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Background and Aims: The clinical evolution of acute ischemic stroke patients with isolated proximal posterior cerebral artery (PCA) occlusion treated with medical management alone has been poorly described. We aimed to determine the clinical and radiological factors associated with poor functional outcome in this population., Methods: We conducted a multicenter international retrospective study of consecutive stroke patients with isolated occlusion of the first (P1) or second (P2) segment of PCA admitted within 6 h from symptoms onset in 26 stroke centers in France, Switzerland, and the United States, treated with the best medical management alone. Poor functional outcome was defined as a modified Rankin scale (mRS) ⩾2 at 3 months or no return to pre-stroke mRS. The associations between pretreatment variables and poor outcome were studied in univariable and then multivariable analyses, as well as the association between poor outcome and key follow-up radiological variables., Results: Overall, 585 patients were included. The median age was 74 years (interquartile range (IQR) = 63-83), median National Institutes of Health Stroke Scale (NIHSS) was 6 (3-10), 80% received intravenous thrombolysis (IVT), and 22% and 78% had P1 and P2 occlusions, respectively. Poor outcome occurred in 56% of patients. In multivariable analysis focusing on pretreatment variables, age (adjusted odds ratio (OR) = 1.12 per 5-year increase [95% confidence interval (CI) = 1.05-1.20]; p  = 0.001), NIHSS score (aOR = 1.12 per each point increase [1.08-1.18]; p  < 0.001), infarct volume (aOR = 1.16 per 5 mL increase [1.07-1.25]; p  < 0.001), and the lack of IVT use (aOR = 1.79 [1.10-2.94], p  = 0.020) were independently associated with poor outcome. Regarding 24-h follow-up radiological variables, complete recanalization (defined as no clot in the vascular tree at or beyond the primary occlusive lesion, aOR = 0.37 [95% CI = 0.21-0.65], p  < 0.001) and parenchymal hematoma occurrence (aOR = 2.37 [95% CI = 1.01-5.56], p  = 0.048) were independently associated with poor 3-month outcome., Conclusions: Poor outcome occurred in more than half of medically treated PCA-related acute stroke patients. Facilitating IVT use may improve functional outcome. Therapeutic approaches aimed at enhancing recanalization and reducing hemorrhagic transformation need to be studied in clinical trials., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr M.R.H. reports grants from Swiss National Science Foundation, SITEM Research Support Funds, and Swiss Heart Foundation, not directly related to this manuscript. Professor C.R. receives fees from OTR3 for her participation in a DSMB. Y.B. reports personal fees from BMS, Pfizer, Medtronic, Amgen, Servier, NovoNordisk, Novartis, and Laboratoire XO, outside the submitted work. Dr G.W.A. reports stock holdings in iSchemaView; compensation from Biogen, iSchemaView, and Genentech for consultant services. Dr G.T. reports lecture fees from Guerbert France and consultant services for AI-Stroke. Professor M.M. reports consulting fees from Acticor Biotech, and Boerhinger. Dr P.S. receives speaker fees from Acticor Biotech. Other authors have nothing to disclose.

Background: In patients with an acute ischemic stroke, the penumbra is defined as ischemic tissue that remains salvageable when reperfusion occurs. However, the expected clinical recovery congruent with penumbral salvage is not always observed., Aims: We aimed to determine whether the magnetic resonance imaging (MRI)-defined penumbra includes irreversible neuronal loss that impedes expected clinical recovery after reperfusion., Methods: In the prospective French Acute Multimodal Imaging Study to Select Patients for Mechanical Thrombectomy (FRAME) and an observational cohort of patients with large vessel occlusions undergoing endovascular treatment, we quantified penumbral integrity by fluid-attenuated inversion recovery (FLAIR) changes. We studied the influence of recanalization status on the evolution of penumbral FLAIR changes and studied penumbral FLAIR changes as predictor of tissue fate and functional outcome on the 90-day modified Rankin Scale (mRS)., Results: Recanalization status did not modify the evolution of rFLAIR signal intensity (SI) over time in the total cohort, but was associated with lower SI in the FRAME subset (b = -0.06, p for interaction = 0.04). Median rFLAIR SI was higher at baseline in the subsequently infarcted penumbra compared to the salvaged (ratio = 1.07, standard deviation (SD) = 0.07 vs 1.03, SD = 0.06 p < 0.0001, n = 150). The severity and extent of rFLAIR SI changes did not predict 90-day functional outcome in univariate (p = 0.09) and multivariate logistic regression (p = 0.4)., Conclusions: Recanalization status did not influence the evolution of penumbral FLAIR changes. FLAIR SI changes in the baseline penumbra were associated with tissue fate, but not functional outcome., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: L.S. reports grants from Research Foundation Flanders and the Belgian American Educational Foundation during the conduct of the study; other (congress participation) from Daiichi Sankyo outside the submitted work. R.L. has no personal disclosures, but reports consultancy fees paid to the institution from iSchemaView and Boehringer Ingelheim. J.-M.O. reports consultancy fees from Abbvie, Acticor, and Bioxodes and speaker fees from Boehringer Ingelheim and Bristol Myers Squibb. C.C. reports consultant for MicroVention, Medtronic, Stryker, Cerenovus, and MIVI. J.J.H. is a consultant for Medtronic and MicroVention and is a member of the medical and scientific advisory board for iSchemaView.

Background: Mechanical thrombectomy (MT) has become a standard treatment for acute ischemic strokes (AIS). However, MT failure occurs in approximately 10-30% of cases, leading to severe repercussions (with mortality rates up to 40% according to observational data). Among the available rescue techniques, rescue intracranial stenting (RIS) appears as a promising option., Objective: This trial is poised to demonstrate the superiority of RIS in addition to the best medical treatment (BMT) in comparison with BMT alone, in improving the functional outcomes at 3 months for patients experiencing an AIS due to a large vessel occlusion refractory to MT (rLVO)., Methods: Permanent Intracranial STenting for Acute Refractory large vessel occlusions (PISTAR) is a multicenter prospective randomized open, blinded endpoint trial conducted across 11 French University hospitals. Adult patients (≥18 years) with an acute intracranial occlusion refractory to standard MT techniques will be randomized 1:1 during the procedure to receive either RIS+BMT (intervention arm) or BMT alone (control arm)., Results: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin Scale score ≤2 and evaluated by an independent assessor blinded to the randomization arm. Secondary outcomes include hemorrhagic complications, all adverse events, and death. The number of patients to be included is 346. Two interim analyses are planned with predefined stopping rules., Conclusion: The PISTAR trial is the first randomized controlled trial focusing on the benefit of RIS in rLVOs. If positive, this study will open new insights into the management of AIS., Trial Registration Number: NCT06071091., Competing Interests: Competing interests: NS reports a conflict of interest with Medtronic, Balt Extrusion, Microvention (consultant). FC reports a conflict of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core laboratory), Penumbra, Stryker (payment for reading), and Artedrone (board). The other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Decompressive hemicraniectomy (DH) improves survival and functional outcome in large middle cerebral artery (MCA) infarcts. However, long-term cognitive outcomes after DH remain underexplored. In a cohort of patients with large right-hemisphere MCA infarction undergoing DH, we assessed the rates of long-term cognitive impairment over 3-year follow-up., Methods: We prospectively evaluated consecutive patients included in the Lille Decompressive Surgery Database (May 2005-April 2022) undergoing DH according to existing guidelines for large hemisphere MCA infarction. We included patients with right-sided stroke and screened with the Mini-Mental State Examination (MMSE) in at least one of the prespecified follow-ups (3-month, 1-year, 3-year). Cognitive impairment was defined as an MMSE score < 24. We included only right-hemisphere strokes to avoid testing biases related to severe aphasia. We compared clinical and neuroimaging data in patients with and without cognitive impairment., Results: Three hundred four patients underwent DH during the study period. Among 3-month survivors, 95 had a right-hemisphere stroke and underwent at least one cognitive screening (median age = 51 years, 56.8% men). Forty-four patients (46.3%) exhibited cognitive impairment at least once during the 3-year follow-up. Baseline characteristics did not significantly differ between patients with and without cognitive impairment. Regarding long-term temporal trends, cognitive impairment was observed in 23 of 76 (30.3%), 25 of 80 (31.3%), and 19 of 66 (28.8%) patients at 3-month, 1-year, and 3-year follow-up, respectively, and it was associated with higher rates of functional disability (all p < 0.05)., Conclusions: The persistently high rates of cognitive impairment after DH highlight the importance of cognitive monitoring to improve the long-term management of survivors., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Introduction: Even with reperfusion therapies, the prognosis of patients with basilar artery occlusion (BAO) related stroke remains poor. We aimed to test the hypothesis that the presence of prodromal symptoms, an easily available anamnestic data, is a key determinant of poor functional outcome., Patients and Methods: Data from patients with BAO treated in Lille, France, with mechanical thrombectomy (MT) between 2015 and 2021 were prospectively collected. The presence of prodromal symptoms was defined by previous transient neurological deficit or gradual progressive clinical worsening preceding a secondary sudden clinical worsening. We compared the characteristics of patients with and without prodromal symptoms. We built multivariate logistic regression models to study the association between the presence of prodromal symptoms and functional (mRS 0-3 and mortality), and procedural (successful recanalization and early reocclusion) outcomes., Results: Among the 180 patients, 63 (35%) had prodromal symptoms, most frequently a vertigo. Large artery atherosclerosis was the predominant cause of stroke (41.3%). The presence of prodromal symptoms was an independent predictor of worse 90-day functional outcome (mRS 0-3: 25.4% vs 47.0%, odds ratio (OR) 0.39; 95% confidence interval (CI) 0.16-0.86) and 90-day mortality (OR 2.17; 95% CI 1.02-4.65). Despite similar successful recanalization rate, the proportion of early basilar artery reocclusion was higher in patients with prodromal symptoms (23.8% vs 5.6%, p  = 0.002)., Discussion and Conclusion: More than one third of BAO patients treated with MT had prodromal symptoms, especially patients with large-artery atherosclerosis. Clinicians should systematically screen for prodromal symptoms given the poor related functional outcome and increased risk of early basilar artery reocclusion., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.C. declares the following type of interests: speaker fees (Amgen and Bristol-Myers Squibb); Data And Safety Monitoring Board for Biogen and Bayer; grant funding from the French ministry of health (Programme Hospitalier de Recherche Clinique): A3ICH and TICH-3 Fr studies.Other authors: none.

Introduction: Recently, four randomized controlled trials (RCTs) have demonstrated the benefits of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) and a large ischemic core at baseline (LIC). The purpose of this study was to investigate the features influencing the clinical outcome and the benefits of mechanical thrombectomy in this subgroup., Methods: We conducted a multicenter retrospective aggregate cohort study of patients with AIS-LVO and a LIC, assessed with quantitative core volume measures, treated with MT between 2012 and 2019. The data were queried through four registries, including patients with core volumes ≥50cc. Multivariable logistic regression models were employed to determine factors independently associated with clinical outcomes in patients with successful recanalization (modified-Thrombolysis-in-Cerebral-Infarction-score, mTICI=2b-3) and unsuccessful recanalization group (mTICI=0-2a). The primary endpoint was a favorable functional outcome at day-90, defined as a modified Rankin scale (mRS) of 0-3, accounting for the inherent severity of AIS with baseline LIC. Secondary outcomes included functional independence (mRS 0-2) at day-90, mortality, and symptomatic Intracranial Hemorrhage (sICH)., Results: A total of 460 patients were included (mean age 66±14.2 years; 39.6 % females). The mean baseline NIHSS was 20±5.2, and the core volume was 103.2±54.6 ml. Overall, 39.8 % (183/460) of patients achieved a favorable outcome at day-90 (mRS 0-3). Successful recanalization was significantly associated with a more frequent favorable outcome (aOR, 4.79; 95 %CI, 2.73-8.38; P<0.01) and functional independence (P<0.01). This benefit remained significant in older patients and in patients with cores above 100cc. At 90 days, 147/460 patients (32 %) were deceased, with successful recanalization significantly associated with less frequent mortality (OR, 0.34; 95 %CI, 0.22-0.53; P<0.01). The rate of sICH was 17.4 % and did not differ significantly between groups., Conclusions: In this large, pooled-cohort study of AIS-LVO patients with infarct cores over 50cc at baseline, we demonstrated that successful recanalization was associated with a better functional outcome, lower mortality, and similar rates of symptomatic intracranial hemorrhage for a wide spectrum of patients., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: With the expanding eligibility for endovascular therapy (EVT) of patients presenting in the late window (6-24 hours after last known well), we aimed to derive a score to predict favorable outcomes associated with EVT versus best medical management., Methods and Results: A multinational observational cohort of patients from the CLEAR (Computed Tomography for Late Endovascular Reperfusion) study with proximal intracranial occlusion (2014-2022) was queried (n=58 sites). Logistic regression analyses were used to derive a 9-point score for predicting good functional outcome (modified Rankin Scale score 0-2 or return to premorbid modified Rankin Scale score) at 90 days, with sensitivity analyses for prespecified subgroups conducted using bootstrapped random forest regressions. Secondary outcomes included 90-day functional independence (modified Rankin Scale score 0-2), poor outcome (modified Rankin Scale score 5-6), and 90-day survival. The score was externally validated with a single-center cohort (2014-2023). Of the 3231 included patients (n=2499 EVT), a 9-point score included age, early computed tomography ischemic changes, and stroke severity, with higher points indicating a higher probability of a good functional outcome. The areas under the curve for the primary outcome among EVT and best medical management subgroups were 0.72 (95% CI, 0.70-0.74) and 0.87 (95% CI, 0.84-0.90), respectively, with similar performance in the external validation cohort (area under the curve, 0.71 [95% CI, 0.66-0.76]). There was a significant interaction between the score and EVT for good functional outcome, functional independence, and poor outcome (all P interaction <0.001), with greater benefit favoring patients with lower and midrange scores., Conclusions: This score is a pragmatic tool that can estimate the probability of a good outcome with EVT in the late window., Registration: URL: https://www.Clinicaltrials.gov; Unique identifier: NCT04096248.

Background: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well., Methods: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT., Results: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P <0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P =0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P =0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P =0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P =0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well., Conclusions: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248., Competing Interests: Disclosures Drs Demeestere and Lemmens reported institutional research fees from Genentech. Dr Strbian reported consultancy fees from AstraZeneca and Boehringer Ingelheim. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz AI, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options in Viz AI, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus and Stryker. Dr Nagel reported consultancy for Brainomix; speaker with Boehringer ingelheim and Pfizer. Dr Yamagami reported research grants from Bristol Myers Squibb; lecturer’s fees from Stryker, Medtronic, Johnson & Johnson, Bayer, Daiichi Sankyo, Bristol Myers Squibb, Otuska Pharmaceutical; advisory board for Daiichi Sankyo. Dr Puetz reported lecturer for Daiichi Sankyo. Dr Haussen reported consultancy for Vesalio, Cerenovus, Stryker, Brainomix, Poseydon Medical, and Chiesi USA; Data Safety and Monitoring Board from Jacobs Institute; and stock options in Viz AI. Dr Ribo reported consultancy for Medtronic, MiniMed, Cerenovus, AptaTargets, Stryker, Philips; stock holdings in Methinks, Nora, and Anaconda Biomed. Dr Michel reported grants from University of Lausanne and Swiss National Science Foundation (SNF). Dr Marto reported consulting from Amicus Therapeutics, Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Henon reported fees from Novartis and a grant from Sanofi-Aventis. Dr Gutierrez reported consultancy fees from Medtronic, Stryker and Microvention, and a grant from Methinks, Microvention, Stryker and the National Institutes of Health. Dr Siegler reported a grant from Philips and Viz AI. Dr Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, CSL Behring; lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer Ingelheim, Daiichi Sankyo, Bayer and Bristol-Meyers Squibb. Dr Sheth reported consultancy for Imperative Care, Viz AI, Penumbra; compensation from Motif Neurosciences; grants from National Institutes of Health. Dr Dobrocky reported consultancy fees from MicroVention. Dr Kaesmacher reported grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern. Dr Zaidi reported a grant from Genentech. Dr Castonguay reported employment by Medtronic. Dr Uchida reported fees by Bristol Myers Squibb, Daiichi Sankyo, Medtronic and Stryker. Dr Sakai reported research grant from Biomedical Solutions, Medtronic, Terumo, TG Medical; lecturer’s fees from Asahi-Intec, Biomedical Solutions, Daiichi Sankyo, Kaneka, Medtronic, Terumo; advisory board for Johnson & Johnson, Medtronic, Terumo. Dr Toyoda reported lecturer fees from Otsuka, Daiichi Sankyo, Bayer, Novartis, and Bristol-Myers Squibb. Dr Kaiser reported grants from the Joachim Herz Foundation. Dr Möhlenbruch reported grants from Medtronic, Stryker, and MicroVention. Dr Ringleb reported travel support from Bayer and Bristol Myers Squibb; consultancy for Daiichi Sankyo Company and Boehringer Ingelheim. Dr Zaidat reported consultancy fees by Johnson & Johnson, Medtronic and Stryker, Penumbra stock, and a grant from Johson & Johnson, Medtronic, Penumbra and Stryker. Dr Fischer reported research support from SNF, Medtronic, Stryker, Rapid Medical, Penumbra, Phenox; consultancies for Stryker, CSL Behring; advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, Acthera. Dr Nguyen discloses research support from Medtronic to her institution; advisory board for Brainomix, Aruna Bio; Associate Editor Stroke.

Background and Objectives: There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window., Methods: This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used., Results: Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002)., Discussion: In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window., Trial Registration Information: This study was registered at ClinicalTrials.gov under NCT04096248., Classification of Evidence: This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.

Background: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied., Methods: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage., Results: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group., Conclusions: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.)., (Copyright © 2024 Massachusetts Medical Society.)

Background and Purpose: We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability., Methods: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1)., Results: A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995)., Conclusion: A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window.

Background and Purpose: In patients with acute ischemic stroke (AIS) treated with endovascular therapy (EVT), the association of pre-existing cerebral small vessel disease (cSVD) with symptomatic intracerebral hemorrhage (sICH) remains controversial. We tested the hypothesis that the presence of cerebral microbleeds (CMBs) and their burden would be associated with sICH after EVT of AIS., Methods: We conducted a retrospective study combining cohorts of patients that underwent EVT between January 1st 2015 and January 1st 2020. CMB presence, burden, and other cSVD markers were assessed on a pre-treatment MRI, evaluated independently by two observers. Primary outcome was the occurrence of sICH., Results: 445 patients with pretreatment MRI were included, of which 70 (15.7%) demonstrated CMBs on baseline MRI. sICH occurred in 36 (7.6%) of all patients. Univariate analysis did not demonstrate an association between CMB and the occurrence of sICH (7.5% in CMB+ group vs 8.6% in CMB group, p = 0.805). In multivariable models, CMBs' presence was not significantly associated with increased odds for sICH (-aOR- 1.19; 95% CI [0.43-3.27], p = 0.73). Only ASPECTs (aOR 0.71 per point increase; 95% CI [0.60-0.85], p < 0.001) and collaterals status (aOR 0.22 for adequate versus poor collaterals; 95% CI [0.06-0.93], p 0.019) were independently associated with sICH., Conclusion: CMB presence and burden is not associated with increased occurrence of sICH after EVT. This result incites not to exclude patients with CMBs from EVT. The risk of sICH after EVT in patients with more than10 CMBs will require further investigation., Registration: Registration-URL: http://www., Clinicaltrials: gov ; Unique identifier: NCT01062698., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Rationale: Mechanical thrombectomy (MT) associated with the best medical treatment (BMT) has recently shown efficacy for the management of acute ischemic stroke (AIS) secondary to a large vessel occlusion. However, evidence is lacking regarding the benefit of MT for more distal occlusions., Aim: To evaluate the efficacy in terms of good clinical outcome at 3 months of MT associated with the BMT over the BMT alone in AIS related to a distal occlusion., Methods: The DISCOUNT trial is a multicenter open-label randomized controlled trial involving French University hospitals. Adult patients (⩾18 years) with an AIS involving the anterior or posterior circulation secondary to a distal vessel occlusion within 6 h of symptom onset or within 24 h if no hyperintense signal on fluid attenuation inversion recovery acquisition will be randomized 1:1 to receive either MT associated with the BMT (experimental group) or BMT alone (control group). The number of patients to be included is 488., Study Outcomes: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin scale (mRS) ⩽2 and evaluated by an independent assessor blinded to the intervention arm. Secondary outcomes include recanalization of the occluded vessel within 48 h, angiographic reperfusion in the experimental group, 3-month excellent clinical outcome (mRS ⩽ 1), all adverse events, and death. A cost utility analysis will estimate the incremental cost per quality-adjusted life year (QALY) gained., Discussion: If positive, this study will open new insights in the management of AISs., Trial Registration: ClinicalTrials.gov: NCT05030142 registered on 1 September 2021., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.G. has received grants from the French Ministry of Health and is the primary investigator of the TITAN, DIRECT ANGIO, and IA-RESCUE trial, and consulting fees from Boerhinger Ingelheim, Air Liquide, MIVI, Medtronic, Microvention, and Penumbra. A.S. reports conflicts of interest with Medtronic, Balt Extrusion, and Microvention (consultant). F.C. reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board). J.-C.G. reports conflicts of interest with Stryker (consultant), Medtronic (consultant), Microvention (consultant), Balt, and Intradys (consultant). I.D.-Z. reports a conflict of interest with Medtronic (honoraria for research, lecturing and acting as an advisor). G.T. reports a conflict of interest with Guerbet France (Lecturing fees). N.B. reports a conflict of interest with Stryker and QApel (consultant). I.S. reports a conflict of interest with Sanofi Synthé-Labo, Servier, Boheringer Ingelheim, Astra-Zeneca, Novonordisk, Medtronic (consultant), and BMS-Pfizer (Lecturing fees). Prof. Cognard reports a conflict of interest with Medtronic, Stryker, Microvention, Cerenovus, and MIVI (consultant). S.A. reports a conflict of interest with Boehringer Ingelheim, Astra-Zeneca, Pfizer, and Amgen (participation in advisory meetings and satellite symposia). S.A. is also the principal investigator of the Tenecteplase treatment in Ischemic Stroke (TETRIS) registry (financial support from Boehringer Ingelheim) and of the ToGiac trial (supported by a research grant from Roche-Shugai). S.R. reports conflict of interest with Boheringer Ingelheim, Bristol-Myers Squibb (scientific expertise), and Acticor (study coordination).

Background: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period., Methods: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR., Results: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR., Conclusions: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women., Competing Interests: Disclosures Dr Castonguay reports employment by Medtronic. Dr Cordonnier reports compensation from the University of Glasgow for data and safety monitoring services; employment by the University of Lille; compensation from Biogen for consultant services. Dr Fischer reports employment by Universität Basel; compensation from Boehringer Ingelheim and Biogen for expert witness services. Dr Dobrocky reported MicroVention consultancy. Dr Haussen reports compensation from Vesalio, Cerenovus, Chiesi USA, Inc, Stryker, Brainomix, and Poseydon Medical for consultant services; stock options in Viz.ai; compensation from Jacobs Institute for data and safety monitoring services. Dr Henon reports grants from Sanofi-Aventis U.S. LLC. Dr Kaesmacher reports grants from Swiss National Science Foundation to other. Dr Kaiser reported grants from Joachim Herz Foundation. Martinez-Majander reported grants from Finnish Medical Foundation. Dr Marto reported consulting from Amicus Therapeutics and Boehringer Ingelheim; Speaker with Boehringer Ingelheim. Dr Michel reports grants from the Swiss National Science Foundation, Swiss Heart Foundation, and the University of Lausanne to other. Dr Möhlenbruch reports grants from Medtronic, MicroVention, Inc, and Stryker to other. Dr Nagel reports compensation from Brainomix for consultant services. Dr Nguyen discloses research support from Medtronic, Society of Vascular, and Interventional Neurology to her institution; advisory board compensation from Idorsia, Brainomix; Associate Editor of Stroke. Dr Nogueira reported consultancy for Biogen, Brainomix, Corindus, Cerenovus, Stryker, Medtronic, Ceretrieve, Anaconda, Biomed, Vesalio, Imperative Care, NeuroVasc Technologies, Viz.ai, Genentech, Prolong Pharmaceuticals, Perfuze, Phenox, RapidPulse; stock options Viz.ai, Vesalio, Perfuze, Corindus, Brainomix, Ceretrieve; grants from Cerenovus, Stryker; Dr Nogueira reports compensation from Philips for consultant services; stock holdings in Quantanosis AI; compensation from Synchron for data and safety monitoring services; stock holdings in Piraeus Medical; stock options in Viseon, Inc; compensation from Hybernia for consultant services; stock options in Reist/Q’Apel Medical; stock options in Cerebrotech; compensation from Astrocyte and Cerebrotech for consultant services; stock holdings in Brain4Care; stock options in Truvic. Dr Ortega-Gutierrez reports compensation from MicroVention, Inc, Medtronic, and Stryker for consultant services; grants from Stryker, National Institutes of Health, methinks, Siemens, and MicroVention, Inc; and employment by Carver College of Medicine, University of Iowa. Dr Puetz reported as lecturer for Daiichi Sankyo. Dr Puri reports compensation from Medtronic, Stryker, Johnson & Johnson Health Care Systems, Inc, and MicroVention, Inc, for consultant services. Dr Ribo reports compensation from Philips, Stryker Corporation, Cerenovus, Medtronic MiniMed, Inc, and AptaTargets for consultant services; stock holdings in Anaconda Biomed, Methinks, and Nora. Dr Ringleb reports compensation from Daiichi Sankyo Company and Boehringer Ingelheim for consultant services; employment by Heidelberg University Hospital; travel support from Bristol-Myers Squibb and Bayer Healthcare. Dr Sakai reports compensation from Stryker, Asahi Intecc Co, Ltd, Terumo, Medtronic, Johnson & Johnson Medical Devices & Diagnostics Group, Latin America, L.L.C., Daiichi Sankyo Company Ltd, and Kaneka Medics for other services; grants from Medtronic; grants from Terumo. Dr Sheth reports compensation from Motif Neurosciences for other services; compensation from Viz.ai, Imperative Care, Inc, and Penumbra, Inc, for consultant services; grants from National Institutes of Health; employment by UTHealth McGovern Medical School. Dr Strbian reports employment by Helsingin ja Uudenmaan Sairaanhoitopiiri. Dr Uchida reports compensation from Bristol-Myers Squibb, Stryker, Daiichi Sankyo Company, Ltd, and Medtronic for other services. Dr Wouters reports grants from The Research Foundation-Flanders travel and Remmert Adriaan-Laan-Fonds. Dr Yamagami reports compensation from Otsuka Pharmaceutical Co, Ltd. Medtronic, Daiichi Sankyo Company Ltd, Bristol-Myers Squibb, Johnson and Johnson, Bayer. Daiichi Sankyo Company Ltd, and Stryker for other services; grants from Bristol-Myers Squibb. S. Yoshimura reports compensation from Bristol-Myers Squibb, Johnson & Johnson Medical Devices & Diagnostics Group, Latin America, LLC, Bayer, Kaneka Medics, Boehringer Ingelheim, Medtronic Daiichi Sankyo Company, Stryker, and Terumo for other services. S. Ning discloses research support from Society for Interventional Radiology. Dr Zaidat reports grants from Medtronic, Penumbra, Inc, Johnson and Johnson, Stryker to other; compensation from Medtronic and Johnson & Johnson Health Care Systems, Inc, and Penumbra, Inc, for consultant services; stock holdings in Penumbra Inc. The other authors report no conflicts.

Rationale: Mechanical thrombectomy (MT), the standard of care for acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO), is generally not offered to patients with large baseline infarct (core). Recent studies demonstrated MT benefit in patients with anterior circulation stroke and large core (i.e. Alberta Stroke Program Early Computed Tomography Score, ASPECTS 3-5). However, its benefit in patients with the largest core (ASPECTS 0-2) remains unproven., Aim: To compare the efficacy and safety of MT plus best medical treatment (BMT) and of BMT alone in patients with ASPECTS 0-5 (baseline computed tomography (CT) or magnetic resonance imaging (MRI)) and anterior circulation LVO within 7 h of last-seen-well., Sample Size Estimate: To detect with a two-sided test at 5% significance level (80% power) a common odds ratio of 1.65 for 1-point reduction in the 90-day modified Rankin Scale (mRS) score in the MT + BMT arm versus BMT arm and to anticipate 10% of patients with missing primary endpoint, 450 patients are planned to be included by 36 centers in France, Spain, and the United States., Methods and Design: LArge Stroke Therapy Evaluation (LASTE) is an international, multicenter, Prospectively Randomized into two parallel (1:1) arms, Open-label, with Blinded Endpoint (PROBE design) trial. Eligibility criteria are diagnosis of AIS within 6.5 h of last-seen-well (or negative fluid-attenuated inversion recovery (FLAIR) if unknown stroke onset time), ASPECTS 0-5 (ASPECTS 4-5 for ⩾80-year-old patients), and LVO in the anterior circulation (intracranial internal carotid artery (ICA) and M1 or M1-M2 segment of the middle cerebral artery (MCA))., Study Outcomes: The primary endpoint is the day-90 mRS score distribution (shift analysis) with mRS categories 5 and 6 coalesced into one category. Secondary endpoints include day-180 mRS score, rates of 90-day and 180-day mRS score = 0-2 and 0-3, rate of decompressive craniectomy, the National Institutes of Health Stroke Scale (NIHSS) score change, revascularization and infarct volume growth at 24 h, and quality of life at day 90 and 180. Safety outcomes (90-day all-cause mortality, procedural complications, symptomatic intracerebral hemorrhage, and early NIHSS score worsening) are recorded. A dynamic balanced randomization (1:1) is used to distribute eligible patients into the experimental arm and control arm, by incorporating the center and these pre-specified factors: baseline ASPECTS (0-3 vs 4-5), age (⩽70 vs >70 years), baseline NIHSS (<20 vs ⩾20), intravenous thrombolysis (no vs yes), admission mode (Drip-and-Ship vs Mothership), occlusion site (intracranial ICA vs MCA-M1 or M1-M2), intravenous fibrinolysis (no vs yes), and last-seen-well to randomization time (0-4.5 vs >4.5-6.5 h)., Discussion: The LASTE trial will determine MT efficacy and safety in patients with ASPECTS 0-5 and LVO in the anterior circulation., Trial Registration: LASTE Trial NCT03811769., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.F.A., J.L., H.H., G.B., N.N., S.R., F.D.M, M.A., A.D., F.C., and C.A. declare no conflict of interest. V.C. received educational grant, consultation fees, research grant from Medtronic, Stryker, MicroVention, Cerenovus, and Balt; educational grant and consultation fees from phenox. B.L. received a research grant from MicroVention, Balt, and phenox. C.C. received consultation fees as consultant for Medtronic, MicroVention, Stryker, MIVI, and Cerenovus. B.G. received consultation fees from MIVI, Medtronic, MicroVention, and Penumbra. I.S. received consultation fees from Medtronic. G.M. received consultation fees from MicroVention, Stryker, and Balt; paid lectures from Medtronic, Johnson & Johnson, and Phenox. T.J. is advisor and investor for Anaconda, Route92, Viz.ai, FreeOx, Kandu, and Methinks. He received personal fees in his role on Cerenovus DSMB and steering committee and on Contego Medical screening committee. He received grant support from Medtronic and Stryker Neurovascular.

Background: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors., Methods: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay., Results: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses., Conclusion: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Mechanical thrombectomy (MT) has become the standard of care for patients with acute ischemic stroke secondary to large vessel occlusion (LVO) of the anterior circulation. Conversely, its benefit in patients with National Institutes of Health Stroke Scale (NIHSS) score ⩽ 5 is unproven., Aim: To demonstrate the superiority of immediate MT plus best medical treatment (BMT) compared to BMT (with secondary MT in case of deterioration) for increasing the rate of modified Rankin Scale (mRS) score ⩽ 1 at 90 days after minor stroke (NIHSS score ⩽ 5) and anterior circulation LVO., Sample Size Estimates: To detect an absolute increase of 10% (80% power) in the 90-day mRS score = 0-1 rate in the MT + BMT group, by assuming an mRS score = 0-1 rate of 60% in the BMT group and by considering two interim efficacy/futility analyses (after study completion by 274 and 548 patients), 824 patients must be included by 36 centers in France, Spain, and the USA., Methods and Design: MOSTE is an international, multicenter, prospectively randomized into two parallel (1:1) arms, open-label, with blinded endpoint trial. Eligibility criteria are diagnosis of acute ischemic stroke within 23 h of last-seen-well, NIHSS score ⩽ 5, and LVO in the anterior circulation (intracranial internal carotid artery, M1 or M1-M2 segment of the middle cerebral artery)., Study Outcomes: The primary endpoint is the rate of excellent outcome at day 90 (mRS score = 0-1). Secondary endpoints include the rates of 90-day mRS score = 0-2 and score = 0, NIHSS score change, secondary MT, revascularization and infarct volume growth at 24 h, and quality of life and cognitive function at day 90. Safety outcomes (90-day all-cause mortality, procedural complications, symptomatic intracerebral hemorrhage, and rapid NIHSS score worsening) are recorded., Discussion: The MOSTE trial will determine MT efficacy and safety in patients with minor stroke and LVO in the anterior circulation., Trial Registration: MOSTE Trial. NCT03796468., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CA, JL, HH, JFA, SR, NN, ON, GT, FD, AD declare no conflict of interest.BL received a research grant from Microvention, Balt, Phenox.BG received consultation fees from MIVI, Medtronic, Microvention, and Penumbra.IS received consultation fees from Medtronic.CC received consultation fees as Consultant for Medtronic, Microvention, Stryker, MIVI, Cerenovus.GM received consultation fees from Microvention, Stryker, Balt; paid lectures from Medtronic, Johnson & Johnson, Phenox.TGJ is advisor and investor for Anaconda, Route92, Viz.AI, FreeOx, Kandu and Methinks. He received personal fees in his role on Cerenovus DSMB and steering committee and Contego Medical screening committee. He received grant support from Medtronic and Stryker Neurovascular.VC received educational grant, consultation fees, and research grant from Medtronic, Stryker, Microvention, Cerenovus, Balt; educational grant and consultation fees from Phenox.

Background: Preclinical stroke models have recently reported faster infarct growth (IG) when ischemia was induced during daytime. Considering the inverse rest-activity cycles of rodents and humans, faster IG during the nighttime has been hypothesized in humans., Methods: We retrospectively evaluated acute ischemic stroke patients with a large vessel occlusion transferred from a primary to 1 of 3 French comprehensive stroke center, with magnetic resonance imaging obtained at both centers before thrombectomy. Interhospital IG rate was calculated as the difference in infarct volumes on the 2 diffusion-weighted imaging, divided by the time elapsed between the 2 magnetic resonance imaging. IG rate was compared between patients transferred during daytime (7:00-22:59) and nighttime (23:00-06:59) in multivariable analysis adjusting for occlusion site, National Institutes of Health Stroke Scale score, infarct topography, and collateral status., Results: Out of the 329 patients screened, 225 patients were included. Interhospital transfer occurred during nighttime in 31 (14%) patients and daytime in 194 (86%). Median interhospital IG was faster when occurring at night (4.3 mL/h; interquartile range, 1.2-9.5) as compared to the day (1.4 mL/h; interquartile range, 0.4-3.5; P <0.001). In multivariable analysis, nighttime transfer remained independently associated with IG rate ( P <0.05)., Conclusions: Interhospital IG appeared faster in patients transferred at night. This has potential implications for the design of neuroprotection trials and acute stroke workflow., Competing Interests: Disclosures Dr Henon received speaker fees from Sanofi Aventis. Dr Heit reports consulting fees from Medtronic and MicroVention, and he is a member of the medical and scientific advisory board for iSchemaView. Dr Olivot reports consultant services for Acticor, Abbvie, Boehringer-Ingelheim, Pfizer, Bristol-Myers Squibb, and Medtronic. Dr Albers reports stock holdings in iSchemaView; compensation from Biogen, iSchemaView, and Genentech for consultant services. The other authors report no conflicts.

Objective: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection., Methods: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging., Results: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (OR adjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (OR adjusted 1.01, 95% CI 0.83-1.22), and mortality (OR adjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; OR adjusted 0.51, 95% CI 0.33-0.79)., Interpretation: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers., Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke., Design, Setting, and Participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT., Interventions: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated., Main Outcomes and Measures: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score)., Results: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00)., Conclusions and Relevance: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials., Trial Registration: ClinicalTrials.gov Identifier: NCT04734548.

Background: Diffusion-weighted imaging lesion reversal (DWIR) is frequently observed after mechanical thrombectomy for acute ischemic stroke, but little is known about age-related differences and impact on outcome. We aimed to compare, in patients <80 versus ≥80 years old, (1) the effect of successful recanalization on DWIR and (2) the impact of DWIR on functional outcome., Methods: We retrospectively analyzed data of patients treated for an anterior circulation acute ischemic stroke with large vessel occlusion in 2 French hospitals, who underwent baseline and 24-hour follow-up magnetic resonance imaging, with baseline DWI lesion volume ≥10 cc. The percentage of DWIR (DWIR%), was calculated as follows: DWIR%=(DWIR volume/baseline DWI volume)×100. Data on demographics, medical history, and baseline clinical and radiological characteristics were collected., Results: Among 433 included patients (median age, 68 years), median DWIR% after mechanical thrombectomy was 22% (6-35) in patients ≥80, and 19% (interquartile range, 10-34) in patients <80 ( P =0.948). In multivariable analyses, successful recanalization after mechanical thrombectomy was associated with higher median DWIR% in both ≥80 ( P =0.004) and <80 ( P =0.002) patients. In subgroup analyses performed on a minority of subjects, collateral vessels status score (n=87) and white matter hyperintensity volume (n=131) were not associated with DWIR% ( P >0.2). In multivariable analyses, DWIR% was associated with increased rates of favorable 3-month outcomes in both ≥80 ( P =0.003) and <80 ( P =0.013) patients; the effect of DWIR% on outcome was not influenced by the age group ( P interaction=0.185) Conclusions: DWIR might be an important and nonage-dependent effect of arterial recanalization, as it seems to beneficially impact 3-month outcomes of both younger and older subjects treated with mechanical thrombectomy for acute ischemic stroke and large vessel occlusion., Competing Interests: Disclosures Dr Benzakoun reports travel support from Guerbet LLC. Dr Bricout reports compensation from Stryker for consultant services and compensation from Qapel Medical for consultant services. Dr Turc reports compensation from Guerbet France for other services. The other authors report no conflicts.

Background and Purpose: Despite initial successful recanalization after mechanical thrombectomy (MT), some patients with large artery occlusion (LAO)-related stroke will experience an early reocclusion of the injured vessel which may worsen their prognosis. We aimed to investigate the prevalence, associated factors and prognosis of early reocclusion after successful MT in a large prospective cohort of stroke patients with LAO., Methods: We included patients from the Lille reperfusion registry with LAO-related stroke involving M1 segment, internal carotid artery terminus or tandem ICA-M1 occlusion, with successful recanalization after MT and available 24 h imaging follow-up. Early reocclusion was defined as internal carotid artery terminus or M1 occlusion on 24 h magnetic resonance imaging (MRI) or computed tomography (CT) vascular imaging. Multivariable logistic regression models were used to investigate factors associated with early reocclusion and its impact on outcomes., Results: Between 2015 and 2020, 62 of 1015 included patients experienced an early reocclusion (6.1%). Age (odds ratio (OR) per 15 years decrease: 1.38 (1.05-1.81)) antiplatelet use (OR: 0.41 (0.19-0.89)), several device passes (OR: 2.13 (1.18-3.83)), atherosclerosis cause (OR: 2.38 (1.19-4.78)), and early clinical worsening (OR: 2.45 (1.18-5.07)) were independently associated with early reocclusion. Early reocclusion was independently associated with poor prognosis (OR: 7.15 (3.49-14.65)) and mortality (OR: 2.05 (1.07-3.91)) at 3 months., Conclusion: Six percent of patients with LAO-related stroke and initial successful recanalization experienced early reocclusion. This event is associated with a 7-fold increased risk of poor functional outcome and a 2-fold increased risk of mortality. Further efforts are warranted to refine early detection of patients at risk of reocclusion and to improve their management.

Objective: Patients with acute ischemic stroke harboring a large vessel occlusion who present to primary stroke centers often require inter-hospital transfer for thrombectomy. We aimed to determine clinical and imaging factors independently associated with fast infarct growth (IG) during inter-hospital transfer., Methods: We retrospectively analyzed data from acute stroke patients with a large vessel occlusion transferred for thrombectomy from a primary stroke center to one of three French comprehensive stroke centers, with an MRI obtained at both the primary and comprehensive center before thrombectomy. Inter-hospital IG rate was defined as the difference in infarct volumes on diffusion-weighted imaging between the primary and comprehensive center, divided by the delay between the two MRI scans. The primary outcome was identification of fast progressors, defined as IG rate ≥5 mL/hour. The hypoperfusion intensity ratio (HIR), a surrogate marker of collateral blood flow, was automatically measured on perfusion imaging., Results: A total of 233 patients were included, of whom 27% patients were fast progressors. The percentage of fast progressors was 3% among patients with HIR < 0.40 and 71% among those with HIR ≥ 0.40. In multivariable analysis, fast progression was independently associated with HIR, intracranial carotid artery occlusion, and exclusively deep infarct location at the primary center (C-statistic = 0.95; 95% confidence interval [CI], 0.93-0.98). IG rate was independently associated with good functional outcome (adjusted OR = 0.91; 95% CI, 0.83-0.99; P = 0.037)., Interpretation: Our findings show that a HIR > 0.40 is a powerful indicator of fast inter-hospital IG. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers. ANN NEUROL 2023;93:1117-1129., (© 2023 American Neurological Association.)

Background and Purpose: This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD)., Methods: This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015-2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0-2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching., Results: Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10-19] vs. 4 [2-7], P<0.001). The frequency of favorable 3-month outcome did not differ significantly between both groups (EVT: 64.0% vs. IVT: 86.8%; ORadjusted 0.56 [0.24-1.32]). EVT was associated with higher rates of recanalization (80.5% vs. 40.7%; ORadjusted 8.85 [4.28-18.29]) compared to IVT. All secondary analyses showed higher recanalization rates in the EVT-group, which however never translated into better functional outcome rates compared to the IVT-group., Conclusion: We observed no signal of superiority of EVT over IVT regarding functional outcome in CeAD-patients with AIS and LVO despite higher rates of complete recanalization with EVT. Whether pathophysiological CeAD-characteristics or their younger age might explain this observation deserves further research.

Background: Whether endovascular therapy (EVT) added on best medical management (BMM), as compared to BMM alone, is beneficial in acute ischemic stroke with isolated posterior cerebral artery occlusion is unknown., Methods: We conducted a multicenter international observational study of consecutive stroke patients admitted within 6 hours from symptoms onset in 26 stroke centers with isolated occlusion of the first (P1) or second (P2) segment of the posterior cerebral artery and treated either with BMM+EVT or BMM alone. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month good functional outcome (modified Rankin Scale [mRS] score 0-2 or return to baseline modified Rankin Scale). Secondary outcomes were 3-month excellent recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage, and early neurological deterioration., Results: Overall, 752 patients were included (167 and 585 patients in the BMM+EVT and BMM alone groups, respectively). Median age was 74 (interquartile range, 63-82) years, 329 (44%) patients were female, median National Institutes of Health Stroke Scale was 6 (interquartile range 4-10), and occlusion site was P1 in 188 (25%) and P2 in 564 (75%) patients. Baseline clinical and radiological data were similar between the 2 groups following propensity score weighting. EVT was associated with a trend towards lower odds of good functional outcome (odds ratio, 0.81 [95% CI, 0.66-1.01]; P =0.06) and was not associated with excellent functional outcome (odds ratio, 1.17 [95% CI, 0.95-1.43]; P =0.15). EVT was associated with a higher risk of symptomatic intracranial hemorrhage (odds ratio, 2.51 [95% CI, 1.35-4.67]; P =0.004) and early neurological deterioration (odds ratio, 2.51 [95% CI, 1.64-3.84]; P <0.0001)., Conclusions: In this observational study of patients with proximal posterior cerebral artery occlusion, EVT was not associated with good or excellent functional outcome as compared to BMM alone. However, EVT was associated with higher rates of symptomatic intracranial hemorrhage and early neurological deterioration. EVT should not be routinely recommended in this population, but randomization into a clinical trial is highly warranted.

Introduction: Internal carotid artery dissection (ICAD) is a rare cause of acute ischemic stroke with large vessel occlusion (AIS-LVO). We aimed investigating the impact on outcome of internal carotid artery (ICA) patency after mechanical thrombectomy (MT) for AIS-LVO due to occlusive ICAD., Patients and Methods: We included consecutive patients with AIS-LVO due to occlusive ICAD treated with MT from January 2015 to December 2020 in three European stroke centers. We excluded patients with unsuccessful intracranial reperfusion after MT (modified Thrombolysis in Cerebral Infarction (mTICI) score < 2b). We compared 3-month favorable clinical outcome rate, defined as a modified Rankin scale (mRS) score ⩽2, according to ICA status (patency vs occlusion) at the end of MT and at 24-h follow-up imaging, using univariate and multivariable models., Results: Among 70 included patients, ICA was patent in 54/70 (77%) at the end of MT, and in 36/66 (54.5%) patients with 24-h follow-up imaging. Among patients with ICA patency at the end of MT, 32% presented ICA occlusion at 24-h control imaging. Favorable 3-month outcome occurred in 41/54 (76%) patients with ICA patency post-MT and in 9/16 (56%) patients with occluded ICA post-MT ( p  = 0.21). Rates of favorable outcome were significantly higher in patients with 24-h ICA patency compared to patients with 24-h ICA occlusion (32/36 [89%] vs 15/30 [50%]), with an adjusted odds ratio of 4.67 (95% CI: 1.26-17.25)., Discussion and Conclusion: Obtaining sustained (24-h) ICA patency after MT could be a therapeutic target for improving functional outcome in patients with AIS-LVO due to ICAD., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Background and Objectives: Current guidelines do not address recommendations for mechanical thrombectomy (MT) in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with preexisting modified Rankin Scale (mRS) > 1. In this study, we evaluated the outcomes of MT vs medical management in patients with prestroke disability presenting in the 6- to 24-hour time window with acute LVO., Methods: We analyzed a multinational cohort (61 sites, 6 countries from 2014 to 2020) of patients with prestroke (or baseline) mRS 2 to 4 and anterior circulation LVO treated 6-24 hours from TLSW. Patients treated in the extended time window with MT vs medical management were compared using multivariable logistic regression and inverse probability of treatment weighting (IPTW). The primary outcome was the return of Rankin (ROR, return to prestroke mRS by 90 days)., Results: Of 554 included patients (448 who underwent MT), the median age was 82 years (interquartile range [IQR] 72-87) and the National Institutes of Health Stroke Scale (NIHSS) was 18 (IQR 13-22). In both MV logistic regression and IPTW analysis, MT was associated with higher odds of ROR (adjusted OR [aOR] 3.96, 95% CI 1.78-8.79 and OR 3.10, 95% CI 1.20-7.98, respectively). Among other factors, premorbid mRS 4 was associated with higher odds of ROR (aOR, 3.68, 95% CI 1.97-6.87), while increasing NIHSS (aOR 0.90, 95% CI 0.86-0.94) and decreasing Alberta Stroke Program Early Computed Tomography Scale score (aOR per point 0.86, 95% CI 0.75-0.99) were associated with lower odds of ROR. Age, intravenous thrombolysis, and occlusion location were not associated with ROR., Discussion: In patients with preexisting disability presenting in the 6- to 24-hour time window, MT is associated with a higher probability of returning to baseline function compared with medical management., Classification of Evidence: This investigation's results provide Class III evidence that in patients with preexisting disability presenting 6-24 hours from the TLSW and acute anterior LVO stroke, there may be a benefit of MT over medical management in returning to baseline function., (© 2022 American Academy of Neurology.)

Background: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients., Methods: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3)., Results: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH., Conclusions: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04096248.

Background: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly., Methods: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models., Results: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratio adjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratio adjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratio adjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar., Conclusions: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Background: Recent studies in the general stroke population treated with endovascular treatment (EVT) reported that higher pre-treatment lesional volumes were independently associated with poor neurological outcome and functional dependence after stroke. However, it has been not evaluated in older patients., Aim: We test the association between the pre-treatment lesional volume on diffusion-weighted magnetic resonance imaging and relevant outcome measures in older adults with stroke treated with EVT., Methods: We included consecutive older adults with stroke (⩾80 years old) treated with EVT in two academic comprehensive stroke centers. The association between pre-treatment lesional volume and relevant outcome measures (poor outcome (modified Rankin scale 4-6), 3-month mortality and symptomatic intracerebral hemorrhage (sICH)) was evaluated using univariate and multivariable models., Results: Five hundred seventy-nine patients were included (mean age: 85.6 ± 4.1, median lesional volume was 10 ml; interquartile range: 3-30 ml). Pre-treatment lesional volume was associated with poor functional outcome (adjusted odds ratio (aOR): 1.87, 95% confidence interval (CI): 1.60-2.20, for +1 logarithmic increase of lesional volume), 3-month mortality (aOR: 1.50, CI: 1.28-1.76), and sICH (aOR: 1.67, CI: 1.27-2.20). A threshold lesional volume >35 ml predicted 90% of patients with poor functional outcome and a cut-off >51 ml predicted 90% of patients dead at 3 months., Conclusions: Pre-treatment lesional volume might contribute, in association with other relevant clinical features, to the selection of older stroke patients who will benefit from EVT.

Background: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT-as compared to no-IVT-may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation., Methods: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score <6) isolated internal carotid artery occlusion patients treated within 4.5 hours of symptoms onset with either IVT or antithrombotic therapy between 2006 and 2020 (inclusion date varied among centers). Primary outcome was END within 24 hours (≥4 National Institutes of Health Stroke Scale points increase within 24 hours), and secondary outcomes were END within 7 days (END 7d ) and 3-month modified Rankin Scale score 0 to 1., Results: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END 7d occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07-3.92]; P =0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P =0.09). However, END 7d and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END 7d : adjusted hazard ratio, 1.29 [95% CI, 0.75-2.23]; P =0.37; modified Rankin Scale score of 0-1: adjusted odds ratio, 1.1 [95% CI, 0.6-2.2]; P =0.71). END 7d occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9-10.1) versus 20.4 hours (interquartile range, 7.8-34.4), respectively, P <0.01., Conclusions: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END-particularly END due to artery-to-artery embolism-occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population.

Background: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy., Methods: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume)., Results: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P =0.03. However, mismatch volume modified the effect of bridging on clinical outcome ( P interaction =0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only ( P interaction =0.002)., Conclusions: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

Background: Determine if early venous filling (EVF) after complete successful recanalization with mechanical thrombectomy in acute ischemic stroke is an independent predictor of symptomatic intracranial hemorrhage (sICH) and integrate EVF into a risk score for sICH prediction., Methods: Consecutive patients with anterior acute ischemic stroke treated by mechanical thrombectomy issued from patients enrolled in the THRACE trial (Thrombectomie des Artères Cérébrales) and from 2 prospective registries were included and divided into a derivation (Center I; n=402) and validation cohorts (THRACE and center 2; n=507). EVF was evaluated by 2 blinded readers. sICH was defined according to the modified European cooperative acute stroke study II. Clinical and radiological data were analyzed in the derivation cohort (C1) to identify independent predictors of sICH and construct a predictive score test on the validation cohort (THRACE + C2)., Results: Symptomatic ICH rate was similar between the two cohorts (9.9% and 8.9% respectively, P =0.9). Time from onset-to-successful recanalization >270 minutes (odds ratio [OR], 7.8 [95% CI, 2.5-24]), Alberta Stroke Program Early CT Score (≤5 [OR, 2.49 (95% CI, 1.8-8.1) or 6-7 [OR, 1.15 (95% CI, 1.03-4.46)]), glucose blood level >7 mmol/L (OR, 2.92 [95% CI, 1.26-6.7]), and EVF presence (OR, 11.9 [95% CI, 3.8-37.5]) were independent predictors of sICH and constituted the Time-Alberta Stroke Program Early CT-Glycemia-EVF score. Time-Alberta Stroke Program Early CT-Glycemia-EVF score was associated with an increased risk of sICH in the derivation cohort (OR increase per unit, 1.99 [95% CI, 1.53-2.59]; P <0.001) with area under the curve, 0.832 [95% CI, 0.767-0.898]. The score had good performance in the validation cohort (area under the curve, 0.801 [95% CI, 0.69-0.91])., Conclusions: Time-Alberta Stroke Program Early CT-Glycemia-EVF score is a simple tool with readily available clinical variables with good performances for sICH prediction after mechanical thrombectomy., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01062698.

Background and Purpose: To determine the influence of the cerebral small vessel disease (SVD) burden on collateral recruitment in patients treated with mechanical thrombectomy (MT) for anterior circulation acute ischemic stroke (AIS)., Methods: Patients with AIS due to large vessel occlusion (LVO) from the Thrombectomie des Artères Cérébrales (THRACE) trial and prospective cohorts from 2 academic comprehensive stroke centers treated with MT were pooled and retrospectively analyzed. Collaterals' adequacy was assessed using the American Society of Interventional and Therapeutic Radiology/Society of Interventional Radiology (ASITN/SIR) score on initial digital subtraction angiography and dichotomized as good (3,4) versus poor (0-2) collaterals. The SVD burden was rated with the global SVD score on MRI. Multivariable logistic regression analyses were used to determine relationships between SVD and ASITN/SIR scores., Results: A total of 312 participants were included (53.2% males, mean age 67.8 ± 14.9 years). Two hundred and seven patients had poor collaterals (66.4%), and 133 (42.6%) presented with any SVD signature. In multivariable analysis, patients demonstrated worse leptomeningeal collaterality with increasing SVD burden before and after adjustment for SVD risk factors (adjusted odds ratio [aOR] 0.69; 95%CI [0.52-0.89] and aOR 0.66; 95%CI [0.5-0.88], respectively). Using individual SVD markers, poor collaterals were significantly associated with the presence of lacunes (aOR 0.40, 95% CI [0.20-0.79])., Conclusion: Our study provides evidence that in patients with AIS due to LVO treated with MT, the burden of SVD assessed by pre-treatment MRI is associated with poorer recruitment of leptomeningeal collaterals., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: I ntracranial vertebral dissections have polymorphs clinical presentations and can lead to haemorrhagic complications if they are intracranial. We here describe a case of a thrombosed dissecting aneurysm of postero-inferior cerebellar artery (PICA) revealed by a Wallenberg syndrome preceded by headaches., Case: A 23-year-old patient, without neurological or vascular past medical history, was admitted for dizziness preceded by headache. The clinical examination on admission revealed an incomplete Wallenberg syndrome, associating hemiface sensitive deficit, Horner's syndrome, dysmetria and nystagmus. The brain MRI showed a latero-medullary infarct with a homolateral PICA thrombosed dissecting aneurysm., Conclusion: The diagnosis of intracranial dissecting aneurysms needs particular caution because aneurysm sac thrombosis can give false reassurance on angiographic MR sequences. Moreover, the anatomic features of intracranial artery walls make them prone to sub-adventitial dissection and subsequent subarachnoid haemorrhages. Therefore, antithrombotic therapy should be used with caution, due to the risk of bleeding in these intracranial dissections., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: Patients with anterior circulation ischemic strokes due to large vessel occlusion (AIS-LVO) and very severe neurological deficits (National Institutes of Health Stroke Scale (NIHSS) score > 25) were under-represented in clinical trials on endovascular treatment (EVT). We aimed to evaluate safety and outcomes of EVT in patients with very severe vs. severe (NIHSS score 15-25) neurological deficits., Methods: We included consecutive patients undergoing EVT for AIS-LVO between January 2015 and December 2019 at Lille University Hospital. We compared rates of parenchymal hemorrhage (PH), symptomatic intracranial hemorrhage (SICH), procedural complications, and 90-day mortality between patients with very severe vs. severe neurological deficit using univariable and multivariable logistic regression analyses. Functional outcome (90-days modified Rankin Scale) was compared between groups using ordinal logistic regression analysis., Results: Among 1484 patients treated with EVT, 108 (7%) had pre-treatment NIHSS scores > 25, 873 (59%) with NIHSS scores 15-25 and 503 (34%) with NIHSS scores < 15. Rates of PH, SICH, successful recanalization, and procedural complications were similar in patients with NIHSS scores > 25 and NIHSS 15-25. Patients with NIHSS > 25 had a lower likelihood of improved functional outcome ( adj common OR 0.31[95% CI 0.21-0.47]) and higher odds of mortality at 90 days ( adj OR 2.3 [95% CI 1.5-3.7]) compared to patients with NIHSS 15-25. Successful recanalization was associated with better functional outcome ( adj common OR 3.8 [95% CI 1.4-10.4]), and lower odds of mortality ( adj OR 0.3 [95% CI 0.1-0.9]) in patients with very severe stroke. The therapeutic effect of recanalization on functional outcome and mortality was similar in both groups., Conclusions: In patients with very severe neurological deficit, EVT was safe and successful recanalization was strongly associated with better functional outcome at 90 days., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Distal medium vessel occlusions (DMVOs) are increasingly recognized as a next target for endovascular thrombectomy (EVT). Our objective was to investigate safety and clinical outcomes of EVT for DMVO of the middle cerebral artery (MCA)., Methods: We analyzed data of the Lille Reperfusion Registry from January 2017 to September 2020. Patients with a primary or secondary DMVO of the MCA seen on pretreatment angiogram were included. Only patients with a eTICI score 2b50-2b67 on initial angiogram were considered. Baseline characteristics, angiographic clinical, and safety outcomes were compared between patients treated with EVT or standard medical treatment (no-EVT)., Results: Of the 171 patients included, 96 received EVT (46.9% male, 68.7 ± 15.8 years) and 75 received standard medical treatment (44% male, 73.9 ± 13.1 years). EVT patients had a better improvement of the NIHSS score at discharge (adjusted mean difference: 3.71; 95% CI: 1.18-6.24). In the distal M2 occlusions subgroup, EVT was significantly associated with a higher rate of early neurologic improvement (adjusted OR: 3.62 95% CI: 1.31-10.03), NIHSS improvement at discharge (adjusted mean difference: 5.23; 95% CI: 2.18-8.29), and improved modified Rankin Scale score at 3 months (adjusted common OR for 1 point improvement: 3.06; 95% CI: 1.30 to 7.23). Symptomatic intracranial hemorrhage occurred in 3.1% in the EVT group and in 9.5% in the no-EVT group., Conclusions: EVT for DMVO of the MCA appears to be safe and may lead to improved clinical outcomes. This effect was especially pronounced in patients with distal M2 occlusions, warranting randomized trials to validate this result., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Neuropsychiatric (NP) symptoms are prominent features of cognitive decline, but they have been understudied in patients with spontaneous intracerebral haemorrhage (ICH). In ICH survivors, we aimed at assessing NP symptoms prevalence and profiles, and their influence on long-term outcomes., Methods: We analysed data from consecutive 6-month ICH survivors enrolled in the Prognosis of Intracerebral Haemorrhage study. We performed NP evaluation using the Neuropsychiatric Inventory Questionnaire. Patients underwent long-term clinical follow-up after ICH (median follow-up time 7.2 years, IQR 4.8-8.2)., Results: Out of 560 patients with ICH, 265 survived at 6 months. NP evaluation 6 months after ICH was feasible in 202 patients. NP symptoms were present in 112 patients (55%), and in 36 out of 48 patients (75%) with post-ICH dementia. Affective symptoms were present in 77 patients (38%), followed by vegetative symptoms (52 patients, 26%) and hyperactivity (47 patients, 23%). Apathy and hyperactivity were associated with post-ICH dementia and cerebral amyloid angiopathy MRI profile (all p<0.05). Apathy and hyperactivity prevailing over affective symptoms at 6-month follow-up were associated with higher risks of developing new-onset dementia (HR 5.40; 95% CI 2.27 to 12.84), while presence or severity of NP symptoms were not., Conclusion: NP symptoms were present in more than half of 6-month ICH survivors, with higher prevalence and severity in patients with post-ICH dementia. Distinctive NP profile might be associated to cognitive status and inform on long-term dementia risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The net clinical benefit of mechanical thrombectomy (MT) in patients with anterior circulation ischaemic stroke associated with large vessel occlusion (AIS-LVO) related to carotid artery dissection (CAD) is uncertain. The aim of the study was to investigate the safety and clinical outcomes of patients treated by MT for a CAD-related stroke., Methods: We included consecutive patients with AIS-LVO treated by MT between 1st 2015 and January 1st 2020 at Lille University Hospital. We compared the safety and clinical outcomes, including successful recanalisation, defined as a modified thrombolysis in cerebral infarction (mTICI) ≥ 2b and favourable functional outcome at 3 months (defined as a modified Rankin Scale (mRS) ≤ 2 or equal to pre-stroke), in patients with CAD-related stroke versus patients with other aetiologies., Results: We included 1422 patients, among them, 43 patients with CAD-related AIS-LVO were matched to 86 patients with other aetiologies. Procedural complications, sICH (ECASS-3 criteria) and mortality rates were similar in the two groups (OR 0.85, 95% CI 0.21-3.49, p = 0.82; OR 1.54 95% CI 0.33-2.79, p = 0.58; OR 0.18 95% CI 0.02-1.46, p = 0.11, respectively), as well as the rates of intracranial angiographic successful recanalisation and favourable functional outcome (OR 0.67 (95% CI 0.26-1.73, p = 0.41; OR 1.26 (95% CI 0.61-2.64, p = 0.53). In patients with CAD-related stroke, intracranial angiographic success after MT was significantly associated with favourable functional outcome., Conclusions: In patients with AIS-LVO related to CAD, safety profiles and clinical outcomes after MT are similar compared to matched patients with other stroke aetiologies., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Advanced imaging for patient selection in mechanical thrombectomy is not widely available., Objective: To compare the clinical outcomes of patients selected for mechanical thrombectomy by noncontrast computed tomography (CT) vs those selected by computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) in the extended time window., Design, Setting, and Participants: This multinational cohort study included consecutive patients with proximal anterior circulation occlusion stroke presenting within 6 to 24 hours of time last seen well from January 2014 to December 2020. This study was conducted at 15 sites across 5 countries in Europe and North America. The duration of follow-up was 90 days from stroke onset., Exposures: Computed tomography with Alberta Stroke Program Early CT Score, CTP, or MRI., Main Outcomes and Measures: The primary end point was the distribution of modified Rankin Scale (mRS) scores at 90 days (ordinal shift). Secondary outcomes included the rates of 90-day functional independence (mRS scores of 0-2), symptomatic intracranial hemorrhage, and 90-day mortality., Results: Of 2304 patients screened for eligibility, 1604 patients were included, with a median (IQR) age of 70 (59-80) years; 848 (52.9%) were women. A total of 534 patients were selected to undergo mechanical thrombectomy by CT, 752 by CTP, and 318 by MRI. After adjustment of confounders, there was no difference in 90-day ordinal mRS shift between patients selected by CT vs CTP (adjusted odds ratio [aOR], 0.95 [95% CI, 0.77-1.17]; P = .64) or CT vs MRI (aOR, 0.95 [95% CI, 0.8-1.13]; P = .55). The rates of 90-day functional independence (mRS scores 0-2 vs 3-6) were similar between patients selected by CT vs CTP (aOR, 0.90 [95% CI, 0.7-1.16]; P = .42) but lower in patients selected by MRI than CT (aOR, 0.79 [95% CI, 0.64-0.98]; P = .03). Successful reperfusion was more common in the CT and CTP groups compared with the MRI group (474 [88.9%] and 670 [89.5%] vs 250 [78.9%]; P < .001). No significant differences in symptomatic intracranial hemorrhage (CT, 42 [8.1%]; CTP, 43 [5.8%]; MRI, 15 [4.7%]; P = .11) or 90-day mortality (CT, 125 [23.4%]; CTP, 159 [21.1%]; MRI, 62 [19.5%]; P = .38) were observed., Conclusions and Relevance: In patients undergoing proximal anterior circulation mechanical thrombectomy in the extended time window, there were no significant differences in the clinical outcomes of patients selected with noncontrast CT compared with those selected with CTP or MRI. These findings have the potential to widen the indication for treating patients in the extended window using a simpler and more widespread noncontrast CT-only paradigm.

Background: The net clinical benefit of mechanical thrombectomy (MT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) and mild neurological deficit is uncertain., Aims: To investigate efficacy and safety of MT in patients with acute AIS-LVO and mild neurological deficit by evaluating i) the influence of recanalisation on three-month outcome and ii) mortality, symptomatic intracerebral hemorrhage (sICH) and procedural complications., Methods: We included consecutive patients with acute AIS-LVO and National Institute of Stroke Scale (NIHSS) score<8, treated by MT at Lille University Hospital. Recanalisation was graded according to modified thrombolysis in cerebral infarction (mTICI) score, mTICI 2b/2c/3 being considered successful. We recorded procedural complications and classified intra-cerebral hemorrhages (ICH) and sICH according with European Cooperative Acute Stroke Study (ECASS) and ECASS2 criteria. Three-month outcome was evaluated by modified Rankin scale (mRS). Excellent and favourable outcomes were respectively defined as mRS 0-1 and 0-2 (or similar to pre-stroke)., Results: We included 95 patients. At three months, 56 patients (59. 0%) achieved an excellent outcome and 69 (72, 6%) a favourable outcome, both being more frequent in patients with successful recanalisation than in patients without (excellent outcome 71, 1% versus 10, 5%, P<0.001 and favourable outcome 82.9% versus 31.6%, P<0.001). The difference remained unchanged after adjustment for age and pre-MT infarct volume. Similar results were observed in patients with pre-MT NIHSS ≤5. Death occurred in five patients (5.3%), procedural complications in 12 (12.6%), any ICH in 38 (40.0%), including 3 (3.2%) sICH., Conclusions: Achieving successful recanalisation appears beneficial and safe in acute AIS-LVO patients with NIHSS<8 before MT., (Copyright © 2020. Published by Elsevier Masson SAS.)

The benefits of mechanical thrombectomy (MT) for patients with acute ischemic stroke (AIS) and a large ischemic core (LIC) at presentation are uncertain. We aimed to obtain up-to-date aggregate estimates of the outcomes following MT in patients with volumetrically assessed LIC. We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-conformed, PROSPERO-registered, systematic review and meta-analysis of studies that included patients with AIS and a baseline LIC treated with MT, reported ischemic core volume quantitatively, and included patients with a LIC defined as a core volume ≥50 mL. The search was restricted to studies published between January 2015 and June 2020. Random-effects-meta-analysis was used to assess the effect of MT on 90-day unfavorable outcome (i.e., modified Rankin Scale [mRS] 3-6), mortality, and symptomatic intracranial hemorrhage (sICH) occurrence. Sensitivity analyses were performed for imaging-modality (computed tomography-perfusion or magnetic resonance-diffusion weighted imaging) and LIC-definition (≥50 or ≥70 mL). We analyzed 10 studies (954 patients), including six (682 patients) with a control group, allowing to compare 332 patients with MT to 350 who received best-medical-management alone. Overall, after MT the rate of patients with mRS 3-6 at 90 days was 74% (99% confidence interval [CI], 67 to 84; Z-value=7.04; I2=92.3%) and the rate of 90-day mortality was 36% (99% CI, 33 to 40; Z-value=-7.07; I2=74.5). Receiving MT was associated with a significant decrease in mRS 3-6 odds ratio (OR) 0.19 (99% CI, 0.11 to 0.33; P<0.01; Z-value=-5.92; I2=62.56) and in mortality OR 0.60 (99% CI, 0.34 to 1.06; P=0.02; Z-value=-2.30; I2=58.72). Treatment group did not influence the proportion of patients experiencing sICH, OR 0.96 (99% CI, 0.2 to 1.49; P=0.54; Z-value=-0.63; I2=64.74). Neither imaging modality for core assessment, nor LIC definition influenced the aggregated outcomes. Using aggregate estimates, MT appeared to decrease the risk of unfavorable functional outcome in patients with a LIC assessed volumetrically at baseline.

Objective: To determine whether the association between increasing number of clot retrieval attempts (CRA) and unfavorable outcome is due to an increase in emboli to new territory (ENT) and greater infarct growth (IG) in successfully recanalized patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO)., Methods: Data were extracted from 2 pooled multicentric prospective registries of consecutive patients with anterior AIS-LVO treated with mechanical thrombectomy (MT) between January 2016 and 2019. Patients with pretreatment and 24-hour posttreatment diffusion-weighted imaging (DWI) achieving successful recanalization, defined as expanded Thrombolysis in Cerebral Infarction Scale score of 2B, 2C, or 3, were included. ENT were assessed and IG was measured by voxel-based segmentation after DWI coregistration. Associations between number of CRA, ENT, IG, and 3-month outcome were analyzed., Results: Four hundred nineteen patients achieving successful recanalization were included. ENT occurrence was strongly correlated with increasing CRA (ρ = 0.73, p = 10 -4 ). In multivariable linear analysis, IG was independently associated with CRA (β = 1.6 per retrieval attempt, 95% confidence interval [CI] 0.97-9.74, p = 0.03) and ENT (β = 2.7 [95% CI 1.21-4.1], p = 0.03). Unfavorable functional outcome (3-month modified Rankin Scale score >2) increased with each additional CRA. IG was an independent predictor of unfavorable outcome (odds ratio 1.05 [95% CI 1.02-1.07] per 1-mL IG increase, p = 10 -4 ) in binary logistic regression analysis., Conclusions: Increasing number of CRA in acute stroke is correlated with an increased ENT rate and increased IG volume, affecting functional outcome even when successful recanalization is achieved., Classification of Evidence: This study provides Class II evidence that, for patients with acute stroke undergoing successful recanalization, an increasing number of CRA is associated with poorer functional outcome., (© 2021 American Academy of Neurology.)