Bio


As a Professor in the Department of Neurology and Neurological Sciences at Stanford University Medical Center, I split my time between clinical activities on the inpatient stroke service and in the ambulatory stroke clinic at Stanford Hospital, clinical stroke research, and education. I am board-certified in Neurology and Vascular Neurology and have additional advanced training in MR imaging and Epidemiology. I am the director of Stanford’s Stroke Research Fellowship and co-director of Stanford’s Stroke Recovery Program. I am the co-principal investigator of the Stanford Regional Coordinating Center (RCC) for StrokeNet, an NINDS-funded network of 25 RCCs that is responsible for conducting all major NINDS-funded stroke trials.

Clinical Focus


  • Stroke
  • Cerebrovascular Disease
  • Vascular Neurology

Academic Appointments


Professional Education


  • Fellowship: Stanford University Vascular Neurology Fellowship (2004) CA
  • Residency: UCSF Dept of Neurology (2003) CA
  • Internship: Greater Baltimore Medical Center Internal Medicine Residency (2000) MD
  • Medical Education: University Medical Center Utrecht (1997) Netherlands
  • Board Certification: American Board of Psychiatry and Neurology, Vascular Neurology (2012)
  • Board Certification: American Board of Psychiatry and Neurology, Neurology (2004)
  • MS, Stanford University, Epidemiology (2008)
  • Ph.D., Univ of Utrecht, The Netherlands, Diffusion-Weighted MRI in Stroke (2002)
  • M.D., Univ of Utrecht, The Netherlands (1997)

Current Research and Scholarly Interests


My research is focused on clinical trials for stroke, spanning the full breadth of stroke care, including acute intervention, prevention, and recovery trials. The majority of my NIH funded research has centered on the use of imaging biomarkers (specifically multiomadal CT and MRI) to select patients for acute stroke interventions. I have served as the principal investigator of CRISP, a prospective cohort study to assess the utility of CT perfusion for patient selection and the Protocol Director of DEFUSE 3, a Phase 3 randomized controlled trial of endovascular therapy for acute stroke in the 6-16 hour time-window. DEFUSE 3 was conducted at 38 US sites and was the first trial to be funded and executed through StrokeNet, the NINDS clinical stroke trial network.

Clinical Trials


  • Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III Recruiting

    The overall objective of this Phase III clinical trial is to obtain information from a population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of current clinical practice and national demographics of ICH regarding the benefit (or lack thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS). This application requests funding for five years to initiate a Phase III randomized clinical trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA) with EVD+ placebo in the management and treatment of subjects with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH defined as ICH < 30 cc and obstruction of the 3rd or 4th ventricles by intraventricular blood clot).

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  • Computed Tomography Perfusion (CTP) to Predict Response to Recanalization in Ischemic Stroke Project (CRISP) Not Recruiting

    The overall goal of the CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is to develop a practical tool to identify acute stroke patients who are likely to benefit from endovascular therapy. The project has two main parts. During the first part, the investigators propose to develop a fully automated system (RAPID) for processing of CT Perfusion (CTP) images that will generate brain maps of the ischemic core and penumbra. There will be no patient enrollment in part one of this project. During the second part, the investigators aim to demonstrate that physicians in the emergency setting, with the aid of a fully automated CTP analysis program (RAPID), can accurately predict response to recanalization in stroke patients undergoing revascularization. To achieve this aim the investigators will conduct a prospective cohort study of 240 consecutive stroke patients who will undergo a CTP scan prior to endovascular therapy. The study will be conducted at four sites (Stanford University, St Luke's Hospital, University of Pittsburgh Medical Center, and Emory University/Grady Hospital). Patients will have an early follow-up MRI scan within 12+/-6 hours to assess reperfusion and a late follow-up MRI scan at day 5 to determine the final infarct.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie M Kemp, BS, 650-723-4481.

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  • Effectiveness of BP Remote Monitoring With Virtual Physician Management in Hypertensive Patients. Not Recruiting

    To assess the feasibility and adoptability of DailyDoctor's remote monitoring clinical decision support software tool in helping physicians virtually manage systolic blood pressures among patients with history of stroke or TIA to a target systolic blood pressure (<140 mmHg or a lower target range specified by referring physicians) using remote monitoring and independent clinical judgement.

    Stanford is currently not accepting patients for this trial.

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  • Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-4) Not Recruiting

    The purpose of the study is to determine whether desmoteplase is effective and safe in the treatment of patients with acute ischaemic stroke when given within 3 to 9 hours from onset of stroke symptoms.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maarten Lansberg, (650) 723 - 4448.

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  • Efficacy and Safety Trial of Transcranial Laser Therapy Within 24 Hours From Stroke Onset (NEST-3) Not Recruiting

    The purpose of this pivotal study is to demonstrate safety and efficacy of transcranial laser therapy (TLT) with the NeuroThera® Laser System in the treatment of subjects diagnosed with acute ischemic stroke. The initiation of the TLT procedure must be feasible for each subject between 4.5 and 24 hours of stroke onset.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie Kemp, (650) 723 - 4481.

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  • Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 Not Recruiting

    This is a study to evaluate the hypothesis that FDA cleared thrombectomy devices plus medical management leads to superior clinical outcomes in acute ischemic stroke patients at 90 days when compared to medical management alone in appropriately selected subjects with the Target mismatch profile and an MCA (M1 segment) or ICA occlusion who can be randomized and have endovascular treatment initiated between 6-16 hours after last seen well.

    Stanford is currently not accepting patients for this trial.

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  • Feasibility of Home-based Virtual Reality Rehabilitation for the Upper Extremity in Subacute and Chronic Stroke Not Recruiting

    Regaining upper extremity function is very important for stroke survivors to increase their independence and ability to perform activities of daily living (ADLs). Outpatient stroke rehabilitation currently takes place in a therapy clinic, however access can be limited by financial resources and transportation difficulties. The Feasibility of Home-Based Virtual Reality Rehabilitation for the Upper Extremity in Subacute and Chronic Stroke Study seeks to explore the safety, usability, and efficacy of a home based virtual reality biofeedback system to promote distal upper extremity (wrist and hand) recovery after stroke. The purpose of the study is to assess the feasibility of using a home-based virtual reality system to increase the dose of upper extremity rehabilitation in subacute and chronic stroke patients.

    Stanford is currently not accepting patients for this trial.

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  • Imaging Collaterals in Acute Stroke (iCAS) Not Recruiting

    Stroke is caused by a sudden blockage of a blood vessel that delivers blood to the brain. Unblocking the blood vessel with a blood clot removal device restores blood flow and if done quickly may prevent the disability that can be caused by a stroke. However, not all stroke patients benefit from having their blood vessel unblocked. The aim of this study is to determine if special brain imaging, called MRI, can be used to identify which stroke patients are most likely to benefit from attempts to unblock their blood vessel with a special blood clot removal device. In particular, we will assess in this trial whether a noncontrast MR imaging sequence, arterial spin labeling (ASL), can demonstrate the presence of collateral blood flow (compared with a gold standard of the angiogram) and whether it is useful to predict who will benefit from treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Gregory Zaharchuk, MD, 650-723-4448.

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  • Insulin Resistance Intervention After Stroke Trial Not Recruiting

    The purpose of this study is to determine if pioglitazone is effective in preventing future strokes or heart attacks among non-diabetic persons who have had a recent ischemic stroke.

    Stanford is currently not accepting patients for this trial. For more information, please contact Madelleine Garcia, (650) 725 - 2326.

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  • Transient Ischemic Attack (TIA) Triage and Evaluation of Stroke Risk Not Recruiting

    Transient ischemic attack (TIA) is a transient neurological deficit (speech disturbance, weakness…), caused by temporary occlusion of a brain vessel by a blood clot that leaves no lasting effect. TIA diagnosis can be challenging and an expert stroke evaluation combined with magnetic resonance imaging (MRI) could improve the diagnosis accuracy. The risk of a debilitating stroke can be as high as 5% during the first 72 hrs after TIA. TIA characteristics (duration, type of symptoms, age of the patient), the presence of a significant narrowing of the neck vessels responsible for the patient's symptoms (symptomatic stenosis), and an abnormal MRI are associated with an increased risk of stroke. An emergent evaluation and treatment of TIA patients by a stroke specialist could reduce the risk of stroke to 2%. Stanford has implemented an expedited triage pathway for TIA patients combining a clinical evaluation by a stroke neurologist, an acute MRI of the brain and the vessels and a sampling of biomarkers (Lp-PLA2). The investigators are investigating the yield of this unique approach to improve TIA diagnosis, prognosis and secondary stroke prevention. The objective of this prospective cohort study is to determine which factors will help the physician to confirm the diagnosis of TIA and to define the risk of stroke after a TIA.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie Kemp, BS, 650-723-4481.

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  • Virtual Reality Glove for Hand and Arm Rehabilitation After Stroke Not Recruiting

    The Virtual Reality Glove for Hand and Arm Rehabilitation (vREHAB) trial is a randomized, controlled, phase 3 trial aiming to evaluate the safety, usability, and efficacy of a virtual reality biofeedback system (Neofect RAPAEL Smart Glove) to promote recovery of distal arm and hand function in the acute and subacute period after stroke, as compared to standard of care therapy. The aims of the study is to demonstrate: 1. the effect of Smart Glove use on functional recovery, in addition to standard of care rehabilitation therapy. 2. the feasibility of increasing the dose of rehabilitation in acute stroke patients with the Smart Glove. 3. the effect of Smart Glove use on quality of life.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie Kemp, 650-723-4481.

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2023-24 Courses


All Publications


  • Varicella Zoster Vasculopathy Exacerbated by Tofacitinib in a Patient With Ulcerative Colitis. Stroke Lyman, K. A., Sreekrishnan, A., Thatikunta, P., McConnell, R., Lansberg, M. G., Mijalski Sells, C. M. 2023

    View details for DOI 10.1161/STROKEAHA.122.042228

    View details for PubMedID 37021571

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • Cost-Effectiveness of Cilostazol Added to Aspirin or Clopidogrel for Secondary Prevention After Noncardioembolic Stroke. Journal of the American Heart Association Zhou, L. W., Kraler, L., de Havenon, A., Lansberg, M. G. 2022: e024992

    Abstract

    Background The objective of the study was to assess the cost-effectiveness of cilostazol (a selective phosphodiesterase 3 inhibitor) added to aspirin or clopidogrel for secondary stroke prevention in patients with noncardioembolic stroke. Methods and Results A Markov model decision tree was used to examine lifetime costs and quality-adjusted life years (QALYs) of patients with noncardioembolic stroke treated with either aspirin or clopidogrel or with additional cilostazol 100mg twice daily. Cohorts were followed until all patients died from competing risks or ischemic or hemorrhagic stroke. Probabilistic sensitivity analysis using Monte Carlo simulation was used to model 10000 cohorts of 10000 patients. The addition of cilostazol to aspirin or clopidogrel is strongly cost saving. In all 10000 simulations, the cilostazol strategy resulted in lower health care costs compared with aspirin or clopidogrel alone (mean $13488 cost savings per patient; SD, $8087) and resulted in higher QALYs (mean, 0.585 more QALYs per patient lifetime; SD, 0.290). This result remained robust across a variety of sensitivity analyses, varying cost inputs, and treatment effects. At a willingness-to-pay threshold of $50000/QALY, average net monetary benefit from the addition of cilostazol was $42743 per patient over their lifetime. Conclusions Based on the best available data, the addition of cilostazol to aspirin or clopidogrel for secondary prevention following noncardioembolic stroke results in significantly reduced health care costs and a gain in lifetime QALYs.

    View details for DOI 10.1161/JAHA.121.024992

    View details for PubMedID 35656996

  • 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

  • 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

  • Prognostication of ICU Patients by Providers with and without Neurocritical Care Training. Neurocritical care Finley Caulfield, A., Mlynash, M., Eyngorn, I., Lansberg, M. G., Afjei, A., Venkatasubramanian, C., Buckwalter, M. S., Hirsch, K. G. 2022

    Abstract

    BACKGROUND: Predictions of functional outcome in neurocritical care (NCC) patients impact care decisions. This study compared the predictive values (PVs) of good and poor functional outcome among health care providers with and without NCC training.METHODS: Consecutive patients who were intubated for≥72h with primary neurological illness or neurological complications were prospectively enrolled and followed for 6-month functional outcome. Medical intensive care unit (MICU) attendings, NCC attendings, residents (RES), and nurses (RN) predicted 6-month functional outcome on the modified Rankin scale (mRS). The primary objective was to compare these four groups' PVs of a good (mRS score 0-3) and a poor (mRS score 4-6) outcome prediction.RESULTS: Two hundred eighty-nine patients were enrolled. One hundred seventy-six had mRS scores predicted by a provider from each group and were included in the primary outcome analysis. At 6months, 54 (31%) patients had good outcome and 122 (69%) had poor outcome. Compared with other providers, NCC attendings expected better outcomes (p<0.001). Consequently, the PV of a poor outcome prediction by NCC attendings was higher (96%[95% confidence interval [CI] 89-99%]) than that by MICU attendings (88% [95% CI 80-93%]), RES (82% [95% CI 74-88%]), and RN (85% [95% CI 77-91%]) (p=0.047, 0.002, and 0.012, respectively). When patients who had withdrawal of life-sustaining therapy (n=67) were excluded, NCC attendings remained better at predicting poor outcome (NCC 90% [95% CI 75-97%] vs. MICU 73% [95% CI 59-84%], p=0.064). The PV of a good outcome prediction was similar among groups (MICU 65% [95% CI 52-76%], NCC 63% [95% CI 51-73%], RES 71% [95% CI 55-84%], and RN 64% [95% CI 50-76%]).CONCLUSIONS: Neurointensivists expected better outcomes than other providers and were better at predicting poor functional outcomes. The PV of a good outcome prediction was modest among all providers.

    View details for DOI 10.1007/s12028-022-01467-6

    View details for PubMedID 35314970

  • 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

  • Self-report Does Not Align With Objective Assessments Of Memory And Fine Motor Functioning In Stroke Survivors Mendez, M. P., Drag, L. L., Mlynash, M., Musabbir, M., Kim, D. K., Lansberg, M. G., Buckwalter, M. S. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Cost Effectiveness Of Cilostazol Added To Aspirin Or Plavix For Secondary Stroke Prevention Following Non-cardioembolic Stroke Zhou, L., Kraler, L., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Arcadia CSI (Cognition And Silent Infarcts): Update Lazar, R. M., Lansberg, M. G., Howard, G., Sheth, K. N., Tirschwell, D. L., Wintermark, M., Harris, T., Myers, T., Kemp, S. M., Cassarly, C., Broderick, J. P., Kamel, H., Elkind, M. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • 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
  • 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
  • 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
  • Depression And Not Cognitive Ability Is Most Strongly Associated With Long-term Functional Outcomes Following Stroke. Drag, L. L., Musabbir, M., Mlynash, M., Mendez, M. P., Kim, D. K., Aghaeepour, N., Lansberg, M. G., Buckwalter, M. S. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Higher White Blood Cell Count In The First Week After Stroke Predicts Worse Cognitive Outcomes In A Population With Smaller Ischemic Strokes Musabbir, M., Kim, D., Drag, L., Mlynash, M., Mendez, M., Lansberg, M. G., Smith, C. J., Buckwalter, M. S. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • 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
  • Design of a Wearable Vibrotactile Stimulation Device for Individuals With Upper-Limb Hemiparesis and Spasticity IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING Seim, C. E., Ritter, B., Starner, T. E., Flavin, K., Lansberg, M. G., Okamura, A. M. 2022; 30: 1277-1287

    Abstract

    Vibratory stimulation may improve post-stroke symptoms such as spasticity; however, current studies are limited by the large, clinic-based apparatus used to apply this stimulation. A wearable device could provide vibratory stimulation in a mobile form, enabling further study of this technique. An initial device, the vibrotactile stimulation (VTS) Glove, was deployed in an eight-week clinical study in which sixteen individuals with stroke used the device for several hours daily. Participants reported wearing the glove during activities such as church, social events, and dining out. However, 69% of participants struggled to extend or insert their fingers to don the device. In a follow-up study, eight individuals with stroke evaluated new VTS device prototypes in a three-round iterative design study with the aims of creating the next generation of VTS devices and understanding features that influence interaction with a wearable device by individuals with impaired upper-limb function. Interviews and interaction tasks were used to define actionable design revisions between each round of evaluation. Our analysis identified six new themes from participants regarding device designs: hand supination is challenging, separate finger attachments inhibit fit and use, fingers may be flexed or open, fabric coverage impacts comfort, a reduced concern for social comfort, and the affected hand is infrequently used. Straps that wrap around the arm and fixtures on the anterior arm were other challenging features. We discuss potential accommodations for these challenges, as well as social comfort. New VTS device designs are presented and were donned in an average time of 48 seconds.

    View details for DOI 10.1109/TNSRE.2022.3174808

    View details for Web of Science ID 000797424600010

    View details for PubMedID 35552152

  • 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

  • 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

  • Effect of dihydropyridine calcium channel blockers on blood pressure variability in the SPRINT trial: a treatment effects approach. Journal of hypertension de Havenon, A., Petersen, N., Wolcott, Z., Goldstein, E., Delic, A., Sheibani, N., Anadani, M., Sheth, K. N., Lansberg, M., Turan, T., Prabhakaran, S. 2021

    Abstract

    OBJECTIVE: Increased visit-to-visit blood pressure variability (vvBPV) has negative effects on multiple organ systems. Prior research has suggested that dihydropyridine calcium channel blockers (CCB) may reduce vvBPV, which we attempted to verify in a high-quality dataset with robust statistical methodology.METHODS: We performed a post hoc analysis of the SPRINT trial and included participants who were on a dihydropyridine CCB either 0 or 100% of follow-up study visits. The primary outcome was vvBPV, defined as residual standard deviation (rSD) of SBP from month 6 until study completion. We estimated the average treatment effect of the treated (ATET) after augmented inverse-probability-weighting (AIPW) matching.RESULTS: Of the 9361 participants enrolled in SPRINT, we included 5020, of whom 1959 were on a dihydropyridine CCB and 3061 were not; mean age was 67.4 ± 9.2 years, 34.5% were men, 65.9% were white, 49.4% were randomized to intensive blood pressure control, and the rSD was 10.1 ± 4.0 mmHg. Amlodipine represented greater than 95% of dihydropyridine CCB use. After AIPW matching of demographics and other antihypertensive medications, the ATET estimation for participants on a dihydropyridine CCB was an rSD that was 2.05 mmHg lower (95% CI -3.19 to -0.91). We did not find that other antihypertensive medications classes decreased vvBPV, and several increased it.CONCLUSION: In the SPRINT trial, consistent use of a dihydropyridine CCB was associated with a 2 mmHg reduction in vvBPV. The implication of this hypothesis-generating finding in a high-quality dataset is that future trials to reduce vvBPV could consider using dihydropyridine CCBs.

    View details for DOI 10.1097/HJH.0000000000003033

    View details for PubMedID 34694261

  • 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

  • Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities. Stroke de Havenon, A., Sheth, K. N., Madsen, T. E., Johnston, K. C., Turan, T. N., Toyoda, K., Elm, J. J., Wardlaw, J. M., Johnston, S. C., Williams, O. A., Shoamanesh, A., Lansberg, M. G. 2021: STROKEAHA121035002

    Abstract

    Cilostazol is a PDE3 (phosphodiesterase III) inhibitor with a long track record of safety that is Food and Drug Administration and European Medicines Agency approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with noncardioembolic stroke. The onset of benefit appears after 60 to 90 days of treatment, which is consistent with cilostazol's pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms, and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial (CSPS.com [Cilostazol Stroke Prevention Study for Antiplatelet Combination]). Due to limitations of prior trials, such as open-label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have experienced a noncardioembolic ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.121.035002

    View details for PubMedID 34517768

  • 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

  • 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

  • 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

  • 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

  • Cerebral CT Perfusion in Acute Stroke: The Effect of Lowering the Tube Load and Sampling Rate on the Reproducibility of Parametric Maps DIAGNOSTICS Ioannidis, G. S., Christensen, S., Nikiforaki, K., Trivizakis, E., Perisinakis, K., Hatzidakis, A., Karantanas, A., Reyes, M., Lansberg, M., Marias, K. 2021; 11 (6)

    Abstract

    The aim of this study was to define lower dose parameters (tube load and temporal sampling) for CT perfusion that still preserve the diagnostic efficiency of the derived parametric maps. Ninety stroke CT examinations from four clinical sites with 1 s temporal sampling and a range of tube loads (mAs) (100-180) were studied. Realistic CT noise was retrospectively added to simulate a CT perfusion protocol, with a maximum reduction of 40% tube load (mAs) combined with increased sampling intervals (up to 3 s). Perfusion maps from the original and simulated protocols were compared by: (a) similarity using a voxel-wise Pearson's correlation coefficient r with in-house software; (b) volumetric analysis of the infarcted and hypoperfused volumes using commercial software. Pearson's r values varied for the different perfusion metrics from 0.1 to 0.85. The mean slope of increase and cerebral blood volume present the highest r values, remaining consistently above 0.7 for all protocol versions with 2 s sampling interval. Reduction of the sampling rate from 2 s to 1 s had only modest impacts on a TMAX volume of 0.4 mL (IQR -1-3) (p = 0.04) and core volume of -1.1 mL (IQR -4-0) (p < 0.001), indicating dose savings of 50%, with no practical loss of diagnostic accuracy. The lowest possible dose protocol was 2 s temporal sampling and a tube load of 100 mAs.

    View details for DOI 10.3390/diagnostics11061121

    View details for Web of Science ID 000665593600001

    View details for PubMedID 34205442

  • Evaluation of Systolic Blood Pressure, Use of Aspirin and Clopidogrel, and Stroke Recurrence in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial. JAMA network open de Havenon, A., Johnston, S. C., Easton, J. D., Kim, A. S., Sheth, K. N., Lansberg, M., Tirschwell, D., Mistry, E., Yaghi, S. 2021; 4 (6): e2112551

    Abstract

    Importance: Elevated systolic blood pressure (SBP) after acute ischemic stroke and transient ischemic attack (TIA) is associated with future stroke risk.Objective: To explore the association of dual antiplatelet therapy (DAPT) with stroke recurrence among patients with acute ischemic stroke and TIA with or without elevated baseline SBP.Design, Setting, and Participants: This cohort study performed a post hoc subgroup analysis of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which was a multicenter trial conducted from 2010 to 2018 at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand. Patients enrolled in POINT with available blood pressure and outcome data were included in this cohort. Statistical analysis was performed from November 2020 to January 2021.Exposures: Baseline SBP less than 140 mm Hg vs greater than or equal to 140 mm Hg and the interaction term of SBP (<140 mm Hg vs ≥140 mm Hg)*treatment group (aspirin vs DAPT).Main Outcomes and Measures: The primary outcome was ischemic stroke during 90 days of follow-up. The statistical analysis fit Cox proportional hazards models adjusted for patient age, race, premorbid hypertension, diabetes, and final diagnosis of the qualifying event (stroke vs TIA).Results: Among 4781 patients in the cohort, the mean (SD) age was 64.6 (13.1) years; 2142 (44.8%) were male individuals, 3487 (72.9%) were White individuals, and 266 (5.6%) had a primary outcome of ischemic stroke during follow-up. There were 946 patients (19.8%) with baseline SBP less than 140 mm Hg and 3835 (80.2%) with SBP greater than or equal to 140 mm Hg. The interaction term (SBP*treatment) was significant (P for interaction=.03). In the subgroup of patients with SBP less than 140 mm Hg, the hazard ratio (HR) of DAPT vs aspirin alone for ischemic stroke was 0.36 (95% CI, 0.18-0.72; P=.004), whereas the HR in the subgroup with SBP greater than or equal to 140 mm Hg was 0.79 (95% CI, 0.60-1.02; P=.08). When evaluating the outcome of ischemic stroke within 7 days of randomization, the interaction term was significant (P for interaction=.02), and the HR for patients with DAPT with SBP less than 140 mm Hg was 0.19 (95% CI, 0.07-0.55; P=.002).Conclusions and Relevance: In the POINT trial, patients with SBP less than 140 mm Hg at presentation received a greater benefit from 90 days of DAPT than those with higher baseline SBP, particularly for reduction of early ischemic stroke recurrence. Additional research is needed to replicate these findings and potentially test whether mild SBP reduction and DAPT within 12 hours of stroke onset lowers early risk of stroke recurrence.

    View details for DOI 10.1001/jamanetworkopen.2021.12551

    View details for PubMedID 34086033

  • 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

  • Assistance from Automated ASPECTS Software Improves Reader Performance. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Delio, P. R., Wong, M. L., Tsai, J. P., Hinson, H. E., McMenamy, J., Le, T. Q., Prabhu, D., Mann, B. S., Copeland, K., Kwok, K., Haerian, H., Lansberg, M. J., Heit, J. J. 2021; 30 (7): 105829

    Abstract

    PURPOSE: To compare physicians' ability to read Alberta Stroke Program Early CT Score (ASPECTS) in patients with a large vessel occlusion within 6 hours of symptom onset when assisted by a machine learning-based automatic software tool, compared with their unassisted score.MATERIALS AND METHODS: 50 baseline CT scans selected from two prior studies (CRISP and GAMES-RP) were read by 3 experienced neuroradiologists who were provided access to a follow-up MRI. The average ASPECT score of these reads was used as the reference standard. Two additional neuroradiologists and 6 non-neuroradiologist readers then read the scans both with and without assistance from the software reader-augmentation program and reader improvement was determined. The primary hypothesis was that the agreement between typical readers and the consensus of 3 expert neuroradiologists would be improved with software augmented vs. unassisted reads. Agreement was based on the percentage of the individual ASPECT regions (50 cases, 10 regions each; N=500) where agreement was achieved.RESULTS: Typical non-neuroradiologist readers agreed with the expert consensus read in 72% of the 500 ASPECTS regions, evaluated without software assistance. The automated software alone agreed in 77%. When the typical readers read the scan in conjunction with the software, agreement improved to 78% (P<0.0001, test of proportions). The software program alone achieved correlations for total ASPECT scores that were similar to the expert readers who had access to the follow-up MRI scan to help enhance the quality of their reads.CONCLUSION: Typical readers had statistically significant improvement in their scoring of scans when the scan was read in conjunction with the automated software, achieving agreement rates that were comparable to neuroradiologists.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2021.105829

    View details for PubMedID 33989968

  • Predicting Infarct Core From Computed Tomography Perfusion in Acute Ischemia With Machine Learning: Lessons From the ISLES Challenge. Stroke Hakim, A., Christensen, S., Winzeck, S., Lansberg, M. G., Parsons, M. W., Lucas, C., Robben, D., Wiest, R., Reyes, M., Zaharchuk, G. 2021: STROKEAHA120030696

    Abstract

    BACKGROUND AND PURPOSE: The ISLES challenge (Ischemic Stroke Lesion Segmentation) enables globally diverse teams to compete to develop advanced tools for stroke lesion analysis with machine learning. Detection of irreversibly damaged tissue on computed tomography perfusion (CTP) is often necessary to determine eligibility for late-time-window thrombectomy. Therefore, the aim of ISLES-2018 was to segment infarcted tissue on CTP based on diffusion-weighted imaging as a reference standard.METHODS: The data, from 4 centers, consisted of 103 cases of acute anterior circulation large artery occlusion stroke who underwent diffusion-weighted imaging rapidly after CTP. Diffusion-weighted imaging lesion segmentation was performed manually and acted as a reference standard. The data were separated into 63 cases for training and 40 for testing, upon which quality metrics (dice score coefficient, Hausdorff distance, absolute lesion volume difference, etc) were computed to rank methods based on their overall performance.RESULTS: Twenty-four different teams participated in the challenge. Median time to CTP was 185 minutes (interquartile range, 180-238), the time between CTP and magnetic resonance imaging was 36 minutes (interquartile range, 25-79), and the median infarct lesion size was 15.2 mL (interquartile range, 5.7-45). The best performance for Dice score coefficient and absolute volume difference were 0.51 and 10.1 mL, respectively, from different teams. Based on the ranking criteria, the top team's algorithm demonstrated for average Dice score coefficient and average absolute volume difference 0.51 and 10.2 mL, respectively, outperforming the conventional threshold-based method (dice score coefficient, 0.3; volume difference, 15.3). Diverse algorithms were used, almost all based on deep learning, with top-ranked approaches making use of the raw perfusion data as well as methods to synthetically generate complementary information to boost prediction performance.CONCLUSIONS: Machine learning methods may predict infarcted tissue from CTP with improved accuracy compared with threshold-based methods used in clinical routine. This dataset will remain public and can be used to test improvement in algorithms over time.

    View details for DOI 10.1161/STROKEAHA.120.030696

    View details for PubMedID 33957774

  • 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

  • A dynamic simulation framework for CT perfusion in stroke assessment built from first principles. Medical physics Divel, S. E., Christensen, S., Segars, W. P., Lansberg, M. G., Pelc, N. J. 2021

    Abstract

    PURPOSE: Physicians utilize cerebral perfusion maps (e.g., cerebral blood flow, cerebral blood volume, transit time) to prescribe the plan of care for stroke patients. Variability in scanning techniques and post-processing software can result in differences between these perfusion maps. To determine which techniques are acceptable for clinical care, it is important to validate the accuracy and reproducibility of the perfusion maps. Validation using clinical data is challenging due to the lack of a gold standard to assess cerebral perfusion and the impracticality of scanning patients multiple times with different scanning techniques. In contrast, simulated data from a realistic digital phantom of the cerebral perfusion in acute stroke patients would enable studies to optimize and validate the scanning and post-processing techniques.METHODS: We describe a complete framework to simulate CT perfusion studies for stroke assessment. We begin by expanding the XCAT brain phantom to enable spatially varying contrast agent dynamics and incorporate a realistic model of the dynamics in the cerebral vasculature derived from first principles. A dynamic CT simulator utilizes the time concentration curves to define the contrast agent concentration in the object at each time point and generates CT perfusion images compatible with commercially available post-processing software. We also generate ground truth perfusion maps to which the maps generated by post-processing software can be compared.RESULTS: We demonstrate a dynamic CT perfusion study of a simulated patient with an ischemic stroke and the resulting perfusion maps generated by post-processing software. We include a visual comparison between the computer-generated perfusion maps and the ground truth perfusion maps. The framework is highly tunable; users can modify the perfusion properties (e.g., occlusion location, CBF, CBV, and MTT), scanner specifications (e.g., focal spot size and detector configuration), scanning protocol (e.g., kVp and mAs), and reconstruction parameters (e.g., slice thickness and reconstruction filter).CONCLUSIONS: This framework provides realistic test data with the underlying ground truth that enables a robust assessment of CT perfusion techniques and post-processing methods for stroke assessment.

    View details for DOI 10.1002/mp.14887

    View details for PubMedID 33877693

  • 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

  • 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
  • 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

  • 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

  • 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
  • Penumbra Consumption Rates Based on T Max Delay and Reperfusion Status: A Post-Hoc Analysis of the Defuse-3 Trial Yaghi, S., Raz, E., Dehkharghani, S., Riina, H., McTaggart, R., Jayaraman, M., Prabhakaran, S., Liebeskind, D. S., Khatri, P., Mac Grory, B. C., Lansberg, M. G., Albers, G. W., De Havenon, A. H. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • Assistance From Automated ASPECTS Software Improves Reader Performance. Delio, P. R., Wong, M. L., Tsai, J. P., Hinson, H. E., McMenamy, J., Le, T., Prabhu, D., Mann, B., Copeland, K., Kwok, K., Haerian, H., Lansberg, M. G., Heit, J. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • RAPID-LVO for Automated Detection of Intracranial Large Vessel Occlusion in Ct Angiography of the Brain. Dehkharghani, S., Lansberg, M. G., Venkatsubramanian, C., Cereda, C. W., Lima, F. O., Coelho, H., Rocha, F. A., Qureshi, A. Y., Haerian, H. D., Montalverne, F., Copeland, K., Heit, J. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • Intensive Blood Pressure Reduction and Secondary Stroke Risk: A Posthoc Analysis of the Sps3 Trial de Havenon, A. H., Lansberg, M. G., Falcone, G. J., Noche, R., Yaghi, S., Sheth, K. N. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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

  • Mapping causal circuit dynamics in stroke using simultaneous electroencephalography and transcranial magnetic stimulation. BMC neurology Rolle, C. E., Baumer, F. M., Jordan, J. T., Berry, K., Garcia, M., Monusko, K., Trivedi, H., Wu, W., Toll, R., Buckwalter, M. S., Lansberg, M., Etkin, A. 2021; 21 (1): 280

    Abstract

    Motor impairment after stroke is due not only to direct tissue loss but also to disrupted connectivity within the motor network. Mixed results from studies attempting to enhance motor recovery with Transcranial Magnetic Stimulation (TMS) highlight the need for a better understanding of both connectivity after stroke and the impact of TMS on this connectivity. This study used TMS-EEG to map the causal information flow in the motor network of healthy adult subjects and define how stroke alters these circuits.Fourteen stroke patients and 12 controls received TMS to two sites (bilateral primary motor cortices) during two motor tasks (paretic/dominant hand movement vs. rest) while EEG measured the cortical response to TMS pulses. TMS-EEG based connectivity measurements were derived for each hemisphere and the change in connectivity (ΔC) between the two motor tasks was calculated. We analyzed if ΔC for each hemisphere differed between the stroke and control groups or across TMS sites, and whether ΔC correlated with arm function in stroke patients.Right hand movement increased connectivity in the left compared to the right hemisphere in controls, while hand movement did not significantly change connectivity in either hemisphere in stroke. Stroke patients with the largest increase in healthy hemisphere connectivity during paretic hand movement had the best arm function.TMS-EEG measurements are sensitive to movement-induced changes in brain connectivity. These measurements may characterize clinically meaningful changes in circuit dynamics after stroke, thus providing specific targets for trials of TMS in post-stroke rehabilitation.

    View details for DOI 10.1186/s12883-021-02319-0

    View details for PubMedID 34271872

  • Home-based Virtual Reality Therapy for Hand Recovery After Stroke. PM & R : the journal of injury, function, and rehabilitation Lansberg, M. G., Legault, C. n., MacLellan, A. n., Parikh, A. n., Muccini, J. n., Mlynash, M. n., Kemp, S. n., Buckwalter, M. S., Flavin, K. n. 2021

    Abstract

    Many stroke survivors suffer from arm and hand weakness, but there are only limited efficacious options for arm therapy available.To assess the feasibility of unsupervised home-based use of a virtual reality device (Smart Glove) for hand rehabilitation post stroke.Prospective single-arm study consisting of a 2-week run-in phase with no device use followed by an 8-week intervention period.Participants were recruited at the Stanford Neuroscience Outpatient Clinic.Twenty chronic stroke patients with upper extremity impairment.Participants were instructed to use the Smart Glove 50 minutes per day, 5 days per week for 8 weeks.We measured (1) compliance, (2) patients' impression of the intervention, and (3) efficacy measures including the upper extremity Fugl-Meyer (UE-FM), the Jebsen-Taylor hand function test (JTHFT) and the Stroke Impact Scale (SIS).Of 20 subjects, 7 (35%) met target compliance of 40 days use, and 6 (30%) used the device for 20-39 days. Eighty-five percent of subjects were satisfied with the therapy, with 80% reporting improvement in hand function. During the run-in phase there were no improvements in hand function. During the intervention, patients improved by a mean of 26.6 ± 48.8 seconds on the JTHFT (P = 0.03), by 16.1 ± 15.3 points on the hand-domain of the SIS (P < 0.01) and there was a trend towards improvement on the UE-FM (2.2 ± 5.5 points, P = 0.10).Unsupervised use of the Smart Glove in the home environment may improve hand/arm function in subacute/chronic stroke patients. A randomized controlled trial is needed to confirm these results. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/pmrj.12598

    View details for PubMedID 33773059

  • High-Performance Automated Anterior Circulation CT Angiographic Clot Detection in Acute Stroke: A Multireader Comparison. Radiology Dehkharghani, S. n., Lansberg, M. n., Venkatsubramanian, C. n., Cereda, C. n., Lima, F. n., Coelho, H. n., Rocha, F. n., Qureshi, A. n., Haerian, H. n., Mont'Alverne, F. n., Copeland, K. n., Heit, J. n. 2021: 202734

    Abstract

    Background Identification of large vessel occlusion (LVO) is critical to the management of acute ischemic stroke and prerequisite to endovascular therapy in recent trials. Increasing volumes and data complexity compel the development of fast, reliable, and automated tools for LVO detection to facilitate acute imaging triage. Purpose To investigate the performance of an anterior circulation LVO detection platform in a large mixed sample of individuals with and without LVO at cerebrovascular CT angiography (CTA). Materials and Methods In this retrospective analysis, CTA data from recent cerebrovascular trials (CRISP [ClinicalTrials.gov NCT01622517] and DASH) were enriched with local repositories from 11 worldwide sites to balance demographic and technical variables in LVO-positive and LVO-negative examinations. CTA findings were reviewed independently by two neuroradiologists from different institutions for intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) M1 LVO; these observers were blinded to all clinical variables and outcomes. An automated analysis platform was developed and tested for prediction of LVO presence and location relative to reader consensus. Discordance between readers with respect to LVO presence or location was adjudicated by a blinded tertiary reader at a third institution. Sensitivity, specificity, and receiver operating characteristics were assessed by an independent statistician, and subgroup analyses were conducted. Prespecified performance thresholds were set at a lower bound of the 95% CI of sensitivity and specificity of 0.8 or greater at mean times to notification of less than 3.5 minutes. Results A total of 217 study participants (mean age, 64 years ± 16 [standard deviation]; 116 men; 109 with positive findings of LVO) were evaluated. Prespecified performance thresholds were exceeded (sensitivity, 105 of 109 [96%; 95% CI: 91, 99]; specificity, 106 of 108 [98%; 95% CI: 94, 100]). Sensitivity and specificity estimates across age, sex, location, and vendor subgroups exceeded 90%. The area under the receiver operating characteristic curve was 99% (95% CI: 97, 100). Mean processing and notification time was 3 minutes 18 seconds. Conclusion The results confirm the feasibility of fast automated high-performance detection of intracranial internal carotid artery and middle cerebral artery M1 occlusions. © RSNA, 2021 See also the editorial by Kloska in this issue.

    View details for DOI 10.1148/radiol.2021202734

    View details for PubMedID 33434110

  • Factors Associated with Hospital-Acquired Delirium in Patients 18–65 Years Old J GEN INTERN MED Rohatgi, N., Weng, Y., Ahuja, N., Lansberg, M. G. 2021
  • Characteristics of Younger and Older Adults with Hospital-Acquired Delirium: a Claims Data Study Spanning 14 years J GEN INTERN MED Rohatgi, N., Weng, Y., Ahuja, N., Lansberg, M. G. 2021
  • 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

  • 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

  • Affective Ratings of Vibrotactile Signals in Older Adults With and Without History of Stroke Seim, C. E., Ritter, B., Flavin, K. E., Lansberg, M. G., Okamura, A. M., IEEE IEEE. 2021: 457-462
  • 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

  • Simulation of contrast agent dynamics in digital brain phantom for CT perfusion optimization Divel, S. E., Christensen, S., Lansberg, M. G., Pelc, N. J., Chen, G. H., Bosmans, H. SPIE-INT SOC OPTICAL ENGINEERING. 2021

    View details for DOI 10.1117/12.2549741

    View details for Web of Science ID 000671890600039

  • 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

  • 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

  • Hypoperfusion Intensity Ratio Predicts Malignant Edema and Functional Outcome in Large-Vessel Occlusive Stroke with Poor Revascularization. Neurocritical care Murray, N. M., Culbertson, C. J., Wolman, D. N., Mlynash, M., Lansberg, M. G. 2020

    Abstract

    BACKGROUND AND OBJECTIVE: Malignant cerebral edema (MCE) is a well-known complication in patients with acute ischemic stroke with core infarcts≥80mL caused by large-vessel occlusions. MCE can also develop in patients with smaller infarcts with moderate -to-large volume of tissue at risk who do not achieve successful revascularization with endovascular thrombectomy (ET). Features that predict the development of MCE in this population are not well-described. We aim to identify predictors of MCE and 90-day functional outcome in stroke patients with an anterior circulation large vessel occlusion (LVO) and a<80mL ischemic core who do not achieve complete reperfusion.METHODS: We reviewed our institutional stroke registry and included patients who achieved unsuccessful revascularization, mTICI 0-2a, after ET and whose baseline imaging was notable for a core infarct<80mL, a Tmax>6s volume≥80mL, and a mismatch ratio≥1.8. MCE was defined as≥5mm of midline shift on follow-up imaging, obtained 6-48h after the pre-ET perfusion scan.RESULTS: Thirty-six patients met inclusion criteria. Unadjusted analysis demonstrated that younger age, higher systolic blood pressure, larger core volume, and higher hypoperfusion intensity ratio (HIR) were associated with MCE (all p<0.02). In multivariate logistic regression analysis, age, HIR, and core infarct volume were independent predictors of MCE. The optimal HIR threshold to predict MCE was≥0.54 (OR 14.7, 95% CI 2.4-78.0, p=0.003). HIR was also associated with 3-month mRS (HIR≥0.54 for mRS of 3-6: OR 10.8, 95% CI 1.9-44.0, p=0.02).CONCLUSIONS: Younger age, larger core infarct volume, and higher HIR are predictive of MCE in patients with anterior circulation LVO, moderate-to-large tissue at risk, and suboptimal revascularization. HIR is correlated with three-month functional outcomes.

    View details for DOI 10.1007/s12028-020-01152-6

    View details for PubMedID 33200332

  • 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

  • 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

  • Decision-Making Visual Aids for Late, Imaging-Guided Endovascular Thrombectomy for Acute Ischemic Stroke. Journal of stroke Moshayedi, P., Liebeskind, D. S., Jadhav, A., Jahan, R., Lansberg, M., Sharma, L., Nogueira, R. G., Saver, J. L. 2020; 22 (3): 377–86

    Abstract

    BACKGROUND AND PURPOSE: Speedy decision-making is important for optimal outcomes from endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Figural decision aids facilitate rapid review of treatment benefits and harms, but have not yet been developed for late-presenting patients selected for EVT based on multimodal computed tomography or magnetic resonance imaging.METHODS: For combined pooled study-level randomized trial (DAWN and DEFUSE 3) data, as well as each trial singly,100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of EVT for patients with AIS and large vessel occlusion using automated (algorithmic) and expert-guided joint outcome table specification.RESULTS: Among imaging-selected patients 6 to 24 hours from last known well, for the full 7-category modified Rankin Scale (mRS), EVT had number needed to treat to benefit 1.9 (interquartile range [IQR], 1.9 to 2.1) and number needed to harm 40.0 (IQR, 29.2 to 58.3). Visual displays of treatment effects among 100 patients showed that, with EVT: 52 patients have better disability outcome, including 32 more achieving functional independence (mRS 0 to 2); three patients have worse disability outcome, including one more experiencing severe disability or death (mRS 5 to 6), mediated by symptomatic intracranial hemorrhage and infarct in new territory. Similar features were present in person-icon figures based on a 6-level mRS (levels 5 and 6 combined) rather than 7-level mRS, and based on the DAWN trial alone and DEFUSE 3 trial alone.CONCLUSIONS: Personograph visual decision aids are now available to rapidly educate patients, family, and healthcare providers regarding benefits and risks of EVT for late-presenting, imaging-selected AIS patients.

    View details for DOI 10.5853/jos.2019.03503

    View details for PubMedID 33053953

  • Improved Segmentation and Detection Sensitivity of Diffusion-weighted Stroke Lesions with Synthetically Enhanced Deep Learning. Radiology. Artificial intelligence Federau, C., Christensen, S., Scherrer, N., Ospel, J. M., Schulze-Zachau, V., Schmidt, N., Breit, H., Maclaren, J., Lansberg, M., Kozerke, S. 2020; 2 (5): e190217

    Abstract

    Purpose: To compare the segmentation and detection performance of a deep learning model trained on a database of human-labeled clinical stroke lesions on diffusion-weighted (DW) images to a model trained on the same database enhanced with synthetic stroke lesions.Materials and Methods: In this institutional review board-approved study, a stroke database of 962 cases (mean patient age ± standard deviation, 65 years ± 17; 255 male patients; 449 scans with DW positive stroke lesions) and a normal database of 2027 patients (mean age, 38 years ± 24; 1088 female patients) were used. Brain volumes with synthetic stroke lesions on DW images were produced by warping the relative signal increase of real strokes to normal brain volumes. A generic three-dimensional (3D) U-Net was trained on four different databases to generate four different models: (a) 375 neuroradiologist-labeled clinical DW positive stroke cases (CDB); (b) 2000 synthetic cases (S2DB); (c) CDB plus 2000 synthetic cases (CS2DB); and (d) CDB plus 40000 synthetic cases (CS40DB). The models were tested on 20% (n = 192) of the cases of the stroke database, which were excluded from the training set. Segmentation accuracy was characterized using Dice score and lesion volume of the stroke segmentation, and statistical significance was tested using a paired two-tailed Student t test. Detection sensitivity and specificity were compared with labeling done by three neuroradiologists.Results: The performance of the 3D U-Net model trained on the CS40DB (mean Dice score, 0.72) was better than models trained on the CS2DB (Dice score, 0.70; P < .001) or the CDB (Dice score, 0.65; P < .001). The deep learning model (CS40DB) was also more sensitive (91% [95% confidence interval {CI}: 89%, 93%]) than each of the three human readers (human reader 3, 84% [95% CI: 81%, 87%]; human reader 1, 78% [95% CI: 75%, 81%]; human reader 2, 79% [95% CI: 76%, 82%]), but was less specific (75% [95% CI: 72%, 78%]) than each of the three human readers (human reader 3, 96% [95% CI: 94%, 98%]; human reader 1, 92% [95% CI: 90%, 94%]; human reader 2, 89% [95% CI: 86%, 91%]).Conclusion: Deep learning training for segmentation and detection of stroke lesions on DW images was significantly improved by enhancing the training set with synthetic lesions.Supplemental material is available for this article.© RSNA, 2020.

    View details for DOI 10.1148/ryai.2020190217

    View details for PubMedID 33937840

  • 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

  • Perioperative Stroke Risk Reduction in Patients With Patent Foramen Ovale. JAMA neurology Rohatgi, N., Smilowitz, N. R., Lansberg, M. G. 2020

    View details for DOI 10.1001/jamaneurol.2020.2619

    View details for PubMedID 32744603

  • Natalizumab in acute ischemic stroke (ACTION II): a randomized, placebo-controlled trial. Neurology Elkind, M. S., Veltkamp, R., Montaner, J., Johnston, S. C., Singhal, A. B., Becker, K., Lansberg, M. G., Tang, W., Kasliwal, R., Elkins, J. 2020

    Abstract

    OBJECTIVE: We evaluated the effect of two doses of natalizumab on functional outcomes in acute ischemic stroke (AIS) patients.METHODS: In this double-blind phase 2b trial, AIS patients aged 18-80 years with National Institutes of Health Stroke Scale scores of 5-23 from 53 US and European sites were randomized 1:1:1 to receive a single dose of 300 or 600 mg intravenous natalizumab or placebo, with randomization stratified by treatment window (≤9 or >9 to ≤24 hours from patient's last known normal state). The primary endpoint was a composite measure of excellent outcome (modified Rankin Scale score ≤1 and Barthel Index score ≥95) at day 90 assessed in all patients receiving a full dose. Sample size was estimated from a Bayesian model; p values were not used for hypothesis testing.RESULTS: An excellent outcome was less likely with natalizumab than with placebo (natalizumab 300 mg or 600 mg odds ratio 0.60; 95% confidence interval 0.39-0.93). There was no effect modification by time to treatment or use of thrombolysis/thrombectomy. For natalizumab 300 mg, 600 mg, or placebo, there were no differences in incidence of adverse events (90%, 92%, and 92%, respectively), serious adverse events (26%, 33%, and 21%, respectively), or deaths (7%, 5%, and 6%, respectively).CONCLUSIONS: Natalizumab administered ≤24 hours after AIS did not improve patient outcomes.CLINICALTRIALSGOV IDENTIFIER: NCT02730455 CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with AIS, an excellent outcome was less likely in patients treated with natalizumab than with placebo.

    View details for DOI 10.1212/WNL.0000000000010038

    View details for PubMedID 32591475

  • 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

  • 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

  • Review of Perfusion Imaging in Acute Ischemic Stroke: From Time to Tissue. Stroke Demeestere, J., Wouters, A., Christensen, S., Lemmens, R., Lansberg, M. G. 2020: STROKEAHA119028337

    View details for DOI 10.1161/STROKEAHA.119.028337

    View details for PubMedID 32008460

  • 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
  • Development of a Comprehensive Neuropsychological Battery to Assess Post-Stroke Cognitive Functioning Drag, L., Aghaeepour, N., Mlynash, M., Osborn, E., Rah, E., Buckwalter, M., Lansberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • How to Design Woke Stroke Tech: The STORIES Project Eakin, M., Gian, A., Kim, F., Muccini, J., Lansberg, M., Flavin, K. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Home-Based Virtual Reality Therapy for Hand Recovery After Stroke MacLellan, A., Legault, C., Parikh, A., Lugo, L., Kemp, S., Mlynash, M., Buckwalter, M., Flavin, K., Lansberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • 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
  • 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
  • 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

  • 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

  • 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

  • A longitudinal study of the post-stroke immune response and cognitive functioning: the StrokeCog study protocol. BMC neurology Drag, L. L., Mlynash, M. n., Nassar, H. n., Osborn, E. n., Kim, D. E., Angst, M. S., Aghaeepour, N. n., Buckwalter, M. n., Lansberg, M. G. 2020; 20 (1): 313

    Abstract

    Stroke increases the risk of cognitive impairment even several years after the stroke event. The exact mechanisms of post-stroke cognitive decline are unclear, but the immunological response to stroke might play a role. The aims of the StrokeCog study are to examine the associations between immunological responses and long-term post-stroke cognitive trajectories in individuals with ischemic stroke.StrokeCog is a single-center, prospective, observational, cohort study. Starting 6-12 months after stroke, comprehensive neuropsychological assessment, plasma and serum, and psychosocial variables will be collected at up to 4 annual visits. Single cell sequencing of peripheral blood monocytes and plasma proteomics will be conducted. The primary outcome will be the change in global and domain-specific neuropsychological performance across annual evaluations. To explain the differences in cognitive change amongst participants, we will examine the relationships between comprehensive immunological measures and these cognitive trajectories. It is anticipated that 210 participants will be enrolled during the first 3 years of this 4-year study. Accounting for attrition, an anticipated final sample size of 158 participants with an average of 3 annual study visits will be available at the completion of the study. Power analyses indicate that this sample size will provide 90% power to detect an average cognitive change of at least 0.23 standard deviations in either direction.StrokeCog will provide novel insight into the relationships between immune events and cognitive change late after stroke.

    View details for DOI 10.1186/s12883-020-01897-9

    View details for PubMedID 32847540

  • Sex Differences in Oral Anticoagulation and Outcomes of Stroke and Intracranial Bleeding in Newly Diagnosed Atrial Fibrillation. Journal of the American Heart Association Yong, C. M., Tremmel, J. A., Lansberg, M. G., Fan, J. n., Askari, M. n., Turakhia, M. P. 2020: e015689

    Abstract

    Background Female sex is an independent predictor of stroke in patients with atrial fibrillation (AF). Older data suggest undertreatment with anticoagulation among women compared with men. However, it is unknown if novel therapies and updated guidelines have impacted sex differences in AF treatment and outcomes. Methods and Results We performed a retrospective cohort study of 2.3 million women and men with a new diagnosis of AF and CHA2DS2-VASc ≥2 from Marketscan US commercial claims data from 2008 to 2015 to determine whether women with AF remain undertreated and whether this difference mediates observed differences in outcomes. There were 358 649 patients with newly diagnosed AF (43% women). Compared with men, women were older, with higher CHA2DS2-VASc scores, and higher comorbidity burden (P<0.0001 for all). Oral anticoagulation-eligible women with CHA2DS2-VASc scores ≥2 were more likely to not receive anticoagulation (50.0% women versus 43.9% men). Women, compared with men, had a higher risk of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% CI, 1.21-1.32; P<0.0001) and hospitalization (aHR, 1.06; 95% CI, 1.05-1.07, P<0.0001) but had a lower risk of intracranial bleeding (aHR, 0.91; 95% CI, 0.83-0.99, P=0.03). In mediation analysis, nonreceipt of oral anticoagulation partially mediated the observed increased risk of stroke and decreased risk of intracranial bleeding in women. Conclusions In the care of newly diagnosed AF in the United States, women, compared with men, are less likely to receive oral anticoagulation. This appears to mediate the increased risk of both stroke and hospitalization but also appears to mediate lower observed intracranial bleeding risk.

    View details for DOI 10.1161/JAHA.120.015689

    View details for PubMedID 32394763

  • 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

  • What predicts poor outcome after successful thrombectomy in late time windows? Journal of neurointerventional surgery Heit, J. J., Mlynash, M. n., Christensen, S. n., Kemp, S. M., Lansberg, M. G., Marks, M. P., Olivot, J. M., Gregory, A. W. 2020

    Abstract

    Thrombectomy for acute ischemic stroke treatment leads to improved outcomes, but many patients do not achieve a good outcome despite successful reperfusion. We determined predictors of poor outcome after successful thrombectomy (TICI 2b-3) with an emphasis on modifiable factors.Patients from the randomized DEFUSE 3 trial who underwent thrombectomy with TICI 2b-3 revascularization were included. Primary outcome was a poor outcome at 90 days (modified Rankin Scale score 3-6).70 patients were included. Poor outcome patients were older (73.5 vs 66.5 years; P=0.01), more likely to be female (68% vs 39%; P=0.02), had higher NIHSS scores (20 vs 13; P<0.001), and had poor cerebral perfusion collaterals (hypoperfusion intensity ratio) (median 0.45 vs 0.38; P=0.03). Following thrombectomy, poor outcome patients had larger 24 hour' core infarctions (median 59.5 vs 29.9 mL; P=0.01), more core infarction growth (median 33.6 vs 13.4 mL; P<0.001), and more mild (65% vs 50%; P=0.02) and severe (18% vs 0%; P=0.01) reperfusion hemorrhage. In a logistic regression analysis, the presence of any reperfusion hemorrhage (OR 3.3 [95% CI, 1.67 to 5]; P=0.001), age (OR 1.1 [95% CI, 1.03 to 1.11], P=0.004), higher NIHSS (OR 1.25 [95% CI, 1.07 to 1.41], P=0.002), and time from imaging to femoral artery puncture (OR 5 [95% CI, 1.16 to 16.67], P=0.03) independently predicted poor outcomes.In late time windows, both mild and severe reperfusion hemorrhage were associated with poor outcomes. Older age, higher NIHSS, and increased time from imaging to arterial puncture were also associated with poor outcomes despite successful revascularization.https://clinicaltrials.gov/ct2/show/NCT02586415.

    View details for DOI 10.1136/neurintsurg-2020-016125

    View details for PubMedID 32554693

  • Stroke epidemiology and stroke policies in China from 1980 to 2017: A systematic review and meta-analysis. International journal of stroke : official journal of the International Stroke Society Hu, S., Cui, B., Mlynash, M., Zhang, X., Mehta, K. M., Lansberg, M. G. 2019: 1747493019873562

    Abstract

    BACKGROUND: Stroke is the leading cause of death and years of life lost in China, and this problem is growing because stroke risk factors such as hypertension and hypercholesteremia have been on the rise as China experiences the demographic transition. The Chinese government has created public health initiatives in the form of guidelines, policies and programs to combat this problem, but the dissemination and effectiveness of these policies are not well known.AIMS: The aim of this study was to determine trends in stroke incidence, prevalence, and stroke-related mortality in China and to report these trends in the context of stroke initiatives that have been enacted by the Chinese government.SUMMARY OF REVIEW: We systematically reviewed articles on stroke rates and stroke initiatives from 1980 to 2017. A meta-regression including 11 studies showed that stroke incidence remained stable at 128.3 per 100,000 per year from 1980 to 2005 and has increased by 21.3 per 100,000 per year since then to 298.7 per 100,000 per year in 2013. A meta-regression including seven studies demonstrated a gradual decline in stroke-related mortality by 6.5 per 100,000 per year since 1980 (a decline from 369.2 in 1980 to 154.7 per 100,000 per year in 2013). Average stroke prevalence was 898.4 per 100,000 over the entire time-period. Limitations included heterogeneity between the studies. We identified 12 stroke initiatives, the first of which was enacted in 2006.CONCLUSIONS: Despite numerous public health initiatives aimed at combating stroke that started in 2006, stroke incidence in China has increased over the last decade, likely as a result of aging and urbanization of the Chinese population.

    View details for DOI 10.1177/1747493019873562

    View details for PubMedID 31543073

  • CT perfusion in acute stroke: Practical guidance for implementation in clinical practice JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Christensen, S., Lansberg, M. G. 2019; 39 (9): 1664–68
  • 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

  • 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

  • Initiative for prevention and early identification of delirium in medical-surgical units: Lessons learnt in the past five years. The American journal of medicine Rohatgi, N., Weng, Y., Bentley, J., Lansberg, M. G., Shepard, J., Mazur, D., Ahuja, N., Hopkins, J. 2019

    Abstract

    BACKGROUND: Delirium is an acute change in mental status affecting 10-64% of hospitalized patients, and may be preventable in 30-40% cases. In October 2013, a task force for delirium prevention and early identification in medical-surgical units was formed at our hospital. We studied if our standardized protocol prevented delirium among high-risk patients.METHODS: We studied 105,455 patient encounters between November 2013 and January 2018. Since November 2013, there has been ongoing education to decrease deliriogenic medications use. Since 2014, nurses screen all patients for presence or absence of delirium using confusion assessment method (CAM). Since 2015, nurses additionally screen all patients for risk of delirium. In 2015, a physician order set for delirium was created. Non-pharmacological measures are implemented for high-risk or CAM positive patients.RESULTS: 98.8% of patient encounters had CAM screening, and 99.6% had delirium risk screening. Since 2013, odds of opiate use decreased by 5.0% per year (P<0.001), and odds of benzodiazepines use decreased by 8.0% per year (P<0.001). There was no change in anticholinergics use. In the adjusted analysis, since 2015, odds of delirium decreased by 25.3% per year among high-risk patients (N=21,465; P<0.001). Among high-risk patients or those diagnosed with delirium (N=22,121), estimated LOS decreased by 0.13days per year (P<0.001), odds of inpatient mortality decreased by 16.0% per year (P=0.011), and odds of discharge to nursing home decreased by 17.1% per year (P<0.001).CONCLUSION: With high clinician engagement and simplified workflows, our delirium initiative has shown sustained results.

    View details for DOI 10.1016/j.amjmed.2019.05.035

    View details for PubMedID 31228413

  • 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
  • A YEAR-LONG IMMUNE PROFILE OF THE SYSTEMIC RESPONSE IN ACUTE STROKE SURVIVORS Tsai, A., Berry, K., Beneyto, M. M., Gaudilliere, D., Ganio, E. A., Culos, A., Ghaemi, M. S., Choisy, B., Djebali, K., Einhaus, J. F., Bertrand, B., Tanada, A., Stanley, N., Fallahzadeh, R., Baca, Q., Quach, L. N., Osborn, E., Drag, L., Lansberg, M., Angst, M., Gaudilliere, B., Buckwalter, M. S., Aghaeepour, N. LIPPINCOTT WILLIAMS & WILKINS. 2019: 155
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • A year-long immune profile of the systemic response in acute stroke survivors. Brain : a journal of neurology Tsai, A. S., Berry, K., Beneyto, M. M., Gaudilliere, D., Ganio, E. A., Culos, A., Ghaemi, M. S., Choisy, B., Djebali, K., Einhaus, J. F., Bertrand, B., Tanada, A., Stanley, N., Fallahzadeh, R., Baca, Q., Quach, L. N., Osborn, E., Drag, L., Lansberg, M. G., Angst, M. S., Gaudilliere, B., Buckwalter, M. S., Aghaeepour, N. 2019

    Abstract

    Stroke is a leading cause of cognitive impairment and dementia, but the mechanisms that underlie post-stroke cognitive decline are not well understood. Stroke produces profound local and systemic immune responses that engage all major innate and adaptive immune compartments. However, whether the systemic immune response to stroke contributes to long-term disability remains ill-defined. We used a single-cell mass cytometry approach to comprehensively and functionally characterize the systemic immune response to stroke in longitudinal blood samples from 24 patients over the course of 1 year and correlated the immune response with changes in cognitive functioning between 90 and 365 days post-stroke. Using elastic net regularized regression modelling, we identified key elements of a robust and prolonged systemic immune response to ischaemic stroke that occurs in three phases: an acute phase (Day 2) characterized by increased signal transducer and activator of transcription 3 (STAT3) signalling responses in innate immune cell types, an intermediate phase (Day 5) characterized by increased cAMP response element-binding protein (CREB) signalling responses in adaptive immune cell types, and a late phase (Day 90) by persistent elevation of neutrophils, and immunoglobulin M+ (IgM+) B cells. By Day 365 there was no detectable difference between these samples and those from an age- and gender-matched patient cohort without stroke. When regressed against the change in the Montreal Cognitive Assessment scores between Days 90 and 365 after stroke, the acute inflammatory phase Elastic Net model correlated with post-stroke cognitive trajectories (r = -0.692, Bonferroni-corrected P = 0.039). The results demonstrate the utility of a deep immune profiling approach with mass cytometry for the identification of clinically relevant immune correlates of long-term cognitive trajectories.

    View details for DOI 10.1093/brain/awz022

    View details for PubMedID 30860258

  • 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: STROKEAHA118024134

    Abstract

    Background and Purpose- Hypoperfusion intensity ratio (HIR) is associated with collateral status in acute ischemic stroke patients with anterior circulation large vessel occlusion. We assessed whether HIR was correlated to patient eligibility for mechanical thrombectomy (MT). Methods- We performed a retrospective cohort study of consecutive acute ischemic stroke patients with a proximal middle cerebral artery or internal carotid artery occlusion who underwent MT triage with computed tomography or magnetic resonance perfusion imaging. Clinical data, ischemic core (mL), HIR (defined as time-to-maximum [TMax] >10 seconds/TMax >6 seconds), mismatch volume between core and penumbra, and MT details were assessed. Primary outcome was favorable HIR collateral score (HIR <0.4) between patients who underwent MT (MT+) and those who did not (MT-) according to American Heart Association guidelines both in the <6 hours and 6 to 24 hours windows. Secondary outcomes were favorable HIR score in MT- subgroups (National Institutes of Health Stroke Scale <6 versus core >70 mL) and core-penumbra mismatch volumes. Patients who did not meet guidelines were not included. Results- We included 197 patients (145 MT+ and 52 MT-). MT+ patients had a significantly lower median HIR compared with MT- patients (0.4 [interquartile range, 0.2-0.5] versus 0.6 [interquartile range, 0.5-0.8]; P<0.001) and a higher mismatch volume (96 versus 27 mL, P<0.001). Among MT- patients, 43 had a core >70 mL, and 9 had a National Institutes of Health Stroke Scale <6. MT- patients with National Institutes of Health Stroke Scale <6 had a lower HIR than MT- patients with core >70 mL (0.2 [interquartile range, 0.2-0.3] versus 0.7 [interquartile range, 0.6-0.8], P<0.001) but their HIR was not significantly different that MT+ patients. Conclusions- Patients who meet American Heart Association guidelines for thrombectomy are more likely to have favorable collaterals (low HIR). HIR may be used as a marker of eligibility for MT triage.

    View details for PubMedID 30841821

  • 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
  • Feasibility and Utility of Home-Based Gait Analysis Using Body-Worn Sensors Huang, E., Sharp, M. T., Osborn, E., MacLellan, A., Mlynash, M., Kemp, S., Buckwalter, M. S., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • Deep Immune Profiling of the Post-Stroke Peripheral Immune Response Reveals Tri-phasic Response and Correlations With Long-Term Cognitive Outcomes Tsai, A. S., Berry, K., Beneyto, M. M., Gaudilliere, D., Ganio, E. A., Choisy, B., Djebali, K., Baca, Q., Quach, L., Drag, L., Lansberg, M. G., Angst, M. S., Gaudilliere, B., Buckwalter, M. S., Aghaeepour, N. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Optimizing CT Perfusion Thresholds for Identification of Ischemic Core in Hyperacute Stroke. Legault, C., Lansberg, M., Heit, J., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Thrombectomy With Conscious Sedation Increases Functional Independence Compared to General Anesthesia: A DEFUSE-3 Post-hoc Analysis Dornbos, D. L., Powers, C. J., Mlynash, M., Gulati, D., Torbey, M., Nimjee, S. M., Lansberg, M. G., Marks, M. P. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • 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
  • 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

  • A Relative Noncontrast CT Map to Detect Early Ischemic Changes in Acute Stroke. Journal of neuroimaging : official journal of the American Society of Neuroimaging Srivatsan, A., Christensen, S., Lansberg, M. G. 2019

    Abstract

    BACKGROUND AND PURPOSE: Early ischemic changes on noncontrast computed tomography (NCCT) are often subtle. We developed a novel postprocessing technique that aids in detecting such changes.METHODS: NCCT maps were generated that display the relative density difference between corresponding voxels in contralateral hemispheres (ratio maps of the NCCT [rNCCT]). Voxels with a relative density difference below .95 were designated as infarct. We pilot tested the rNCCT for infarct segmentation on 6 consecutive subjects enrolled in the CT Perfusion to predict Response in Ischemic Stroke Project (CRISP) study and applied the inclusion criteria of an adequate quality NCCT and successful endovascular reperfusion This seems too complex for the abstract, specially since all the abbreviations are now spelled out. This definition is defined in the methods section of the manuscript in detail. Can be deleted here from the abstract. rNCCT infarct segmentation was compared to baseline NCCT, baseline CTP, and day-5 follow-up fluid-attenuated inversion recovery (FLAIR).RESULTS: Five of the six selected cases met the inclusion criteria. Their median time from symptom onset to CT was 4.95hours (standard deviation [SD], ±3.5; range, 1.05-10.45), and median NIHSS was 13. Early ischemic changes were identified on the rNCCT in all five cases and on the standard NCCT in three of the five cases. Lesions outlined by the rNCCT maps trended toward a better estimation of the day-5 FLAIR volume (median difference=6.2mL) than the ischemic core volumes assessed on baseline CTP (median difference=51.7mL) in the four cases with a day-5 FLAIR (P=.1).CONCLUSION: In this proof-of-concept study, the rNCCT appears promising for detecting and quantifying early ischemic changes. These findings should be confirmed in a larger cohort.

    View details for PubMedID 30681223

  • 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

  • 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

  • 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

  • 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

  • CT perfusion in acute stroke: Practical guidance for implementation in clinical practice. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Christensen, S., Lansberg, M. G. 2018: 271678X18805590

    View details for PubMedID 30346227

  • 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

  • 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

  • Prognostic Value of BEFAST vs. FAST to Identify Stroke in a Prehospital Setting. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors Pickham, D., Valdez, A., Demeestere, J., Lemmens, R., Diaz, L., Hopper, S., de la Cuesta, K., Rackover, F., Miller, K., Lansberg, M. 2018: 0

    Abstract

    BACKGROUND: Use of prehospital stroke scales may enhance stroke detection and improve treatment rates and delays. Current scales, however, may lack detection accuracy. As such, we examined if coordination and diplopia (Balance and Eyes) assessments increase the accuracy of the Face-Arms-Speech-Time (FAST) scale in a multi-site prospective study of emergency response activations for presumed stroke.METHODS: This was a prospective study of emergency response activations for presumed stroke in Santa Clara County, California. Emergency medical responders were trained in the BEFAST scale and administered the scale on scene to all patients who were within 6hours of onset of neurological symptoms. Patient's final diagnosis (stroke vs no stroke) was based on review of hospital records. We compared the performance of the BEFAST and FAST scales for stroke detection.RESULTS: Three hundred fifty-nine patients were included in our analysis. Compared to non-stroke patients (n=200), stroke patients (n=159) more often scored positive on each of the five elements of the BEFAST scale (p<0.05 for each). In multivariable analysis, only facial droop and arm weakness were independent predictors of stroke (p<0.05). BEFAST and FAST scale accuracy for stroke identification was comparable (AUC=0.70 vs. AUC=0.69, p=0.36). Optimal cutoff for stroke detection was ≥1 for both scales. At this threshold, the PPV was 0.49 for the BEFAST and 0.53 for the FAST scale, and NPV was 0.93 for BEFAST and 0.86 for FAST.CONCLUSION: Adding coordination and diplopia assessments to face, arm, and speech assessment does not improve stroke detection in the prehospital setting.

    View details for DOI 10.1080/10903127.2018.1490837

    View details for PubMedID 30118372

  • 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

  • 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
  • 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

  • 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
  • Thrombectomy for Stroke with Selection by Perfusion Imaging NEW ENGLAND JOURNAL OF MEDICINE Vinny, P., Vishnu, V. Y., Srivastava, M. 2018; 378 (19): 1849

    View details for Web of Science ID 000431774400019

    View details for PubMedID 29745632

  • 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

  • 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

  • Visual Aids for Patient, Family, and Physician Decision Making About Endovascular Thrombectomy for Acute Ischemic Stroke STROKE Tokunboh, I., Vales Montero, M., Almeida, M., Sharma, L., Starkman, S., Szeder, V., Jahan, R., Liebeskind, D., Gonzalez, N., Demchuk, A., Froehler, M. T., Goyal, M., Lansberg, M. G., Lutsep, H., Schwamm, L., Saver, J. L. 2018; 49 (1): 90-+

    Abstract

    Rapid decision making optimizes outcomes from endovascular thrombectomy for acute cerebral ischemia. Visual displays facilitate swift review of potential outcomes and can accelerate decision processes.From patient-level, pooled randomized trial data, 100 person-icon arrays (Kuiper-Marshall personographs) were generated showing beneficial and adverse effects of endovascular thrombectomy for patients with acute cerebral ischemia and large vessel occlusion using (1) automated (algorithmic) and (2) expert-guided joint outcome table specification.For the full 7-category modified Rankin Scale, thrombectomy added to IV tPA (intravenous tissue-type plasminogen activator) alone had number needed to treat to benefit 2.9 (95% confidence interval, 2.6-3.3) and number needed to harm 68.9 (95% confidence interval, 40-250); thrombectomy for patients ineligible for IV tPA had number needed to treat to benefit 2.3 (95% confidence interval, 2.1-2.5) and number needed to harm 100 (95% confidence interval, 62.5-250). Visual displays of treatment effects on 100 patients showed: with thrombectomy added to IV tPA alone, 34 patients have better disability outcome, including 14 more normal or near normal (modified Rankin Scale, 0-1); with thrombectomy for patients ineligible for IV tPA, 44 patients have a better disability outcome, including 16 more normal or nearly normal. Displays also showed that harm (increased modified Rankin Scale final disability) occurred in 1 of 100 patients in both populations, mediated by increased new territory infarcts. The person-icon figures integrated these outcomes, and early side-effects, in a single display.Visual decision aids are now available to rapidly educate healthcare providers, patients, and families about benefits and risks of endovascular thrombectomy, both when added to IV tPA in tPA-eligible patients and as the sole reperfusion treatment in tPA-ineligible patients.

    View details for PubMedID 29222229

  • 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

  • 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

  • Stroke Recovery and Rehabilitation Research: Issues, Opportunities, and the National Institutes of Health StrokeNet. Stroke Cramer, S. C., Wolf, S. L., Adams, H. P., Chen, D., Dromerick, A. W., Dunning, K., Ellerbe, C., Grande, A., Janis, S., Lansberg, M. G., Lazar, R. M., Palesch, Y. Y., Richards, L., Roth, E., Savitz, S. I., Wechsler, L. R., Wintermark, M., Broderick, J. P. 2017; 48 (3): 813-819

    View details for DOI 10.1161/STROKEAHA.116.015501

    View details for PubMedID 28174324

    View details for PubMedCentralID PMC5330812

  • Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial. The Lancet. Neurology Elkins, J., Veltkamp, R., Montaner, J., Johnston, S. C., Singhal, A. B., Becker, K., Lansberg, M. G., Tang, W., Chang, I., Muralidharan, K., Gheuens, S., Mehta, L., Elkind, M. S. 2017; 16 (3): 217-226

    Abstract

    In animal models of acute ischaemic stroke, blocking of the leukocyte-endothelium adhesion by antagonism of α4 integrin reduces infarct volumes and improves outcomes. We assessed the effect of one dose of natalizumab, an antibody against the leukocyte adhesion molecule α4 integrin, in patients with acute ischaemic stroke.In this double-blind, phase 2 study, patients with acute ischaemic stroke (aged 18-85 years) from 30 US and European clinical sites were randomly assigned (1:1) to 300 mg intravenous natalizumab or placebo with stratification by treatment window and baseline infarct size. Patients, investigators, and study staff were masked to treatment assignments. The primary endpoint was the change in infarct volume from baseline to day 5 and was assessed in the modified intention-to-treat population. Secondary endpoints were the change in infarct volume from baseline to day 30, and from 24 h to days 5 and 30; the National Institute of Health Stroke Scale (NIHSS) at baseline, 24 h, and at days 5 (or discharge), 30, and 90; and modified Rankin Scale (mRS) and Barthel Index (BI) at days 5 (or discharge), 30, and 90. This trial is registered with ClinicalTrials.gov, number NCT01955707.Between Dec 16, 2013, and April 9, 2015, 161 patients were randomly assigned to natalizumab (n=79) or placebo (n=82). Natalizumab did not reduce infarct volume growth from baseline to day 5 compared with placebo (median absolute growth 28 mL [range -8 to 303] vs 22 mL [-11 to 328]; relative growth ratio 1·09 [90% CI 0·91-1·30], p=0·78) or to day 30 (4 mL [-43 to 121] vs 4 mL [-28 to 180]; 1·05 [0·88-1·27], p=0·68), from 24 h to day 5 (8 mL [-30 to 177] vs 7 mL [-13 to 204]; 1·00 [0·89-1·12], p=0·49), and from 24 h to day 30 (-5 mL [-93 to 81] vs -5 mL [-48 to 48]; 0·98 [0·87-1·11], p=0·40). No difference was noted between the natalizumab and placebo groups in the NIHSS (score ≤1 or ≥8 point improvement) from baseline at 24 h, day 5 (or discharge), day 30 (27 [35%] vs 36 [44%]; odds ratio 0·69 [90% CI 0·39-1·21], p=0·86), and day 90 (36 [47%] vs 37 [46%]; 1·10 [0·63-1·93], p=0·39). More patients in the natalizumab group than in the placebo group had mRS scores of 0 or 1 at day 30 (13 [18%] vs seven [9%]; odds ratio 2·88 [90% CI 1·20-6·93], p=0·024) and day 90 (18 [25%] vs 16 [21%]; 1·48 [0·74-2·98], p=0·18); and BI (score ≥95) at day 90 (34 [44%] vs 26 [33%]; 1·91 [1·07-3·41], p=0·033) but not significantly at day 5 or day 30 (26 [34%] vs 26 [32%]; 1·13 [0·63-2·00], p=0·37). Natalizumab and placebo groups had similar incidences of adverse events (77 [99%] of 78 patients vs 81 [99%] of 82 patients), serious adverse events (36 [46%] vs 38 [46%]), and deaths (14 [18%] vs 13 [16%]). Two patients in the natalizumab group died because of adverse events assessed as related to treatment by the investigator (pneumonia, and septic shock and multiorgan failure).Natalizumab administered up to 9 h after stroke onset did not reduce infarct growth. Treatment-associated benefits on functional outcomes might warrant further investigation.Biogen.

    View details for DOI 10.1016/S1474-4422(16)30357-X

    View details for PubMedID 28229893

  • 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

  • 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

  • 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

  • Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials. Stroke; a journal of cerebral circulation Spokoyny, I., Lansberg, M., Thiessen, R., Kemp, S. M., Aksoy, D., Lee, Y., Mlynash, M., Hirsch, K. G. 2016; 47 (10): 2652-2655

    Abstract

    Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians.A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform.A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening.We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields.

    View details for DOI 10.1161/STROKEAHA.116.013456

    View details for PubMedID 27608822

    View details for PubMedCentralID PMC5039105

  • 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

  • Detection of Atrial Fibrillation Among Patients With Stroke Due to Large or Small Vessel Disease: A Meta-Analysis. Journal of the American Heart Association Demeestere, J., Fieuws, S., Lansberg, M. G., Lemmens, R. 2016; 5 (9)

    Abstract

    Recent trials have demonstrated that extended cardiac monitoring increases the yield of paroxysmal atrial fibrillation (AF) detection in patients with cryptogenic stroke. The utility of extended cardiac monitoring is uncertain among patients with stroke caused by small and large vessel disease. We conducted a meta-analysis to estimate the yield of AF detection in this population.We searched PubMed, Cochrane, and SCOPUS databases for studies on AF detection in stroke patients and excluded studies restricted to patients with cryptogenic stroke or transient ischemic attack. We abstracted AF detection rates for 3 populations grouped by stroke etiology: large vessel stroke, small vessel stroke, and stroke of undefined etiology (a mixture of cryptogenic, small vessel, large vessel, and other stroke etiologies). Our search yielded 30 studies (n=5687). AF detection rates were similar in patients with large vessel (2.2%, 95% CI 0.3-5.5; n=830) and small vessel stroke (2.4%, 95% CI 0.4-6.1; n=520). No studies had a monitoring duration longer than 7 days. The yield of AF detection in the undefined stroke population was higher (9.2%; 95% CI 7.1-11.5) compared to small vessel stroke (P=0.02) and large vessel stroke (P=0.02) populations.AF detection rate is similar in patients with small and large vessel strokes (2.2-2.4%). Because no studies reported on extended monitoring (>7 days) in these stroke populations, we could not estimate the yield of AF detection with long-term cardiac monitoring. Randomized controlled trials are needed to examine the utility of AF detection with long-term cardiac monitoring (>7 days) in this patient population.

    View details for PubMedID 27671319

  • Effects of Alteplase for Acute Stroke on the Distribution of Functional Outcomes: A Pooled Analysis of 9 Trials. Stroke; a journal of cerebral circulation Lees, K. R., Emberson, J., Blackwell, L., Bluhmki, E., Davis, S. M., Donnan, G. A., Grotta, J. C., Kaste, M., von Kummer, R., Lansberg, M. G., Lindley, R. I., Lyden, P., Murray, G. D., Sandercock, P. A., Toni, D., Toyoda, K., Wardlaw, J. M., Whiteley, W. N., Baigent, C., Hacke, W., Howard, G. 2016; 47 (9): 2373-2379

    Abstract

    Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity.Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s).Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13-91; P=0.004).Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4); the earlier that treatment is initiated, the greater the benefit.

    View details for DOI 10.1161/STROKEAHA.116.013644

    View details for PubMedID 27507856

    View details for PubMedCentralID PMC5024752

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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 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

  • 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

  • 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

  • Diagnostic yield of extenced cardiac patch monitoring in patients with stroke or TIA FRONTIERS IN NEUROLOGY Tung, C. E., Su, D., Turakhia, M. P., Lansberg, M. G. 2015; 5
  • Imaging selection in ischemic stroke: feasibility of automated CT-perfusion analysis INTERNATIONAL JOURNAL OF STROKE Campbell, B. C., Yassi, N., Ma, H., Sharma, G., Salinas, S., Churilov, L., Meretoja, A., Parsons, M. W., Desmond, P. M., Lansberg, M. G., Donnan, G. A., Davis, S. M. 2015; 10 (1): 51-54

    Abstract

    Advanced imaging may refine patient selection for ischemic stroke treatment but delays to acquire and process the imaging have limited implementation.We examined the feasibility of imaging selection in clinical practice using fully automated software in the EXTEND trial program.CTP and perfusion-diffusion MRI data were processed using fully-automated software to generate a yes/no 'mismatch' classification that determined eligibility for trial therapies. The technical failure/mismatch classification error rate and time to image and treat with CT vs. MR-based selection were examined.In a consecutive series of 776 patients from five sites over six-months the technical failure rate of CTP acquisition/processing (uninterpretable maps) was 3·4% (26/776, 95%CI 2·2-4·9%). Mismatch classification was overruled by expert review in an additional 9·0% (70/776, 95%CI 7·1-11·3%) due to artifactual 'perfusion lesion'. In 154 consecutive patients at one site, median additional time to acquire CTP after non-contrast CT was 6·5 min. Subsequent RAPID processing time varied from 3-10 min across 20 trial centers (median 5 min 20 s). In the EXTEND trial, door-to-needle times in patients randomized on the basis of CTP (n = 47) were median 78 min shorter than MRI-selected (n = 16) patients (P < 0·001).Automated CTP-based mismatch selection is rapid, robust in clinical practice, and associated with faster treatment decisions than MRI. This technological advance has the potential to improve the standardization and reproducibility of interpretation of advanced imaging and extend use to practice settings beyond highly specialized academic centers.

    View details for DOI 10.1111/ijs.12381

    View details for Web of Science ID 000346156500017

    View details for PubMedID 25319251

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • Diagnostic Yield of Extended Cardiac Patch Monitoring in Patients with Stroke or TIA. Frontiers in neurology Tung, C. E., Su, D., Turakhia, M. P., Lansberg, M. G. 2014; 5: 266-?

    Abstract

    It is important to evaluate patients with transient ischemic attack (TIA) or stroke for atrial fibrillation (AF) because the detection of AF changes the recommended anti-thrombotic regimen from treatment with an antiplatelet agent to oral anticoagulation. This study describes the diagnostic yield of a patch-based, single-use, and water-resistant 14-day continuous cardiac rhythm monitor (ZIO Patch) in patients with stroke or TIA.We obtained data from the manufacturer and servicer of the ZIO Patch (iRhythm Technologies). Patients who were monitored between January 2012 and June 2013 and whose indication for monitoring was TIA or stroke were included. The duration of monitoring, the number and type of arrhythmias, and the time to first arrhythmia were documented.One thousand one hundred seventy-one monitoring reports were analyzed. The mean monitor wear time was 10.9 days and the median wear time was 13.0 days (interquartile range 7.2-14.0). The median analyzable time relative to the total wear time was 98.7% (IQR 96.0-99.5%). AF was present in 5.0% of all reports. The mean duration before the first episode of paroxysmal AF (PAF) was 1.5 days and the median duration was 0.4 days. 14.3% of first PAF episodes occurred after 48 h. The mean PAF burden was 12.7% of the total monitoring duration.Excellent quality of the recordings and very good patient compliance coupled with a substantial proportion of AF detection beyond the first 48 h of monitoring suggest that the cardiac patch is superior to conventional 48-h Holter monitors for AF detection in patients with stroke or TIA.

    View details for DOI 10.3389/fneur.2014.00266

    View details for PubMedID 25628595

  • Bilateral internal carotid artery occlusion associated with the antiphospholipid antibody syndrome. Case reports in neurology Anand, P., Mann, S. K., Fischbein, N. J., Lansberg, M. G. 2014; 6 (1): 50-54

    Abstract

    A 39-year-old woman presented with a right-hemispheric stroke 1 year after she had suffered a left-hemispheric stroke. Her diagnostic workup was notable for bilateral occlusions of the internal carotid arteries at their origins and a positive lupus anticoagulant antibody test. There was no evidence of carotid dissection or another identifiable cause for her carotid occlusions. These findings suggest that the antiphospholipid antibody syndrome may be implicated in the pathological changes that resulted in occlusions of the extracranial internal carotid arteries. Young stroke patients who present with unexplained internal carotid artery occlusions may benefit from testing for the presence of antiphospholipid antibodies.

    View details for DOI 10.1159/000360473

    View details for PubMedID 24707268

    View details for PubMedCentralID PMC3975723

  • Ferumoxytol enhanced resting state fMRI and relative cerebral blood volume mapping in normal human brain. NeuroImage D'Arceuil, H., Coimbra, A., Triano, P., Dougherty, M., Mello, J., Moseley, M., Glover, G., Lansberg, M., Blankenberg, F. 2013; 83: 200-209

    Abstract

    The brain demonstrates spontaneous low-frequency (<0.1Hz) cerebral blood flow (CBF) fluctuations, measurable by resting state functional MRI (rs-fMRI). Ultra small superparamagnetic iron oxide particles have been shown to enhance task-based fMRI signals (cerebral blood volume fMRI or CBV-fMRI), compared to the BOLD effect, by a factor of ≈2.5 at 3T in primates and humans. We evaluated the use of ferumoxytol for steady state, resting state FMRI (CBV-rs-fMRI) and relative cerebral blood volume (rCBV) mapping, at 3T, in healthy volunteers. All standard resting state networks (RSNs) were identified in all subjects. On average the RSN Z statistics (MELODIC independent components) and volumes of the visual and default mode (DMN) networks were comparable. rCBV values were averaged for the visual (Vis) and DMN networks and correlated with the corresponding DMN and visual network Z statistics. There was a negative correlation between the rCBV and the Z statistics for the DMN, for both BOLD and CBV-rs-fMRI contrast (R(2)=0.63, 0.76). A similar correlation was not found for the visual network. Short repetition time rs-fMRI data were Fourier transformed to evaluate the effect of ferumoxytol on cardiac and respiratory fluctuations in the brain rs-BOLD, CBV signals. Cardiac and respiratory fluctuations decreased to baseline within large vessels post ferumoxytol. Robust rs-fMRI and CBV mapping is possible in normal human brain.

    View details for DOI 10.1016/j.neuroimage.2013.06.066

    View details for PubMedID 23831413

  • 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

  • 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

  • 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

  • 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

  • Interaction between time to treatment and reperfusion therapy in patients with acute ischemic stroke. Journal of neurointerventional surgery Lansberg, M. G., Dabus, G. 2013; 5: i48-51

    View details for DOI 10.1136/neurintsurg-2013-010728

    View details for PubMedID 23572462

  • 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

  • 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 PubMedID 23444008

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • Antithrombotic and Thrombolytic Therapy for Ischemic Stroke Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Lansberg, M. G., O'Donnell, M. J., Khatri, P., Lang, E. S., Nguyen-Huynh, M. N., Schwartz, N. E., Sonnenberg, F. A., Schulman, S., Vandvik, P. O., Spencer, F. A., Alonso-Coello, P., Guyatt, G. H., Akl, E. A. 2012; 141 (2): E601S-E636S

    Abstract

    This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA).We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence.In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B).These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes.

    View details for DOI 10.1378/chest.11-2302

    View details for Web of Science ID 000208839900017

    View details for PubMedCentralID PMC3278065

  • Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Guyatt, G. H., Eikelboom, J. W., Gould, M. K., Garcia, D. A., Crowther, M., Murad, M. H., Kahn, S. R., Falck-Ytter, Y., Francis, C. W., Lansberg, M. G., Akl, E. A., Hirsh, J. 2012; 141 (2): e185S-94S

    Abstract

    This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available.

    View details for DOI 10.1378/chest.11-2289

    View details for PubMedID 22315260

  • Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Vandvik, P. O., Lincoff, A. M., Gore, J. M., Gutterman, D. D., Sonnenberg, F. A., Alonso-Coello, P., Akl, E. A., Lansberg, M. G., Guyatt, G. H., Spencer, F. A. 2012; 141 (2): e637S-68S

    Abstract

    This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies.The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.We present 23 recommendations for pertinent clinical questions. For primary prevention of cardiovascular disease, we suggest low-dose aspirin (75-100 mg/d) in patients aged > 50 years over no aspirin therapy (Grade 2B). For patients with established coronary artery disease, defined as patients 1-year post-acute coronary syndrome, with prior revascularization, coronary stenoses > 50% by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing, we recommend long-term low-dose aspirin or clopidogrel (75 mg/d) (Grade 1A). For patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI) with stent placement, we recommend for the first year dual antiplatelet therapy with low-dose aspirin in combination with ticagrelor 90 mg bid, clopidogrel 75 mg/d, or prasugrel 10 mg/d over single antiplatelet therapy (Grade 1B). For patients undergoing elective PCI with stent placement, we recommend aspirin (75-325 mg/d) and clopidogrel for a minimum duration of 1 month (bare-metal stents) or 3 to 6 months (drug-eluting stents) (Grade 1A). We suggest continuing low-dose aspirin plus clopidogrel for 12 months for all stents (Grade 2C). Thereafter, we recommend single antiplatelet therapy over continuation of dual antiplatelet therapy (Grade 1B).Recommendations continue to favor single antiplatelet therapy for patients with established coronary artery disease. For patients with acute coronary syndromes or undergoing elective PCI with stent placement, dual antiplatelet therapy for up to 1 year is warranted.

    View details for DOI 10.1378/chest.11-2306

    View details for PubMedID 22315274

    View details for PubMedCentralID PMC3278064

  • Antithrombotic Therapy in Peripheral Artery Disease Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Alonso-Coello, P., Bellmunt, S., McGorrian, C., Anand, S. S., Guzman, R., Criqui, M. H., Akl, E. A., Vandvik, P. O., Lansberg, M. G., Guyatt, G. H., Spencer, F. A. 2012; 141 (2): E669S-E690S
  • Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Alonso-Coello, P., Bellmunt, S., McGorrian, C., Anand, S. S., Guzman, R., Criqui, M. H., Akl, E. A., Olav Vandvik, P., Lansberg, M. G., Guyatt, G. H., Spencer, F. A. 2012; 141 (2): e669S-90S

    Abstract

    This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD).The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.The most important of our 20 recommendations are as follows. In patients aged ≥ 50 years with asymptomatic PAD or asymptomatic carotid stenosis, we suggest aspirin (75-100 mg/d) over no therapy (Grade 2B) for the primary prevention of cardiovascular events. For secondary prevention of cardiovascular disease in patients with symptomatic PAD (including patients before and after peripheral arterial bypass surgery or percutaneous transluminal angioplasty), we recommend long-term aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 1A). We recommend against the use of warfarin plus aspirin in patients with symptomatic PAD (Grade 1B). For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, we suggest single rather than dual antiplatelet therapy (Grade 2C). For patients with refractory claudication despite exercise therapy and smoking cessation, we suggest addition of cilostazol (100 mg bid) to aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 2C). In patients with critical limb ischemia and rest pain unable to undergo revascularization, we suggest the use of prostanoids (Grade 2C). In patients with acute limb ischemia due to acute thrombosis or embolism, we recommend surgery over peripheral arterial thrombolysis (Grade 1B).Recommendations continue to favor single antiplatelet therapy for primary and secondary prevention of cardiovascular events in most patients with asymptomatic PAD, symptomatic PAD, and asymptomatic carotid stenosis. Additional therapies for relief of limb symptoms should be considered only after exercise therapy, smoking cessation, and evaluation for peripheral artery revascularization.

    View details for DOI 10.1378/chest.11-2307

    View details for PubMedID 22315275

    View details for PubMedCentralID PMC3278062

  • Approach to Outcome Measurement in the Prevention of Thrombosis in Surgical and Medical Patients Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Guyatt, G. H., Eikelboom, J. W., Gould, M. K., Garcia, D. A., Crowther, M., Murad, M. H., Kahn, S. R., Falck-Ytter, Y., Francis, C. W., Lansberg, M. G., Akl, E. A., Hirsh, J. 2012; 141 (2): E185S-E194S

    Abstract

    This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available.

    View details for DOI 10.1378/chest.11-2289

    View details for Web of Science ID 000208839900007

    View details for PubMedCentralID PMC3278047

  • Primary and Secondary Prevention of Cardiovascular Disease Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Vandvik, O., Lincoff, A. M., Gore, J. M., Gutterman, D. D., Sonnenberg, F. A., Alonso-Coello, P., Akl, E. A., Lansberg, M. G., Guyatt, G. H., Spencer, F. A. 2012; 141 (2): E637S-E668S
  • Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Lansberg, M. G., O'Donnell, M. J., Khatri, P., Lang, E. S., Nguyen-Huynh, M. N., Schwartz, N. E., Sonnenberg, F. A., Schulman, S., Vandvik, P. O., Spencer, F. A., Alonso-Coello, P., Guyatt, G. H., Akl, E. A. 2012; 141 (2): e601S-36S

    Abstract

    This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA).We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence.In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B).These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes.

    View details for DOI 10.1378/chest.11-2302

    View details for PubMedID 22315273

    View details for PubMedCentralID PMC3278065

  • Cost comparison between the atraumatic and cutting lumbar puncture needles NEUROLOGY Tung, C. E., So, Y. T., Lansberg, M. G. 2012; 78 (2): 109-113

    Abstract

    The aim of this study was to determine which type of spinal needle is preferred from a cost perspective, taking into account costs of the spinal needle and treatment of postlumbar puncture headache.A decision-analytic model was created to determine the cost of diagnostic lumbar punctures using atraumatic and cutting needles. We assumed a health care system perspective and based the analysis on the treatment of a patient facing event probabilities derived from prior studies. The economic outcome measure was the difference in estimated costs between the 2 needles. One-way and probabilistic sensitivity analyses tested the robustness of the model.Lumbar puncture performed with the atraumatic needle is associated with an average cost savings of $26.07 per patient. Average total health care costs are $166.08 with the atraumatic needle, compared to $192.15 with the cutting needle. There is 94% certainty that the atraumatic needle is cost-saving compared to the cutting needle based on probabilistic sensitivity analysis. Use of the atraumatic needle over the cutting needle by neurologists alone may result in $10.4 million in cost savings to the US health care system per year.The atraumatic spinal needle is associated with an overall cost savings to the US health care system. The balance of costs and benefits favors the use of the atraumatic needle over the cutting needle for diagnostic lumbar puncture.

    View details for PubMedID 22205758

  • 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

  • Cost-Effectiveness of Tissue-Type Plasminogen Activator in the 3-to 4.5-Hour Time Window for Acute Ischemic Stroke STROKE Tung, C. E., Win, S. S., Lansberg, M. G. 2011; 42 (8): 2257-2262

    Abstract

    The aim of this study was to determine the cost-effectiveness of tissue-type plasminogen activator (tPA) treatment in the 3- to 4.5-hour time window after ischemic stroke.Decision-analytic and Markov state-transition models were created to determine the cost-effectiveness of treatment of ischemic stroke patients with intravenous tPA administered in the 3- to 4.5-hour time window compared with medical therapy without tPA. Health benefits were measured in quality-adjusted life-years (QALYs). The economic outcome measure of the model was the difference in estimated healthcare costs between the 2 treatment alternatives. The incremental cost-effectiveness ratio was calculated by dividing the cost difference by the difference in QALYs. One-way sensitivity and probabilistic analyses were performed to test the robustness of the model.The administration of tPA compared with standard medical therapy resulted in a lifetime gain of 0.28 QALYs for an additional cost of $6050, yielding an incremental cost-effectiveness ratio of $21 978 per QALY. One-way sensitivity analyses demonstrated that the incremental cost-effectiveness ratio was most sensitive to the cost of hospitalization for patients who received tPA. Based on probabilistic analysis, there is an 88% probability that tPA is the preferred treatment at a willingness-to-pay threshold of $50 000 per QALY.The balance of costs and benefits favors treatment with intravenous tPA in the 3- to 4.5-hour time window. This supports, from a societal perspective, the use of tPA therapy in this treatment time window for acute ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.111.615682

    View details for Web of Science ID 000293077400034

    View details for PubMedID 21719767

    View details for PubMedCentralID PMC3164239

  • 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

  • Meta-analysis of randomized intra-arterial thrombolytic trials for the treatment of acute stroke due to middle cerebral artery occlusion JOURNAL OF NEUROINTERVENTIONAL SURGERY Fields, J. D., Khatri, P., Nesbit, G. M., Liu, K. C., Barnwell, S. L., Lutsep, H. L., Clark, W. M., Lansberg, M. G. 2011; 3 (2): 151-155

    Abstract

    Randomized clinical trials supporting the use of intra-arterial administration of thrombolytics (IAT) for the treatment of stroke due to middle cerebral artery (MCA) occlusion have been positive on some, but not all, endpoints. A meta-analysis was performed to estimate with more precision the effect of IAT on several key clinical endpoints.All randomized trials of IAT in the treatment of MCA stroke were identified by PUBMED search and by hand search of potentially relevant references. Trial methodologies were assessed for compatibility in study protocols and statistical analysis. A meta-analysis was performed evaluating the effect of IAT on functional outcome at 90 days and symptomatic intracranial hemorrhage (SICH) within 24 h.Three trials met the criteria for the meta-analysis. IAT treated patients were significantly more likely to have a modified Rankin scale (mRS) ≤ 1 (31% vs 20%, OR 2.0, 95% CI 1.2 to 3.4, p=0.01); mRS ≤ 2 (43% vs 31%, OR 1.9, 95% CI 1.2 to 3.0, p=0.01); and NIH Stroke Scale score 0 or 1 (23% vs 12%, OR 2.4, 95% CI 1.3 to 4.4, p=0.007) at the 90 day follow-up. There was no effect on mortality at 90 days (20% vs 19%, OR 0.84, 95% CI 0.5 to 1.5). The risk of SICH was significantly increased in the active treatment arms (11% vs 2%, OR 4.6, 95% CI 1.3 to 16, p=0.02).Our meta-analysis demonstrates that all standard functional endpoints for stroke trials were substantially improved in the active treatment arms. Despite an increased risk of SICH, there was no effect on mortality. These results support endovascular treatment of acute ischemic stroke due to MCA occlusion with intra-arterial thrombolytics.

    View details for DOI 10.1136/jnis.2010.002766

    View details for PubMedID 21990808

  • 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

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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

  • 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

  • A comparison of cooling techniques to treat cardiac arrest patients with hypothermia. Stroke research and treatment Finley Caulfield, A., Rachabattula, S., Eyngorn, I., Hamilton, S. A., Kalimuthu, R., Hsia, A. W., Lansberg, M. G., Venkatasubramanian, C., BAUMANN, J. J., Buckwalter, M. S., Kumar, M. A., Castle, J. S., Wijman, C. A. 2011; 2011: 690506-?

    Abstract

    Introduction. We sought to compare the performance of endovascular cooling to conventional surface cooling after cardiac arrest. Methods. Patients in coma following cardiopulmonary resuscitation were cooled with an endovascular cooling catheter or with ice bags and cold-water-circulating cooling blankets to a target temperature of 32.0-34.0°C for 24 hours. Performance of cooling techniques was compared by (1) number of hourly recordings in target temperature range, (2) time elapsed from the written order to initiate cooling and target temperature, and (3) adverse events during the first week. Results. Median time in target temperature range was 19 hours (interquartile range (IQR), 16-20) in the endovascular group versus. 10 hours (IQR, 7-15) in the surface group (P = .001). Median time to target temperature was 4 (IQR, 2.8-6.2) and 4.5 (IQR, 3-6.5) hours, respectively (P = .67). Adverse events were similar. Conclusion. Endovascular cooling maintains target temperatures better than conventional surface cooling.

    View details for DOI 10.4061/2011/690506

    View details for PubMedID 21822470

  • Utility of the anesthetic test dose to avoid catastrophic injury during cervical transforaminal epidural injections SPINE JOURNAL Smuck, M., Maxwell, M. D., Kennedy, D., Rittenberg, J. D., Lansberg, M. G., Plastaras, C. T. 2010; 10 (10): 857-864

    Abstract

    Reports of serious complications from cervical transforaminal epidural corticosteroid injections often consider accidental intra-arterial injection the most likely mechanism of injury. As a result, many physicians have instituted methods to prevent intravascular injections. Routine use of the anesthetic test dose is one such method. The utility of the anesthetic test dose in this function has not been characterized in the current literature.The aim of this study was to determine the utility of injecting an anesthetic test dose before cervical transforaminal epidural corticosteroid injection and estimate the rate of false-negative intravascular contrast injection using live fluoroscopy and digital subtraction angiography (DSA).Two-center retrospective study.A consecutive cohort of men and women, ages of 23 to 83, who underwent cervical transforaminal epidural injection and received the anesthetic test dose after contrast injection was negative for vascular uptake, observed using live fluoroscopy or DSA.Response to the anesthetic test dose was documented in each procedure note and recorded as either positive or negative.Records of three physiatrists at two academic spine centers (Center A and Center B) were reviewed to identify all patients who received a cervical transforaminal epidural injection during the preceding 5 years, resulting in a cohort of consecutively treated patients at each center. Each patient record was reviewed for demographics, indication for injection, procedure level and side, needle gauge, use of DSA, volume and type of anesthetic test dose used, and result of test dose injection. The test dose was considered positive if the following occurred: agitation or other sudden central nervous system change; gross motor deficits and/or paresthesias in the trunk, legs, or contralateral arm; systemic symptoms of anesthetic toxicity including cardiac arrhythmia, perioral numbness, metallic taste, dizziness, and/or ringing in the ear. For analysis, injections were separated into groups to compare results at Center A to Center B and to compare injections that used DSA to those that did not. The incidence of a positive response was calculated as a percentage from the total number of injections in the group. Differences between groups were analyzed for statistical significance using the Fisher exact test.Six hundred seventy-eight injections were included. Of these, 349 were performed at Center A with test doses given after contrast injection under live fluoroscopy. The remaining 329 were performed at Center B, 183 also using live fluoroscopy, and 146 using DSA. The overall incidence of a positive anesthetic test dose was 0.59% (4/678). There was no significant difference between the incidence at each of the two centers (0.86% [3/349] vs. 0.30% [1/329]; p=.63). The overall incidence after live fluoroscopy was 0.75% (4/532) and after DSA was 0% (0/146), but this difference was not statistically significant (p=.58). Positive symptoms elicited by test dose administration included midneck and contralateral arm pain, metallic taste, dizziness, tachycardia, full body paresthesias, auditory changes, slurred speech, and motor ataxia. In all four cases with a positive response, the procedure was immediately terminated, symptoms resolved, and no lasting complications were observed.The routine use of an anesthetic test dose appears to be safe and capable of detecting potentially dangerous intravascular injections undetected by conventional techniques. Positive responses occur in a small portion of those who receive the test dose injection. Further studies are required to determine the optimal dose and concentration of anesthetic to be used and the time required for observation after test dose administration.

    View details for DOI 10.1016/j.spinee.2010.07.003

    View details for Web of Science ID 000283190400002

    View details for PubMedID 20692210

  • 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

  • STROKE Taking stock-patient selection for acute stroke therapy NATURE REVIEWS NEUROLOGY Lansberg, M. 2010; 6 (7): 358-359

    View details for DOI 10.1038/nrneurol.2010.75

    View details for Web of Science ID 000279624100002

    View details for PubMedID 20639911

  • Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists NEUROLOGY Caulfield, A. F., GABLER, L., Lansberg, M. G., Eyngorn, I., Mlynash, M., Buckwalter, M. S., Venkatasubramanian, C., Wijman, C. A. 2010; 74 (14): 1096-1101

    Abstract

    Physician prediction of outcome in critically ill neurologic patients impacts treatment decisions and goals of care. In this observational study, we prospectively compared predictions by neurointensivists to patient outcomes at 6 months.Consecutive neurologic patients requiring mechanical ventilation for 72 hours or more were enrolled. The attending neurointensivist was asked to predict 6-month 1) functional outcome (modified Rankin scale [mRS]), 2) quality of life (QOL), and 3) whether supportive care should be withdrawn. Six-month functional outcome was determined by telephone interviews and dichotomized to good (mRS 0-3) and poor outcome (mRS 4-6).Of 187 eligible patients, 144 were enrolled. Neurointensivists correctly predicted 6-month functional outcome in 80% (95% confidence interval [CI], 72%-86%) of patients. Accuracy for a predicted good outcome was 63% (95% CI, 50%-74%) and for poor outcome 94% (95% CI, 85%-98%). Excluding patients who had life support withdrawn, accuracy for good outcome was 73% (95% CI, 60%-84%) and for poor outcome 87% (95% CI, 74%-94%). Accuracy for exact agreement between neurointensivists' mRS predictions and actual 6-month mRS was only 43% (95% CI, 35%-52%). Predicted accuracy for QOL was 58% (95% CI, 39%-74%) for good/excellent and 67% (95% CI, 46%-83%) for poor/fair. Of 27 patients for whom withdrawal of care was recommended, 1 patient survived in a vegetative state.Prediction of long-term functional outcomes in critically ill neurologic patients is challenging. Our neurointensivists were more accurate in predicting poor outcome than good outcome in patients requiring mechanical ventilation >or=72 hours.

    View details for Web of Science ID 000276354400005

    View details for PubMedID 20368630

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Favorable Outcome From A Locked-In State Despite Extensive Pontine Infarction By MRI NEUROCRITICAL CARE Samaniego, E. A., Lansberg, M. G., DeGeorgia, M., Venkatasubramanian, C., Wijman, C. A. 2009; 11 (3): 369-371

    Abstract

    Outcome prediction of patients who are in a locked-in state is challenging. Extensive pontine infarction on diffusion weighted imaging MRI (DWI) has been proposed as a poor prognosticator. We report on three patients with a locked-in state with unexpected favorable recoveries despite DWI evidence of widespread pontine ischemia.Report of three cases.Three young patients (32-, 30-, and 16-years-old) presented with a locked-in state caused by pontine infarction. The first patient did not receive any acute stroke therapies, the second patient underwent endovascular therapy 20 h after symptom onset resulting in partial recanalization of the basilar artery, and the third patient progressed to a locked-in state despite having received intravenous tissue plasminogen activator. The DWI of all three patients demonstrated acute and widespread pontine infarction involving more than two-thirds of the pons. Two patients regained full independence in their activities of daily living. The third patient remained wheelchair bound, but lives with her family, eats independently, uses a typewriter and wrote a book.Patients who are in a locked-in state may have substantial functional recovery despite DWI evidence of extensive pontine infarction.

    View details for DOI 10.1007/s12028-009-9268-y

    View details for Web of Science ID 000271943800011

    View details for PubMedID 19707888

  • Profiles of Neurological Outcome Prediction Among Intensivists NEUROCRITICAL CARE Racine, E., Dion, M., Wijman, C. A., Illes, J., Lansberg, M. G. 2009; 11 (3): 345-352

    Abstract

    Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability.Based on a clinical vignette describing a comatose patient suffering from post-anoxic brain injury intensivists were asked in a semi-structured interview about the patient's specific neurological prognosis and about prognostication in general. Qualitative research methods were used to identify areas of variability in prognostication and to classify physicians according to specific prognostication profiles. Quantitative statistics were used to assess for associations between prognostication profiles and physicians' demographic and practice characteristics.Eighteen intensivists participated. Functional outcome predictions varied along an evaluative dimension (fair/good-poor) and a confidence dimension (certain-uncertain). More experienced physicians tended to be more pessimistic about the patient's functional outcome and more certain of their prognosis. Attitudes toward quality of life varied along an evaluative dimension (good-poor) and a "style" dimension (objective-subjective). Older and more experienced physicians were more likely to express objective judgments of quality of life and to predict a worse quality of life for the patient than their younger and less experienced counterparts.Various prognostication profiles exist among intensivists. These may be dictated by factors such as physicians' age and clinical experience. Awareness of these associations may be a first step to more uniform prognostication.

    View details for DOI 10.1007/s12028-009-9225-9

    View details for Web of Science ID 000271943800008

    View details for PubMedID 19430929

  • 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

  • Efficacy and Safety of Tissue Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic Stroke A Metaanalysis STROKE Lansberg, M. G., Bluhmki, E., Thijs, V. N. 2009; 40 (7): 2438-2441

    Abstract

    The Third European Cooperative Acute Stroke Study (ECASS-3) demonstrated a benefit of treatment with intravenous tissue plasminogen activator (tPA) for acute stroke in the 3- to 4.5-hour time-window. Prior studies, however, have failed to demonstrate a significant benefit of tPA for patients treated beyond 3 hours. The purpose of this study was to produce reliable and precise estimates of the treatment effect of tPA by pooling data from all relevant studies.A metaanalysis was undertaken to determine the efficacy of tPA in the 3- to 4.5-hour time-window. The effect of tPA on favorable outcome and mortality was assessed.The metaanalysis included data from patients treated in the 3- to 4.5-hour time-window in ECASS-1 (n=234), ECASS-2 (n=265), ECASS-3 (n=821) and The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) (n=302). tPA treatment was associated with an increased chance of favorable outcome (odds ratio 1.31; 95% CI: 1.10 to 1.56; P=0.002) and no significant difference in mortality (odds ratio 1.04; 95% CI: 0.75 to 1.43; P=0.83) compared to placebo treated patients.Treatment with tPA in the 3- to 4.5-hour time-window is beneficial. It results in an increased rate of favorable outcome without adversely affecting mortality.

    View details for DOI 10.1161/STROKEAHA.109.552547

    View details for Web of Science ID 000267467900026

    View details for PubMedID 19478213

    View details for PubMedCentralID PMC2725521

  • Treatment Time-Specific Number Needed to Treat Estimates for Tissue Plasminogen Activator Therapy in Acute Stroke Based on Shifts Over the Entire Range of the Modified Rankin Scale STROKE Lansberg, M. G., Schrooten, M., Bluhmki, E., Thijs, V. N., Saver, J. L. 2009; 40 (6): 2079-2084

    Abstract

    To make informed treatment decisions, patients and physicians need to be aware of the benefits and risks of a proposed treatment. The number needed to treat (NNT) for benefit and harm are intuitive and statistically valid measures to describe a treatment effect. The aim of this study is to calculate treatment time-specific NNT estimates based on shifts over the entire spectrum of clinically relevant functional outcomes.The pooled data set of the first 6 major randomized acute stroke trials of intravenous tissue plasminogen activator was used for this study. The data were stratified by 90-minute treatment time windows. NNT for benefit and NNT for harm estimates were determined based on expert generation of joint outcome distribution tables. NNT for benefit estimates were also calculated based on joint outcome distribution tables generated by a computer model.NNT for benefit estimates based on the expert panel were 3.6 for patients treated between 0 and 90 minutes, 4.3 with treatment between 91 and 180 minutes, 5.9 with treatment between 181 and 270 minutes, and 19.3 with treatment between 271 and 360 minutes. The computer simulation yielded very similar results. The NNT for harm estimates for the corresponding time intervals are 65, 38, 30, and 14.Up to 4(1/2) hours after symptom onset, tissue plasminogen activator therapy is associated with more benefit than harm, whereas there is no evidence of a net benefit in the 4(1/2)- to 6-hour time window. The NNT estimates for each 90-minute epoch provide useful and intuitive information based on which patients may be able to make better informed treatment decisions.

    View details for DOI 10.1161/STROKEAHA.108.540708

    View details for Web of Science ID 000266302200025

    View details for PubMedID 19372447

    View details for PubMedCentralID PMC2881642

  • 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

  • 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
  • Tissue Plasminogen Activator Does Not Benefit Most Eligible Patients With Stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Schwartz, N. E. 2009; 66 (4): 540-541

    View details for Web of Science ID 000265104400025

    View details for PubMedID 19364946

  • 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

  • Cost-effectiveness analysis of mechanical thrombectomy in acute ischemic stroke Clinical article JOURNAL OF NEUROSURGERY Patil, C. G., Long, E. F., Lansberg, M. G. 2009; 110 (3): 508-513

    Abstract

    Mechanical thrombectomy is increasingly being used for the treatment of large-vessel ischemic stroke in patients who arrive outside of the 3-hour tissue plasminogen activator time window. In this study, the authors evaluated the cost and effectiveness of mechanical thrombectomy compared with standard medical therapy in patients who are ineligible to receive tissue plasminogen activator.Clinical outcomes of an open-label study of mechanical thrombectomy were compared with a hypothetical control group with a lower recanalization rate (18 vs 60%) and a lower rate of symptomatic intracranial hemorrhage (0.6 vs 7.8%) than the active treatment group. A Markov cost-effectiveness model was built to compare the health benefits and costs associated with mechanical thrombectomy compared with standard medical therapy. All probabilities, quality-of-life factors, and costs were estimated from the published literature. Univariate sensitivity analyses were performed to assess how variations in model parameters affect health and economic outcomes.Treatment of acute ischemic stroke with mechanical thrombectomy increased survival time by 0.54 quality-adjusted life years (QALYs), compared with standard medical therapy (2.37 vs 1.83 QALYs), at an increased cost of $6600. This yielded an incremental cost-effectiveness ratio (ICER) of $12,120 per QALY gained, a value generally considered cost-effective. Sensitivity analysis showed that mechanical thrombectomy remained cost-effective (ICER < $50,000 per QALY gained) for all model inputs varied over a reasonable range, except for age at stroke treatment. For patients older than 82 years of age, the treatment was only borderline cost-effective (ICER of $50,000-100,000 per QALY gained).The treatment of large-vessel ischemic stroke with mechanical thrombectomy appears to be costeffective. These results require validation when data from a randomized, controlled trial of mechanical thrombectomy become available.

    View details for DOI 10.3171/2008.8.JNS08133

    View details for Web of Science ID 000263868000017

    View details for PubMedID 19025358

    View details for PubMedCentralID PMC2669322

  • 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

  • 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

  • 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

  • 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

  • Concurrent presentation of perimesencephalic subarachnoid hemorrhage and ischemic stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lansberg, M. G. 2008; 17 (4): 248-250

    Abstract

    Perimesencephalic subarachnoid hemorrhage (SAH) is a relatively benign form of SAH. The etiology of this condition is unknown but venous leakage has been believed to be the most likely cause. This report describes a patient with perimesencephalic SAH who presented with a concurrent acute pontine infarct demonstrated on diffusion-weighted magnetic resonance imaging. These findings suggest that in some instances perimesencephalic SAH is caused by rupture of a perforating artery.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.03.005

    View details for PubMedID 18589349

    View details for PubMedCentralID PMC2483244

  • 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

  • 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

  • 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
  • Delirium following abrupt discontinuation of fluoxetine CLINICAL NEUROLOGY AND NEUROSURGERY Blum, D., Maldonado, J., Meyer, E., Lansberg, M. 2008; 110 (1): 69-70

    Abstract

    Sudden discontinuation of serotonin reuptake inhibitors (SRI) can lead to a number of psychological (e.g., nervousness, anxiety, crying spells, psychomotor agitation, irritability, depersonalization, decreased mood, memory disturbances, confusion, decreased concentration, and/or slowed thinking) and somatic (e.g., nausea, dizziness, headache) symptoms. Recent studies have shown that withdrawal symptoms are common with paroxetine, venlafaxine and fluvoxamine, but relatively rare and mild with fluoxetine cessation, likely as a result of its longer half-life. We report an unusual case of a patient who developed delirium after abrupt discontinuation of fluoxetine.

    View details for DOI 10.1016/j.clineuro.2007.08.016

    View details for Web of Science ID 000252799500013

    View details for PubMedID 17913343

  • 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

  • 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

  • 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

  • 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

  • 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

  • "Paradoxical" transtentorial herniation due to CSF drainage in the presence of a hemicraniectomy NEUROLOGY Fields, J. D., Lansberg, M. G., Skirboll, S. L., Kurien, P. A., Wijman, C. A. 2006; 67 (8): 1513-1514

    View details for Web of Science ID 000241494800046

    View details for PubMedID 17060591

  • 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

  • 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

  • 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

  • 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
  • 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

  • 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

  • Comparison of diffusion-weighted MRI and CT in acute stroke - Reply NEUROLOGY Marks, M. P., Albers, G., Lansberg, M. 2000; 55 (11): 1760-1760
  • 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

  • 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

  • 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

  • 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

  • Intra-arterial rtPA treatment of stroke assessed by diffusion- and perfusion-weighted MRI STROKE Lansberg, M. G., Tong, D. C., Norbash, A. M., Yenari, M. A., Moseley, M. E. 1999; 30 (3): 678-680

    Abstract

    Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) are new techniques that can be used for the evaluation of acute ischemic stroke. However, their potential role in the management of patients treated with recombinant tissue plasminogen activator (rtPA) has yet to be determined.The authors present the case of a 73-year-old man who was treated with intra-arterial rtPA, and they compare findings on DWI and PWI scans with angiography. PWI revealed decreased cerebral perfusion corresponding to an area that was not successfully recanalized, but revealed no abnormality in regions in which blood flow was restored. DWI was unremarkable in the region that was reperfused early (3 hours) but revealed hyperintensity in an area that was reperfused 3. 5 hours after symptom onset and in the area that was not reperfused.Findings on PWI correlated well with angiography, and DWI detected injured tissue in the hyperacute stage, whereas conventional MRI findings were negative. This suggests that these techniques may be useful to noninvasively evaluate the success of thrombolytic therapy.

    View details for Web of Science ID 000078913700040

    View details for PubMedID 10066870

  • 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

  • Method for decreasing CT simulation time of complex phantoms and systems through separation of material specific projection data SPIE Medical Imaging 2017: Physics of Medical Imaging Divel, S. E., Christensen, S., Wintermark, M., Lansberg, M. G., Pelc, N. J. 2017: 1013259

    View details for DOI 10.1117/12.2254076