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Background: In the ESCAPE-NA1 trial, treatment with nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, was associated with improved functional outcome among patients with acute ischaemic stroke due to large vessel occlusion undergoing endovascular thrombectomy without co-treatment with an intravenous thrombolytic agent. There was no benefit when intravenous thrombolytic agent co-treatment was used. We sought to confirm the clinical benefit of nerinetide in the absence of previous intravenous thrombolytic drug treatment., Methods: In this multicentre, randomised, double-blind, placebo-controlled study, done in 77 centres in Canada (16), the USA (16), Germany (21), Italy (four), the Netherlands (three), Norway (four), Switzerland (three), Australia (eight), and Singapore (two), we enrolled patients with acute ischaemic stroke due to anterior circulation large vessel occlusion within 12 h from onset. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation (baseline National Institutes of Health Stroke Scale [NIHSS] score >5), who had been functioning independently in the community (Barthel Index score >90) before the stroke, had Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and who were not treated with a plasminogen activator. Patients were randomly allocated (1:1) to receive intravenous infusion of nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, based upon estimated or actual weight (if known) or saline placebo using a real-time, dynamic, internet-based, stratified randomised minimisation procedure. All patients underwent endovascular thrombectomy. The primary outcome was a favourable functional outcome 90 days from randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. The analysis was by intention to treat and adjusted for time from stroke onset to randomisation (≤4·5 h [yes or no]), age, sex, baseline NIHSS score, occlusion location, time from qualifying imaging to randomisation, baseline ASPECTS, and region. Secondary outcomes were measures of mortality, worsening of stroke, improved functional independence, and measures of neurological disability. This trial is registered with ClinicalTrials.gov, NCT04462536., Findings: From Dec 6, 2020, to Jan 31, 2023, 850 patients were assigned to receive nerinetide (n=454) or placebo (n=396). 206 (45%) participants in the nerinetide group and 181 (46%) participants in the placebo group achieved an mRS score of 0-2 at 90 days (odds ratio 0·97, 95% CI 0·72-1·30; p=0·82). Serious adverse events occurred equally between groups., Interpretation: While nerinetide did not improve outcomes in patients with acute ischaemic stroke, it was not associated with excess adverse events. Further study is needed to identify the ideal timing of treatment and the sub-population of stroke patients who might benefit from treatment combined with current reperfusion therapies., Funding: Canadian Institutes for Health Research and NoNO., Competing Interests: Declaration of interests AHA reports an unrestricted grant from Boehringer-Ingelheim for the TenCRAOS trial. DJG reports share ownership in NoNO. MAA reports Advisory Board membership for Fluid Biomed and Palmera Medical. NA reports salary support from the American Heart Association for her role as section editor in Stroke and from the Florida Stroke Registry. JMC reports grants from Bayer and AstraZeneca and is a co-founder and shareholder of TrianecT. AMD reports a grant from Medtronic, DSMC membership for the WE TRUST study (sponsored by Phillips), DSMC chairman for the LT 3001-203 and LT3001-205 studies (sponsored by Lumosa), and board chairmanship for the Canadian Stroke Consortium (non-profit sector). DWJD reports grants from Stryker Neurovascular, Medtronic, Cerenovus, Penumbra, and Thrombolytic Science, DSMC chairmanship for the ACT-Global and LATE-MT studies, and past chairmanship of the CONTRAST Consortium. AE reports board membership of the Norwegian Stroke Organization. TSF reports payment for advisory board roles for Bayer, Novartis, HLS Therapeutics, and AstraZeneca and board membership for Destine Health and the Vancouver General Hospital–University of British Columbia Foundation. SF reports consulting fees and honoria from Microvention, Rapid Medical,and Stryker Neurovascular. DG reports grants from Microvention and consulting fees from Navigantis. MG reports grants from Medtronic and Cerenovus; consulting fees from Microvention, Stryker Neurovascular, Medronic, Mentice, Phillips, and Penumbra; and stock ownership in Circle Neurovascular. JG reports consulting fees from Medtronic and Johnson & Johnson/Cerenovus. AEH reports grants from GE Healthcare and Viz.ai, consulting fees or honoraria from Medtronic, Microvention, Stryker Neurovascular, Penumbra, Cerevonus, Xcath, Imperative Care, Perfuze, Route 92, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera Therapeutics, Proximie, NovaSignal, and Vesalio, DSMC membership for the COMMAND study, and is the past-president of the Society of Vascular and Interventional Neurology. KJH reports share ownership in NoNO. VH reports grants and consulting fees from Wallaby/Phenox. MDH reports grants from NoNO and Canadian Institutes of Health Research (CIHR) which directly supported the ESCAPE-NEXT study, past grants from NoNO, Medtronic, Boehringer-Ingelheim, CIHR, and Heart & Stroke Foundation; consulting fees from Sun Pharma and Brainsgate, patents licensed to Circle Neurovascular, DSMC charimanship for the DUMAS and Oncover Hiltonel trials, DSMC membership for the ARTESIA, BRAIN-AF and LAAOS-4 trials, stock ownership in Circle Neurovascular, and is the current president of the Canadian Neurological Sciences Federation (non-profit sector). MH reports consulting fees or honoraria from Balt, Medtronic, Stryker Neurovascular, Microvention, Phenox, Cerenovus, Siemens, and Rapid Medical. MEK reports consulting fees from Medtronic and Penumbra and stock or stock options from Basecamp Vascular, Radical Catheter Technology, and Endostream. TL reports grants from Cerus, Stryker Neurovascular, and Phenox and DSMC membership in the CLOT OUT study. NL reports consulting fees from Medtronic and honoraria from Medtronic, Penumbra, Balt, Cerenovus, Microvention, and Stryker Neurovascular. JLM reports advisory board membership for the SECRET study and board membership for the Canadian Stroke Consortium (non-profit sector). BKM reports grants for the CIHR. MM reports consulting fees from Stryker Neurovascular. MP reports grants from German Research Foundation and honoraria from Merck. SP reports grants from BMS/Pfizer, Boehringer-Ingelheim, Danichi-Sankyo, EU, German Federal Joint Committee Innovation Fund, German Federal Ministry of Education of Research, Helena Laboratories, and Werfen; consulting fees from Alexion, AstraZeneca, Daichi-Sankyo, and Werfen; and honoraria from Alexion, Bayer, Boehringer-Ingelheim, BMS/Pfizer, and Portola. AYP reports grants from Brain Canada, Heart & Stroke Foundation Canada, and CIHR, honoraria from Roche Canada, safety committee chairmanship for the ACT trial, and fellowship certification committee chairmanship for the Canadian Stroke Consortium (non-profit sector). M-NP reports grants from Swiss National Science Foundation, Bangerter-Rhyner Stiftung, Stryker Neurovascular, Phenox, Medtronic, Penumbra, and Siemens Healthineers and honoraria from Stryker Neurovascular, Medtronic, Pneumbra, Acandis, and Siemens Healthineers. ASP reports DSMC membership for Cerevasc and Keep, stock or stock options in NTI, Galaxy, Agile, and Perfuse, and a consultancy role for Cerenovus, Agile, Arsenal, Route 92, Stryker Neurovascular, Rapid, and Spryte. MR reports grants from the National Institutes of Health (NIH). RHS reports grants from the NIH, CIHR, and Ontario Brain Institute, DSMC membership for Hoffman La Roche, and stock or stock options in FollowMD. JWT reports consulting fees from Medtronic, Stryker Neurovascular, and Qure.ai. MT reports stock and CEO role in NoNO. PJvD reports consulting fees from Stryker Neurovascular, Phillips, Medtronic, and Siemens. WvZ reports consulting fees or honoraria from Phillips, Bayer, Stryker Neurovascular, Medtronic, Nico Lab, Cerenovus, and DSMC membership in the WeTrust, Athena, and InExtremis trials. MW reports grants from Ab medica, Acandis, Cerenovus, Kaneka Pharmaceuticals, Medtronic, Microvention, Phenox, Siemens Healthcare, and Stryker Neurovascular, consulting fees from Stryker Neurovascular, honoraria from Bracco Imaging, Medtronic, Siemens Healthcare, and Stryker Neurovascular. LLLY reports grants from National Medical Research Council (Singapore) and the Ministry of Education, advisory board membership for AstraZeneca, vice-president role for the Society of Neurointerventional Surgery, stock or stock options in Cereflo and medical advisor roles for Sunbird-bio, Cortirio, and See-mode. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. Published by Elsevier Ltd.. All rights reserved.)

Background: The availability of mechanical thrombectomy (MT) for acute ischemic stroke is limited, and vast disparities exist between countries. We aim to create a MT access score to measure the drivers of access to help quantify and accelerate treatment worldwide., Methods: We used a systematic review complemented by a modified Delphi method. In the first of 3 rounds, 4 independent investigators performed a systematic literature review using key search terms that drive MT access, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In the second round, a panel of 6 anonymous international experts selected key attributes needed for scoring. In the final round, a total of 12 attributes were selected on consensus, each given a score on a 0 to 3 scale. An ultimate MT access score (range, 0-36) was proposed as a new tool to use in identifying barriers to MT access and assist in providing an initial framework for public health interventions., Results: Of 2864 abstracts screened, 121 studies were included in the final systematic review. A total of 34 attributes that potentially drive MT access were initially identified. In the final round, 12 attributes were selected by the expert panel: public awareness, emergency medical services transportation, prehospital large vessel occlusion screening, interhospital transfer policy, emergency department protocols, stroke imaging protocols, emergency department stroke expertise or telestroke availability, interventionalists, MT-capable centers, device availability, and insurance coverage. These attributes were weighted as part of the final score of 0 to 36., Conclusions: The MT access score represents the first tool to quantify barriers to global MT access. Its implementation stands not just as an academic achievement but as a beacon of hope for improving stroke care and outcomes worldwide, bringing us a step closer to bridging the gap in stroke treatment disparities., Competing Interests: Dr Ganesh reports grants from MicroVention Inc; compensation from Biogen and Alexion Pharmaceuticals for other services; stock options in SnapDx Inc; and stock holdings in Collavidence Inc. Dr Saver reports compensation from Stream Medical, Boehringer Ingelheim (prevention only), CSL Behring, Johnson & Johnson Health Care Systems Inc, Bayer, BrainQ, Biogen, Roche, BrainsGate, Medtronic USA Inc, Aeromics, and Abbott Laboratories for consultant services; compensation from Occlutech and MIVI Neuroscience for data and safety monitoring services; and stock options in MindRhythm, Rapid Medical, and Neuronics Medical. Dr Kamel reports an ownership stake in TET Medical; compensation from American Medical Association and Javelin Medical for consultant services; compensation from Boehringer Ingelheim, Novo Nordisk, and AstraZeneca for end point review committee services; and compensation from Medtronic and Janssen Biotech for other services. Dr Jauch reports compensation from RapidAI for consultant services. Dr Toth reports compensation from Kaneka Pharma America LLC, Penumbra Inc, and EBSCO for consultant services; and compensation from Medtronic USA Inc for other services. Dr Venkatasubba Rao reports stock holdings in Migegesys; compensation from DECISIO for other services; and compensation from Medical Expert Consulting for expert witness services. Dr Amuluru reports compensation from Medtronic for consultant services. Dr Szeder reports compensation from Medtronic for consultant services. Dr Urrutia reports grants from Genentech. Dr Yavagal reports compensation from Stryker Corporation, Gravity Medical Technology, Vascular Dynamics, Athersys, Johnson & Johnson Health Care Systems Inc, Poseydon, and Medtronic USA Inc for consultant services; and stock options in Rapid Medical, Poseydon, and Athersys. Dr Ortega-Gutierrez reports grants from National Institutes of Health, Methinks, National Institutes of Health, Siemens, MicroVention Inc, and Stryker; compensation from MicroVention Inc, Stryker, and Medtronic for consultant services; and employment by Carver College of Medicine, University of Iowa. The other authors report no conflicts.

Background: Clinicians need simple and highly predictive prognostic scores to assist practical decision-making. We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy., Methods: Using the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration data set (n=1764), patients in the endovascular thrombectomy arm were divided randomly into a derivation cohort (n=430) and a validation cohort (n=441). From a set of candidate predictors, logistic regression modeling using forward variable selection was used to select a model that was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≤2 at 90 days. The score was validated in validation cohort, control arm (n=893), and external validation cohorts from the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke; n=1066) and INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography; n=614)., Results: In the derivation cohort, we selected 2 significant predictors of mRS ≤2 (National Institutes of Health Stroke Scale score at 24 hours and age [β-coefficient, 0.34 and 0.06]) and derived the HERMES-24 score: age (years)/10+National Institutes of Health Stroke Scale score at 24 hours. The HERMES-24 score was highly predictive for mRS ≤2 (c-statistic 0.907 [95% CI, 0.879-0.935]) in the derivation cohort. In the validation cohort and the control arm, the HERMES-24 score predicts mRS ≤2 (c-statistic, 0.914 [95% CI, 0.886-0.944] and 0.909 [95% CI, 0.887-0.930]). Observed provability of mRS ≤2 ranged between 3.1% and 3.4% when HERMES-24 score ≥25, while it ranged between 90.6% and 93.0% when HERMES-24 score <10 in the derivation cohort, validation cohort, and control arm. The HERMES-24 score also showed c-statistics of 0.894 and 0.889 for mRS ≤2 in the ESCAPE-NA1 and INTERRSeCT populations., Conclusions: The post-treatment HERMES-24 score is a simple validated score that predicts a 3-month outcome after anterior circulation large vessel occlusion stroke regardless of intervention, which helps prognostic discussion with families on day 2., Competing Interests: Dr Brown reports consulting for B. Braun Interventional Systems, Inc, Medtronic, MicroVention, Inc, and the University of Calgary and is employed by BRIGHT Research Partners. Dr Goyal reports grants from Medtronic, Stryker, MicroVention, and Mentice; consulting for Stryker, Microvention, and Mentice; and a patent for systems and methods for acute stroke diagnosis with GE Healthcare. Dr Menon reports stock holdings in Circle Neurovascular Imaging and compensation from Roche and Boehringer Ingelheim. Dr Campbell reports grants from Covidien, Medtronic, and the National Health and Medical Research Council of Australia and fellowships from the National Heart Foundation of Australia, the National Stroke Foundation of Australia, and the Royal Australasian College of Physicians. Dr Mitchell reports consulting for Stryker and MicroVention and grants from Medtronic and Stryker. Dr Jovin reports consulting for Contego Medical; grants/contracts from Medtronic and Stryker; data safety monitoring board participation with Johnson & Johnson CERENOVUS; and stock holdings in Anaconda, Basking, Freeox Biotech, Galaxy, Gravity, Kandu, Methinks, Route92, StataDX, and Vizai. Dr Saver reports consulting for Abbott Laboratories, Aeromics, Biogen, Boehringer Ingelheim, BrainQ, BrainsGate, CSL Behring, Johnson & Johnson Health Care Systems, Medtronic, MindRhythm, Roche, and Stream Medical; data safety monitoring board participation with MIVI Neuroscience; and stock holdings in Neuronics Medical and Rapid Medical. Dr Muir reports consulting for Boehringer Ingelheim, Bayer, and Daiichi Sankyo. Dr White reports consulting for MicroVention and grants from the UK National Institutes for Health Research, MicroVention, Stryker, Medtronic, and Penumbra. Dr Bracard reports grants from the French Ministry of Health; others from GE Medical Systems; and nonfinancial support from MicroVention Europe. Dr Roos reports stock holdings in Nicolab. Dr van Zwam reports grants/contracts from Bayer HealthCare Pharmaceuticals, Stryker, and Johnson & Johnson; employment by Maastricht Universitair Medisch Centrum; and data safety monitoring board participation with Philips. Dr Hill reports consulting for BrainsGate; grants/contracts from Biogen, Boehringer Ingelheim, the Canadian Institutes of Health Research, Medtronic MicroVention, and NoNO; end point review committee participation with Merck; employment by the University of Calgary; and a patent for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients with Circle Neurovascular Imaging. Dr Demchuk reports consulting for Boehringer Ingelheim, HLS Therapeutics, Hoffmann-La Roche, Medtronic, Nova-Signal, and Servier; data safety monitoring board participation with Philips and Lumosa; others from Novo Nordisk AS, Pfizer, and Astra Zeneca; and stock and patent for Stroke imaging software with Circle Neurovascular Imaging. The other authors report no conflicts.

Background: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients., Methods: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction., Results: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P <0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively)., Conclusions: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV., Competing Interests: Disclosures Dr Catanese reports compensation from Roche. Dr Shankar reports a grant from Medtronic. Dr Poppe reports grants from the Heart and Stroke Foundation of Canada, the Fondation Brain Canada, and Stryker and compensation from Roche. Dr Swartz reports grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada; compensation from Roche and the Sunnybrook Research Institute; and stock holdings in FollowMD, Inc. Dr Hill reports grants from the Canadian Institutes of Health Research, Roche, Medtronic, MicroVention, Inc, Boehringer Ingelheim, and NoNO, Inc; compensation from Brainsgate and Merck; and a patent issued for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients licensed to Circle Neurovascular Imaging. Dr Sajobi reports the role as a consultant to Circle Neurovascular Imaging. Dr Menon reports stock holdings in Circle Neurovascular Imaging and compensation from Roche and Boehringer Ingelheim. Dr Demchuk reports compensation from Roche, Lumosa, Boehringer Ingelheim, NovaSignal, Philips, and Medtronic; stock holdings in Circle Neurovascular Imaging; and a patent issued for Stroke imaging software licensed to Circle Neurovascular Imaging. Dr Ganesh reports grants from the Canadian Institutes of Health Research, the Alzheimer Society of Canada, the Heart and Stroke Foundation of Canada, the Fondation Brain Canada, the Sunnybrook Research Institute, the Canadian Cardiovascular Society, Alberta Innovates, Campus Alberta Neuroscience, the Government of Canada, Wellcome Trust, MicroVention, Inc, and Panmure House; compensation from the Canadian Association of Neuroscience Nurses, Biogen, and Atheneum for consultant services; MD Analytics, Creative Research Designs, CTC Communications, Corporation, Alexion Pharmaceuticals, Figure 1, Rhodes Scholarships, MyMedicalPanel, and DeepBench; and stock holdings in Collavidence, Inc, and SnapDx, Inc. Dr Ganesh is a Review Editor of Stroke for Frontiers in Neurology and an Editorial Board Member of Stroke of the American Heart Association and Neurology and Neurology: Clinical Practice of American Academy of Neurology and reports travel supports from the American Heart Association, the American Academy of Neurology, and the University of Calgary. The other authors report no conflicts.

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: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion., Aims: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL., Methods: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed., Results: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group., Conclusion: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.Y.P. is the Principal investigator of the EASI-TOC trial of carotid stenting, partially funded by Stryker, Brain Canada, Heart and Stroke Foundation of Canada, and the Canadian Stroke Consortium and is in the advisory board of and receives speaker honoraria from Roche Canada. Other authors report no conflict of interest.

Introduction: The aim of the study was to investigate the impact of time interval between start of intravenous thrombolysis (IVT) to start of endovascular thrombectomy (EVT) on stroke outcomes., Methods: Data from the Quality Improvement and Clinical Research (QuICR) provincial stroke registry from Alberta, Canada, were used to identify stroke patients who received IVT and EVT from January 2015 to December 2019. We assessed the impact of the time interval between IVT bolus to EVT puncture (needle-to-puncture times [NPT]) on outcomes. Radiological outcomes included successful initial recanalization (revised Arterial Occlusive Lesion 2b-3), successful initial and final reperfusion (modified thrombolysis in cerebral infarction 2b-3). Clinical outcomes were 90-day modified Rankin Scale (mRS) and mortality., Results: Of the 680 patients, 233 patients (median age: 73, 41% females) received IVT + EVT. Median NPT was 38 min (IQR, 24-60). Arrival during working hours was independently associated with shorter NPT (p &lt; 0.001). Successful initial recanalization and initial and final reperfusion were observed in 12%, 10%, and 83% of patients, respectively. NPT was not associated with initial successful recanalization (OR 0.97 for every 10-min increase of NPT, 95% CI: 0.91-1.04), initial successful reperfusion (OR 1.01, 95% CI: 0.96-1.07), or final successful reperfusion (OR: 1.03, 95% CI: 0.97-1.08). Every 10-min delay in NPT was associated with lower odds of functional independence at 90 days (mRS ≤2; OR: 0.93; 95% CI, 0.88-0.97). Patients with shorter NPT (≤38 min) had lower 90-day mRS scores (median 1 vs. 3; OR: 0.54 [0.31-0.91]) and had lower mortality (6.1% vs. 21.2%; OR, 0.23 [0.10-0.57]) than the longer NPT group., Conclusion: Shorter NPT did not impact reperfusion outcomes but was associated with better clinical outcome., (© 2023 S. Karger AG, Basel.)

Background: Distal embolization (DE) is a common complication of endovascular treatment (EVT). We investigated the association of radiological thrombus characteristics and treatment details with DE., Methods: Patients with thin-slice (≤2.5 mm) baseline noncontrast computed tomography and computed tomography angiography from the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) were included. Thrombus annotation was performed manually on coregistered scans by experienced readers. We assessed thrombus location, distance from internal carotid artery terminus, length, perviousness, absolute attenuation, and hyperdense artery sign. In addition, we evaluated balloon guide catheter use during EVT, first-line EVT approach, the number of thrombectomy passes, and prior intravenous thrombolysis administration. DE was defined as the occurrence of emboli distal to the target artery or in new territories during EVT. The association between thrombus characteristics, treatment details, and DE was evaluated using descriptive statistics and multivariable mixed-effects logistic regression, resulting in adjusted odds ratios (aOR) with 95% CI. Interaction between IVT and radiological thrombus characteristics was assessed by adding interaction terms in separate models., Results: In total, 496 out of 1105 (44.9%) ESCAPE-NA1 patients were included. DE was detected in 251 out of 496 patients (50.6%). Patients with DE had longer thrombi (median, 28.5 [interquartile range, 20.8-42.3] mm versus 24.4 [interquartile range, 17.1-32.4] mm; P <0.01). There were no statistically significant differences in the other thrombus characteristics. Factors associated with DE were thrombus length (aOR, 1.02 [95% CI, 1.01-1.04]), balloon guide catheter use (aOR, 0.49 [95% CI, 0.29-0.85]), and number of passes (aOR, 1.24 [95% CI, 1.04-1.47]). In patients with hyperdense artery sign, IVT was associated with reduced odds of DE (aOR, 0.55 [95% CI, 0.31-0.97]), P for interaction=0.04., Conclusions: DE was associated with longer thrombi, no balloon guide catheter use, and more EVT passes. IVT was associated with a reduced risk of DE in patients with hyperdense artery sign. These findings may support treatment decisions on IVT and EVT approaches.

Recombinant tissue plasminogen activator improves outcomes in acute ischemic stroke. Alteplase may result in thrombus migration (TM) distally to a critical arterial supply that can worsen perfusion to eloquent brain tissue. Alteplase-related stroke recanalization and clot migration in vertebral artery (VA) occlusion whereby the clot migrates to the basilar artery (BA) may be harmful. We identified seven subjects with isolated symptomatic vertebral occlusion. Two cases suffered early neurologic deterioration due to TM from VA to BA following alteplase. Precautionary transfer to thrombectomy centers may be warranted in alteplase-treated symptomatic VA occlusions in case of migration to basilar occlusion.

Background: Age and infarct volume are strong predictors of outcome in patients with ischemic stroke who underwent endovascular therapy (EVT). We aimed to investigate the impact of ischemic core volume (ICV) on stroke outcome after EVT in elderly., Methods: Using the HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaboration, a patient-level meta-analysis of 7 randomized trials in which patients were enrolled from December 2010 to April 2015) dataset, we categorized patients into those aged <75 and ≥75 years. ICV was calculated on computed tomography perfusion or magnetic resonance diffusion-weighted imaging. The association between ICV and the benefit of EVT over best medical treatment on outcome (modified Rankin Scale [mRS] at 90 days) and an ICV threshold for high likelihood (≥90%) of very poor outcome (mRS score ≥5) after EVT were investigated., Results: A total of 899 patients who had baseline ICV data, 247 patients aged ≥75 years, of which 118 were randomized in the EVT arm. Patients aged ≥75 years required smaller ICV to achieve mRS score ≤3 than those aged <75 years in the EVT arm (median 10.7 mL versus 23.9 mL, P <0.001). In patients aged ≥75 years, modeling of outcome in both treatment arms revealed potential loss of effect for EVT at ICV of ≥50 mL or ≥85 mL for achieving mRS score ≤3 or ≤4, respectively. Treatment effect of EVT was significant in ICV <50 mL for mRS ≤3 (odds ratio 2.38, 95% confidence interval 1.35-4.22). ICV ≥132 mL was a threshold for high likelihood of very poor outcome after EVT. However, EVT still predicted at least 30% rate of mRS ≤3 at 150 mL ICV if near-complete or complete reperfusion was achieved., Conclusions: Baseline ICV has an impact on stroke outcome after EVT in the elderly, but elderly patients with large ICV may still benefit from EVT if near-complete or complete reperfusion is achieved. Young patients seem to benefit from EVT regardless of ICV status.

Background and Purpose: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors., Methods: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted., Results: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p &lt; 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p &lt; 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p &lt; 0.001)., Conclusion: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates., (© 2022 European Academy of Neurology.)

Background: Cerebral edema after large hemispheric infarction is associated with poor functional outcome and mortality. Net water uptake (NWU) quantifies the degree of hypoattenuation on unenhanced-computed tomography (CT) and is increasingly used to measure cerebral edema in stroke research. Hemorrhagic transformation and parenchymal contrast staining after thrombectomy may confound NWU measurements. We investigated the correlation of NWU measured postthrombectomy with volumetric markers of cerebral edema and association with functional outcomes., Methods: In a pooled individual patient level analysis of patients presenting with anterior circulation large hemispheric infarction (core 80-300 mL or Alberta Stroke Program Early CT Score ≤5) in the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set, cerebral edema was defined as the volumetric expansion of the ischemic hemisphere expressed as a ratio to the contralateral hemisphere(rHV). NWU and midline-shift were compared with rHV as the reference standard on 24-hour follow-up CT, adjusted for hemorrhagic transformation and the use of thrombectomy. Association between edema markers and day 90 functional outcomes (modified Rankin Scale) was assessed using ordinal logistic regression., Results: Overall (n=144), there was no correlation between NWU and rHV (r s =0.055, P =0.51). In sub-group analyses, a weak correlation between NWU with rHV was observed after excluding patients with any degree of hemorrhagic transformation (r s =0.211, P =0.015), which further improved after excluding thrombectomy patients (r s =0.453, P =0.001). Midline-shift correlated strongly with rHV in all sub-group analyses (r s >0.753, P =0.001). Functional outcome at 90 days was negatively associated with rHV (adjusted common odds ratio, 0.46 [95% CI, 0.32-0.65]; P <0.001) and midline-shift (adjusted common odds ratio, 0.85 [95% CI, 0.78-0.92]; P <0.001) but not NWU (adjusted common odds ratio, 1.00 [95% CI, 0.97-1.03]; P =0.84), adjusted for age, baseline National Institutes of Health Stroke Scale, and thrombectomy. Prognostic performance of NWU improved after excluding patients with hemorrhagic transformation and thrombectomy (adjusted odds ratio, 0.90 [95% CI, 0.80-1.02]; P =0.10)., Conclusions: NWU correlated poorly with conventional markers of cerebral edema and was not associated with clinical outcome in the presence of hemorrhagic transformation and thrombectomy. Measuring NWU postthrombectomy requires validation before implementation into clinical research. At present, the use of NWU should be limited to baseline CT, or follow-up CT only in patients without hemorrhagic transformation or treatment with thrombectomy.

Background: Intravenous alteplase is currently the only evidence-based treatment for medium-vessel occlusion stroke (MeVO; M2/3, A2/3, and P2/3 vessel segment occlusions), but due to its limited efficacy, endovascular treatment (EVT) is increasingly performed in these patients. In this case-based survey study, we examined the influence of intravenous alteplase treatment on physicians' decision-making for EVT in primary MeVO stroke., Methods: In an international web-based survey among physicians involved in acute stroke care, participants provided their EVT decision for six quasi-identical fictional MeVO case scenarios (three with and without intravenous alteplase administered). Each scenario showed radiological images and clinical information in the form of a short case vignette. We compared EVT decisions ("immediate EVT", "no EVT", or "wait for alteplase effect" [in case scenarios with alteplase treatment only]) for case scenarios with and without alteplase treatment. Clustered multivariable logistic regression was performed to assess the effect of alteplase on treatment decision., Results: The survey was completed by 366 physicians from 44 countries, resulting in 2196 responses included in this study. In alteplase-treated cases, 641/1098 (58.4%) responses favored immediate EVT, (279/1098 [25.4%]) favored no EVT and 178/1098 (16.2%) opted to wait for alteplase effect. In non-alteplase-treated case scenarios, 846/1098 (78.7%) were in favor of and 252/1098 (21.3%) against EVT. Intravenous alteplase was associated with a lower chance of a decision in favor of immediate EVT (adjusted OR 0.38 [95%CI 0.31 to 0.46])., Conclusions: Intravenous alteplase is an important factor in EVT decision-making for MeVO stroke. However, even in alteplase-treated patients, more than half of the physicians decided to proceed with EVT without waiting for alteplase effect., Competing Interests: Competing interests: Dr. Menon reports editorial board membership at Stroke (Assistant Editor). Dr. Fiehler reports grants and personal fees from Stryker, Acandis, Microvention, Medtronic, personal fees from Codman, Ceronovus, Penumbra, Phenox, other (stock ownership) from Tegus outside the submitted work; and editorial board memberships at Journal of NeuroInterventional Surgery (Associate Editor) and Clinical Neuroradiology (Editor); and executive functions with University Medical Center Hamburg-Eppendorf, Eppdata GmbH. Dr. Chen reports personal fees from Stryker, personal fees from Microvention, Medtronic, Genentech, Ceronovus, Penumbra, outside the submitted work; and editorial board membership at Journal of NeuroInterventional Surgery (Commissioning Editor). Dr. Sakai has nothing to disclose. Dr. Goyal reports personal fees from Stryker, personal fees from Mentice, personal fees from Microvention, personal fees from Medtronic, outside the submitted work; and editorial board membership at Stroke (Consulting Editor); in addition, Dr. Goyal has a patent for systems of acute stroke diagnosis issued and licensed., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial., Methods: ESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling., Results: Among 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0-2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0-2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1)., Conclusions: Tandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting)., Competing Interests: Competing interests: AYP: Research grant from Stryker for EASI-TOC study, PI of EASI-TOC study. JMO: funds from the University of Basel Research Foundation, Julia Bangerter Rhyner Foundation, Freiwillige Akademische Gesellschaft Basel. RGN: fees/compensation from Stryker, Medtronic, Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals, Brainomix, Viz.ai, Corindus Vascular Robotics, Vesalio, and Ceretrieve; member of the Physician Advisory Board for Cerenovus/Neuravi. ADM: grants from NoNO; honoraria from Medtronic; patent Circle NVI. BKM: shares in Circle NVI; patent for systems of triage in acute stroke. MT: CEO of NoNO; patents owned by NoNO. MDH: grants from Canadian Institutes for Health Research, Alberta Innovates, NoNO, Heart & Stroke Foundation of Canada, National Institutes of Neurological Disorders and Stroke, Covidien, Boehringer-Ingleheim, Stryker, and Medtronic; fees from Merck; patent for systems of acute stroke diagnosis; stock in Calgary Scientific. MG: personal fees from Mentice, Medtronic, Microvention, Stryker; patent for systems of acute stroke diagnosis. BKM holds a patent on systems of triage in acute stroke and stock ownership in Circle Neurovascular Inc. MG is a consultant for Medtronic, Stryker, Microvention, GE Healthcare, and Mentice. MDH reports grants from CIHR during the conduct of the study, grants from Medtronic, and grants from NoNO Inc outside the submitted work. In addition, he has a patent to US Patent Office number: 62/086,077 issued and licensed, and Director, Board of Circle Neurovascular, Director, Board of the Canadian Neuroscience Federation, and Director, Board of the Canadian Stroke Consortium., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Collateral assessment using CT angiography is a promising modality for selecting patients for endovascular thrombectomy (EVT) in the late window (6-24 hours). The outcome of these patients compared with those selected using perfusion imaging is not clear., Methods: We pooled data from seven trials and registries of EVT-treated patients in the late-time window. Patients were classified according to the baseline imaging into collateral imaging alone (collateral cohort) and perfusion plus collateral imaging (perfusion cohort). The primary outcome was the proportion of patients achieving independent 90-day functional outcome (modified Rankin Scale 'mRS' 0-2). We used the propensity score-weighting method to balance important predictors between the cohorts., Results: In 608 patients, the median onset/last-known-well to emergency arrival time was 8.8 hours and 53.2% had wake-up strokes. Both cohorts had collateral imaging and 379 (62.3%) had perfusion imaging. Independent functional outcome was achieved in 43.1% overall: 168/379 patients (45.5%) in the perfusion cohort versus 94/214 (43.9%) in the collateral cohort (p=0.71). A logistic regression model adjusting for inverse-probability-weighting showed no difference in 90-day mRS score of 0-2 among the perfusion versus collateral cohorts (adjusted OR 1.05, 95% CI 0.69 to 1.59, p=0.83) or in a favourable shift in 90-day mRS (common adjusted OR 1.01, 95% CI 0.69 to 1.47, p=0.97)., Conclusion: This pooled analysis of late window EVT showed comparable functional outcomes in patients selected for EVT using collateral imaging alone compared with patients selected using perfusion and collateral imaging., Prospero Registration Number: CRD42020222003., Competing Interests: Competing interests: MAA reports being a member of the scientific advisory board of Palmera Medical. AD reports personal fees from Medtronic. MG reports grants or personal fees from Medtronic, Stryker, Microvention, Cerenovus, and has a patent Systems of Acute Stroke Diagnosis issued to GE Healthcare. MDH has received grant support from Medtronic, consultant fees from Boehringer Ingelheim and speaker’s fees from Amgen. SM acted as a consultant for Cerenovus. BKM reports shares in Circle NVI; patent for systems of triage in acute stroke. Dr Patrik reports research grants from the Swiss Heart Foundation and the Swiss National Science Foundation. DT received honoraria as a member of advisory board of Abbott, Boehringer Ingelheim, Bayer, Pfizer-BMS, Medtronic and Daiichi Sankyo. The other authors report no conflicts., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to explore the preference of stroke physicians to treat patients with primary medium vessel occlusion (MeVO) stroke with immediate endovascular treatment (EVT) in an international cross-sectional survey, as there is no clear guideline recommendation for EVT in these patients., Methods: In the survey MeVO-Finding Rationales and Objectifying New Targets for IntervEntional Revascularization in Stroke (MeVO-FRONTIERS), participants were shown four cases of primary MeVOs (six scenarios per case) and asked whether they would treat those patients with EVT. Multivariable logistic regression with clustering by respondent was performed to assess factors influencing the decision to treat. Dominance analysis was performed to assess the influence of factors within the scenarios on decision making., Results: Overall, 366 participants (56 women; 15%) from 44 countries provided 8784 answers to 24 scenarios. Most physicians (59.2%) would treat patients immediately with EVT. Younger patient age (incidence rate ratio (IRR) 1.24, 99% CI 1.19 to 1.30), higher National Institutes of Health Stroke Scale (NIHSS) score (IRR 1.69, 99% CI 1.57 to 1.82), and small core volume (IRR 1.35, 99% CI 1.24 to 1.46) were positively associated with the decision to treat with EVT. Interventionalists (IRR 1.26, 99% CI 1.01 to 1.56) were more likely to treat patients with MeVO immediately with EVT. In the dominance analysis, factors influencing the decision in favor of EVT were (in order of importance): baseline NIHSS, core volume, alteplase use, patients' age, and occlusion site., Conclusions: Most physicians in this survey were interventionalists and would treat patients with MeVO stroke immediately with EVT. This finding supports the need for robust clinical evidence., Competing Interests: Competing interests: AMD reports editorial board membership at International Journal of Stroke (Editor). BKM reports editorial board membership at Stroke (Assistant Editor). MC reports personal fees from Stryker, personal fees from Microvention, Medtronic, Genentech, Cerenovus, Penumbra outside the submitted work; and editorial board membership at Journal of NeuroInterventional Surgery (Commissioning Editor). JF reports grants and personal fees from Stryker, Acandis, Microvention, Medtronic, personal fees from Codman, Ceronovus, Penumbra, Phenox, other (stock ownership) from Tegus outside the submitted work; and editorial board memberships at Journal of NeuroInterventional Surgery (Associate Editor) and Clinical Neuroradiology (Editor); and Executive functions with University Medical Center Hamburg-Eppendorf, Eppdata GmbH. MG reports personal fees from Stryker, personal fees from Mentice, Microvention, and Medtronic outside the submitted work; and editorial board membership at Stroke (Consulting Editor). In addition, NG has a patent for Systems of acute stroke diagnosis issued and licensed. PC, MK, NS, NK, JMO, RM, NS have nothing to disclose., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Strokes are a longstanding complication of acute type A aortic dissection (ATAAD) repair. Understanding the neuroanatomy, mechanism, and severity of stroke will facilitate efforts to improve prediction, prevention, and treatment strategies., Methods: Retrospective review of patients who sustained stroke from a consecutive series of patients undergoing ATAAD repair. Neuroimaging was interpreted by two stroke neurologists blinded to clinical results. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS). Residual disability at 30 days was assessed using the modified Rankin Scale (mRS)., Results: Twenty percent (38/189) of patients undergoing repair for ATAAD had stroke (unilateral 58%, bi-hemispheric 42% [p = .33]). All strokes were ischemic. No significant lateralization (right vs. left) was noted with unilateral strokes (26% vs. 32%, p = .67). Etiology of stroke was embolic (58%), hypoperfusion (26%), mixed (11%), and unknown (5%). There were no intraoperative variables that correlated with the neuroanatomy or mechanism of stroke. Preoperative carotid dissection was seen in 40% (n = 15), while postoperatively 10% (n = 4) sustained intracranial large vessel occlusion (LVO). Strokes were moderate or severe (NIHSS ≥ 9) in 97% of cases, with 66% incidence of moderate residual disability (mRS ≥ 3) at 1 month postoperatively., Conclusions: Strokes associated with ATAAD are severe at presentation resulting in significant disability. One in 10 strokes is due to LVO and potentially amenable to endovascular treatment. Heterogeneity in both location and etiology of stroke makes prevention challenging. Future trials may evaluate the role of early neuroimaging and simultaneous treatment of stroke given advancements in endovascular therapy., (© 2021 Wiley Periodicals LLC.)

Background and Purpose: Sex-related differences exist in many aspects of acute stroke and were mainly investigated in the early time window with conflicting results. However, data regarding sex disparities in late presenters are scarce. Therefore, we sought to investigate differences in outcomes between women and men treated with endovascular treatment in the late time window., Methods: Analyses were based on the SOLSTICE Consortium (Selection of Late-Window Stroke for Thrombectomy by Imaging Collateral Extent), which was an individual-patient level analysis of seven trials and registries. Baseline characteristics, 90-day functional independence (modified Rankin Scale score ≤2), mortality, and symptomatic intracranial hemorrhage were compared between women and men. Effect of sex on the association of age and successful reperfusion (final Thrombolysis in Cerebral Infarction 2b-3) with outcomes was assessed using multivariable logistic regression adjusted for age, National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, time from onset to puncture, occlusion location, intravenous thrombolysis, and successful reperfusion, with interaction terms., Results: Among 608 patients treated with endovascular treatment, 50.5% were women. Women were older than men (median age of 72 versus 68 years, P =0.02) and had a lower prevalence of tandem occlusions (14.0% versus 22.9%, P =0.005). Workflow times were similar between sexes. Adjusted outcomes did not differ between women and men. Functional independence at 90 days was achieved by 127 out of 292 women (43.5%) and 135 out of 291 men (46.4%). Mortality at 90 days (54 [18.5%] versus 48 [16.5%]) and symptomatic intracranial hemorrhage (37 [13.3%] versus 33 [11.6%]) were similar between women and men. There was no sex-by-age interaction on functional outcomes. However, men had higher likelihood of mortality ( P interaction =0.003) and symptomatic intracranial hemorrhage ( P interaction =0.017) with advancing age. Sex did not influence the relation between successful reperfusion and outcomes., Conclusions: In this multicenter analysis of late patients treated with endovascular treatment, sex was not associated with functional outcome. However, sex influenced the association between age and safety outcomes, with men experiencing worse outcomes with advancing age.

Background: 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., Methods: 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., Findings: 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]; p interaction =0·0087)., Interpretation: 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., Funding: Stryker Neurovascular., Competing Interests: Declaration of interests TGJ is adviser and investor for Anaconda, Route92, Viz.ai, FreeOx, Blockade Medical and Methinks. He received personal fees in his role on the Data Safety Monitoring Board and steering committee from Cerenovus and on the screening committee for Contego Medical. He received stock as an advisory board member for Corindus. He received grant support for Medtronic and from Stryker Neurovascular in his capacity as principal investigator for DAWN and AURORA. RGN reports consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Imperative Care, Medtronic, Phenox, Prolong Pharmaceuticals, and Stryker Neurovascular and stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz.ai, and Perfuze. AMD is a shareholder and patent holder in Circle NVI (imaging-based software). He has also received honoraria from Medtronic for consulting services. SOM is the recipient of a research grant by the Brazilian Ministry of Health (RESILIENT trial) and has received speaker fees from Boehringer Ingelheim, Medtronic, Penumbra, Bayer, Pfizer and advisory board fees from Boehringer Ingelheim. JM is a consultant for Endostream, Viseon, Imperative Care, RIST, Synchron, Viz.ai, Perflow, CVAid, and Cerebrotech, and a shareholder in Rebound, BlinkTBI, Endostream, Viseon, Imperative Care, Serenity, Cardinal Consulting, NTI, RIST, Synchron, Viz.ai, and Cerebrotech. MR is adviser and shareholder in Anaconda Biomed and Methinks and received grants and personal fees from Medtronic, personal fees from Stryker, Cerenovus, and Apta Targets. SO-G has received consultant fees from Medtronic, Stryker, and Siemens. MDH reports personal fees from Sun Pharma, grants from Boehringer Ingelheim, Stryker, NoNO, and Medtronic, outside the submitted work; he has a patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients issued to US Patent office Number: 62/086,077 and owns stock in Pure Web, a company that makes, among other products, medical imaging software; is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group, is a director of the Canadian Stroke Consortium, a not-for-profit group, is a director of Circle NeuroVascular, and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart and Stroke Foundation of Canada, and National Institutes of Neurological Disorders and Stroke. FOL has received lecture fees from Boehringer Ingelheim. DCH serves as a consultant for Stryker and Vesalio, and holds stock options in Viz.ai. SB's employer, Bright Research Partners, has received payments from the University of Pittsburgh for the statistical work related to the current study and from the University of Calgary and Medtronic outside the current project. MG reports grants or personal fees from Medtronic, Stryker, Microvention, Cerenovus, and has a patent Systems of Acute Stroke Diagnosis issued to GE Healthcare. AHS is the recipient of NIH grants and owns stock or stock options in Adona Medical, Amnis Therapeutics, BlinkTBI, Buffalo Technology Partners, Cardinal Consultants, Cerebrotech Medical Systems, Cognition Medical, Endostream Medical, Imperative Care, International Medical Distribution Partners, Neurovascular Diagnostics, Q'Apel Medical, Radical Catheter Technologies, Rebound Therapeutics, Rist Neurovascular, Sense Diagnostics, Serenity Medical, Silk Road Medical, Spinnaker Medical, StimMed, Synchron, Three Rivers Medical, Vastrax, ICIS, and Viseon; consultant for Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA, Cerebrotech Medical Systems, Cerenovus, Corindus, Integra, Medtronic, MicroVention, Minnetronix Neuro, Northwest University – DSMB Chair for HEAT Trial, Penumbra, Rapid Medical, Rebound Therapeutics, Serenity Medical, Silk Road Medical, StimMed, Stryker, Three Rivers Medical, VasSol, and W L Gore and Associates; principal investigator or on the Steering Committee for Cerenovus LARGE Trial and ARISE II Trial, Medtronic SWIFT PRIME and SWIFT DIRECT Trials, MicroVention FRED Trial and CONFIDENCE Study, POSITIVE Trial, Penumbra 3D Separator Trial, COMPASS Trial, and the INVEST Trial. JJH discloses consulting fees from Medtronic, Microvention, and iSchemaView. MPM owns stock in ThrombX Medica. DSL is consultant to Cerenovus, Genentech, Stryker, Medtronic as Imaging Core Lab. GWA is the principal investigator of the DEFUSE 3 study, which provided National Institutes of Health grant funding to Stanford University; he has equity interest in iSchemaView, and is a consultant for Genentech and iSchemaView. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Importance: Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes., Objective: To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome., Design, Setting, and Participants: This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter trial conducted from March 2017 to August 2019. Patients who participated in ESCAPE-NA1 and had available 90-day modified Rankin Scale (mRS) scores and 24-hour to 48-hour posttreatment follow-up parenchymal imaging were included., Exposures: Small FIV (volume ≤25th percentile) and large FIV (volume ≥75th percentile) on 24-hour computed tomography/magnetic resonance imaging. Baseline factors, outcomes, treatments, and poststroke serious adverse events (SAEs) were compared between discrepant cases (ie, patients with 90-day mRS score ≥3 despite small FIV or those with mRS scores ≤2 despite large FIV) and nondiscrepant cases., Main Outcomes and Measures: Area under the curve (AUC) and goodness of fit of prespecified logistic models, including pretreatment (eg, age, cancer, vascular risk factors) and treatment-related and posttreatment (eg, SAEs) factors, were compared with stepwise regression-derived models for ability to identify small FIV with higher mRS score and large FIV with lower mRS score., Results: Among 1091 patients (median [IQR] age, 70.8 [60.8-79.8] years; 549 [49.7%] women; median [IQR] FIV, 24.9 mL [6.6-92.2 mL]), 42 of 287 patients (14.6%) with FIV of 7 mL or less (ie, ≤25th percentile) had an mRS score of at least 3; 65 of 275 patients (23.6%) with FIV of 92 mL or greater (ie, ≥75th percentile) had an mRS score of 2 or less. Prespecified models of pretreatment factors (ie, age, cancer, vascular risk factors) associated with low FIV and higher mRS score performed similarly to models selected by stepwise regression (AUC, 0.92 [95% CI, 0.89-0.95] vs 0.93 [95% CI, 0.90-0.95]; P = .42). SAEs, specifically infarct in new territory, recurrent stroke, pneumonia, and congestive heart failure, were associated with low FIV and higher mRS scores; stepwise models also identified 24-hour hemoglobin as treatment-related/posttreatment factor (AUC, 0.92 [95% CI, 0.90-0.95] vs 0.94 [95% CI, 0.91-0.96]; P = .14). Younger age was associated with high FIV and lower mRS score; stepwise models identified absence of diabetes and higher baseline hemoglobin as additional pretreatment factors (AUC, 0.76 [95% CI, 0.70-0.82] vs 0.77 [95% CI, 0.71-0.83]; P = .82). Absence of SAEs, especially stroke progression, symptomatic intracerebral hemorrhage, and pneumonia, was associated with high FIV and lower mRS score2; stepwise models also identified 24-hour hemoglobin level, glucose, and diastolic blood pressure as posttreatment factors associated with discrepant cases (AUC, 0.80 [95% CI, 0.74-0.87] vs 0.79 [95% CI, 0.72-0.86]; P = .92)., Conclusions and Relevance: In this study, discrepancies between functional outcome and post-EVT infarct volume were associated with differences in pretreatment factors, such as age and comorbidities, and posttreatment complications related to index stroke evolution, secondary prevention, and quality of stroke unit care. Besides preventing such complications, optimization of blood pressure, glucose levels, and hemoglobin levels are potentially modifiable factors meriting further study.

Background and Purpose: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management., Methods: We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0-2a. Proportions of good outcome (modified Rankin scale 0-2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained., Results: We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81-2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56-2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00-22.97)., Conclusion: Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient's lifetime., Methods: Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis., Results: The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (-$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care., Conclusions: Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient's lifetime.Clinical Trial Registration: NCT01778335.

Background: Patient age and baseline Alberta Stroke Program Early CT score (ASPECTS) are both independent predictors of outcome in acute ischemic stroke patients treated with endovascular therapy (EVT). We assessed the combined effect of age and ASEPCTS on clinical outcome in acute ischemic stroke patients with LVO with and without EVT, and EVT treatment effect in different age/ASPECTS subgroups., Methods: The HERMES collaboration pooled data of seven randomized controlled trials that tested the efficacy of EVT. Adjusted logistic regression was performed to test for multiplicative interaction of age and ASPECTS with the primary outcome (ordinal mRS) and secondary outcomes (mRS 0-2/0-1/0-3) in the EVT and control arms. Patients were then stratified by age (<75 vs ≥ 75 years) and ASPECTS (0-5/6-7/8-10), and adjusted effect-size estimates for the association of EVT were derived for the six age/ASPECTS subgroups., Results: 1735 patients were included in the analysis. There was no multiplicative interaction between age and ASPECTS on clinical outcomes. In the exploratory subgroup analysis, we found a nominally negative point estimate for the association of EVT with clinical outcome in the ASPECTS 0-5/age ≥75, subgroup (acOR 0.36, 95% CI 0.07 to 1.89). The point estimate for moderate outcome (mRS0-3) nominally favored EVT (aOR 1.24, 95% CI 0.16 to 9.84). In all other subgroups, effect size-estimates consistently favored EVT., Conclusion: There was no multiplicative interaction of age and ASPECTS on clinical outcomes in EVT or control arm patients. Outcomes in patients ≥75 years with ASPECTS 0-5 were poor, irrespective of treatment. Further investigation to define the role of EVT and range of acceptable outcomes in this subgroup is warranted., Competing Interests: Competing interests: JMO is supported by the University of Basel Research Foundation, Julia Bangerter Rhyner Foundation, and Freiwillige Akademische Gesellschaft Basel. Mayank Goyal is a consultant for Medtronic, Stryker, Microvention, GE Healthcare, and Mentice., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion, but the association between radiologic hemorrhage severity and outcome is controversial. Purpose To investigate the prevalence and impact on outcome of intracranial hemorrhage and hemorrhage severity after endovascular stroke treatment. Materials and Methods The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial enrolled participants with acute large vessel occlusion stroke who underwent endovascular treatment from March 1, 2017, to August 12, 2019. Evidence of any intracranial hemorrhage, hemorrhage multiplicity, and radiologic severity, according to the Heidelberg classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], and parenchymal hematoma type 2 [PH2]) was assessed at CT or MRI 24 hours after endovascular treatment. Good functional outcome, defined as a modified Rankin score of 0-2 at 90 days, was compared between participants with intracranial hemorrhage and those without intracranial hemorrhage at follow-up imaging and between hemorrhage subtypes. Poisson regression was performed to obtain adjusted effect size estimates for the presence of any intracranial hemorrhage and hemorrhage subtypes at good functional outcome. Results Of 1097 evaluated participants (mean age, 69 years ± 14 [standard deviation]; 551 men), any degree of intracranial hemorrhage was observed in 372 (34%). Good outcomes were less often achieved among participants with hemorrhage than among those without hemorrhage at follow-up imaging (164 of 372 participants [44%] vs 500 of 720 [69%], respectively; P < .01). After adjusting for baseline variables and infarct volume, intracranial hemorrhage was not associated with decreased chances of good outcome (adjusted risk ratio [RR] = 0.91 [95% CI: 0.82, 1.02], P = .10), but there was a graded relationship of radiologic hemorrhage severity and outcomes, whereby PH1 (RR = 0.77 [95% CI: 0.61, 0.97], P = .03) and PH2 (RR = 0.41 [95% CI: 0.21, 0.81], P = .01) were associated with decreased chances of good outcome. Conclusion Any degree of intracranial hemorrhage after endovascular treatment was seen in one-third of participants. A graded association existed between radiologic hemorrhage severity and outcome. Hemorrhagic infarction was not associated with outcome, whereas parenchymal hematoma was strongly associated with poor outcome, independent of infarct volume. © RSNA, 2021 Clinical trial registration no. NCT01778335 Online supplemental material is available for this article.

Background: Acute ischemic stroke may affect women and men differently. We aimed to evaluate sex differences in outcomes of endovascular treatment (EVT) for ischemic stroke due to large vessel occlusion in a population-based study in Alberta, Canada., Methods and Results: Over a 3-year period (April 2015-March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. The primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at their premorbid living situation without an increase in the level of care within 90 days of the index stroke event. In adjusted analysis, EVT was associated with an increase of 90-day home-time by an average of 6.08 (95% CI -2.74-14.89, p-value 0.177) days in women compared to an average of 11.20 (95% CI 1.94-20.46, p-value 0.018) days in men. Further analysis revealed that the association between EVT and 90-day home-time in women was confounded by age and onset-to-treatment time., Conclusions: We found a nonsignificant nominal reduction of 90-day home-time gain for women compared to men in this province-wide population-based study of EVT for large vessel occlusion, which was only partially explained by confounding.

Objective: Decisions to treat large-vessel occlusion with endovascular therapy (EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients' comorbidities. We explored EVT/alteplase decision-making by stroke experts in the setting of comorbidity/disability., Methods: In an international multi-disciplinary survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case scenarios. Five included comorbidities (cancer, cardiac/respiratory/renal disease, mild cognitive impairment [MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions., Results: Among 607 physicians (38 countries), EVT was chosen less often in comorbidity-related scenarios (79.6% under current resources, 82.7% assuming ideal conditions) versus six "level-1A" scenarios for which EVT/alteplase was clearly indicated by current guidelines (91.1% and 95.1%, respectively, odds ratio [OR] [current resources]: 0.38, 95% confidence interval 0.31-0.47). However, EVT was chosen more often in comorbidity-related scenarios compared to all other 17 scenarios (79.6% versus 74.4% under current resources, OR: 1.34, 1.17-1.54). Responses favoring alteplase for comorbidity-related scenarios (e.g. 75.0% under current resources) were comparable to level-1A scenarios (72.2%) and higher than all others (60.4%). No comorbidity independently diminished EVT odds when considering all scenarios. MCI and dependence carried higher alteplase odds; cancer and cardiac/respiratory/renal disease had lower odds. Being older/female carried lower EVT odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT-, lower alteplase odds), practicing in East Asia (higher EVT odds), and in interventional neuroradiology (lower alteplase odds vs neurology)., Conclusion: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT. Differences in decision-making by patient age/sex merit further study.

Objective: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature., Methods: We pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0-1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0-2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation., Results: Among 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions ( p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04). After propensity score matching, clinical outcomes between the 2 groups were not significantly different. EVT patients had an 8.6% (95% confidence interval [CI] -8.8% to 26.1%) higher rate of excellent 90-day outcome, despite a 22.3% (95% CI, 3.0%-41.6%) higher risk of neurologic deterioration at 24 hours., Conclusions: EVT for LVO in patients with low NIHSS score was associated with increased risk of neurologic deterioration at 24 hours. However, both EVT and medical management resulted in similar proportions of excellent clinical outcomes at 90 days., Classification of Evidence: This study provides Class III evidence that for patients with acute anterior circulation ischemic strokes and LVO with NIHSS < 6, EVT and medical management result in similar outcomes at 90 days., (© 2020 American Academy of Neurology.)

Background: The benefit of endovascular treatment (EVT) is highly time-dependent, and treatment delays reduce patients' chances to achieve a good outcome. In this survey-based study, we aimed to evaluate current in-hospital EVT workflow characteristics across different countries and hospital settings, and to quantify the time-savings that could be achieved by optimizing particular workflow steps., Methods: In a multinational survey, neurointerventionalists were asked to provide specific information about EVT workflows in their current working environment. Workflow characteristics were summarized using descriptive statistics and stratified by country and physician characteristics, such as age, career stage, personal and institutional caseload., Results: Among 248 respondents from 48 countries, pre-notification of the neurointerventional team was used in 70% of cases. The emergency department (ED) and CT scanner, and the CT scanner and neuroangiography suite, were on different floors in 23% and 38%, respectively. Redundant procedures in the ED were often routinely performed, such as chest x-rays (in 6%). General anesthesia was the most frequently used anesthesia protocol for EVT (42%), and an anesthesiologist was available in 82% for this purpose. 52% of the participants used a pre-prepared EVT kit., Conclusion: The current structure of EVT workflows offers possibilities for improvement. While some bottlenecks, such as the spatial department set-up, cannot easily be resolved, pre-notification tools and pre-prepared EVT kits are more straightforward to implement and could help to reduce treatment delays, and thereby improve patient outcomes., Competing Interests: Competing interests: MG is a consultant for Medtronic, Stryker, Microvention, GE Healthcare, Mentice. JMO is supported by the University of Basel Research Foundation, Julia Bangerter Rhyner Foundation and Freiwillige Akademische Gesellschaft Basel., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Since 2015, endovascular therapy has been established as a standard of care for acute stroke. This has caused major challenges regarding the organization of systems of care, which have to meet the increasing demand for thrombectomies. This study aims to evaluate how endovascular therapy decisions made by European and North American physicians under their current local resources differ from those made under assumed ideal conditions., Methods: In an international, multidisciplinary survey, physicians involved in acute stroke care were asked to give their treatment decisions to 10 out of 22 randomly assigned stroke case-scenarios. Participants stated (a) their treatment approach under assumed ideal conditions (without any external limitations) and (b) the treatment they would pursue under their current local resources. Resources gaps (ideal minus current endovascular therapy rates) were calculated for different countries/states/provinces and correlated to economic and healthcare key metrics (gross domestic product-per-capita, public or private health insurance coverage, etc.)., Results: A total of 607 physicians, among them 218 from North America and 136 from 25 European countries, responded to the survey. Resources gaps in the majority of North American states/provinces and European countries were small (<5%). The highest gaps were observed among few European countries, namely Poland (30%) and the United Kingdom (33%). The magnitude of the resources gap did not correlate to national economic or healthcare metrics., Discussion and Conclusion: In the majority of North American states/provinces and European countries covered in this study, the discrepancy between endovascular therapy decisions under current local resources and assumed ideal conditions seems to be small, even in countries with a limited economic status and healthcare infrastructure.

Background A heterogeneous patient population receives endovascular treatment (EVT) for acute ischemic stroke caused by proximal large-vessel occlusion every day. We aimed to conduct a population-based study of EVT in the province of Alberta, Canada, to understand the effectiveness in a complete population and how the magnitude of effect differs from the artificial world of clinical trials. Methods and Results Within a 3-year period (April 2015 to March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT [Computed Tomography] to Recanalization Times) trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database method. Primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at premorbid living situation without increase in level of care within 90 days of index stroke event. Median age of patients was 70 years (interquartile range, 59-81 years), and 47.8% were women. Median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13-20). EVT was associated with an increased 90-day home-time by an average of 8.5 days compared with medical treatment alone using Cragg hurdle regression ( P =0.009). Age and higher National Institutes of Health Stroke Scale score were associated with decreased 90-day home-time (both P <0.001). Multivariable logistic regression showed no association between EVT and mortality at 90 days (odds ratio, 0.76; 95% CI, 0.47-1.24). Conclusions EVT for acute ischemic stroke caused by proximal large-vessel occlusion was effective in our province-wide population-based study and results in an increase of 90-day home-time by ~8.5 days.

Background: Endovascular treatment is recommended in clinical practice in Japan. However, its utilization and comprehensiveness are less well described., Aims: To report endovascular treatment utilization and overall geographical coverage in Japan and to analyze regional differences in the number of endovascular treatments, specialists, and endovascular treatment-capable hospitals., Methods: A national survey of members of the Japanese Society for NeuroEndovascular Therapy (JSNET) was conducted in 2017 and 2018. The total number of endovascular treatment cases per year was estimated, and the number of endovascular treatment cases per 100,000 people was calculated using the 2015 census. The distribution of treatment hospitals and JSNET specialists was mapped and the population coverage rate was determined., Results: The total number of endovascular treatment cases in Japan increased by 34.5% from 2016 (7702) to 2017 (10,360). The number of endovascular treatment-capable hospitals in Japan increased from 597 in 2016 to 693 in 2017, with an average annual caseload of 14.9 in 2017. The number of JSNET specialists per hospital decreased from 1.81 in 2016 to 1.76 in 2017 because of the increase in endovascular treatment-capable hospitals. Only 50 (7.2%) hospitals had > 40 endovascular treatment cases annually. The majority (97.7%) of the Japanese population lives within a 60-min drive of any endovascular treatment-capable hospital. However, only 70.4% live within a 60-min drive of a high-volume center (>40 cases annually)., Conclusions: Utilization of endovascular treatment in Japan is increasing; however, the number of cases per hospital remains low, as is the number of specialists per endovascular treatment-capable hospital. Increased number of specialists and centralization of endovascular treatment services may improve patient outcomes.

Background and Purpose: Differences in the treatment practice of female and male physicians have been shown in several medical subspecialties. It is currently not known whether this also applies to endovascular stroke treatment. The purpose of this study was to explore whether there are differences in endovascular treatment decisions made by female and male stroke physicians and neurointerventionalists., Methods: In an international survey, stroke physicians and neurointerventionalists were randomly assigned 10 case scenarios and asked how they would treat the patient: (A) assuming there were no external constraints and (B) given their local working conditions. Descriptive statistics were used to describe baseline demographics, and the adjusted OR for physician gender as a predictor of endovascular treatment decision was calculated using logistic regression., Results: 607 physicians (97 women, 508 men, 2 who did not wish to declare) participated in this survey. Physician gender was neither a significant predictor for endovascular treatment decision under assumed ideal conditions (endovascular therapy was favored by 77.0% of female and 79.3% of male physicians, adjusted OR 1.03, P=0.806) nor under current local resources (endovascular therapy was favored by 69.1% of female and 76.9% of male physicians, adjusted OR 1.03, P=0.814)., Conclusion: Endovascular therapy decision making between male and female physicians did not differ under assumed ideal conditions or under current local resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The decision to proceed with endovascular thrombectomy should ideally be made independent of inconvenience factors, such as daytime. We assessed the influence of patient presentation time on endovascular therapy decision making under current local resources and assumed ideal conditions in acute ischemic stroke with level 2B evidence for endovascular treatment., Methods and Materials: In an international cross sectional survey, 607 stroke physicians from 38 countries were asked to give their treatment decisions to 10 out of 22 randomly assigned case scenarios. Eleven scenarios had level 2B evidence for endovascular treatment: 7 daytime scenarios (7:00 am-5:00 pm) and four night time cases (5:01 pm- 6:59 am). Participants provided their treatment approach assuming (A) there were no practice constraints and (B) under their current local resources. Endovascular treatment decisions in the 11 scenarios were analyzed according to presentation time with adjustment for patient and physician characteristics., Results: Participants selected endovascular therapy in 74.2% under assumed ideal conditions, and 70.7% under their current local resources of night time scenarios, and in 67.2% and 63.8% of daytime scenarios. Night time presentation did not increase the probability of a treatment decision against endovascular therapy under current local resources or assumed ideal conditions., Conclusion: Presentation time did not influence endovascular treatment decision making in stroke patients in this international survey., Competing Interests: Competing interests: MG is a consultant for Medtronic, Stryker, Microvention, GE Healthcare, and Mentice. UF is a consultant for Medtronic, Stryker, andCSL Behring, and co-PI of the SWIFT DIRECT trial (Medtronic). FT works as a consultant for Balt and Stryker. BWB works as a consultant for Penumbra, Medtronic, Stryker, 880 Medical and Metactive, owns stock options (Penumbra,Viz.ai), and has ownership interests on Route 92 and Marblehead. GS issupported by the Heart and Stroke Foundation of Canada Career Award., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose- The American Heart Association and the American Stroke Association guidelines for early management of patients with ischemic stroke offer guidance to physicians involved in acute stroke care and clarify endovascular treatment indications. The purpose of this study was to assess concordance of physicians' endovascular treatment decision-making with current American Heart Association and the American Stroke Association stroke treatment guidelines using a survey-approach and to explore how decision-making in the absence of guideline recommendations is approached. Methods- In an international cross-sectional survey (UNMASK-EVT), physicians were randomly assigned 10 of 22 case scenarios (8 constructed with level 1A and 11 with level 2B evidence for endovascular treatment and 3 scenarios without guideline coverage) and asked to declare their treatment approach (1) under their current local resources and (2) assuming there were no external constraints. The proportion of physicians offering endovascular therapy (EVT) was calculated. Subgroup analysis was performed for different specialties, geographic regions, with regard to physicians' age, endovascular, and general stroke treatment experience. Results- When facing level 1A evidence, participants decided in favor of EVT in 86.8% under current local resources and in 90.6% under assumed ideal conditions, that is, 9.4% decided against EVT even under assumed ideal conditions. In case scenarios with level 2B evidence, 66.3% decided to proceed with EVT under current local resources and 69.7% under assumed ideal conditions. Conclusions- There is potential for improving thinking around the decision to offer endovascular treatment, since physicians did not offer EVT even under assumed ideal conditions in 9.4% despite facing level 1A evidence. A majority of physicians would offer EVT even for level 2B evidence cases.

Background: The Society of Neurointerventional Surgery revised its operational definition of emergent large vessel occlusion (ELVO) recently to include proximal M2 segment middle cerebral artery (MCA) occlusions. We sought to assess the benefit of endovascular thrombectomy (EVT) over best medical care for M2 segment MCA occlusion., Methods: Patient level data from trials in the HERMES Collaboration were included. The HERMES core laboratory identified patients with M2 segment MCA occlusions and further classified them as proximal versus distal, anterior versus posterior division, and dominant versus co-dominant versus non-dominant. Primary outcome was modified Rankin Scale (mRS) score 0-2 at 90 days. Secondary outcomes were modified Thrombolysis in Cerebral Infarction (mTICI) rates at end of procedure, 90-day mRS shift, 90-day mRS 0-1, 24 hours National Institute of Health Stroke Scale (NIHSS) score 0-2, symptomatic intracerebral hemorrhage (ICH), and death., Results: 130 patients with M2 MCA (proximal location n=116 vs distal n=14, anterior division n=72 vs posterior n=58, dominant n=73 vs co-dominant n=50 vs non-dominant n=7) were included. Successful reperfusion (mTICI 2b or 3) among those undergoing EVT was seen in 59.2% of patients. Treatment effect favored EVT (adjusted OR 2.39, 95% CI 1.08 to 5.28, p=0.03) for 90-day mRS 0-2 (58.2% EVT vs 39.7% control). Direction of benefit favored EVT for other outcomes. Treatment effect favoring EVT was maximal in patients with proximal M2 segment MCA occlusions (n=116, adjusted OR 2.68, 95% CI 1.13 to 6.37) and in dominant M2 segment MCA occlusions (n=73, adjusted OR 4.08, 95% CI 1.08 to 15.48). No sICH (0%) was observed in patients treated with EVT compared with five (7.9%) in the control arm., Conclusion: Patients with proximal M2 segment MCA occlusions eligible for EVT trial protocols benefited from EVT., Competing Interests: Competing interests: MDH owns stock in Calgary Scientific Inc, a company that focuses on medical imaging software, is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart & Stroke Foundation of Canada, National Institutes of Neurological Disorders and Stroke. YBWEMR reports Stock ownership of Nico-Lab, outside the submitted work. BCVC reports grants from National Health and Medical Research Council, Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation, National Stroke Foundation of Australia, Covidien (Medtronic) during the conduct of the study. KM reports grants from Medtronic and from Codman outside the submitted work. AMD reports personal fees from Medtronic during the conduct of the study. TJ has consulted for Codman Neurovascular and Neuravi; holds stock in Silk Road, Anaconda, Route 92, and Blockade; received travel expenses from Stryker as primary investigator of the DAWN trial and from Fundacio Ictus related to the REVASCAT and RACECAT trials. PM reports receiving consulting fees from Medtronic and Stryker, personal fees from Stryker and Microvention outside the submitted work. PW reports grants from National Institutes for Health Research, the Stroke Association, Medtronic (Covidien), and Codman and has consulted for Microvention Terumo and Codman. AvdL reports grants from Dutch Heart Foundation, and consulting fees from AngioCare BV, from Covidien/EV3, from MEDAC Gmbh/LAMEPRO, from Stryker, from Penumbra Inc, during the conduct of the study; grants from Stryker, grants from Penumbra Inc, grants from Medtronic outside the submitted work. JLS has acted as a scientific consultant regarding trial design and conduct for Medtronic. SB reports personal fees from University of Calgary during the conduct of the study; personal fees from Medtronic outside the submitted work. MG reports grants from Medtronic and personal fees from Stryker, Medtronic, Microvention, and Cerenovus during the conduct of the study; grants from Stryker outside the submitted work. In addition, MG has a patent Systems of Acute Stroke Diagnosis issued to GE Healthcare., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose- Little is known about the real-life factors that clinicians use in selection of patients that would receive endovascular treatment (EVT) in the real world. We sought to determine patient, practitioner, and health system factors associated with therapeutic decisions around endovascular treatment. Methods- We conducted a multinational cross-sectional web-based study comprising of 607 clinicians and interventionalists from 38 countries who are directly involved in acute stroke care. Participants were randomly allocated to 10 from a pool of 22 acute stroke case scenarios. Each case was classified as either Class I, Class II, or unknown evidence according to the current guidelines. We used logistic regression analysis applying weight of evidence approach. Main outcome measures were multilevel factors associated with EVT, adherence to current EVT guidelines, and practice gaps between current and ideal practice settings. Results- Of the 1330 invited participants, 607 (45.6%) participants completed the study (53.7% neurologists, 28.5% neurointerventional radiologists, 17.8% other clinicians). The weighed evidence approach revealed that National Institutes of Health Stroke Scale (34.9%), level of evidence (30.2%), ASPECTS (Alberta Stroke Program Early CT Score) or ischemic core volume (22.4%), patient's age (21.6%), and clinicians' experience in EVT use (19.3%) are the most important factors for EVT decision. Of 2208 responses that met Class I evidence for EVT, 1917 (86.8%) were in favor of EVT. In case scenarios with no available guidelines, 1070 of 1380 (77.5%) responses favored EVT. Comparison between current and ideal practice settings revealed a small practice gap (941 of 6070 responses, 15.5%). Conclusions- In this large multinational survey, stroke severity, guideline-based level of evidence, baseline brain imaging, patients' age and physicians' experience were the most relevant factors for EVT decision-making. The high agreement between responses and Class I guideline recommendations and high EVT use even when guidelines were not available reflect the real-world acceptance of EVT as standard of care in patients with disabling acute ischemic stroke.

Background and Purpose- Endovascular therapy has been shown to be highly efficacious based on 90-day modified Rankin Scale score. We examined actual daily healthcare utilization from stroke onset to 1 year afterward from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Time) and registry data. Methods- We examined patients from Alberta, Canada, that was enrolled into the ESCAPE trial and the Quality Improvement and Clinical Research registry in the 2016/2017 fiscal year. Through data linkages to several administrative data sets, the daily location of each patient was assessed in various healthcare settings. Results- A total of 286 patients were analyzed, 52 patients were in the treatment arm, and 47 patients were in the control arm of the ESCAPE trial while 187 patients received endovascular therapy as usual care (2016/2017 fiscal year). The odds of a patient being out of a healthcare setting over 1 year was significantly higher when they received endovascular therapy: 3.46 (1.68-7.30) in ESCAPE trial patients and 2.00 (1.08-3.75) in the Quality Improvement And Clinical Research patients. Conclusions- Endovascular therapy significantly reduces healthcare utilization up to 1 year after a stroke.

Background: Revascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials., Methods: The HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography., Results: Angiography of 801 subjects was available, including 797 defined by non-invasive imaging (154 internal carotid artery (ICA), 583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2). Among 729 subjects in whom the reperfusion grade could be established, using eTICI (3=100%, 2C=90-99%, 2b67=67-89%, 2b50=50-66%) of the conventional angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218 eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and 60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days showed that increasing TICI grades were linked with better outcomes, with significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50 (p=0.017), and 2b50 versus 2b67 (p=0.014)., Conclusions: The benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions in clinical outcomes and may be used in future studies and routine practice., Competing Interests: Competing interests: DSL reports having received grant funding from NINDS and consulting fees as an imaging core laboratory from Stryker and Medtronic. RJ reports consulting with Medtronic. CBLMM reports having received grant funding from the Dutch Heart Foundation and European Commission and an unrestricted grant from Stryker. AvdL reports consulting fees from Stryker and grant funding from the Dutch Heart Foundation, AngioCare BV, Medtronic/Covidien/EV3, MEDAC Gmbh/LAMEPRO, Penumbra, Top Medical/Concentric, and Stryker, received by the Erasmus University Medical Center. LSR proctors for Stryker and Medtronic. PW discloses institutional research grant support within the last 2 years from Microvention Terumo. He declares the following relevant professional relationships: Chair of the European Society of Minimally Invasive Neurotherapeutics Guidelines Committee, sits on the Policy Working Group for Thrombectomy of NHS England and represents the Royal College of Radiologists on the UK Intercollegiate Stroke Working party (none of these are associated with financial reimbursement). He reports the following modest consultancy work: member of Stryker’s Global Hemorrhagic Stroke Advisory Board and educational consultancy work for Microvention Terumo. He has no other interests to declare. MG reports being the principal investigator of an unrestricted research grant to the University of Calgary for the HERMES collaboration by Medtronic. He also reports consulting services with Medtronic, Stryker, Microvention, Cerenovus and a licensing agreement with GE Healthcare re systems of acute stroke diagnosis., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose- Hyperglycemia is a negative prognostic factor after acute ischemic stroke but is not known whether glucose is associated with the effects of endovascular thrombectomy (EVT) in patients with large-vessel stroke. In a pooled-data meta-analysis, we analyzed whether serum glucose is a treatment modifier of the efficacy of EVT in acute stroke. Methods- Seven randomized trials compared EVT with standard care between 2010 and 2017 (HERMES Collaboration [highly effective reperfusion using multiple endovascular devices]). One thousand seven hundred and sixty-four patients with large-vessel stroke were allocated to EVT (n=871) or standard care (n=893). Measurements included blood glucose on admission and functional outcome (modified Rankin Scale range, 0-6; lower scores indicating less disability) at 3 months. The primary analysis evaluated whether glucose modified the effect of EVT over standard care on functional outcome, using ordinal logistic regression to test the interaction between treatment and glucose level. Results- Median (interquartile range) serum glucose on admission was 120 (104-140) mg/dL (6.6 mmol/L [5.7-7.7] mmol/L). EVT was better than standard care in the overall pooled-data analysis adjusted common odds ratio (acOR), 2.00 (95% CI, 1.69-2.38); however, lower glucose levels were associated with greater effects of EVT over standard care. The interaction was nonlinear such that significant interactions were found in subgroups of patients split at glucose < or >90 mg/dL (5.0 mmol/L; P=0.019 for interaction; acOR, 3.81; 95% CI, 1.73-8.41 for patients < 90 mg/dL versus 1.83; 95% CI, 1.53-2.19 for patients >90 mg/dL), and glucose < or >100 mg/dL (5.5 mmol/L; P=0.004 for interaction; acOR, 3.17; 95% CI, 2.04-4.93 versus acOR, 1.72; 95% CI, 1.42-2.08) but not between subgroups above these levels of glucose. Conclusions- EVT improved stroke outcomes compared with standard treatment regardless of glucose levels, but the treatment effects were larger at lower glucose levels, with significant interaction effects persisting up to 90 to 100 mg/dL (5.0-5.5 mmol/L). Whether tight control of glucose improves the efficacy of EVT after large-vessel stroke warrants appropriate testing.

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

Background: Endovascular therapy (EVT) is standard of care in patients with acute disabling ischemic stroke attributable to large-vessel occlusion and is more effective when delivered quickly. It is currently unclear whether time targets achieved in clinical trials can be achieved in clinical practice. We describe interval times from patient arrival in the emergency department (door) to first pass (treatment initiation) in patients receiving EVT within Get With The Guidelines-Stroke hospitals and analyze patient- and hospital-level variables associated with these times., Methods: Data are from sites participating fully as Comprehensive Stroke Centers within Get With The Guidelines-Stroke hospitals from October 2014 to September 2016. Workflow times analyzed include door to imaging, imaging to arterial access, arterial access to first pass, and the composite door to first pass time. Data are described overall and by calendar-year quarters. Multivariable modeling was used to identify patient- and hospital-level variables associated with workflow times., Results: Among 2929 patients with EVT from 195 hospitals (median age, 71 years [interquartile range {IQR}, 60-81]; 50.7% female; median baseline National Institute of Health Stroke Score, 17 [IQR, 12-22]; median annual EVT administration number, 16 [IQR, 10-27]), median door to first pass time was 130 minutes (IQR, 101-170 minutes), door to imaging time was 12 minutes (IQR, 7-20 minutes), imaging to arterial puncture time was 93 minutes (IQR, 68-126 minutes), and arterial puncture to first pass time was 18 minutes (IQR, 4-31 minutes). Overall, 3% patients achieved a door to first pass time ≤60 minutes. A statistically significant linear time trend was noted for door to first pass time (quarter 4 year 2014 median time, 134.5 minutes to quarter 3 year 2016 median time, 128 minutes, P=0.002). In multivariable analysis, older age, arrival during nonregular hours, and history of diabetes mellitus were associated with longer door to first pass time. Hospitals achieving shorter door to intravenous alteplase administration (door to needle) times were more likely to achieve faster door to first pass time ( P<0.001). Each 5 cases/y increase in EVT case volume was associated with a 3% shorter door to first pass time, up to a case volume of 40 per year ( P<0.001)., Conclusions: Although EVT treatment times are modestly improving, additional efforts are needed to streamline workflow so that the true potential of this treatment is realized. These data may inform benchmark goals for EVT workflow times.

Background: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion., Methods: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered., Findings: Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69-2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0-4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94-16·49; p interaction =0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30-13·44, p interaction =0·012)., Interpretation: EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline., Funding: Medtronic., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and purpose Ischemic stroke patients must be transferred to comprehensive stroke centers for endovascular treatment, but this transfer can be interpreted post hoc as "futile" if patients do not ultimately undergo the procedure or have a poor outcome. We posit that transfer decisions must instead be evaluated in terms of appropriateness at the time of decision-making. Methods We propose a classification schema for Appropriateness of Transfer for Endovascular Thrombectomy based on patient, logistic, and center characteristics. Results The classification outline characteristics of patients that are 1. Appropriate for transfer for endovascular treatment; 2. Inappropriate for transfer; and 3. Appropriate for transfer for higher level of care. Conclusions Appropriate transfer decisions for endovascular treatment are significant for patient outcomes. A more nuanced understanding of transfer decision-making and a classification for such transfers can help minimize inappropriate transfers in acute stroke.

Background: Tandem occlusions of the extracranial carotid and intracranial carotid or middle cerebral artery have a particularly poor prognosis without treatment. Several management strategies have been used with no clear consensus recommendations. We examined subjects with tandem occlusions enrolled in the ESCAPE trial and their outcomes., Methods: Data are from the ESCAPE trial. Additional data were sought on interventions for each subject., Results: There were 54 (17%) subjects with tandem extracranial and intracranial occlusions. Patients in the endovascular treatment arm (n=30) were more likely to be younger (median age 66 years, p<0.01), male (66.7%, p=0.03), diabetic, and without atrial fibrillation. Subjects with tandem occlusions were more likely to have intracranial internal carotid artery occlusions than M1 occlusions (p<0.01). Of the 30 intervention-arm subjects, 17 (57%) underwent emergency endovascular treatment of the extracranial disease, 10 subjects before and seven subjects after intracranial thrombectomy. Of the remaining 13 subjects, only four required staged carotid revascularization due to persistent severe carotid stenosis; four had cervical pseudo-occlusions with no residual stenosis after large distal carotid thrombus burden aspiration/retrieval. Outcomes were similar between subjects with and without tandem lesions. The use of antithrombotic agents after acute carotid artery stenting was variable but no symptomatic intracerebral hemorrhage was seen in subjects who underwent emergency endovascular treatment of extracranial carotid artery., Conclusions: Tandem occlusions occurred in one-sixth of patients and were treated highly variably within the ESCAPE trial. While outcomes were similar, the best method to treat the carotid artery in patients with tandem occlusion awaits further randomized data., Trial Registration Number: NCT01778335., Competing Interests: Competing interests: Conflicts of interest: BKM: membership of the Steering and Executive Committee, ESCAPE trial that received support from Covidien; Site Principal Investigator, SOCRATES Trial, sponsored by Astra Zeneca; honoraria from Penumbra; a provisional patent 62/086,077 for triaging systems in ischemic stroke; research funding from Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Canada, Alberta Innovates Health Solutions, Hotchkiss Brain Institute and the Faculty of Medicine, University of Calgary and salary support from CIHR; holds the current Heart and Stroke Foundation/University of Calgary Professorship in Stroke Imaging and receives salary support through the CIHR New Investigator Award. MG: partial support for ESCAPE trial provided to University of Calgary; helped in design and conduct of SWIFT PRIME trial (compensation significant (>$10,000 or 5%)); compensation for speaking engagements from Covidien (significant) and Stryker (modest); patent for Systems of stroke diagnosis licensed to GE Healthcare (compensation significant). AMD: research support from Covidien/Medtronic; unrestricted grant for ESCAPE trial (no compensation); Speaker’s Bureau: Medtronic (significant >$10,000 compensation). DR: grants and personal fees from University of Calgary during the conduct of the study. JT: personal fees from Neuravi, Galway and Ireland outside the submitted work. DFF: personal fees from Covidien, Stryker, Penumbra, Microvention and Siemens during the conduct of the study. BWB: personal fees from Penumbra, Stryker Neurovascular, Covidien (Medtronic), Rapid Medical and Silk Road Medical outside the submitted work. MDH: grants from Covidien (Medtronic), Alberta Innovates Health Solutions, Heart & Stroke Foundation, Hotchkiss Brain Institute, Canadian Stroke Prevention Intervention Networks (CSPIN) (Institute of Circulatory and Respiratory Health, CIHR), Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, non-financial support from Alberta Health Services during the conduct of the study; personal fees from Merck; non-financial support from Hoffmann-La Roche Canada outside the submitted work; patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients pending to US Patent Office Number: 62/086,077 and owns stock in Calgary Scientific, a company that focuses on medical imaging software. The other authors report no conflicts of interest., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: We describe the implementation of minimal sufficient balance randomization, a covariate-adaptive randomization technique, used for the "Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing CT to recanalization times" (ESCAPE) trial., Methods: The ESCAPE trial is a prospective, multicenter, randomized clinical trial that enrolled subjects with the following main inclusion criteria: less than 12 h from symptom onset, age 18 years or older, baseline NIHSS score > 5, ASPECTS score > 5 and computed tomography angiography (CTA) evidence of carotid T/L or M1-segment middle cerebral artery (MCA) occlusion, and at least moderate collaterals by CTA. Patients were randomized using a real-time, dynamic, Internet-based, minimal sufficient balance randomization method that balanced the study arms with respect to baseline covariates including age, sex, baseline NIHSS score, site of arterial occlusion, baseline ASPECTS score and treatment with intravenously administered alteplase., Results: Permutation-based tests of group differences confirmed group balance across several baseline covariates including sex (p = 1.00), baseline NIHSS score (p = 0.95), site of arterial occlusion (p = 1.00), baseline ASPECTS score (p = 0.28), treatment with intravenously administered alteplase (p = 0.31), and age (p = 0.67)., Conclusion: Results from the ESCAPE trial demonstrate the feasibility and the benefit of this covariate adaptive randomization scheme in small-sample trials and for data monitoring endeavors., Trial Registration: ESCAPE trial - NCT01778335 - at www.clinicaltrials.gov . Registered on 29 January 2013.

While the overall complication rates for endovascular treatment for acute stroke has been extremely low in recent trials, it is important to separate out and accurately document complications. One of these complications that is usually related to the endovascular intervention is Infarct in New Territory (INT). We propose a standardized methodology for documenting INT after the procedure. This new classification takes into account variations in vascular anatomy and location of the occlusion. In addition, given that after the recent trials, vascular imaging (eg, CT angiography (CTA)) is now the standard of care in the work up of acute ischemic stroke, this classification utilizes the information on the pre-procedure non-invasive vascular imaging, the angiography images from end of procedure and the location of lesions on the follow-up scan., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Purpose: The trajectory of neurological improvement after stroke treatment is clinically likely to be an important prognostic signal. We compared the accuracy of early longitudinal National Institutes of Health Stroke Scale (NIHSS) measurement versus other early markers of stroke severity post treatment in predicting subjects' 90-day stroke outcome., Methods: Data are from the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Stroke severity was assessed at baseline, 1, 2, 5, 30, and 90 days. Subjects' functional outcome was assessed using the modified Rankin Scale at baseline, 30 days, and 90 days. Group-based trajectory model was used to identify distinct subgroups of longitudinal trajectories of NIHSS measured over the first 2, 5, and 30 days. The accuracy of baseline NIHSS, infarct volume, 24-hour change in NIHSS, infarct volume, and disease severity trajectory subgroups in predicting 90-day stroke outcome were assessed using logistic regression analysis., Results: Group-based trajectory model of the 2-day longitudinal NIHSS data revealed 3 distinct subgroups of NIHSS trajectories-large improvement (41.6%), minimal improvement (31.1%), and no improvement (27.3%) subgroups. Individuals in the large improvement group were more likely were more likely to exhibit good outcomes after 90 days than those in the minimal improvement or no improvement subgroup. Among candidate predictors, the 2-day trajectory subgroup variable was the most accurate in predicting 90-day modified Rankin Scale at 84.5%., Conclusions: Early trajectory of neurological improvement defined by 2-day longitudinal NIHSS data predicts functional outcomes with greater accuracy than other common variables., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335., (© 2016 American Heart Association, Inc.)

Importance: Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation., Objective: To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage., Design, Setting, and Patients: Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites., Exposures: Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment., Main Outcomes and Measures: The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation., Results: Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, -6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, -5.2% [95% CI, -8.3% to -2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, -0.9% to 4.2%])., Conclusions and Relevance: In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.