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Background and Objectives: In recent years, researchers have sought to address the challenges of obtaining informed consent for participation in acute stroke trials. We studied outcomes related to the use of deferral of consent in the phase 3 Alteplase Compared to Tenecteplase (AcT) trial., Methods: As part of our protocol, we captured methods of consent, participant withdrawals, door-to-randomization times, and door-to-needle times. Participants at 3 sites were invited to complete a survey of attitudes regarding consent for AcT and for acute stroke trials generally., Results: The AcT trial enrolled 1,600 participants from 22 centers across Canada of whom 1,537 were enrolled through deferral of consent (96.0%) and 63 (4.0%) were enrolled by prospective verbal consent followed by written informed consent. Of those enrolled by deferral of consent, 95% (1,454/1,537) consented to ongoing participation. Door-to-randomization times were similar regardless of method of consent, with an overall median of 30 minutes (interquartile range [IQR] 22-42): 29 minutes (IQR 22-42) in the deferral of consent group vs 32 minutes (IQR 25-44) in the prospective consent group ( p = 0.1602). Survey respondents overwhelming agreed or strongly agreed with the use of deferral of consent in AcT (86%) and in any acute stroke trial (76%)., Discussion: Deferral of consent was broadly acceptable to participants in the AcT trial as demonstrated by low rates of withdrawal and by survey results. Door-to-randomization times using deferral of consent in AcT were short, although a system of prospective verbal consent used at 1 center took only slightly longer. These results support the importance of innovation around consent for acute stroke trials.

Background: Young adults with stroke have distinct professional and social roles making them vulnerable to symptoms of post-stroke depression (PSD) and post-stroke anxiety (PSA). Prior reviews have examined the prevalence of anxiety and depression in stroke populations. However, there are a lack of studies that have focused on these conditions in young adults., Objective: We performed a systematic review and meta-analysis of observational studies that reported on symptoms of PSD, PSA and comorbid PSD/PSA in young adults aged 18 to 55 years of age., Methods: MEDLINE, EMBASE, SCOPUS and PsycINFO were searched for studies reporting the prevalence of symptoms of PSD and/or PSA in young adults with stroke from inception until June 23, 2023. We included studies that evaluated depression and/or anxiety symptoms with screening tools or interviews following ischemic or hemorrhagic stroke. Validated methods were employed to evaluate risk of bias., Results: 4748 patients from twenty eligible studies were included. Among them, 2420 were also evaluated for symptoms of PSA while 847 participants were evaluated for both PSD and PSA symptoms. Sixteen studies were included in the random effects meta-analysis for PSD symptoms, with a pooled prevalence of 31 % (95 % CI 24-38 %). Pooled PSA symptom prevalence was 39 % (95 % CI 30-48 %) and comorbid PSD with PSA symptom prevalence was 25 % (95 % CI 12-39 %). Varying definitions of 'young adult', combinations of stroke subtypes, and methods to assess PSD and PSA contributed to high heterogeneity amongst studies., Conclusions: We identified high heterogeneity in studies investigating the prevalence of symptoms of PSD and PSA in young adults, emphasizing the importance of standardized approaches in future research to gain insight into the outcomes and prognosis of PSD and PSA symptoms following stroke in young adults. Larger longitudinal epidemiological studies as well as studies on tailored interventions are required to address the mental health needs of this important population., Funding: None., Competing Interests: Declaration of competing interest The authors have no disclosures., (Copyright © 2024. Published by Elsevier Inc.)

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

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: Subgroup analyses are widely used to evaluate the heterogeneity of treatment effects in randomized clinical trials. However, there is a limited investigation of the quality of prespecified and reported subgroup analyses in stroke trials. This study evaluated the credibility of subgroup analyses in stroke trials., Methods and Analysis: We searched Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science from inception to 24 March 2021. Three reviewers screened, extracted, and analyzed the data from the publications. Primary publications of stroke trials that reported at least one subgroup effect and had published corresponding study protocols were included. The Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN) was used to examine the quality of the subgroup effects reported, with each subgroup effect assigned a credibility rating ranging from very low to high. Subgroup effects with two or more "definitely no" responses received a low credibility rating. The risk of bias was assessed using the Cochrane Risk-of-Bias tool for randomized trials version 2., Results: Seventy-four articles met the inclusion criteria and reported a combined total of 647 subgroup effects. The median sample size was 1264 (interquartile range (IQR): 380-3876), and the median number of subgroups prespecified in the protocol was 6 (IQR: 2-10). Sixty-one (82%) studies used the univariate test of interaction. Of the total 647 subgroup effects reported in these studies, 319 (49%) were reported in acute stroke trials, while 423 (65%) had low credibility., Conclusion: The quality of subgroup analysis reporting in stroke trials remains poor. More effort is needed to train trialists on the best methods for designing and performing subgroup analyses, and how to report the results., Trial Registration Number: We prospectively registered the review with International Prospective Register for Systematic Reviews (registration number: CRD42020223133)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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

Background: The 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: Platelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters., Methods: CD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student's t-test and χ 2 test were performed as appropriate., Results: The mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p<0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively)., Conclusions: The vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis., Competing Interests: Competing interests: RK reports NIH funding (R01 NS076491, R43 NS110114 and R44 NS107111), is a research consultant for Cerenovus, Insera Therapeutics, Marblehead Medical, Microvention, MIVI Neuroscience, Neurogami Medical and Triticum, and has stock in Neurosigma (money paid to institution). AJY receives research support from Medtronic, Cerenovus, Penumbra and Stryker, and is a consultant for Penumbra, Cerenovus, Zoll Circulation and Vesalio. He is on the Scientific Advisory Board of XCath and Nico-lab, and has equity interest in Insera Therapeutics. JEDA declares competing interests in the form of employment (modest compensation) from Medtronic and Penumbra. AMD received honoraria from Medtronic for Continuing Medical Education events. RGN declares competing interests in the form of Stryker (DAWN Trial (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With TREVO) Principal Investigator, no compensation; TREVO Registry Steering Committee, no compensation; TREVO-2 Trial Principal Investigator, modest compensation; consultant, modest compensation), Medtronic (SWIFT Trial (Solitaire With the Intention for Thrombectomy) Steering Committee, modest compensation; SWIFT-Prime Trial Steering Committee, no compensation; STAR Trial (Solitaire FR Thrombectomy for Acute Revascularisation) Angiographic Core Lab, significant compensation), Penumbra (no compensation), Cerenovus/Neuravi (ENDOLOW Trial Principal Investigator, EXCELLENT Registry Principal Investigator, ARISE-2 Trial (Analysis of Revascularization in Ischemic Stroke With EmboTrap) Steering Committee, no compensation; Physician Advisory Board, modest compensation), Phenox (Physician Advisory Board, modest compensation), Anaconda (Physician Advisory Board, modest compensation), Genentech (Physician Advisory Board, modest compensation), Biogen (Physician Advisory Board, modest compensation), Prolong Pharmaceuticals (Physician Advisory Board, modest compensation), IschemaView (Speaker, modest compensation), Brainomix (Research Software Use, no compensation), Sensome (Research Device Use, no compensation), Viz-AI (Physician Advisory Board, stock options), Philips (Research Software Use, no compensation; Speaker, modest compensation), and Corindus Vascular Robotics (Physician Advisory Board, stock options). DFK is President of Marblehead Medical and has a patent pending in balloon catheter technologies, and receives research support from Cerenovus, Insera Therapeutics, Medtronic, MicroVention, MIVI Neuroscience, NeuroSave, Neurogami Medical, Sequent Medical and Insera, and has stock in Neurosigma (money paid to institution). He is on the Scientific Advisory Board of Triticum and previously served on a SAB for Boston Scientific. WB is CMO of Marblehead Medical and has a patent pending in balloon catheter technologies, and he is a consultant for Cerenovus and Microvention. He reports NIH funding (R01 NS105853). MJG is a member of the JNIS Editorial Board., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Background: Compositional and structural features of retrieved clots by thrombectomy can provide insight into improving the endovascular treatment of ischemic stroke. Currently, histological analysis is limited to quantification of compositions and qualitative description of the clot structure. We hypothesized that heterogeneous clots would be prone to poorer recanalization rates and performed a quantitative analysis to test this hypothesis., Methods: We collected and did histology on clots retrieved by mechanical thrombectomy from 157 stroke cases (107 achieved first-pass effect (FPE) and 50 did not). Using an in-house algorithm, the scanned images were divided into grids (with sizes of 0.2, 0.3, 0.4, 0.5, and 0.6 mm) and the extent of non-uniformity of RBC distribution was computed using the proposed spatial heterogeneity index (SHI). Finally, we validated the clinical significance of clot heterogeneity using the Mann-Whitney test and an artificial neural network (ANN) model., Results: For cases with FPE, SHI values were smaller (0.033 vs 0.039 for grid size of 0.4 mm, P=0.028) compared with those without. In comparison, the clot composition was not statistically different between those two groups. From the ANN model, clot heterogeneity was the most important factor, followed by fibrin content, thrombectomy techniques, red blood cell content, clot area, platelet content, etiology, and admission of intravenous tissue plasminogen activator (IV-tPA). No statistical difference of clot heterogeneity was found for different etiologies, thrombectomy techniques, and IV-tPA administration., Conclusions: Clot heterogeneity can affect the clot response to thrombectomy devices and is associated with lower FPE. SHI can be a useful metric to quantify clot heterogeneity., Competing Interests: Competing interests: MJG is on the editorial board of the Journal of NeuroInterventional Surgery., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Determining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication., Objective: To estimate infarct progression rate in patients with AIS with large vessel occlusion (LVO) and determine its predictors and impact on clinical outcome., Methods: Data are from the ESCAPE-NA1 Trial. Patients with AIS with time from last known well to randomization <6 hours and near-complete reperfusion following endovascular treatment were included. Infarct growth rate (mL/h) was estimated by dividing 24 hour infarct volume (measured by non-contrast CT or diffusion-weighted magnetic resonance imaging) by time from last known well to reperfusion. Multivariable linear regression was used to assess the association of patient baseline variables with log-transformed infarct progression rate. The association of infarct progression rate and good outcome (modified Rankin Scale score 0-2) was determined using multivariable logistic regression., Results: Four hundred and nine patients were included in the study. Median infarct progression rate was 4.74 mL/h (IQR 1.25-14.84). Collateral status (β: -0.81 (95% CI -1.20 to -0.41)), Alberta Stroke Program Early CT Score (ASPECTS, β: -0.34 (95% CI -0.46 to -0.23)), blood glucose(β: 0.09 (95% CI 0.02 to 0.16)), and National Institutes of Health Stroke Scale (NIHS score (β: 0.07 (95% CI 0.04 to 0.10)) were associated with log-transformed infarct progression rate. Clinical and imaging baseline variables explained 23% of the variance in infarct progression rate. Infarct progression rate was significantly associated with good outcome (aOR per 1 mL/h increase: 0.96 (95% CI 0.95 to 0.98))., Conclusion: In this sample of patients presenting within the early time window with LVO and near-complete recanalization, infarct progression rate was significantly associated with good outcome. A significant association between ASPECTS, collateral status, blood glucose, and NIHSS score was observed, but baseline imaging and clinical characteristics explained only a small proportion of the interindividual variance. More research on measurable factors affecting infarct growth is needed., Competing Interests: Competing interests: AMD: stock options and patients (Circle Neurovascular); honoraria for CME events (Boehringer Ingelheim); consultant (Medtronic). AYP: research grant to the institution (Stryker); payment/honoraria for lectures: C-CHANGE education program (update on stroke guidelines for general practitioners); participation on a data safety monitoring board or advisory board (FLOW trial); chair, Canadian Stroke Consortium National Stroke Fellowship Program. RGN: grant to Emory University (Cerenovus); consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron; consulting fees for medical legal consultations; stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze; investor in Viz-AI, Perfuze, Cerebrotech, Reist LLC, Truvic, and Viseon. MVJ: treasurer, Society of Neurointerventional Surgery 2019–2021; vice president, Society of Neurointerventional Surgery 2021–present. MDH: grants to the University of Calgary for ESCAPE-NA1 (NoNO Inc); grants to the University of Calgary for ESCAPE-NA1 (CIHR); grants to the University of Calgary for ESCAPE-NA1 and the QuICR Alberta Stroke Program (Alberta Innovates); grants to the University of Calgary for TEMPO 2 (Boehringer Ingelheim); grants to the University of Calgary (Biogen); paid work for adjudication of clinical trial outcomes (Sun Pharma), US patent 62/086,077 and 10,916,346 (licensed to Circle Neurovascular); DSMC Chair (RACECAT, Oncovir Hiltonel, DUMAS Trials); DSMB member (ARTESIA, BRAIN-AF trials); president Canadian Neurological Sciences Federation (not for profit); board member founder and part ownership (Circle Neurovascular). MT: NoNO Inc. shareholder; president and CEO of NoNO Inc., owns patent for Nerinetide/NA1. MG: honoraria from Medtronic, Microvention, Mentice, and Stryker (teaching and advice on acute stroke intervention); ESCAPE-NA1 was funded through a grant to the University of Calgary from NoNO Inc., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial., Methods: Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built., Results: Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46)., Conclusion: The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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 thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care., Methods: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual., Findings: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis., Funding: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit., Competing Interests: Declaration of interests BKM has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. SBC is principal investigator of the TEMPO-2 trial, for which Boehringer Ingelheim provides the study drug (tenecteplase). LC has received payments by Servier and consulting fees from Ischaemavie RAPID, Circle NV, and Canadian Medical Protective Association. JS has a grant from Medtronic to the University of Manitoba. AMD has received consulting fees from Medtronic and honoraria from Boehringer Ingelheim. LCG is on advisory boards for AstraZeneca and Servier and has stock options in AstraZenca. ASh has received consulting fees from Bayer, Servier Canada, Daiichi Sanyko Compan, AstraZeneca, VarmX, and Takeda; honoraria from Bayer and Daiichi Sankyo; is on an advisory board for Bayer; and has stock options in Ensho. MDH has received consulting fees from Sun Pharma and Brainsgate and has stock options in Circle NVI. DJG has received consulting fees from HSL Therapeutics. APo has received a project research grant from Stryker and honoraria from BMS-Pfizer. TTS has received consulting fees from Circle NVI. RHS has stock options in FollowMD and receives salary support for research from the Heart & Stroke Foundation of Canada, Sandra Black Centre for Brain Resilience & Recovery, and Ontario Brain Institute. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The objective of this paper was to explore the utility of time to maximum concentration (T max )-based target mismatch on computed tomography perfusion (CTP) in predicting radiological and clinical outcomes in patients with acute ischemic stroke (AIS) with anterior circulation large vessel occlusion (LVO) selected for endovascular treatment (EVT)., Methods: Patients with AIS underwent CTP within 24 hours from onset followed by EVT. Critically hypoperfused tissue and ischemic core volumes were automatically calculated using T max thresholds >9.5 seconds and >16 seconds, respectively. The difference between T max  > 9.5 seconds and T max  > 16 seconds volumes and the ratio between T max  > 9.5 seconds and T max  > 16 seconds volumes were considered ischemic penumbra and T max mismatch ratio, respectively. Final infarct volume (FIV) was measured on follow-up non-contrast computed tomography (CT) at 24 hours. Favorable clinical outcome was defined as 90-day modified Rankin Scale 0 to 2. Predictors of FIV and outcome were assessed with multivariable logistic regression. Optimal T max volumes for identification of good outcome was defined using receiver operating curves., Results: A total of 393 patients were included, of whom 298 (75.8%) achieved successful recanalization and 258 (65.5%) achieved good outcome. In multivariable analyses, all T max parameters were independent predictors of FIV and outcome. T max  > 16 seconds volume had the strongest association with FIV (beta coefficient = 0.596 p <0.001) and good outcome (odds ratio [OR] = 0.96 per 1 ml increase, 95% confidence interval [CI] = 0.95-0.97, p < 0.001). T max  > 16 seconds volume had the highest discriminative ability for good outcome (area under the curve [AUC] = 0.88, 95% CI = 0.842-0.909). A T max  > 16 seconds volume of ≤67 ml best identified subjects with favorable outcome (sensitivity = 0.91 and specificity = 0.73)., Interpretation: T max target mismatch predicts radiological and clinical outcomes in patients with AIS with LVO receiving EVT within 24 hours from onset. ANN NEUROL 2022;91:878-888., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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: Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine., Objective: To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots., Methods: As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells)., Results: MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1-4] vs 1 [1-3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI., Conclusions: Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device., Competing Interests: Competing interests: RK reports NIH funding (R01 NS076491, R43 NS110114, and R44 NS107111), is a research consultant for Cerenovus, Insera Therapeutics LLC, Marblehead Medical LLC, Microvention Inc, MIVI Neuroscience Inc, Neurogami Medical Inc, and Triticum Inc, and has stock in Neurosigma Inc (money paid to institution). AJY receives research support from Medtronic, Cerenovus, Penumbra, and Stryker, and is a consultant for Penumbra, Cerenovus, Zoll Circulation, and Vesalio. He is on the Scientific Advisory Board of XCath and Nico-lab, and has equity interest in Insera Therapeutics LLC. JEDA declares competing interests in the form of employment (modest compensation) from Medtronic and Penumbra. AMD received honoraria from Medtronic for continuing medical education events.RGN declares competing interests in the form of Stryker (DAWN Trial (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With TREVO) principal investigator, no compensation; TREVO Registry Steering Committee, no compensation; TREVO-2 Trial principal investigator, modest compensation; consultant, modest compensation), Medtronic (SWIFT Trial (The Solitaire With the Intention for Thrombectomy) Steering Committee, modest compensation; SWIFT-Prime Trial Steering Committee, no compensation; STAR Trial (Solitaire FR Thrombectomy for Acute Revascularisation) Angiographic Core Lab, significant compensation), Penumbra (no compensation), Cerenovus/Neuravi (ENDOLOW Trial principal investigator, EXCELLENT Registry principal investigator, ARISE-2 Trial (Analysis of Revascularization in Ischemic Stroke With EmboTrap) Steering Committee, no compensation; Physician Advisory Board, modest compensation), Phenox (Physician AdvisoryBoard, modest compensation), Anaconda (Physician Advisory Board, modest compensation), Genentech (Physician Advisory Board, modest compensation), Biogen (Physician Advisory Board, modest compensation), Prolong Pharmaceuticals (Physician Advisory Board, modest compensation), IschemaView (speaker, modest compensation), Brainomix (Research Software Use, no compensation), Sensome (Research Device Use, no compensation), Viz-AI (Physician Advisory Board, stock options), Philips (Research Software Use, no compensation; speaker, modest compensation), and Corindus Vascular Robotics (Physician Advisory Board, stock options).DFK is president of Marblehead Medical and has patent pending in balloon catheter technologies, and receives research support from Cerenovus, Insera Therapeutics LLC, Medtronic, MicroVention, MIVI Neuroscience Inc, NeuroSave, Neurogami Medical Inc, Sequent Medical and Insera, and has stock in Neurosigma Inc (money paid to institution). He is on the Scientific Advisory Board of Triticum and previously served on a SAB for Boston Scientific.WB is CMO of Marblehead Medical and has a patent pending in balloon catheter technologies, and he is a consultant for Cerenovus and Microvention. He reports NIH funding (R01 NS105853). The other authors report no conflicts., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background and Purpose: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition., Materials and Methods: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables., Results: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group., Conclusions: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: We declare no competing interests.

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 and Aim: Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT., Methods: Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software., Results: 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05)., Conclusion: Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.

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.)

Background: Multiphase CTA (mCTA) is an established tool for endovascular treatment decision-making and outcome prediction in acute ischemic stroke, but its interpretation requires some degree of experience. We aimed to determine whether mCTA-based prediction of clinical outcome and final infarct volume can be improved by assessing collateral status on time-variant mCTA color maps rather than using a conventional mCTA display format., Methods: Patients from the PRove-IT cohort study with anterior circulation large vessel occlusion were included in this study. Collateral status was assessed with a three-point scale using the conventional display format. Collateral extent and filling dynamics were then graded on a three-point scale using time-variant mCTA color-maps (FastStroke, GE Healthcare, Milwaukee, WI, USA). Multivariable logistic regression was performed to determine the association of conventional collateral score, color-coded collateral extent and color-coded collateral filling dynamics with good clinical outcome and final infarct volume (volume below vs. above median infarct volume in the study sample)., Results: A total of 285 patients were included in the analysis and 53% (152/285) of the patients achieved a good outcome. Median infarct volume on follow-up was 12.6 ml. Color-coded collateral extent was significantly associated with good outcome (adjusted odds ratio [ adj OR] 0.53, 95% confidence interval [CI]:0.36-0.77) while color-coded collateral filling dynamics ( adj OR 1.30 [95%CI:0.88-1.95]) and conventional collateral scoring ( adj OR 0.72 [95%C:0.48-1.08]) were not. Both color-coded collateral extent ( adj OR 2.67 [95%CI:1.80-4.00]) and conventional collateral scoring ( adj OR 1.84 [95%CI:1.21-2.79]) were significantly associated with follow-up infarct volume, while color-coded collateral filling dynamics were not ( adj OR 1.21 [95%CI:0.83-1.78])., Conclusion: In this study, collateral extent assessment on time-variant mCTA maps improved prediction of good outcome and has similar value in predicting follow-up infarct volume compared to conventional mCTA collateral grading., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Intra-carotid cold infusion (ICCI) appears as a promising method for hypothermia-mediated brain protection from ischemic stroke. Recent clinical pilot studies indicate easy implementation of ICCI into endovascular acute ischemic stroke treatment. Current rodent ICCI-in-stroke models limit ICCI to the post-reperfusion phase. To establish a method for continuous ICCI over the duration of intra-ischemia to post-reperfusion in rodent stroke models, a novel system was developed. Eighteen male Sprague-Dawley rats were included. Intraluminal filament method was used for transient middle cerebral artery occlusion (MCAO). Normal saline (~ 0 °C) was delivered (≤ 2.0 mL/min) into the internal carotid artery via a customized infusion system without interruption during MCAO (intra-ischemia) to after filament withdrawal (post-reperfusion). Bilateral cortical and striatal temperatures were monitored. Hypothermia goals were a temperature reduction in the ischemic hemisphere by 2 °C prior to reperfusion and thereafter maintenance of regional brain hypothermia at ~ 32 °C limiting the administered ICCI volume to ½ of each rat's total blood volume. During ischemia, maximum brain cooling rate was achieved with ICCI at 0.5 mL/min. It took 2 min to reduce ischemic striatal temperature by 2.3 ± 0.3 °C. After reperfusion, brain cooling was continued at 2 mL/min ICCI first (over 42 s) and maintained at 32.1 ± 0.3 °C at 0.7 mL/min ICCI over a duration of 15 ± 0.8 min. ICCI (total 12.6 ± 0.6 mL) was uninterrupted over the duration of the studied phases. First system that allows continuous ICCI during the phases of intra-ischemia to post-reperfusion in small animals for selective brain cooling and for investigations of other neuroprotective infusions.

Background: We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ 2 test for categorical variables., Results: 1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%)., Conclusions: Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology., Competing Interests: Competing interests: None declared., (© 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.)

Objective: To determine public health and cost consequences of time delays to endovascular thrombectomy (EVT) for patients, health care systems, and society, we estimated quality-adjusted life-years (QALYs) of EVT-treated patients and associated costs based on times to treatment., Methods: The Markov model analysis was performed from US health care and societal perspectives over a lifetime horizon. Contemporary data from 7 trials within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration served as data source. Aside from cumulative lifetime costs, we calculated the net monetary benefit (NMB) to determine the economic value of care. We used a contemporary willingness-to-pay threshold of $100,000 per QALY for NMB calculations., Results: Every 10 minutes of earlier treatment resulted in an average gain of 39 days (95% prediction interval 23-53 days) of disability-free life. Overall, the cumulative lifetime costs for patients with earlier or later treatment were similar. Patients with later treatment had higher morbidity-related costs but over a shorter time span due to their shorter life expectancy, resulting in similar lifetime costs as in patients with early treatment. Regarding the economic value of care, every 10 minutes of earlier treatment increased the NMB by $10,593 (95% prediction interval $5,549-$14,847) and by $10,915 (95% prediction interval $5,928-$15,356) taking health care and societal perspectives, respectively., Conclusions: Any time delay to EVT reduces QALYs and decreases the economic value of care provided by this intervention. Health care policies to implement efficient prehospital triage and to accelerate in-hospital workflow are urgently needed., (© 2020 American Academy of Neurology.)

Introduction: Non-stenotic (<50%) carotid plaques have recently been recognized as a potential source of stroke. This meta-analysis aims to summarize the prevalence of non-stenotic carotid plaques in stroke patients in general and in patients with embolic stroke of undetermined source in particular., Methods: We performed a comprehensive systematic review of the literature and meta-analysis on acute ischemic stroke patients in whom carotid imaging was performed using the MEDLINE, Embase and Cochrane database, including studies published up to December 2019. Keywords were "stroke", "transient ischemic attack", "carotid", "plaque", "atherosclerosis" and "disease". Included studies had ≥10 patients with acute ischemic stroke and reported the prevalence of non-stenotic (<50%%stenosis) carotid plaques detected on any imaging modality., Results: We included forty-five studies (n = 18304 patients, 48.4% males, mean age 63.6 years) in our meta-analysis. Imaging modalities used were ultrasound (n = 26 studies), CT-angiography (n = 7), magnetic resonance-imaging (n = 8) and catheter angiography (n = 4). The overall prevalence of non-stenotic carotid plaques was 51% (95% CI: 43 - 59). 10 studies included mainly patients with embolic stroke of undetermined source (>50% of all patients). The pooled prevalence of non-stenotic carotid plaques in these studies was 55% (95% CI: 42 - 68). 23 studies explicitly reported ipsilateral non-stenotic carotid plaques, the pooled prevalence of which was 51% (95% CI: 45 - 59)., Conclusions: In this meta-analysis, non-stenotic carotid plaques were present in more than 50% of all acute ischemic stroke patients, with a slightly higher prevalence in ESUS patients. Given the potential role of non-stenotic carotid plaques in stroke etiology, particularly in ESUS, further research should aim to identify criteria that predict the stroke risk associated with non-stenotic carotid plaques., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose of Review: Therapeutic hypothermia (TH) in stroke demonstrates robust neuroprotection in animals but clinical applications remain controversial. We assessed current literature on the efficacy of TH in ischemic stroke., Recent Findings: We conducted a meta-analysis comparing TH versus controls in studies published until June 2019. Controlled studies reporting on ≥ 10 adults with acute ischemic stroke were included. Primary outcome was functional independence (modified Rankin Scale [mRS] ≤ 2). Twelve studies (n = 351 TH, n = 427 controls) were included. Functional independence did not differ between groups (RR 1.17, 95% CI 0.93-1.46, random-effects p = 0.2). Five studies reported individual mRS outcomes and demonstrated a shift toward better outcome with TH (unadjusted cOR 1.57, 95% CI 1.01-2.44, p = 0.05). Overall complications were higher with TH (RR 1.18, 95% CI 1.06-1.32, p < 0.01). We did not observe an overall beneficial effect of TH in this analysis although some studies showed a shift toward better outcome. TH was associated with increased complications.

Background: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke., Methods: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018., Findings: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups., Interpretation: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo., Funding: Canadian Institutes for Health Research, Alberta Innovates, and NoNO., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Purpose- The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society. Methods- A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy-treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence. Results- Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and $20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy-treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and $36.8 million for the healthcare system and society, respectively. Conclusions- Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate.

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: Current studies on clot characterization in acute ischemic stroke focus on fibrin and red blood cell composition. Few studies have examined platelet composition in acute ischemic stroke clots. We characterize clot composition using the Martius Scarlet Blue stain and assess associations between platelet density and CT density., Materials and Method: Histopathological analysis of the clots collected as part of the multi-institutional STRIP registry was performed using Martius Scarlet Blue stain and the composition of the clots was quantified using Orbit Image Analysis (www.orbit.bio) machine learning software. Prior to endovascular treatment, each patient underwent non-contrast CT (NCCT) and the CT density of each clot was measured. Correlations between clot components and clinical information were assessed using the χ 2 test., Results: Eighty-five patients were included in the study. The mean platelet density of the clots was 15.7% (2.5-72.5%). There was a significant correlation between platelet-rich clots and the absence of hyperdensity on NCCT, (ρ=0.321, p=0.003*, n=85). Similarly, there was a significant inverse correlation between the percentage of platelets and the mean Hounsfield Units on NCCT (ρ=-0.243, p=0.025*, n=85)., Conclusion: Martius Scarlet Blue stain can identify patients who have platelet-rich clots. Platelet-rich clots are isodense on NCCT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose- There is contradictory evidence on the impact of the stroke side (hemisphere) on outcomes. We investigated any effect modification by laterality on stroke patients' outcomes in recent endovascular trials. Methods- Individual patient-level data were combined in this meta-analysis of all patients included in randomized trials comparing endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischemic patients with stroke (HERMES [Highly Effective Reperfusion Using Multiple Endovascular Devices] Collaboration). We stratified the 90-day functional outcome assessed by ordinal analysis of the modified Rankin Scale according to the stroke side of patients treated with endovascular therapy versus standard care, adjusted for important prognostic variables. Results- The meta-analysis included 1737 patients (871 right hemispheric strokes and 866 left hemispheric) from 7 trials. Baseline median National Institutes of Health Stroke Scale scores were significantly higher in left (20) versus right (16) hemispheric strokes (P<0.001). Other clinical and radiological baseline characteristics were similar. The beneficial response to endovascular therapy assessed by 90-day modified Rankin Scale shift was not modified by the side of the stroke. There were no significant differences between right and left hemispheric stroke in the 90-day functional outcome (modified Rankin Scale score ≤2; 40.7% [95% CI, 37.4%-44.1%] versus 37.6% [95% CI, 37.4%-44.1%]; P=0.19), median final infarct volumes (45 versus 39.5 mL, P=0.51), nor 90-day mortality (15.1% vs 16.8%, P=0.31). Conclusions- Stroke side was not a prognostic factor and did not modify the treatment effect among patients treated in the endovascular or control groups in recent endovascular thrombectomy trials.

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.

Introduction : The dawn of endovascular stroke therapy has reshaped stroke care. Eligible patients need to be rushed to capable centers for intervention. This may entail bypassing closer hospitals that could confirm the diagnosis, administer thrombolytic therapy, then transfer patients for intervention. This has created a set of challenges: identifying endovascular candidates in the field, determining the best transport destination, and getting patients there quickly. Areas covered : This review provides a context for these emerging challenges. Current and emerging clinical prediction instruments for large vessel occlusion (LVO) are reviewed. The workflow in the thrombolysis-only primary stroke centers is reviewed, and interventions aimed at minimizing delays are highlighted. Innovations using mathematical modeling and devices for detection of LVO are reviewed. Expert commentary : More patients are expected to receive endovascular therapy as we push the boundaries for time and imaging criteria. Advances in detection and decision-making aids will improve the speed of treatment. Some patients will arrive at thrombolysis-only centers. This need to be triaged, diagnosed, treated, and transported promptly. Therefore, education of practitioners in these centers is paramount. Creating and facilitating infrastructure for imaging acquisition and sharing in such centers will reflect better care for stroke patients overall.

Selective brain cooling is a promising advent for reducing final infarct volume and improving outcomes in ischemic stroke victims. Despite the robust body of evidence from animal studies, evidence supporting the use of selective hypothermia in stroke patients is lacking. A recent study provided promising results on the safety and possible efficacy of selective brain hypothermia via intraarterial infusion of cooled saline. Better understanding of the patients' population that may attain benefit from this approach will be informative. Details of infarct progression using perfusion imaging will also help understand the mechanism of effect of selective hypothermia to inform future trials.

Background: Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement., Objective: To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality., Methods: Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated., Results: Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14-120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15-131) vs 22 mL (IQR 8-71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively)., Conclusions: In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI., Competing Interests: Competing interests: MG reports grants from Covidien, personal fees from Covidien, during the conduct of the study; MG has a patent for diagnosing strokes (PCT/ CA2013/000761) licensed to GE Healthcare. BKM reports membership of the Steering and Executive Committee, ESCAPE trial that received support from Covidien Inc., Site Principal Investigator, SOCRATES Trial, sponsored by Astra Zeneca, honoraria from Penumbra Inc., a provisional patent 62/086077 for triaging systems in ischemic stroke, research funding from CIHR, HSFC, AIHS, HBI and the Faculty of Medicine, University of Calgary and board membership of QuikFlo Health Inc. WHvZ reports Honoraria; Modest; Stryker (paid to Institution). DWJD reports honoraria; Modest; Stryker (paid to Institution). PJM reports unrestricted grant funding for the EXTEND-IA trial to the Florey Institute of Neuroscience and Mental Health from Covidien (Medtronic), has served as an unpaid consultant to Codman Johnson and Johnson, his organization has received unrestricted research funding and grants from Codman Johnson and Johnson, Medtronic, and Stryker. AMD reports grant support and personal fees from Covidien (Medtronic). AD reports consultant/Advisory Board; Modest; Medtronic Neurovascular (Steering Committee STAR). CBLMM reports speakers' Bureau; Modest; Stryker (paid to institution). GAD reports grants from the Australian National Health & Medical Research Council, non-financial support from, and has served on advisory boards for Boehringer Ingelheim, Astra Zeneca, Bristol Meyers-Squibb, Merck Sharp & Dohme outside the submitted work. BCVC reports research support from the National Health and Medical Research Council of Australia (GNT1043242, GNT1035688), Royal Australasian College of Physicians, Royal Melbourne Hospital Foundation, National Heart Foundation, National Stroke Foundation of Australia and unrestricted grant funding for the EXTEND-IA trial to the Florey Institute of Neuroscience and Mental Health from Covidien (Medtronic). MDH 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 & 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); personal fees from Merck, non-financial support from Hoffmann-La Roche Canada Ltd, outside the submitted work; MDH has a 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 Incorporated, a company that focuses on medical imaging software. AMMB and HAM own stock in Nico.lab, a company that focuses on medical imaging software. TGJ has consulted for Codman Neurovascular and Neuravi, holds stock in Silk Road and Blockade; has acted as an unpaid consultant to Stryker as PI of the DAWN trial and served as an unpaid member of a Medtronic Advisory Board. SMD reports lecture fees from Covidien (Medtronic). ScB acts as consultant for Medtronic. GWA reports equity and consulting for iSchemaView (imaging software) and consulting for Medtronic., (© 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.)

It is estimated that 6.6%-9.3% of stroke patients have unruptured cerebral aneurysms. The safety of recombinant tissue plasminogen activator (r-tPA) for stroke patients with these aneurysms is uncertain. We report the case of a 58-year old male presented with an acute ischemic stroke within 2 hours of symptom onset and was treated with r-tPA. Further investigation showed that the patient had 2 unruptured cerebral aneurysms. He recovered completely from the stroke and was discharged home in a few days with no deficits. Although cerebral aneurysms are considered a relative contraindication for r-tPA, our case provides evidence that it can be safely administered to these patients.

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.