Dr. Anirudh Sreekrishnan is a vascular neurology fellow with research interests in quality improvement within acute stroke care, imaging of stroke and intracerebral hemorrhage, and stroke outcomes. He completed his medical education at Yale School of Medicine with a Masters in Health Science and research in intracerebral hemorrhage outcomes. He then pursued his neurology training at Harvard Medical School affiliated with the Mass General Brigham Hospitals in Boston. Dr. Sreekrishnan plans to continue working as an academic neurologist and neurovascular clinician after fellowship.
Medical Education: Yale University School of Medicine (2017) CT
Board Certification: American Board of Psychiatry and Neurology, Neurology (2021)
Residency: Brigham and Women's and Mass General Hospital Neurology Residency (2021) MA
Internship: Brigham and Women's Hospital Internal Medicine Residency (2018) MA
Infarct Core Growth During Interhospital Transfer For Thrombectomy Is Faster At Night.
Preclinical stroke models have recently reported faster infarct growth (IG) when ischemia was induced during daytime. Considering the inverse rest-activity cycles of rodents and humans, faster IG during the nighttime has been hypothesized in humans.We retrospectively evaluated acute ischemic stroke patients with a large vessel occlusion transferred from a primary to 1 of 3 French comprehensive stroke center, with magnetic resonance imaging obtained at both centers before thrombectomy. Interhospital IG rate was calculated as the difference in infarct volumes on the 2 diffusion-weighted imaging, divided by the time elapsed between the 2 magnetic resonance imaging. IG rate was compared between patients transferred during daytime (7:00-22:59) and nighttime (23:00-06:59) in multivariable analysis adjusting for occlusion site, National Institutes of Health Stroke Scale score, infarct topography, and collateral status.Out of the 329 patients screened, 225 patients were included. Interhospital transfer occurred during nighttime in 31 (14%) patients and daytime in 194 (86%). Median interhospital IG was faster when occurring at night (4.3 mL/h; interquartile range, 1.2-9.5) as compared to the day (1.4 mL/h; interquartile range, 0.4-3.5; P<0.001). In multivariable analysis, nighttime transfer remained independently associated with IG rate (P<0.05).Interhospital IG appeared faster in patients transferred at night. This has potential implications for the design of neuroprotection trials and acute stroke workflow.
View details for DOI 10.1161/STROKEAHA.123.043643
View details for PubMedID 37376988
- Stroke Caused by a Paradoxical Embolus From a Rare Congenital Anomaly in the Adult: Persistent Left Superior Vena Cava Draining into the Left Upper Pulmonary Vein. Circulation. Cardiovascular imaging 2023: e014205
Consensus Recommendations for Standardized Data Elements, Scales, and Time Segmentations in Studies of Human Circadian/Diurnal Biology and Stroke.
Increasing evidence indicates that circadian and diurnal rhythms robustly influence stroke onset, mechanism, progression, recovery, and response to therapy in human patients. Pioneering initial investigations yielded important insights but were often single-center series, used basic imaging approaches, and used conflicting definitions of key data elements, including what constitutes daytime versus nighttime. Contemporary methodologic advances in human neurovascular investigation have the potential to substantially increase understanding, including the use of large multicenter and national data registries, detailed clinical trial data sets, analysis guided by individual patient chronotype, and multimodal computed tomographic and magnetic resonance imaging. To fully harness the power of these approaches to enhance pathophysiologic knowledge, an important foundational step is to develop standardized definitions and coding guides for data collection, permitting rapid aggregation of data acquired in different studies, and ensuring a common framework for analysis. To meet this need, the Leducq Consortium International pour la Recherche Circadienne sur l'AVC (CIRCA) convened a Consensus Statement Working Group of leading international researchers in cerebrovascular and circadian/diurnal biology. Using an iterative, mixed-methods process, the working group developed 79 data standards, including 48 common data elements (23 new and 25 modified/unmodified from existing common data elements), 14 intervals for time-anchored analyses of different granularity, and 7 formal, validated scales. This portfolio of standardized data structures is now available to assist researchers in the design, implementation, aggregation, and interpretation of clinical, imaging, and population research related to the influence of human circadian/diurnal biology upon ischemic and hemorrhagic stroke.
View details for DOI 10.1161/STROKEAHA.122.041394
View details for PubMedID 37272394
Elevated Hypoperfusion Intensity Ratio (HIR) observed in patients with a large vessel occlusion (LVO) presenting in the evening.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
2023; 32 (8): 107172
BACKGROUND: Circadian variability has been implicated in timing of stroke onset, yet the full impact of underlying biological rhythms on acute stroke perfusion patterns is not known. We aimed to describe the relationship between time of stroke onset and perfusion profiles in patients with large vessel occlusion (LVO).METHODS: A retrospective observational study was conducted using prospective registries of four stroke centers across North America and Europe with systematic use of perfusion imaging in clinical care. Included patients had stroke due to ICA, M1 or M2 occlusion and baseline perfusion imaging performed within 24h from last-seen-well (LSW). Stroke onset was divided into eight hour intervals: (1) Night: 23:00-6:59, (2) Day: 7:00-14:59, (3) Evening: 15:00-22:59. Core volume was estimated on CT perfusion (rCBF <30%) or DWI-MRI (ADC <620) and the collateral circulation was estimated with the Hypoperfusion Intensity Ratio (HIR=[Tmax>10s]/[Tmax>6s]). Non-parametric testing was conducted using SPSS to account for the non-normalized dependent variables.RESULTS: A total of 1506 cases were included (median age 74.9 years, IQR 63.0-84.0). Median NIHSS, core volumes, and HIR were 14.0 (IQR 8.0-20.0), 13.0mL (IQR 0.0-42.0), and 0.4 (IQR 0.2-0.6) respectively. Most strokes occurred during the Day (n=666, 44.2%), compared to Night (n=360, 23.9%), and Evening (n=480, 31.9%). HIR was highest, indicating worse collaterals, in the Evening compared to the other timepoints (p=0.006). Controlling for age and time to imaging, Evening strokes had significantly higher HIR compared to Day (p=0.013).CONCLUSION: Our retrospective analysis suggests that HIR is significantly higher in the evening, indicating poorer collateral activation which may lead to larger core volumes in these patients.
View details for DOI 10.1016/j.jstrokecerebrovasdis.2023.107172
View details for PubMedID 37196564
- Varicella Zoster Vasculopathy Exacerbated by Tofacitinib in a Patient With Ulcerative Colitis. Stroke 2023
Association of Soluble ST2 With Functional Outcome, Perihematomal Edema, and Immune Response After Intraparenchymal Hemorrhage.
2023; 100 (13): e1329-e1338
Perihematomal edema (PHE) contributes to poor outcome after deep intraparenchymal hemorrhage (IPH), which is characterized by neuroinflammation and an influx of peripherally derived innate immune cells. We previously identified soluble ST2 (sST2) as a candidate for immune-mediated secondary brain injury. Leveraging prospectively collected cohorts from 2 centers, we sought to determine whether sST2 was associated with functional outcome, PHE, and the immune response following IPH.Patients with deep IPH were enrolled within 36 hours of ictus, and blood was collected for sST2 and immune cell measurement. Hematoma volume and PHE were measured on serial CT scans. Good outcome was defined as a modified Rankin Scale score of 0-3 at 90 days. Linear mixed-effects models were used to analyze the relationship between sST2 and PHE over time. Flow cytometry was used to identify shifts in immune cell populations associated with sST2. Immunohistochemistry of human brain tissue was used to identify ST2-expressing cells in the perihematomal region.The 55 included patients had a median admission Glasgow Coma Scale score of 14 (interquartile range [IQR] 9-15), an intracerebral hemorrhage (ICH) score of 1 (IQR 1-2), and a hematoma volume of 8.6 mL (IQR 3.4-13.8 mL). Receiver operating curve analysis found the sST2 level to be predictive of poor outcome with an area under the curve of 0.763 (95% CI 0.632-0.894) and Youden optimum cut point of 61.8 ng/mL (p < 0.001). sST2 remained an independent predictor after adjustment for ICH score (adjusted odds ratio 2.53, 95% CI 1.03-6.19, p = 0.042). Measurement of PHE found those patients with high sST2 to have greater edema volume over time (β = 1.07, 95% CI 0.51-1.63, p < 0.001). High sST2 was associated with a shift toward an innate peripheral immune response (monocytes and natural killer cells; 68.6% ± 5.1% vs 47.5% ± 4.0%; p = 0.003).Our findings demonstrate that elevated sST2 links the peripheral innate immune response to PHE volume and outcome after IPH. This knowledge is relevant to future studies that seek to identify patients with IPH at highest risk for immune-mediated injury or limit injury through targeted interventions.
View details for DOI 10.1212/WNL.0000000000206764
View details for PubMedID 36549913
View details for PubMedCentralID PMC10065211
- Subcortical Sparing Associated with Ambulatory Independence after Hemicraniectomy for Malignant Infarction. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2021; 30 (8): 105850
Publication and Dissemination of Results in Clinical Trials of Neurology.
2018; 75 (7): 890-891
This review of interventional neurology trials registered in ClinicalTrials.gov classifies trials and compares publication rates and time to publication between 2007 and 2014.
View details for DOI 10.1001/jamaneurol.2018.0674
View details for PubMedID 29710083
View details for PubMedCentralID PMC6145765
Functional Improvement Among Intracerebral Hemorrhage (ICH) Survivors up to 12 Months Post-injury.
2017; 27 (3): 326-333
As survival rates have increased for intracerebral hemorrhage (ICH) patients, there is limited information regarding recovery beyond 3-6 months. This study was conducted to examine recovery curves using the modified Rankin Scale (mRS) and Barthel Index (BI) up to 12 months post-injury.We prospectively enrolled 173 patients admitted with ICH who were subsequently evaluated using the mRS and BI at discharge as well as 3, 6, and 12 months. Repeated measures nonparametric testing was conducted to assess functional trajectories across time.The mRS scores showed significant improvement between discharge (median 4) and 3 (median 4), 6 (median 4), and 12 months (median 3) (p values <0.001). However, the mRS scores did not differ between follow-up time-points (i.e., 3-6, 6-12 months). There was significant improvement in scores using the BI (p values <0.001), showing improvement between discharge (mean 43.0) and 3 (mean 73.0), 6 (mean 78.2), and 12 months (mean 83.4). Additionally, there were differences in the BI between 3 and 12 months (p = 0.013), as well as between 6 and 12 months (p = 0.025).The BI may be a more sensitive measure of long-term recovery post-injury than the mRS, which shows minimal improvement for some survivors after 3 months. BI scores indicate survivors continually improve till 12 months post-injury. These results may have implications for the prognostication of ICH and design of clinical trial outcome measures.
View details for DOI 10.1007/s12028-017-0425-4
View details for PubMedID 28685394
View details for PubMedCentralID PMC5700855
Intracerebral Hemorrhage Location and Functional Outcomes of Patients: A Systematic Literature Review and Meta-Analysis.
2016; 25 (3): 384-391
Intracerebral hemorrhage (ICH) has the highest mortality rate among all strokes. While ICH location, lobar versus non-lobar, has been established as a predictor of mortality, less is known regarding the relationship between more specific ICH locations and functional outcome. This review summarizes current work studying how ICH location affects outcome, with an emphasis on how studies designate regions of interest.A systematic search of the OVID database for relevant studies was conducted during August 2015. Studies containing an analysis of functional outcome by ICH location or laterality were included. As permitted, the effect size of individual studies was standardized within a meta-analysis.Thirty-seven studies met the inclusion criteria, the majority of which followed outcome at 3 months. Most studies found better outcomes on the Modified Rankin Scale (mRS) or Glasgow Outcome Score (GOS) with lobar compared to deep ICHs. While most aggregated deep structures for analysis, some studies found poorer outcomes for thalamic ICH in particular. Over half of the studies did not have specific methodological considerations for location designations, including blinding or validation.Multiple studies have examined motor-centric outcomes, with few studies examining quality of life (QoL) or cognition. Better functional outcomes have been suggested for lobar versus non-lobar ICH; few studies attempted finer topographic comparisons. This study highlights the need for improved reporting in ICH outcomes research, including a detailed description of hemorrhage location, reporting of the full range of functional outcome scales, and inclusion of cognitive and QoL outcomes.
View details for DOI 10.1007/s12028-016-0276-4
View details for PubMedID 27160888
TURN Score Predicts 24-Hour Cerebral Edema After IV Thrombolysis.
2016; 24 (3): 381-8
Cerebral edema is associated with poor outcome after IV thrombolysis. We recently described the TURN score (Thrombolysis risk Using mRS and NIHSS), a predictor of severe outcome after IV thrombolysis. Our purpose was to evaluate its ability to predict 24-h cerebral edema.We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Measures of brain swelling included edema, mass effect and midline shift assessed at baseline, at 24 h and new onset at 24 h. Outcome was assessed using intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day severe outcome, and 90-day mortality. Statistical associations were assessed by logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC).Baseline brain swelling did not predict poor outcome; however, 24-h brain swelling predicted ICH (OR 5.69, P < 0.001), sICH (OR 9.50, P = 0.01), 90-day severe outcome (OR 7.10, P < 0.001), and 90-day mortality (OR 5.65, P = 0.01). Similar results were seen for new brain swelling at 24 h. TURN predicted 24-hour brain swelling (OR 2.5, P < 0.001; AUROC 0.69, 95 % CI 0.63-0.75) and new brain swelling at 24 h (OR 2.1, P < 0.001; AUROC 0.67, 95 % CI 0.61-0.73).Cerebral edema at 24 h is associated with poor outcome and 90-day mortality. TURN predicts ischemic stroke patients who will develop 24-h cerebral edema after IV thrombolysis.
View details for DOI 10.1007/s12028-015-0198-6
View details for PubMedID 26341364