a prior history of stroke than in patients without (10 microemboli versus 3).Microemboli can be found in a significant percentage of selected patients referred for echocardiography. The prevalence of microembolism is greater in patients with a known high risk of embolization (eg, prosthetic valves) and less in patients with a lower risk of embolization (eg, atrial fibrillation). These microemboli may be associated with an increased prevalence of previous stroke in patients with prosthetic valves.

  View details for Web of Science ID A1994PN94200005

  View details for PubMedID 7974534

• ATRIAL-FIBRILLATION AND STROKE - 3 NEW STUDIES, 3 REMAINING QUESTIONS ARCHIVES OF INTERNAL MEDICINE Albers, G. W. 1994; 154 (13): 1443-1448

  Abstract

  Three new studies help clarify important clinical issues regarding antithrombotic therapy for stroke prevention in patients with atrial fibrillation. The European Atrial Fibrillation Trial compared the efficacy of oral anticoagulation, aspirin, and placebo for stroke prevention in patients with atrial fibrillation with a recent stroke or transient ischemic attack. The results of the Stroke Prevention in Atrial Fibrillation II trial, which compared the efficacy of warfarin and aspirin, provide new information regarding the risk of intracranial hemorrhage in elderly patients with atrial fibrillation. Finally, an analysis of pooled data from the first five randomized trials identified clinical features that are predictive of stroke risk in individual patients with atrial fibrillation. These studies address unanswered questions regarding atrial fibrillation and stroke and have significant implications for patient management.

  View details for Web of Science ID A1994NW09000004

  View details for PubMedID 8017999

• TRANSESOPHAGEAL ECHOCARDIOGRAPHY AND CAROTID ULTRASOUND IN PATIENTS WITH CEREBRAL-ISCHEMIA - PREVALENCE OF FINDINGS AND RECURRENT STROKE RISK JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Comess, K. A., DeRook, F. A., Beach, K. W., LYTLE, N. J., Golby, A. J., Albers, G. W. 1994; 23 (7): 1598-1603

  Abstract

  This study was conducted to determine the yield of transesophageal echocardiographic findings in a consecutive series of patients with stroke and transient ischemic attack, with and without carotid stenosis, and to estimate the recurrent stroke risk associated with specific echocardiographic findings.Transesophageal echocardiography has a high yield for identification of potential sources of cardiac embolism in patients with cerebral ischemia; however, the clinical significance of the most commonly detected abnormalities is uncertain.We evaluated 145 consecutively admitted patients with stroke or transient ischemic attack with both transesophageal echocardiography and carotid ultrasound. Patients were followed up prospectively for a mean duration of 18 months to document the rate of recurrent cerebral ischemia.Transesophageal echocardiography detected at least one potential cardiac source of embolism in 45% of the patients. Atrial septal aneurysm and interatrial shunt were detected more frequently in patients who did not have a significant carotid stenosis that could account for their ischemic event. During follow-up, a higher rate of recurrent stroke or transient ischemic attack occurred in patients with positive transesophageal echocardiographic findings, particularly atrial septal aneurysm, interatrial shunt and left atrial thrombus.These data support recent studies that suggest that atrial septal aneurysm and interatrial shunts may be a significant source of cardioembolic stroke. Further studies are needed to clarify the optimal management of patients with these abnormalities.

  View details for Web of Science ID A1994PH37400013

  View details for PubMedID 8195520

• GUIDELINES FOR THE MANAGEMENT OF TRANSIENT ISCHEMIC ATTACKS - FROM THE AD-HOC COMMITTEE ON GUIDELINES FOR THE MANAGEMENT OF TRANSIENT ISCHEMIC ATTACKS OF THE STROKE COUNCIL OF THE AMERICAN-HEART-ASSOCIATION STROKE Feinberg, W. M., Albers, G. W., Barnett, H. J., Biller, J., Caplan, L. R., Carter, L. P., Hart, R. G., Hobson, R. W., Kronmal, R. A., Moore, W. S., ROBERTSON, J. T., Adams, H. P., Mayberg, M. 1994; 25 (6): 1320-1335

  View details for Web of Science ID A1994NP14200052

  View details for PubMedID 8203003

• GUIDELINES FOR THE MANAGEMENT OF TRANSIENT ISCHEMIC ATTACKS - FROM THE AD-HOC-COMMITTEE-ON-GUIDELINES-FOR-THE-MANAGEMENT-OF-TRANSIENT-ISCHEMIC-ATTACKS OF THE STROKE-COUNCIL OF THE AMERICAN-HEART-ASSOCIATION CIRCULATION Feinberg, W. M., Albers, G. W., Barnett, H. J., Biller, J., Caplan, L. R., Carter, L. P., Hart, R. G., Hobson, R. W., Kronmal, R. A., Moore, W. S., ROBERTSON, J. T., Adams, H. P., Mayberg, M. 1994; 89 (6): 2950-2965

  View details for Web of Science ID A1994NQ83000080

  View details for PubMedID 8205721

• TRANSESOPHAGEAL ECHOCARDIOGRAPHIC FINDINGS IN STROKE SUBTYPES STROKE Albers, G. W., Comess, K. A., DeRook, F. A., Bracci, P., Atwood, J. E., Bolger, A., Hotson, J. 1994; 25 (1): 23-28

  Abstract

  Transesophageal echocardiography has a high yield for detecting potential cardiac sources of embolism in patients with clinical risk factors for cardioembolism or unexplained stroke. The yield in other stroke subtypes is unknown.We classified 145 consecutively admitted patients into stroke subtypes based on clinical findings, brain imaging, and carotid ultrasound. Both transesophageal and transthoracic echocardiography were performed to detect left atrial thrombi, spontaneous echo contrast, atrial septal aneurysm, interatrial shunts, ventricular thrombus or aneurysm, and myxomatous mitral valve.Transesophageal echocardiography documented at least one of these findings in 46% of the patients compared with an 8% yield on the transthoracic study (P = .002). The yield of transesophageal echocardiography was substantial in all stroke subgroups. Patients with clinical risk factors for cardiac embolism had the highest frequency of spontaneous echo contrast (P = .001). Atrial septal aneurysms were most frequent in patients with lacunar syndromes (P = .012), and interatrial shunts were common in all stroke subtypes.Transesophageal echocardiographic findings vary considerably between stroke subgroups.

  View details for Web of Science ID A1994MP10600005

  View details for PubMedID 8266377

• Safety, tolerability, and pharmacokinetics of the N-methyl-D-aspartate antagonist dextrorphan in patients with acute stroke 5th Symposium on Pharmacology of Cerebral Ischemia Albers, G. W., Atkinson, R., Kelly, R. E., Rosenbaum, D. M., Paul, K. L., Lesko, L., Rae, J., Pitman, V., Modi, M., Yoo, K., Lehr, L., Magni, G. WISSENSCHAFTLICHE verlagsgesellschaft mbh. 1994: 625–634

  View details for Web of Science ID A1994BD29C00063

• LABORATORY MONITORING OF ORAL ANTICOAGULANT-THERAPY - ARE WE BEING MISLED NEUROLOGY Albers, G. W. 1993; 43 (3): 468-470

  View details for Web of Science ID A1993KT21500002

  View details for PubMedID 8450985

• ANTICOAGULATION AND ATRIAL-FIBRILLATION HERZ Atwood, J. E., Albers, G. W. 1993; 18 (1): 27-38

  Abstract

  The decision to anticoagulate patients with atrial fibrillation (AF) involves weighting the risk of an embolic event without therapy versus the risk of a hemorrhagic event on therapy. Improved methods of monitoring anticoagulation with the International Normalized Ratio (INR), and recent evidence of the efficacy and safety of low-dose warfarin (INR range 2.0 to 3.0) have clarified the role of anticoagulation in AF. Over the past four years, five large prospective randomized trials in patients with nonvalvular atrial fibrillation (NVAF) have reported substantial reductions in stroke in patients treated with low-dose warfarin therapy. The results of these trials, combined with previous studies, suggest that anticoagulation is the treatment of choice for patients with atrial fibrillation associated with rheumatic valvular disease, prosthetic valve disease, and now NVAF. Although the results of the prospective atrial fibrillation trials are very consistent in regard to the efficacy and safety of anticoagulation, there continues to be uncertainty regarding which subgroups of patients are at highest risk for embolic events. Subgroups that appear to be at high risk include patients with hypertension, previous embolic events, structural heart disease (enlarged left atrial size, previous myocardial infarction, left ventricular dysfunction), and older age. Young patients with no evidence of structural heart disease or hypertension (lone atrial fibrillation) have a low embolic rate and do not warrant anticoagulation. Recent studies suggest that there is little difference in the risk of stroke in patients with paroxysmal or chronic AF, therefore this factor should not have a major impact on therapeutic decisions. Anticoagulation is also recommended for patients undergoing elective cardioversion (recent onset of atrial fibrillation greater than two days in duration), and patients with atrial fibrillation and hyperthyroidism because of studies suggesting a higher rate of embolism if these patients are not anticoagulated. The role of aspirin in AF is less clear as only two of the five prospective trials randomized patients to aspirin therapy and only one documented aspirin benefit. Therefore, aspirin appears to offer less benefit but is a satisfactory alternative to warfarin therapy. Aspirin is currently recommend for patients who are poor candidates for anticoagulation or individuals with AF who are considered to be at low risk for stroke.

  View details for Web of Science ID A1993KP28300004

  View details for PubMedID 8454250

• TOLERABILITY OF ORAL DEXTROMETHORPHAN IN PATIENTS WITH A HISTORY OF BRAIN ISCHEMIA CLINICAL NEUROPHARMACOLOGY Albers, G. W., Saenz, R. E., Moses, J. A. 1992; 15 (6): 509-514

  Abstract

  Twelve patients with a history of cerebral ischemia were randomized to treatment with the N-methyl-D-aspartate antagonist dextromethorphan (60 or 90 mg p.o. q.i.d.) or placebo for 2 weeks in a randomized, safety study. Neuropsychological testing did not detect evidence of cognitive dysfunction; however, side effects including lightheadedness, drowsiness, nausea, decreased coordination, and unsteady gait were reported by several patients while taking dextromethorphan.

  View details for Web of Science ID A1992JY06700009

  View details for PubMedID 1477851

• TRANSESOPHAGEAL ECHOCARDIOGRAPHY IN THE EVALUATION OF STROKE ANNALS OF INTERNAL MEDICINE DeRook, F. A., Comess, K. A., Albers, G. W., Popp, R. L. 1992; 117 (11): 922-932

  Abstract

  To review the current role of transesophageal echocardiography in the evaluation of stroke.Articles examining the role of transesophageal echocardiography for evaluation of patients with stroke were identified using computer and bibliography searches.All English-language articles that provided full details on patient selection criteria, methods, and study design were reviewed.Cardiogenic embolism is frequently an uncertain diagnosis merely inferred by finding a potential cardiac source. Transthoracic echocardiography has had a low yield in screening unselected patients with stroke. Several series of patients with stroke have been reported comparing transthoracic and transesophageal echocardiography. Potential cardiac sources of embolism were consistently identified in many more patients by transesophageal echocardiography. Many findings are, however, of uncertain significance; these include spontaneous echo contrast, patent foramen ovale, filamentous strands on the mitral valve, and atrial septal aneurysm.Transesophageal echocardiography is most helpful in patients with stroke who are less than 45 years of age and in those without clinical evidence of heart disease. The indications for its use in the evaluation of stroke remain controversial. Further studies are needed using transesophageal echocardiography in patients with stroke and in control groups, not only to determine the natural history of transesophageal, echocardiographically detected abnormalities but also to evaluate treatment options.

  View details for Web of Science ID A1992JZ27600009

  View details for PubMedID 1443955

• FAILURE OF HIGH-DOSE HEPARIN TO PREVENT RECURRENT CARDIOEMBOLIC STROKES IN A PREGNANT PATIENT WITH A MECHANICAL HEART-VALVE NEUROLOGY Golby, A. J., Bush, E. C., DeRook, F. A., Albers, G. W. 1992; 42 (11): 2204-2206

  Abstract

  A 27-year-old woman with a mechanical heart valve suffered multiple thromboembolic events while pregnant despite anticoagulation with high-dose heparin. Warfarin, the anti-coagulant of choice for patients with prosthetic heart valves, is teratogenic and can cause hemorrhagic complications at delivery. Heparin reduces thromboembolic complications, but is of uncertain efficacy. We discuss alternatives for the prevention of thromboembolic complications in pregnant women with mechanical heart valves.

  View details for Web of Science ID A1992JY62700028

  View details for PubMedID 1436538

• Antithrombotic therapy in atrial fibrillation. Chest Laupacis, A., Albers, G., Dunn, M., Feinberg, W. 1992; 102 (4): 426S-433S

  View details for PubMedID 1395826

• ANTITHROMBOTIC THERAPY IN ATRIAL-FIBRILLATION CHEST Laupacis, A., Albers, G., Dunn, M., Feinberg, W. 1992; 102 (4): S426-S444

  View details for Web of Science ID A1992JT65500012

• RECURRENT TRANSVERSE MYELITIS, MYASTHENIA-GRAVIS, AND AUTOANTIBODIES ANNALS OF NEUROLOGY Lindsey, J. W., Albers, G. W., Steinman, L. 1992; 32 (3): 407-409

  Abstract

  A 45-year-old man with a longstanding diagnosis of myasthenia gravis presented with four episodes of transverse myelitis in 5 years. Each episode improved after treatment with steroids. Laboratory studies revealed no evidence of multiple sclerosis or a structural spinal lesion. He had antinuclear and anti-DNA antibodies and the HLA-A1, B8, DR3 haplotype known to be associated with certain autoimmune diseases. We propose an autoimmune cause for the recurrent episodes of myelitis.

  View details for Web of Science ID A1992JN14500018

  View details for PubMedID 1416813

• ROLE OF TICLOPIDINE FOR PREVENTION OF STROKE STROKE Albers, G. W. 1992; 23 (6): 912-916

  Abstract

  Ticlopidine, an antiplatelet agent with a unique mechanism of action, is now available for clinical use in the United States and Canada.Recently two large randomized trials demonstrated that ticlopidine can reduce the risk of subsequent stroke in patients presenting with a transient ischemic attack or stroke. One study found that ticlopidine was more effective than aspirin for stroke prevention; however, it was less well tolerated than aspirin and was associated with severe but reversible neutropenia in almost 1% of patients.Ticlopidine is effective for both primary and secondary stroke prevention. It has a favorable risk/benefit ratio and is a particularly attractive option for patients who are unable to take aspirin.

  View details for Web of Science ID A1992HW86000023

  View details for PubMedID 1595115

• TREATMENT OF TARDIVE-DYSKINESIA WITH VITAMIN-E 144TH ANNUAL MEETING OF THE AMERICAN PSYCHIATRIC ASSOC Egan, M. F., Hyde, T. M., Albers, G. W., Elkashef, A., Alexander, R. C., Reeve, A., Blum, A., Saenz, R. E., WYATT, R. J. AMER PSYCHIATRIC ASSOCIATION. 1992: 773–77

  Abstract

  Vitamin E (alpha-tocopherol), a free-radical scavenger, has been reported to improve symptoms of tardive dyskinesia. The authors attempted to replicate this finding under more controlled conditions in a larger study group.Fifteen inpatients and six outpatients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these patients were videotaped and rated independently by two trained raters. Levels of neuroleptic medication and vitamin E were measured during both treatment periods. Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis.Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo. For all 18 patients, there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo. In agreement with previous studies, however, the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo. There were no changes in neuroleptic levels during vitamin E treatment.Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less. This effect was not due to an increase in blood levels of neuroleptic medications.

  View details for Web of Science ID A1992HW16300006

  View details for PubMedID 1350428

• DO NMDA ANTAGONISTS PREVENT NEURONAL INJURY - YES ARCHIVES OF NEUROLOGY Albers, G. W., Goldberg, M. P., Choi, D. W. 1992; 49 (4): 418-420

  View details for Web of Science ID A1992HM46300024

  View details for PubMedID 1558524

• LACUNAR STROKE - RELATIONSHIP BETWEEN ATYPICAL ETIOLOGY AND INFARCT SIZE ARCHIVES OF NEUROLOGY Albers, G. W. 1991; 48 (12): 1215-1215

  View details for Web of Science ID A1991GZ42000001

  View details for PubMedID 1845020

• STROKE PREVENTION IN NONVALVULAR ATRIAL-FIBRILLATION ANNALS OF INTERNAL MEDICINE Albers, G. W., Atwood, J. E., Hirsh, J., Sherman, D. G., Hughes, R. A., Connolly, S. J. 1991; 115 (9): 727-736

  Abstract

  There has been considerable uncertainty about the best way to prevent stroke in patients with nonvalvular atrial fibrillation. Recent studies have suggested that low-dose warfarin therapy, in addition to producing fewer bleeding complications, may be as effective as higher-dose therapy in preventing thromboembolic events. Four large, prospective, randomized trials have examined the risks and benefits of warfarin therapy for stroke prophylaxis in patients with nonvalvular atrial fibrillation. All four studies showed a substantially reduced incidence of stroke and a low incidence of significant bleeding in patients treated with warfarin. One of these studies also showed that aspirin reduced the incidence of stroke. The benefits associated with long-term low-dose warfarin therapy appear to exceed the risks for serious bleeding in most patients with atrial fibrillation. Aspirin may be a viable therapeutic option for patients who are unable to take warfarin or for those in subgroups at a low risk for stroke.

  View details for Web of Science ID A1991GL69700012

  View details for PubMedID 1834004

• STROKE PREVENTION IN NONVALVULAR ATRIAL-FIBRILLATION - A REVIEW OF PROSPECTIVE RANDOMIZED TRIALS ANNALS OF NEUROLOGY Albers, G. W., Sherman, D. G., Gress, D. R., Paulseth, J. E., Petersen, P. 1991; 30 (4): 511-518

  Abstract

  Patients with atrial fibrillation are at risk for cerebral embolism; however, the roles of chronic anticoagulation or antiplatelet therapy for stroke prevention in patients with nonvalvular atrial fibrillation have been controversial. Recently, the results of three large prospective randomized trials that examined the risks and benefits of warfarin or aspirin for stroke prophylaxis in patients with nonvalvular atrial fibrillation were reported. All three studies revealed a reduction in the stroke rate for patients treated with warfarin and a small incidence of major bleeding. One of the studies also reported a reduced stroke rate in aspirin-treated patients. The reduction of thromboembolic events associated with chronic warfarin therapy appears to outweigh the risks of significant bleeding for most patients with nonvalvular atrial fibrillation. Aspirin may offer an alternative for subgroups of patients who are at low risk for stroke or those who are not good candidates for anticoagulation.

  View details for Web of Science ID A1991GJ81500001

  View details for PubMedID 1789680

• SAFETY AND TOLERANCE OF ORAL DEXTROMETHORPHAN IN PATIENTS AT RISK FOR BRAIN ISCHEMIA STROKE Albers, G. W., Saenz, R. E., Moses, J. A., Choi, D. W. 1991; 22 (8): 1075-1077

  Abstract

  Experimental ischemia models have shown the antitussive dextromethorphan to be an N-methyl-D-aspartate antagonist with neuroprotective properties. We treated 10 patients with a history of recent stroke or transient ischemic attack with oral dextromethorphan (60 mg q.i.d.) for 3 weeks in a placebo-controlled, double-blind, crossover tolerance study. We documented no clinical evidence of toxicity attributable to dextromethorphan in this preliminary study.

  View details for Web of Science ID A1991GB31200018

  View details for PubMedID 1866755

• INTENSITY OF ANTICOAGULANT TREATMENT AND RISK OF INTRACEREBRAL HEMATOMA STROKE Albers, G. W. 1990; 21 (12): 1758-1758

  View details for Web of Science ID A1990EN83400019

  View details for PubMedID 2264086

• POTENTIAL THERAPEUTIC USES OF N-METHYL-D-ASPARTATE ANTAGONISTS IN CEREBRAL-ISCHEMIA CLINICAL NEUROPHARMACOLOGY Albers, G. W. 1990; 13 (3): 177-197

  View details for Web of Science ID A1990DF11400001

  View details for PubMedID 1972652

• NIFEDIPINE VERSUS PROPRANOLOL FOR THE INITIAL PROPHYLAXIS OF MIGRAINE HEADACHE Albers, G. W., SIMON, L. T., Hamik, A., Peroutka, S. J. 1989; 29 (4): 215-218

  Abstract

  We conducted a randomized open-labeled study of nifedipine versus propranolol for the initial prophylaxis of migraine. Propranolol was effective in 67% of patients (12/18) and well tolerated. Nifedipine was effective in only 30% of patients (6/20). The lack of overall efficacy of nifedipine was attributable to a high incidence of side effects, including an unusual symptom complex resembling erythromelalgia. These side effects led 45% (9/20) of the nifedipine patients to withdraw from the study within two weeks. By contrast, no patient (0/18) withdrew from the study within the first 2 weeks of propranolol therapy. We conclude that nifedipine is not an agent of first choice for the prophylaxis of migraine.

  View details for Web of Science ID A1989U492600001

  View details for PubMedID 2654067

• N-METHYL-D-ASPARTATE ANTAGONISTS - READY FOR CLINICAL-TRIAL IN BRAIN ISCHEMIA ANNALS OF NEUROLOGY Albers, G. W., Goldberg, M. P., Choi, D. W. 1989; 25 (4): 398-403

  Abstract

  Antagonists of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may offer a new approach for the treatment of ischemic brain injury. This strategy is supported by a well-developed scientific foundation and encouraging results in a variety of in vivo and in vitro experimental models. Several specific antagonists, including MK-801, dextrorphan, dextromethorphan, and ketamine, have already been used at low doses in humans for other indications and are potential candidates for Phase I clinical trials.

  View details for Web of Science ID A1989U068400011

  View details for PubMedID 2565699

• TREATMENT RESPONSE IN MALIGNANT OPTIC GLIOMA OF ADULTHOOD NEUROLOGY Albers, G. W., Hoyt, W. F., Forno, L. S., Shratter, L. A. 1988; 38 (7): 1071-1074

  Abstract

  Two adults with malignant optic gliomas displayed dramatic tumor shrinkage and prolonged survival after radiation therapy alone in one case and combined radiation and chemotherapy in the other. Although malignant optic gliomas have been reported to be radiation resistant, marked treatment response may occur and aggressive treatment protocols should be considered.

  View details for Web of Science ID A1988P183900013

  View details for PubMedID 3386825

• LEFT-VENTRICULAR TUMOR MASQUERADING AS MULTIPLE-SCLEROSIS ARCHIVES OF NEUROLOGY Albers, G. W., AVALOS, S. M., Weinrich, M. 1987; 44 (7): 779-780

  Abstract

  A 30-year-old man had relapsing and remitting neurologic symptoms, which had been diagnosed as multiple sclerosis for nine years. Eventually, an unusual left ventricular tumor was discovered. The pathologic diagnosis was cavernous angiectasia, which, to our knowledge, is a previously undescribed histologic entity. Embolization from cardiac tumors can mimic multiple sclerosis and multiple echocardiograms may be required for diagnosis.

  View details for Web of Science ID A1987H920700020

  View details for PubMedID 3593066

• CALCIUM-CHLORIDE FOR TREATMENT OF SUBCUTANEOUS LIPOMAS IN DOGS JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION Albers, G. W., THEILEN, G. H. 1985; 186 (5): 492-494

  Abstract

  Ten dogs were selected for treatment of SC lipomas (n = 18) with intratumor injection of 10% calcium chloride. At 6-month follow-up, 4 tumors had regressed completely and 14 were less than 50% of their original size. Skin necrosis overlying treated tumors developed in 3 dogs.

  View details for Web of Science ID A1985ACT5800009

  View details for PubMedID 3972710