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Background: Thrombolysis for acute stroke is beneficial in selected patients. Because clinical trials generally exclude patients with pre-existing disability, this subgroup of patients has not been studied. We examined the outcomes after thrombolysis of patients with and without disability before their stroke. Methods: We prospectively followed 112 consecutive patients with acute ischemic stroke who were given intravenous thrombolysis treatment according to published protocols. Three-month outcomes of the patients with pre-existing disability (defined as a prestroke score of 2 or more on the modified Rankin scale [MRS]) were compared with those of patients without pre-existing disability (defined as a prestroke MRS score of 0 or 1) and with those of 168 patients similarly treated in the National Institute of Neurological Disorders and Stroke trial. Results: At 3 months after the stroke, patients with pre-existing disability (21% of the 112) had a higher mortality rate than those without (33% v. 14%) (odds ratio 3.2, 95% confidence interval 1.0-10.1) and worse function (median MRS score 3 v. 2, p = 0.03). However, there was little difference between the 2 groups in neurologic impairment among the survivors (median score on the National Institutes of Health stroke scale 4 v. 2, p = 0.41) or in the total proportion of those with an MRS score of 0 or 1 or, for those with a prestroke score greater than 1, a return to the prestroke score (42% v. 41%, p = 0.87). Interpretation: Although the true effectiveness of thrombolysis for acute stroke in patients with pre-existing disability is not known, treated patients appear able to return to their prestroke level of function as often as patients without pre-existing disability, despite a significantly higher mortality rate. [ABSTRACT FROM AUTHOR]

Nonvalvular atrial fibrillation is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. These medications also require strict compliance for efficacy, and they have nontrivial failure rates in higher-risk patients. Left atrial appendage closure is a nonpharmacological method to prevent ischemic strokes in atrial fibrillation without the need for lifelong anticoagulant use, but this procedure has the potential for complications and residual embolic events. This workshop of the Roundtable of Academia and Industry for Stroke Prevention discussed future research needed to further decrease the ischemic and hemorrhagic risks among patients with atrial fibrillation. A direct thrombin inhibitor, factor Xa inhibitors, and left atrial appendage closure are FDA-approved approaches whereas factor XIa inhibitors are currently being studied in phase 3 randomized controlled trials for stroke prevention. The benefits, risks, and shortcomings of these treatments and future research required in different high-risk patient populations are reviewed in this consensus statement., Competing Interests: Disclosures Dr Gurol receives research funding from National Institutes of Health. Dr Gurol’s hospital received research grants from Boston Scientific Corporation; research grants from Pfizer Canada Inc; and research grants from Avid Radiopharmaceuticals Inc. Dr Wright reports employment by National Institute of Neurological Disorders and Stroke. Dr Reddy reports compensation from Corvia Medical for consultant services; stock options in Focused Therapeutics; stock options in Heart Repair Technologies (HRT); stock options in Intershunt; stock options in East End Medical; stock options in Medlumics; stock holdings in Nyra Medical; compensation from W. L. Gore & Associates, Inc, for consultant services; compensation from Biotronik, Inc, for consultant services; stock options in Eximo; compensation from Philips for consultant services; stock options in Laminar; compensation from Biostar Ventures for consultant services; stock options in Axon Therapies; stock holdings in Vizaramed; stock options in Keystone Heart; compensation from CardioFocus, Inc, for consultant services; compensation from Biosense Webster, Inc, for consultant services; stock options in Impulse Dynamics (United States), Inc; stock options in Cardiacare. Israel; stock holdings in Affera; stock options in CardioNXT/AFTx; compensation from Cardionomic for consultant services; stock options in Atacor; compensation from Cardiac for consultant services; stock options in Field Medical; stock holdings in SoundCath; stock options in Oracle Health; compensation from AtriAN-Ireland for consultant services; stock options in Anumana; stock options in Acutus Medical, Inc; stock options in EP Frontiers; stock options in Nuvera; stock options in Javelin; stock options in Valcare; stock options in Middlepeak; stock options in Corisma; stock holdings in Surecor, Inc; stock options in Ablacon Inc; stock options in Atrian; stock options in Neutrace; stock options in Backbeat; compensation from Coremap for consultant services; stock options in Biosig; stock options in Dinova-Hangzhou DiNovA EP Technology; stock options in APN Health; compensation from Farapulse-Boston Scientific for consultant services; stock options in Kardium; compensation from Medtronic USA, Inc, for consultant services; compensation from Recor Medical for consultant services; stock options in Sirona Medical; stock holdings in Farapulse-BostonScientific; stock options in Epix Therapeutics; stock options in Aquaheart; stock options in Fire1; stock options in Pulse Biosciences; stock holdings in Manual Surgical Sciences; stock options in Autonomix; compensation from Abbott Vascular for consultant services; compensation from Abbott Vascular for consultant services; stock holdings in Newpace; compensation from Novo Nordisk for consultant services; stock options in EpiEP; compensation from BioTel Heart-Philips for consultant services; compensation from BOSTON SCIENTIFIC CORPORATION for consultant services; stock options in Restore Medical; stock options in EP Dynamics; stock options in LuxMed; stock options in Affera; stock options in Circa Scientific, Inc; stock holdings in Biostar Ventures; stock options in Cardiacare; compensation from Novartis for consultant services; and stock options in Anumana. Dr Merino reports compensation from American Academy of Neurology for other services and compensation from National Institute of Neurological Disorders and Stroke for data and safety monitoring services. Dr Hsu reports compensation from Biosense Webster, Inc, for consultant services; compensation from Abbott Laboratories for consultant services; compensation from Boston Scientific Corporation for consultant services; compensation from Sanofi US Services Inc for consultant services; compensation from Acutus Medical, Inc, for consultant services; compensation from iRhythm Technologies for consultant services; compensation from ZOLL Medical Corporation for consultant services; grants from Biotronik; compensation from Janssen Pharmaceuticals for consultant services; compensation from Pfizer for consultant services; compensation from Medtronic for consultant services; compensation from Biotronik for consultant services; stock options in Vektor Medical; compensation from AltaThera Pharmaceuticals LLC for consultant services; grants from Biosense Webster, Inc; and compensation from Bristol-Myers Squibb for consultant services.

Introduction: Despite complete recanalization by mechanical thrombectomy, abnormal perfusion can be detected on MRI obtained post-endovascular therapy (EVT). The presence of residual perfusion abnormalities post-EVT may be associated with blood-brain barrier breakdown in response to mechanical disruption of the endothelium from multiple-pass thrombectomy. We hypothesize that multiple-pass versus single-pass thrombectomy is associated with a higher rate of residual hypoperfusion and increased lesion growth at 24 h., Materials and Methods: For this analysis, we included patients presenting to one of two stroke centers between January 2015 and February 2018 with an acute ischemic stroke within 12 h from symptom onset if they had a large vessel occlusion of the anterior circulation documented on magnetic resonance angiography or CTA, baseline MRI pre-EVT with imaging evidence of hypoperfusion, underwent EVT, and had a post-EVT MRI with qualitatively interpretable perfusion-weighted imaging data at 24 h. MRI Tmax maps using a time delay threshold of >6 s were used to quantitate hypoperfusion volumes. Residual hypoperfusion at 24 h was solely defined as Tmax volume >10 mL with >6 s delay. Complete recanalization was defined as modified treatment in cerebral infarction visualized on angiography at EVT completion. Hyperintense acute reperfusion injury marker was assessed on post-EVT pre-contrast fluid-attenuated inversion recovery at 24 h. Major early neurological improvement was defined as a reduction of the admission National Institutes of Health Stroke Scale by ≥8 points or a score of 0-1 at 24 h. Good functional outcome was defined as 0-2 on the modified Rankin Scale on day 30 or 90., Results: Fifty-five patients were included with median age 67 years, 58% female, 45% Black/African American, 36% White/Caucasian, median admission National Institutes of Health Stroke Scale 19, large vessel occlusion locations: 71% M1, 14.5% iICA, 14.5% M2, 69% treated with intravenous recombinant tissue plasminogen activator. Of these, 58% had multiple-pass thrombectomy, 39% had residual perfusion abnormalities at 24 h, and 64% had severe hyperintense acute reperfusion injury marker at 24 h. After adjusting for complete recanalization, only multiple-pass thrombectomy (odds ratio, 4.3 95% CI, 1.07-17.2; p = 0.04) was an independent predictor of residual hypoperfusion at 24 h. Patients with residual hypoperfusion had larger lesion growth on diffusion-weighted imaging (59 mL vs. 8 mL, p < 0.001), lower rate of major early neurological improvement (24% vs. 70%, p = 0.002) at 24 h, and worse long-term outcome based on the modified Rankin Scale at 30 or 90 days, 5 versus 2 (p < 0.001)., Conclusions: Our findings suggest that incomplete reperfusion on post-EVT MRI is present even in some patients with successful recanalization at the time of EVT and is associated with multiple-pass thrombectomy, lesion growth, and worse outcome. Future studies are needed to investigate whether patients with residual hypoperfusion may benefit from immediate adjunctive therapy to limit lesion growth and improve clinical outcome., (© 2021 S. Karger AG, Basel.)

Background: The Training in Research for Academic Neurologists to Sustain Careers and Enhance the Numbers of Diverse Scholars (TRANSCENDS) program is a career advancement opportunity for individuals underrepresented in biomedical research funded by the National Institute of Neurologic Disorders and Stroke and American Academy of Neurology (AAN)., Objective: To report on qualitative and quantitative outcomes in TRANSCENDS., Design: Early career individuals (neurology fellows and junior faculty) from groups underrepresented in medicine (UIM) were competitively selected from a national pool of applicants (2016-2019). TRANSCENDS activities comprised an online Clinical Research degree program, monthly webinars, AAN meeting activities, and mentoring. Participants were surveyed during and after completion of TRANSCENDS to evaluate program components., Outcomes: Of 23 accepted scholars (comprising 4 successive cohorts), 56% were women, 61% Hispanic/Latinx, 30% Black/African American, and 30% assistant professors. To date, 48% have graduated the TRANSCENDS program and participants have published 180 peer-reviewed articles. Mentees' feedback noted that professional skills development (i.e., manuscript and grant writing), networking opportunities, and mentoring were the most beneficial elements of the program. Stated opportunities for improvement included incorporating a mentor-the-mentor workshop, providing more transitional support for mentees in the next stage of their careers, and requiring mentees to provide quarterly reports., Conclusions: TRANSCENDS is a feasible program for supporting UIM neurologists towards careers in research and faculty academic appointments attained thus far have been sustained. Although longer-term outcomes and process enhancements are warranted, programs like this may help increase the numbers of diverse academic neurologists and further drive neurologic innovation., (© 2021 American Academy of Neurology.)

Background and Purpose: Approximately 8% of Blacks have sickle cell trait (SCT), and there are conflicting reports from recent cohort studies on the association of SCT with ischemic stroke (IS). Most prior studies focused on older populations, with few data available in young adults., Methods: A population-based case-control study of early-onset IS was conducted in the Baltimore-Washington region between 1992 and 2007. From this study, 342 Black IS cases, ages 15 to 49, and 333 controls without IS were used to examine the association between SCT and IS. Each participant's SCT status was established by genotyping and imputation. For analysis, χ 2 tests and logistic regression models were performed with adjustment for potential confounding variables., Results: Participants with SCT (n=55) did not differ from those without SCT (n=620) in prevalence of hypertension, previous myocardial infarction, diabetes mellitus, and current smoking status. Stroke cases had increased prevalence in these risk factors compared with controls. We did not find an association between SCT and early-onset IS in our overall population (odds ratio=0.9 [95% CI, 0.5-1.7]) or stratified by sex in males (odds ratio=1.26 [95% CI, 0.56-2.80]) and females (odds ratio=0.67 [95% CI, 0.28-1.69])., Conclusions: Our data did not find evidence of increased risk of early-onset stroke with SCT.

Objectives: To systematically review the literature for reversible diffusion-weighted imaging (DWIR) lesions and to describe its prevalence, predictors, and clinical significance., Methods: Studies were included if the first DWI MRI was performed within 24 hours of stroke onset and follow-up DWI or fluid-attenuated inversion recovery (FLAIR)/T2 was performed within 7 or 90 days, respectively, to measure DWIR. We abstracted clinical, imaging, and outcomes data., Results: Twenty-three studies met the study criteria. The prevalence of DWIR was 26.5% in DWI-based studies and 6% in FLAIR/T2-based studies. DWIR was associated with recanalization or reperfusion of the ischemic tissue with or without the use of tissue plasminogen activator (t-PA) or endovascular therapy, earlier treatment with t-PA, shorter time to endovascular therapy after MRI, and absent or less severe perfusion deficit within the DWI lesion. DWIR was associated with early neurologic improvement in 5 of 6 studies (defined as improvement in the NIH Stroke Scale (NIHSS) score by 4 or 8 points from baseline or NIHSS score 0 to 2 at 24 hours after treatment or at discharge or median NIHSS score at 7 days) and long-term outcome in 6 of 7 studies (defined as NIHSS score ≤1, improvement in the NIHSS score ≥8 points, or modified Rankin Scale score up to ≤2 at 30 or 90 days) likely due to reperfusion., Conclusions: DWIR is seen in up to a quarter of patients with acute ischemic stroke, and it is associated with good clinical outcome following reperfusion. Our findings highlight the pitfalls of DWI to define ischemic core in the early hours of stroke., (© 2020 American Academy of Neurology.)

Objective: We present an exploratory study for identification of sex differences in imaging biomarkers that could further refine selection of patients for acute reperfusion therapy and trials based on sex and imaging targets., Methods: The Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) study included consecutive acute stroke patients who underwent MRI within 24 h of time from last known well and prior to therapy. Those demonstrating a potential therapeutic target on imaging were identified by presence of: (1) arterial occlusion on angiography, (2) focal ischemic region on perfusion maps, or (3) a mismatch of perfusion versus diffusion imaging lesion size. The prevalence of imaging targets within clinically relevant time intervals was calculated for each patient and examined. The relationship of time from stroke onset to probability of detection of imaging targets was evaluated., Results: Of 7007 patients screened, of which 86.7% were scanned with MRI, 1092 patients (477/615 men/women) were included in LESION. The probability of imaging target detection was significantly different between men and women, with women more likely to present with all assessed imaging targets, odds ratios between 1.36 and 1.59, P  < 0.02, adjusted for NIHSS, age, and time from last known well to MRI scan. This trend held for the entire 24-h studied., Interpretation: Women present more often with treatable ischemic stroke than men. The greater probability of potentially viable and/or treatable imaging targets in women at all time points suggests that tissue injury is slower to evolve in women., Competing Interests: Dula reports has nothing to disclose; Luby has nothing to disclose; King has nothing to disclose; Sheth has nothing to disclose; Magadan has nothing to disclose; Davis has nothing to disclose; Gealogo has nothing to disclose; Merino has nothing to disclose; Hsia has nothing to disclose; Merino has nothing to disclose; and Latour has nothing to disclose. Warach reports personal fees from Merck Sharp & Dohme Corporation, personal fees from Genentech, grants from Boehringer Ingelheim, grants from Valtari Bio, personal fees from AbbVie, outside the submitted work; In addition, Warach has a patent Biomarkers for acute ischemic stroke; US Patent number: 9200322 issued.

Background: Within the Thrombolysis In Cerebral Infarction (TICI) classification, TICI 2b has been historically considered successful recanalization. However, TICI 2b may result in worse functional outcomes compared with TICI 3 or a proposed TICI 2c revascularization grade. The aim of this study was to evaluate differences in functional independence at 90 days between TICI 2b, 2c, and 3 grades., Methods: A retrospective review of 185 consecutive patients with anterior cerebral circulation occlusions was performed; 33 patients who were treated >8 hours after onset were excluded. Patient angiograms were graded by 2 experienced neurointerventional physicians. Baseline demographics and functional independence at 90 days were compared., Results: Of 152 patients included in the study, 113 patients achieved TICI grade 2b (n = 37), 2c (n = 34), or 3 (n = 42). A significant difference in functional independence at 90 days was observed between TICI 2b and 2c/3 (P = 0.0008), between 2b and 2c (P = 0.0005), and between 2b and 3 (P = 0.01). There was no significant difference in functional independence between 2c and 3 (P = 0.24)., Conclusions: TICI 2c revascularization is associated with significantly improved outcomes compared with TICI 2b revascularization and similar outcomes compared with TICI 3 revascularization. Using a TICI grading system that includes an additional TICI 2c grade or expands the current definition of TICI 3 allows for refined prediction of functional independence. Achieving TICI 2c/3 reperfusion should be considered during stroke thrombectomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Purpose: There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years., Methods: The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ 2 test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index., Results: The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio, ranging from 1.46 for those smoking <11 cigarettes per day to 5.66 for those smoking 40+ cigarettes per day., Conclusions: We found a strong dose-response relationship between the number of cigarettes smoked daily and ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men., (© 2018 American Heart Association, Inc.)

Intracranial aneurysms uncommonly present with ischemic stroke. Parent artery occlusion due to local extension of the luminal thrombus, aneurysms ejecting emboli to distal arteries, or increased mass effect have been described as possible pathogenic mechanisms. Guidelines for the management of these patients are absent. We present the clinical outcome and radiological characteristics of three patients with spontaneous thrombosis of intracranial aneurysms as a cause of ischemic stroke. This information is relevant given the possible benign history in terms of stroke recurrence and risk of bleeding., (© The Author(s) 2015.)

Background and Purpose: Few studies have investigated the rates of recanalisation after cerebral venous thrombosis (CVT). Our objective was to investigate the recanalisation rate and to identify predictors of recanalisation in patients with CVT., Methods: We included 102 patients with confirmed first-ever, non-septic CVT. All patients received anticoagulation for 12 months or until complete recanalisation. To assess recanalisation, patients underwent MR venography every 3 months until partial or complete recanalisation or for 12 months after diagnosis. We conducted two parallel analyses of complete recanalisation versus partial and no recanalisation versus any recanalisation. As a secondary objective we explored the influence of recanalisation on outcome and recurrent events. We calculated the probability of recanalisation using Kaplan-Meier analysis and conducted multivariate analysis using a Cox model., Results: The mean age of patients was 33.5±11 years (80 (78.4%) women). Survival analysis indicated that 50% of the patients had any recanalisation (grades I, II and III) by 64 days and complete recanalisation (grade III) by 169 days. Adjusted Cox proportional model revealed that age <50 years (HR=11.5 95% CI=1.58 to 84.46, p=0.01) and isolated superior sagittal sinus thrombosis (HR=0.39, 95% CI=0.14 to 1.04, p=0.05) predict complete recanalisation, while age <50 years (HR=4.79; 95% CI=1.69 to 13.5, p=0.003) predicts any recanalisation. Patients with complete recanalisation had a greater chance of good functional outcome (HR=5.17; 95% CI=2.8 to 9.53, p<0.001)., Conclusions: We found that recanalisation occurs over time, until month 11. Complete recanalisation may influence functional outcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Importance: Patients with stroke often have a decline in blood pressure after thrombolysis. Neurologic improvement could result from recanalization or better collateral flow despite persistent occlusion. We hypothesized that neurologic improvement with concurrent decline in blood pressure may be a clinical sign of recanalization after intravenous tissue plasminogen activator., Observations: Patients treated with intravenous tissue plasminogen activator at Suburban Hospital, Bethesda, Maryland, and MedStar Washington Hospital Center, Washington, DC, from 1999 to 2009 were included in the study if they had pretreatment and 24-hour magnetic resonance angiographic scans, National Institutes of Health Stroke Scale scores at those times, and proximal middle cerebral artery occlusion demonstrated prior to treatment. The recanalization status on 24-hour magnetic resonance angiography was classified as none, partial, or complete. Seventeen patients met study criteria. On 24-hour magnetic resonance angiography, 3 patients had no recanalization, 8 had partial recanalization, and 6 had complete recanalization. At 24 hours after thrombolysis, neurologic improvement with concurrent decline in systolic blood pressure of 20 mm Hg or greater was seen in 4 patients with partial recanalization, 4 patients with complete recanalization, and none of the patients with no recanalization., Conclusions and Relevance: Neurologic improvement with concurrent decline in systolic blood pressure of 20 mm Hg or greater after intravenous tissue plasminogen activator may be a clinical sign of recanalization. This observation needs confirmation in a larger cohort., Competing Interests: Disclosures No other disclosures were reported.