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Background: Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays., Methods: We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center., Results: Between January 1, 2018, and December 31, 2021, a total of 6803 patients received EVT at 20 participating centers (median age, 73 years; 50% women; and 50% treated with intravenous thrombolysis). Patients transferred for EVT (n=3376) had lower rates of M2 occlusion (22% versus 27%) and higher rates of basilar occlusion (9% versus 5%) compared with those patients presenting directly at an EVT-capable center (n=3373). Door-to-needle times were shorter in patients receiving intravenous thrombolysis before transfer compared with those presenting directly to an EVT center (32 versus 36 minutes). Patients transferred for EVT had shorter door-to-arterial access times (37 versus 87 minutes) but longer last seen normal-to-arterial access times (322 versus 181 minutes) compared with those presenting directly to an EVT-capable center. No differences in arterial access-to-reperfusion times, successful reperfusion rates (85% versus 86%), or adverse periprocedural events were found between the 2 groups. Patients transferred to EVT centers had a similar likelihood for good functional outcome (modified Rankin Scale score, 0-2; 41% versus 43%; risk ratio, 0.95 [95% CI, 0.88-1.01]; adjusted risk ratio, 0.98 [95% CI, 0.91-1.05]) and a higher risk for all-cause mortality at 90 days (29% versus 25%; risk ratio, 1.15 [95% CI, 1.05-1.27]; adjusted risk ratio, 1.14 [95% CI, 1.03-1.28]) compared with patients presenting directly to an EVT center., Conclusions: Patients transferred for EVT experience significant delays from the time they were last seen normal to the initiation of EVT., Competing Interests: Alexandre Poppe reports grants from the Canadian Institutes of Health Research, compensation from Roche for other services, and grants from the Fondation Brain Canada, the Heart and Stroke Foundation of Canada, and Stryker. Dr Swartz reports grants from the Heart and Stroke Foundation of Canada, compensation from the Sunnybrook Research Institute for other services, compensation from F. Hoffmann-La Roche for consultant services, stock holdings in FollowMD, Inc, and grants from the Ontario Brain Institute and the National Institutes of Health. Dr Catanese reports compensation from Hoffmann-La Roche Limited for consultant services, employment by Hamilton Health Sciences, and grants from Servier Pharmaceuticals LLC. Dr Volders reports compensation from Penumbra, Inc, for consultant services. Dr Kelly reports compensation from Johnson and Johnson, Penumbra, Inc, and Medtronic Vascular, Inc, for consultant services. Dr Kamal reports stock holdings in DESTINE Health and compensation from Medtronic for consultant services. Dr Yu reports grants from the Canadian Institutes of Health Research. Dr Hill reports grants from NoNO, Inc, and Medtronic, compensation from Brainsgate Ltd for consultant services, grants from the Canadian Institutes of Health Research; Medtronic, Boehringer Ingelheim, Medtronic, and MicroVention, Inc, and compensation from Merck for end point review committee services. Dr Sharma reports grants from Bristol Myers Squibb Company to others and compensation from Bayer and AstraZeneca for consultant services. Dr Demchuk reports compensation from Hoffmann-La Roche Limited for consultant services, compensation from Lumosa for data and safety monitoring services, a patent issued for Stroke imaging software licensed to Circle NVI, compensation from Boehringer Ingelheim for consultant services, compensation from Novo Nordisk AS for other services, compensation from Philips for data and safety monitoring services, compensation from NovaSignal for consultant services, and stock holdings in Circle NVI.

Background and Objectives: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial., Methods: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome., Results: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 ( r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3., Discussion: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT., Classification of Evidence: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Background: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days., Methods: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient ( r ) with 95% CI., Results: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase ( P =0.10). Older age ( P <0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale ( P <0.01), and longer stroke onset-to-needle time ( P =0.004) were associated with lower EQ5D index and VAS scores. There was a strong association ( r , 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index ( r , 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores ( r , 0.42 [95% CI, 0.37-0.46])., Conclusions: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249., Competing Interests: Disclosures Dr Menon reports stock in Circle NVI and patents for systems of triage in acute stroke. Dr Sajobi reports consulting fees received from Circle NVI and employment at the University of Calgary. Dr Almekhlafi reports to be on the medical advisory board of Palmera Medical, Inc. Dr Deschaintre reports being part of the Association des neurologues du Québec, the Société des Sciences Vasculaires du Québec, and the Université de Montréal. Dr Coutts reports that Boehringer Ingelheim provided a study drug (tenecteplase) for the TEMPO-2 trial. Dr Catanese reports employment with Hamilton Health Sciences and McMaster University, consulting fees from Hoffmann-La Roche Ltd, and a grant/contract from Servier Pharmaceuticals LLC. Dr Field reports consulting fees from AstraZeneca Canada, Bayer, HLS Therapeutics, and Roche; stock and being a fiduciary officer (board member) in Destine Health; grants/contracts from Boehringer Ingelheim and Bayer; and being an expert witness for the Canadian Medical Protective Association. Dr Siddiqui reports a grant/contract from Allergan and other interests from Bayer and Boehringer Ingelheim. Dr Demchuk reports stock in Circle NVI and patents for stroke imaging software; consulting fees from Servier Pharmaceuticals LLC, NovaSignal, Boehringer Ingelheim, HLS Therapeutics, Inc, Hoffmann-La Roche Ltd, and Medtronic; data and safety monitoring with Philips; and other interests from AstraZeneca Canada, Novo Nordisk AS, and Pfizer Canada, Inc. Dr Hill reports employment with the University of Calgary; consulting fees from Brainsgate Ltd; grants/contracts from Biogen, Inc, Boehringer Ingelheim, the Canadian Institutes of Health Research, Medtronic, MicroVention, Inc, and NoNO, Inc; being part of the end point review committee at Merck; stock in Circle NVI; and patents for systems of triage in acute stroke. Dr Poppe reports grant funding from the Fondation Brain Canada and the Heart and Stroke Foundation of Canada and research funding from Stryker. Dr Swartz reports stock in FollowMD, Inc, and grants/contracts from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the National Institutes of Health, the Ontario Brain Institute, and the Sunnybrook Research Institute. The other authors report no conflicts.

Background: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase)., Methods: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes., Results: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes., Conclusions: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249., Competing Interests: Disclosures Dr Field reports compensation from AstraZeneca, Bayer, BMS-Pfizer, HLS Therapeutics, and Roche for consultant services, the Canadian Medical Protective Association as an expert witness, a grant from Bayer, and is on the board of DESTINE Health. Dr Menon reports stock options in Circle CVI and has consulted for Hoffman-Laroche and Boehringer Ingelheim. Dr Coutts is a principal investigator for the TEMPO-2 trial (A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) with the study drug (tenecteplase) provided by Boehringer Ingelheim. Dr Hill reports compensation from BrainsGate for consultant services, grants from Boehringer Ingelheim, the Canadian Institutes of Health Research, Medtronic, MicroVention, Inc, and NoNo, Inc, end point review committee work for Merck, and employment as a professor with the University of Calgary. Dr Poppe reports grants from Stryker, Fondation Brain Canada, and the Heart and Stroke Foundation of Canada. Dr Demchuk reports compensation from Boehringer Ingelheim, HLS Therapeutics, Hoffman-Laroche, Medtronic, NovaSignal, and Servier for consultant services, others from AstraZeneca, Novo Nordisk, and Pfizer, data safety monitoring board participation with Philips, and stock and patent for stroke imaging software with Circle NVI. Dr Catanese reports compensation from Hoffman-Laroche for consultant fees and a grant from Servier. Dr Yu reports grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada. Dr Deschaintre reports other compensation from the Association des neurologues du Québec, the Société des Sciences Vasculaires du Québec, and the Université du Montréal. Dr Siddiqui reports a grant from Allergan and other compensation from Bayer and Boehringer Ingelheim. Dr Swartz reports grants from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the National Institutes of Health, and the Sunnybrook Research Institute and stock in FollowMD, Inc. The other authors report no conflicts.

A 48-year-old woman was referred with an 18-year history of focal-onset seizures. She also reported years-long slowly progressive right-sided weakness that was corroborated on examination. Repeated brain MRIs over 15 years showed multifocal left hemispheric T2 fluid-attenuated inversion recovery-hyperintense lesions with patchy enhancement and microhemorrhages, no diffusion restriction, and a left cerebellar infarct (Figure 1, A-F). Only 2 nonspecific white matter lesions were seen contralaterally, indicating largely unihemispheric disease. Differential diagnosis included unilateral primary angiitis of the CNS (PACNS), Rasmussen encephalitis, and myelin oligodendrocyte glycoprotein antibody-associated disease. 1 Serum and CSF testing for autoimmune, infectious, and malignant etiologies and whole-body fluorodeoxyglucose-PET, whole-exome genetic sequencing, and MR vessel-wall imaging were nondiagnostic. Brain biopsy revealed vasculitis (Figure 2, A-F), and the patient was diagnosed with unilateral PACNS. Treatment with mycophenolate mofetil has been initiated. Unilateral PACNS is a rare unihemispheric disease characterized by an indolent course and seizures, recognition of which is critical to accurate diagnosis. 1,2 .

Background: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes., Methods: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365., Results: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180., Conclusions: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03178864., Competing Interests: Disclosures Dr Boulos reports compensation from Eisai, Jazz Pharmaceuticals, and Paladin Laboratories for consultant services, and a gift from Braebon Medical Corporation. Dr Demchuk reports compensation from Boehringer Ingleheim, HLS Pharmaceuticals, Hoffmann-Laroche, Metronic NovaSignal, and Servier for consultant services, other from AstraZeneca, Data Safety Monitoring Board participation with Philips, and stock and a patent for stroke imaging software with Circle NVI. Dr Dowlatshahi reports compensation from AstraZeneca for consultant services. Dr Field reports compensation from AstraZeneca, HLS Therapeutics, Servier, Bristol Myers Squibb Pfizer, and Roche for consultant services, from the Canadian Medical Protective Association as an Expert Witness, and is on the board of DESTINE Health. M.D. Hill reports compensation for Brainsgate Ltd for consultant services, grants from the Canadian Institutes of Health Research, Medtronic, Microvention Inc, NoNO Inc, and Boehringer Ingleheim, and end point review committee work for Merck. Dr Lanthier reports compensation from Bayer, Bristol Myers Squibb Pfizer, and Servier for consultant services. Dr Lee reports compensation from Bayer and Bristol Myers Squibb for consultant services. Dr Sposato reports compensation from Bayer, Boehringer Ingleheim, Daiichi Sanko Ltd and Pfizer for consultant services. Dr Weitz reports compensation from Alnylam Pharmaceuticals, Anthos, Bayer, Boehringer Ingleheim, Bristol myers Squibb, Daiichi Sankyo Ltd, Ionis Pharmaceuticals, Janssen Global Services LLC, Merck Company Foundation, Novartis, Pfizer, and Portola Pharmaceuticals for consult services. The other authors report no conflicts.

Background: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase., Methods: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion., Results: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time ( P interaction =0.161) or door-to-needle time ( P interaction =0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively., Conclusions: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes., Registration: URL: https://classic., Clinicaltrials: gov; Unique identifier: NCT03889249., Competing Interests: Disclosures Dr Coutts is principal investigator of the TEMPO-2 trial (A Randomized Controlled Trial of TNK-tPA Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion), for which Boehringer Ingelheim provides the study drug (tenecteplase). Dr Catanese has received payments by Servier and consulting fees from Ischaemavie RAPID, Circle NV, and Canadian Medical Protective Association. Dr Shankar has a grant from Medtronic to the University of Manitoba. Dr Demchuk has received consulting fees from Medtronic and honoraria from Boehringer Ingelheim. Dr Catanese is on advisory boards for AstraZeneca and Servier and has stock options in AstraZenca. Dr Hill has received consulting fees from Sun Pharma and Brainsgate and has stock options in Circle NVI. Dr Poppe has received a project research grant from Stryker and honoraria from BMS-Pfizer. Dr Sajobi has received consulting fees from Circle NVI. Dr Swartz has stock options in FollowMD and receives salary support for research from the Heart & Stroke Foundation of Canada, Sandra Black Center for Brain Resilience & Recovery, and Ontario Brain Institute. Dr Menon has stock options in Circle CVI and has consulted for Biogen, Roche and Boehringer Ingelheim. The other authors report no conflicts.

Background: The use of intravenous thrombolysis is associated with improved clinical outcomes. Whether thrombolysis is associated with reduced incidence of poststroke dementia remains uncertain. We sought to estimate if the use of thrombolysis following first-ever ischemic stroke was associated with a reduced rate of incident dementia using a pragmatic observational design., Methods: We included first-ever ischemic stroke patients from the Ontario Stroke Registry who had not previously been diagnosed with dementia. The primary outcome was incident dementia ascertained by a validated diagnostic algorithm. We employed inverse probability of treatment-weighted Cox proportional hazard models to estimate the cause-specific hazard ratio for the association of thrombolysis and incident dementia at 1 and 5 years following stroke., Results: From July 2003 to March 2013, 7072 patients with ischemic stroke were included, 3276 (46.3%) were female and mean age was 71.0 (SD, 12.8) years. Overall, 38.2% of the cohort (n=2705) received thrombolysis, 77.2% (n=2087) of which was administered within 3 hours of stroke onset. In the first year following stroke, thrombolysis administration was associated with a 24% relative reduction in the rate of developing dementia (cause-specific hazard ratio, 0.76 [95% CI, 0.58-0.97]). This association remained significant at 5 years (cause-specific hazard ratio, 0.79 [95% CI, 0.66-0.91]) and at the end of follow-up (median 6.3 years; cause-specific hazard ratio, 0.79 [95% CI, 0.68-0.89])., Conclusions: Thrombolysis administration following first-ever ischemic stroke was independently associated with a reduced rate of dementia. Incident dementia should be considered as a relevant outcome when evaluating risk/benefit of thrombolysis in ischemic stroke patients.

Objective: To describe sex differences in the presentation, diagnosis, and revision of diagnosis after early brain MRI in patients who present with acute transient or minor neurologic events., Methods: We performed a secondary analysis of a prospective multicenter cohort study of patients referred to neurology between 2010 and 2016 with a possible cerebrovascular event and evaluated with brain MRI within 8 days of symptom onset. Investigators documented the characteristics of the event, initial diagnosis, and final diagnosis. We used multivariable logistic regression analyses to evaluate the association between sex and outcomes., Results: Among 1,028 patients (51% women, median age 63 years), more women than men reported headaches and fewer reported chest pain, but there were no sex differences in other accompanying symptoms. Women were more likely than men to be initially diagnosed with stroke mimic (54% of women vs 42% of men, adjusted odds ratio (OR) 1.60, 95% confidence interval [CI] 1.24-2.07), and women were overall less likely to have ischemia on MRI (10% vs 17%, OR 0.52, 95% CI 0.36-0.76). Among 496 patients initially diagnosed with mimic, women were less likely than men to have their diagnosis revised to minor stroke or TIA (13% vs 20%, OR 0.53, 95% CI 0.32-0.88) but were equally likely to have acute ischemia on MRI (5% vs 8%, OR 0.56, 95% CI 0.26-1.21)., Conclusions: Stroke mimic was more frequently diagnosed in women than men, but diagnostic revisions were common in both. Early brain MRI is a useful addition to clinical evaluation in diagnosing transient or minor neurologic events., (© 2020 American Academy of Neurology.)

Background and Purpose: Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction., Methods: Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models., Results: Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models ( P <0.05). The area under the receiver operating characteristic for mCTA models ranged from 92% to 94% and was not different compared with all CTP models ( P >0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score ( P <0.01) and each delay score category ( P <0.01). Mean Tmax, cerebral blood flow, and cerebral blood volume values were significantly different between each extent score category ( P <0.05)., Conclusions: Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients., (© 2017 American Heart Association, Inc.)

Background and Purpose: Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized controlled trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times)., Methods: The core laboratory identified INTs on 24-hour follow-up imaging, blinded to treatment allocation, after assessing all baseline imaging. INTs were classified into 3 types (I-III) and 2 subtypes (A/B) based on size and if catheter manipulation was likely performed across the vessel territory ostium. Logistic regression was used to understand the effect of multiple a priori identified variables on INT occurrence. Ordinal logistic regression was used to analyze the effect of INTs on modified Rankin Scale shift at 90 days., Results: From 308 patients included, 14 INTs (4.5% overall; 2.8% on follow-up noncontrast computed tomography, 11.7% on follow-up magnetic resonance imaging) were identified (5.0% in endovascular treatment arm versus 4.0% in control arm [P=0.7]). The use of intravenous alteplase was associated with a 68% reduction in the odds of INT occurrence (3.0% with versus 9.1% without; odds ratio, 0.32; 95% confidence interval, 0.11-0.96; adjusted for age, sex, and treatment type). No other variables were associated with INTs. INT occurrence was associated with reduced probability of good clinical outcome (common odds ratio, 0.25; 95% confidence interval, 0.09-0.74; adjusted for age, type of treatment, and follow-up scan)., Conclusions: INTs are uncommon, detected more frequently on follow-up magnetic resonance imaging, and affect clinical outcome. In experienced centers, endovascular treatment is likely not causal, whereas intravenous alteplase may be therapeutic., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335., (© 2016 American Heart Association, Inc.)

Background and Purpose: Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK-tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population., Methods: TNK-Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK-tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ≤5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0-1)., Results: Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01-20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0-1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0-1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09-2.5; P=0.026)., Conclusions: Administration of TNK-tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01654445., (© 2015 American Heart Association, Inc.)