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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: Guidelines recommend the treatment of emergent large vessel ischemic stroke (ELVIS) patients presenting beyond 6 hours of last known well time with endovascular thrombectomy (EVT) based on perfusion computed tomography (CT) neuroimaging. We compared the outcomes (long-term good clinical outcomes, symptomatic intracranial hemorrhage (sICH), and mortality) of ELVIS patients according to the type of CT neuroimaging they underwent., Methods: We searched the following databases: Medline, Embase, CENTRAL, and Scopus from January 1, 2015, to June 14, 2023. We included studies of late-presenting ELVIS patients undergoing EVT that had with data for non-perfusion and perfusion CT neuroimaging. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were pooled using a random effects model., Results: We found 7 observational cohorts. Non-perfusion versus perfusion CT was not statistically significantly different for both long-term clinical (n = 3,224; RR: 0.96; 95% CI 0.86 to 1.06; I2 = 18%) and sICH (n = 3,724; RR: 1.08 95% CI 0.60 to 1.94; I2 = 76%). Perfusion CT had less mortality (n = 3874; RR: 1.22; 95% CI 1.07 to 1.40; I2 = 0%). The certainty of these findings is very low because of limitations in the risk of bias, indirectness, and imprecision domains of the Grading of Recommendations, Assessment, Development and Evaluations., Conclusion: The use of either non-perfusion or perfusion CT neuroimaging may have little to no effect on long-term clinical outcomes and sICH for late-presenting EVT patients. Perfusion CT neuroimaging may be associated with a reduced the risk of mortality. Evidence uncertainty warrants randomized trial data., Competing Interests: The authors have declared that no competing interests exist in relation to this particular work., (Copyright: © 2024 Diestro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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 < 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: The benefit of endovascular thrombectomy (EVT) in stroke patients with a low baseline Alberta Stroke Program Early CT Score (ASPECTS, ≤5) is uncertain. We aim to use random forest regression modeling to predict 90 day home time in patients with low ASPECTS., Methods: We used the Quality Improvement and Clinical Research (QuICR) provincial stroke registry and administrative data from southern Alberta to identify patients who underwent EVT in our center from July 2015 to November 2020. Baseline ASPECTS on non-contrast CT and CT angiography data were scored by a two physician consensus. The primary outcome was the predicted 90 day home time (the number of nights a patient is back at their premorbid living situation without an increase in level of care within 90 days of the stroke) using random forests regression. Estimates were generated using 200 bootstrapped datasets. Covariate contribution to home time was determined using partial dependence plots., Results: Of 657 EVT patients, 85 (12.9%) had baseline ASPECTS ≤5 (mean age 70.9 years, 44.7% women, 93.9% good-moderate collaterals, 60% M1-middle cerebral artery occlusion). Using partial dependence estimates, mean predicted home times were similar in the low ASPECTS (44.3 days) versus higher ASPECTS (43.1) groups. Factors predicting lower 90 day home time in this population were diabetes mellitus (-8.8 days), hypertension (-5.7 days), and atrial fibrillation (-3.6 days). There was no meaningful difference in predicted 90 day home time by sex, baseline National Institutes of Health Stroke Severity Scale score, occlusion site, tandem lesion, collateral grade or thrombolysis., Conclusions: Patients with low ASPECTS who are selected for EVT using demographic and clinical profiles similar to higher ASPECTS patients achieved comparable outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide., Methods: Data are from ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in subjects with acute ischemic stroke who underwent endovascular thrombectomy within 12 hours from onset. Concurrent treatment and outcomes were collected as part of the trial protocol. INTs were identified on core lab imaging review of follow-up brain imaging and defined by the presence of infarct in a new vascular territory, outside the baseline target occlusion(s) on follow-up brain imaging (computed tomography or magnetic resonance imaging). INTs were classified by maximum diameter (<2, 2-20, and >20 mm), number, and location. The association between INT and clinical outcomes (modified Rankin Scale and death) was assessed using standard descriptive techniques and adjusted estimates of effect were derived from Poisson regression models., Results: Among 1092 patients, 103 had INT (9.3%, median age 69.5 years, 49.5% females). There were no differences in baseline characteristics between those with versus without INT. Most INTs (91/103, 88.3%) were not associated with visible occlusions on angiography and 39 out of 103 (37.8%) were >20 mm in maximal diameter. The most common INT territory was the anterior cerebral artery (27.8%). Almost half of the INTs were multiple (46 subjects, 43.5%, range, 2-12). INT was associated with poorer outcomes as compared to no INT on the primary outcome of modified Rankin Scale score of 0 to 2 at 90 days (adjusted risk ratio, 0.71 [95% CI, 0.57-0.89]). Infarct volume in those with INT was greater by a median of 21 cc compared with those without, and there was a greater risk of death as compared to patients with no INT (adjusted risk ratio, 2.15 [95% CI, 1.48-3.13])., Conclusions: Infarcts in a new territory are common in individuals undergoing endovascular thrombectomy for acute ischemic stroke and are associated with poorer outcomes. Optimal therapeutic approaches, including technical strategies, to reduce INT represent a new target for incremental quality improvement of endovascular thrombectomy., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02930018., Competing Interests: Disclosures Dr Demchuk reports receiving grant support and personal fees from Medtronic and has a patent with Circle Cardiovascular Imaging on stroke imaging software. Dr Hill reports unrestricted grant funding for the ESCAPE trial to University of Calgary from Covidien/Medtronic and active/in-kind support consortium of public/charitable sources (Heart and Stroke Foundation, Alberta Innovates Health Solutions, Alberta Health Services) and the University of Calgary (Hotchkiss Brain Institute, Departments of Clinical Neurosciences and Radiology, and Calgary Stroke Program); grant funding from Boehringer Ingelheim, NoNo Inc, and Stryker; personal fees from Merck, nonfinancial support from Hoffmann-La Roche Canada. In addition, Dr Hill has a submitted patent for triaging systems in ischemic stroke and owns stock in Calgary Scientific, a company that focuses on medical imaging software. Dr Goyal reports receiving an unrestricted institutional grant from Medtronic; he received a grant from Stryker and consulting fees from Stryker, Microvention, Mentice; and he holds patent rights in systems and methods for acute stroke diagnosis with GE Healthcare. Dr Field is PI for the SECRET trial (Study of Rivaroxaban for Cerebral Venous Thrombosis) and receives in-kind study medication from Bayer Canada for the study. She is supported by the Vancouver Coastal Health Research Institute, the Michael Smith Foundation for Health Research, the Heart and Stroke Foundation of Canada. Dr Nogueira reports consulting fees for advisory roles with Stryker Neurovascular, Cerenovus, Medtronic, Phenox, RapidPulse, Anaconda, Perfuze, Genentech, Biogen, Prolong Pharmaceuticals, Imperative Care and stock options for advisory roles with Brainomix, Viz-AI, Corindus Vascular Robotics, Vesalio, Ceretrieve, Astrocyte, and Cerebrotec. Dr Swartz reports Grants/Contracts from Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, National Institutes of Health, Ontario Brain Institute, and Sunnybrook Research Institute. Dr Ospel receives consulting fees from NICOLAB. Dr Poppe received research grant from Stryker for EASI-TOC study. Dr Tymianski is CEO of NoNO; patents owned by NoNO. Dr Hill received 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; a patent issued and licensed to US Patent Office Number: 62/086,077; stock in Calgary Scientific. Dr Goyal received personal fees from Mentice, Medtronic, Microvention, Stryker; patent to systems of acute stroke diagnosis. Nonfinancial interests: Dr Poppe is PI of EASI-TOC study. Dr Demchuk is a member of the editorial board at International Journal of Stroke (Editor). Dr Nogueira is a member of the Physician Advisory Board for Cerenovus/Neuravi. Dr Hill is Director, Board of Circle Neurovascular, Director, Board of the Canadian Neuroscience Federation, and Director, Board of the Canadian Stroke Consortium. Dr Goyal is a member of the editorial board at Stroke (Consulting Editor). The other authors report no conflicts.

Background: Trials of endovascular thrombectomy (EVT) for acute stroke have excluded patients with pre-morbid disability. Observational studies may help inform consideration of EVT in this population. We aimed to assess the effectiveness and safety of EVT in patients with pre-morbid disability., Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched MEDLINE and Embase for studies describing outcomes in patients with pre-morbid disability (modified Rankin Scale (mRS) 2-5), treated with EVT or medical management (MM). Random-effects meta-analysis was used to pool outcomes including 90-day return to baseline mRS, symptomatic intracerebral hemorrhage (sICH), and 90-day mortality., Results: We analyzed 14 studies of patients with pre-morbid disability (mRS 2-5, 1373 EVT and 253 MM). The rate of return to baseline mRS was 30.0% (95% CI 25.3% to 34.7%) in patients treated with EVT. Compared with medical therapy, EVT was associated with a higher likelihood of return to baseline mRS (OR 2.37, 95% CI 1.39 to 4.04) and a trend towards lower mortality (OR 0.68, 95% CI 0.46 to 1.02), with similar odds of sICH (OR 1.01, 95% CI 0.49 to 2.08). In studies comparing patients with versus without pre-morbid disability treated with EVT, similar results were found except that pre-morbid disability, when defined more strictly as mRS 3-5, was associated with mortality (OR 3.49, p<0.001)., Conclusion: In eligible patients with pre-morbid disability, observational studies suggest that EVT carries a higher chance of return to baseline mRS compared with patients treated with MM or without pre-morbid disability, although with higher mortality than patients without pre-morbid disability. These findings argue against the routine exclusion of such patients from EVT and merit validation with randomized trials., Competing Interests: Competing interests: Benjamin Beland: travel grant from the American Academy of Neurology. Eva A Mistry: funding from NIH/NINDS (K23NS113858). Mohammed A Almekhlafi: none. Mayank Goyal reports consulting fees from Medtronic, Stryker, Microvention, and Mentice; and has a patent for systems of stroke diagnosis licensed to GE Healthcare. Aravind Ganesh reports membership of editorial boards of Neurology, Neurology: Clinical Practice, and Stroke; research support from the Canadian Institutes of Health Research (CIHR), Canadian Cardiovascular Society, Campus Alberta Neuroscience, Alberta Innovates, and the Sunnybrook Research Institute INOVAIT program; consultation fees from MD Analytics, MyMedicalPanel, and Atheneum; stock options from SnapDx, TheRounds.com, and Advanced Health Analytics (AHA Health Ltd); and a provisional patent application for a system for delivery of remote ischemic conditioning or other cuff-based therapies., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endovascular treatment (EVT) for stroke due to medium vessel occlusion (MeVO) can be technically challenging and specific endovascular tools are needed to safely and effectively recanalize these relatively small and fragile vessels. We aimed to gain insight into availability and desired qualities of endovascular devices used in MeVO stroke and examined barriers to adoption of MeVO EVT in clinical practice on a global scale., Methods: We conducted a case-based international survey among neurointerventionalists. As a part of the survey, participants were asked whether they felt appropriate endovascular tools for MeVO stroke exist and are available to them in their clinical practice. We then examined barriers to adopting MeVO EVT and analyzed them by geographic regions., Results: A total of 263 neurointerventionists participated, of which 178 (67.7%) and 83 (31.6%) provided responses on desired qualities of MeVO EVT tools and on barriers to their adoption in local practice, respectively. The majority 121/178 (68%) felt there was substantial room for improvement regarding existing tools. A large proportion 131/178 (73.6%) felt they had appropriate access to existing tools. The most commonly mentioned barrier for adopting MeVO EVT in North America was "awaiting better tools" (9/28 responses, 32.1%), while "awaiting better evidence" (8/26 responses, 30.8%), and the need for improved "funding" (7/26 responses, 26.9%) were important barriers in Europe., Conclusion: The majority of surveyed neurointerventionalists felt that dedicated MeVO EVT tools can be substantially improved upon. Different regions face various challenges in adoption of MeVO EVT, but overall, physicians are mostly awaiting better MeVO EVT tools., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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.

Introduction: The optimal anaesthesia approach for endovascular treatment (EVT) in acute ischaemic stroke is currently unknown. In stroke due to medium vessel occlusions (MeVO), the occluded vessels are particularly small and more difficult to access, especially in restless or uncooperative patients. In these patients, general anaesthesia (GA) may be preferred by physicians to prevent complications due to patient movement. We investigated physicians' approaches to anaesthesia during EVT for MeVO stroke., Methods: In a worldwide, case-based, online survey, physicians' preferred anaesthesia approach during EVT for MeVO stroke was categorized as "initial GA", "initial GA if necessary" (depending on patient cooperation), "no initial GA, but conversion if necessary" (start with local anaesthesia or conscious sedation), and "no GA". Preferred anaesthesia approaches were reported overall and stratified by physician and patient characteristics., Results: A total of 366 survey participants provided 1464 responses to 4 primary MeVO EVT case-scenarios. One-third of responses (489/1464 [33%]) favoured no initial GA, but conversion if necessary. Both initial GA and initial GA if necessary were preferred in 368/1464 (25%) of responses respectively. No GA was favoured in 244/1464 (17%). Occlusion location, respondent specialization (interventional neuroradiology), higher age, and female respondent sex were significantly associated with GA preference. GA was more often used in Europe than in other parts of the world ( p  < 0.001)., Conclusions: Anaesthesia approaches in MeVO EVT vary across world regions and patient and physician factors. Most physicians in this survey preferred to start with local anaesthesia or conscious sedation and convert to GA if necessary.

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 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.

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 and Purpose: Acute strokes due to large vessel occlusion in hospitalized patients is not uncommon. We performed a systematic review and meta-analysis to investigate the timing and outcome of endovascular thrombectomy (EVT) for in-hospital stroke., Methods: We conducted a meta-analysis of clinical studies published in English until September 2020 in the MEDLINE and Cochrane databases. Studies reporting original data on the characteristics and outcomes of in-hospital stroke patients treated with EVT were included. We extracted data on the time-metrics from last known well (LKW) until reperfusion was achieved. We also collected data on procedural and functional outcomes., Results: Out of 5093 retrieved studies, 8 were included (2,622 patients). The median age was 71.4 years and median NIHSS score on admission was 16. Patients were mostly admitted to the cardiology service (27.3%). The pooled time from LKW to recognition by staff was 72.9 min (95% CI: 40.7 to 105 min). 25.6% received IV tPA. The mean time from stroke recognition to arterial puncture was 134.5 min (95% CI: 94.9 to 174.1). Successful reperfusion occurred in 82.8.% with a pooled mean time from detection to reperfusion of 193.1 min (95% CI: 139.5 to 246.7). The 90-day independent functional outcome was reported in 42% of patients (95% CI 29 to 55%)., Conclusion: EVT can be performed safely and successfully for in-hospital strokes. Noticeable delays from LKW to detection and then to puncture are noted. This calls for better stroke pathways to identify and treat these patients., Background: Stroke in hospitalized patients, referred to as in-hospital stroke (IHS), accounts for 2.2-17% of all strokes. 1 The majority of these are ischemic while intracranial hemorrhage represents 2-11% of all IHS. 1 These patients are expected to have a rapid diagnosis and treatment given the ongoing medical supervision, and therefore favorable outcomes. 1-3 However, existing studies report poor outcomes in patients with IHS with a mortality risk that exceeds that of community-onset stroke (COS): 24.7% vs 9.6%. 4 Surviving IHS patients are also less likely to be discharged home compared to COS (27.7% vs 49.9%) and to be functionally independent at 3 months (31.0% vs 50.4%). 1-4 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known., Objective: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO)., Data Sources: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020., Study Selection: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included., Data Extraction/synthesis: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time., Main Outcomes and Measures: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics., Results: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours., Conclusions and Relevance: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.

Background: Simulation training has been used in the aviation industry and surgical specialties for many years, but integration into neurointerventional practice is lagging behind., Objective: To investigate how neurointerventionalists perceive the usefulness and limitations of simulation tools for the treatment of unruptured intracranial aneurysms (UIAs), and to identify simulation applications that were perceived to be most valuable for endovascular UIA treatment., Methods: A web-based international multidisciplinary survey was conducted among neurointerventionalists. Participants were asked for their perceptions on the usefulness of current simulation tools and the potential impact of future simulation tools in endovascular UIA treatment. They identified simulation applications that could add most value to endovascular UIA treatment and help to specifically reduce endovascular UIA treatment complications., Results: 233 neurointerventionalists from 38 countries completed the survey, most of whom (157/233 (67.4%)) had access to a simulator as a trainee, but only 15.3% used it frequently. Most participants (117/233 (50.2%)) considered currently available simulation tools relatively useful for endovascular UIA treatment, with greater value for trainees than for staff. Simulation of new devices (147/233 (63.1%)) and virtual practice runs in individual patient anatomy (119/233 (51.1%)) were considered most valuable for reducing endovascular UIA treatment complications., Conclusion: Although neurointerventionalists perceived currently available simulation tools relatively useful, they did not use them regularly during their training. A priori testing of new devices and practice runs in individual patient anatomy in a virtual environment were thought to have the greatest potential for reducing endovascular UIA treatment complications., 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, JB Rhyner Foundation, and Freiwillige Akademische Gesellschaft Basel., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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 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.)

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 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: Stentrievers have resulted in faster recanalization times in patients with acute ischemic stroke. Nonetheless, when strokes occur during evenings and weekends, delays are introduced in achieving this goal. We assessed the feasibility of achieving fast and successful endovascular reperfusion in patients with stroke treated during evenings and weekends and whether this has an impact on the outcome., Methods: A retrospective review was performed of a longitudinal database of patients with acute anterior ischemic stroke treated with endovascular therapy in a comprehensive stroke center between January 2011 and December 2012. The imaging to reperfusion time was defined as the time from completion of the unenhanced CT scan to the time of angiographic successful reperfusion (TICI 2b-3). This time interval was compared between patients treated during working hours (Monday to Friday 07:00-18:00 h) and those treated in the evening outside these hours and at weekends. The 24-h NIH Stroke Scale score and 90-day favorable outcome score (modified Rankin scale ≤2) were compared between the two groups., Results: In a cohort of 110 patients, 56 (50.9%) were treated on evenings and weekends. The median imaging to reperfusion time in these patients was 111 min compared with 90 min during working hours (p=0.019). The proportion of patients with successful reperfusion (TICI 2b or 3) during the evenings and weekends was 82.1% compared with 76.7% during working hours (p=0.4). The proportion of patients with a 90-day favorable outcome was not significantly different in the two groups (64.3% in those treated during evenings and weekends vs 52.1% in working hours, p=0.2)., Conclusions: Some delays were encountered during evenings and weekend hours. Despite that, it was feasible to achieve a relatively short imaging to reperfusion times during these hours, in comparison to existing literature. A target universal time metric is needed to assess the timeliness of endovascular therapy in stroke centers., (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: Meaningful delays occurred in the Interventional Management of Stroke (IMS) III trial. Analysis of the work flow will identify factors contributing to the in-hospital delays., Methods and Results: In the endovascular arm of the IMS III trial, the following time intervals were calculated: stroke onset to emergency department arrival; emergency department to computed tomography (CT); CT to intravenous tissue plasminogen activator start; intravenous tissue plasminogen activator start to randomization; randomization to groin puncture; groin puncture to thrombus identification; thrombus identification to start of endovascular therapy; and start of endovascular therapy to reperfusion. The effects of enrollment time, CT angiography use, interhospital transfers, and intubation on work flow were evaluated. Delays occurred notably in the time intervals from intravenous tissue plasminogen activator initiation to groin puncture (median 84 minutes) and start of endovascular therapy to reperfusion (median 85 minutes). The CT to groin puncture time was significantly shorter during working hours than after. Times from emergency department to reperfusion and groin puncture to reperfusion decreased over the trial period. Patients with CT angiography had shorter emergency department to reperfusion and onset to reperfusion times. Transfer of patients resulted in a longer onset to reperfusion time compared with those treated in the same center. Age, sex, National Institutes of Health Stroke Scale score, and intubation did not affect delays., Conclusions: Important delays were identified before reperfusion in the IMS III trial. Delays decreased as the trial progressed. Use of CT angiography and endovascular treatment in the same center were associated with time savings. These data may help in optimizing work flow in current and future endovascular trials., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00359424., (© 2014 American Heart Association, Inc.)

Background and Purpose: The shorter the time interval between the estimation of the ischemic core by imaging and reperfusion, the more likely that core expansion is minimized. We aimed to assess the feasibility of achieving an ultrashort imaging to reperfusion time in routine clinical practice., Methods: The study subjects were a prospective cohort of patients with acute ischemic stroke treated with endovascular therapy in a tertiary center in whom an imaging to reperfusion time of <60 min was achieved., Results: Imaging to reperfusion time of <60 min was accomplished in 11 patients. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 11 and the median baseline Alberta Stroke Program Early CT Score (ASPECTS) was 8. The median time interval from imaging to endovascular reperfusion was 47 min. The median ASPECTS score on the 24 h CT scan was also 8 and the median 24 h NIHSS score was 1. Upon discharge, 82% of patients achieved a modified Rankin scale score of ≤ 1., Conclusions: An imaging to endovascular reperfusion time of <60 min is feasible and resulted in minimal core expansion on follow-up imaging in patients with acute ischemic stroke.

Endovascular neurosurgery is a discipline strongly dependent on imaging. Therefore, technology that improves how much useful information we can garner from a single image has the potential to dramatically assist decision making during endovascular procedures. Furthermore, education in an image-enhanced environment, especially with the incorporation of simulation, can improve the safety of the procedures and give interventionalists and trainees the opportunity to study or perform simulated procedures before the intervention, much like what is practiced in the field of aviation. Here, we examine the use of simulators in the training of fighter pilots and discuss how similar benefits can compensate for current deficiencies in endovascular training. We describe the types of simulation used for endovascular procedures, including virtual reality, and discuss the relevant data on its utility in training. Finally, the benefit of augmented reality during endovascular procedures is discussed, along with future computerized image enhancement techniques.