Importance:Evidence regarding efficacy and safety of thrombectomy in acute ischemic stroke (AIS) due to medium or distal vessel occlusions (MDVOs) is lacking. Objective:To evaluate the benefit of thrombectomy, in addition to medical treatment over medical treatment alone, in patients with an AIS related to a primary and isolated MDVO. Design, Setting, and Participants:Randomized clinical trial conducted at 22 stroke centers in France from November 2021 to April 2025, with planned enrollment of 488 patients. The trial has been stopped after the planned interim analysis on the recommendation of the data and safety monitoring board for futility and increased rate of symptomatic intracranial hemorrhage with thrombectomy. Eligible adult patients had an AIS due to a primary MDVO within 8 hours of symptom onset or within 24 hours of last seen well if no hyperintense signal was present on fluid-attenuated inversion recovery imaging. Intervention:Thrombectomy in addition to medical treatment (n = 123) or medical treatment alone (n = 121). Main Outcomes and Measures:The primary end point was a good clinical outcome at 3 months, defined as a modified Rankin Scale score of 0 to 2, assessed by an independent, blinded assessor. Secondary end points included mortality rate at 3 months and adverse and serious adverse events. Results:Of the 244 patients randomized (median age, 75 years [IQR, 67-81]; 56% male; median National Institutes of Health Stroke Scale score, 8 [IQR, 6-12]), 100 of the 123 patients in the thrombectomy group (81%) received thrombectomy and none of the 121 patients in the control group received thrombectomy; 217 (89%) completed follow-up. At 3 months, 72 of 116 patients (62%) in the thrombectomy group had a good clinical outcome vs 81 of 119 patients (68%) in the control group (odds ratio, 0.73 [95% CI, 0.40-1.31]; P = .29; adjusted absolute difference, -6.8% [95% CI, -19.4% to 5.7%]). The incidence of symptomatic intracranial hemorrhages was higher among the 100 patients who actually received thrombectomy than in those who did not (11% vs 3%, P = .008), as was incidence of subarachnoid hemorrhages (13% vs 2%, P < .001) and embolus migration (5% vs 1%, P = .04). Mortality rate did not significantly differ between the 2 groups (6% vs 8%; P = .49). Conclusions and Relevance:Thrombectomy did not lead to a higher rate of good clinical outcome at 3 months compared with medical treatment alone in patients with acute ischemic stroke related to an MDVO. Hemorrhagic complications were more frequent after thrombectomy. Trial Registration:ClinicalTrials.gov Identifier: NCT05030142.

Abstract Background and aims In acute ischemic stroke due to large-vessel occlusion (AIS-LVO) with a large ischemic core identified at primary stroke centers (PSC) -without rapid access to endovascular therapy (EVT)-, it remains uncertain whether EVT improves functional outcomes over medical management (MM). Methods We performed a post-hoc analysis of the LASTE randomized controlled trial, which compared MM plus EVT and MM alone in anterior circulation AIS-LVO patients with a large ischemic core (ASPECTS 0-5) treated within 6.5 hours of last seen well. This analysis included patients whose baseline imaging was obtained at a PSC and already demonstrated an ASPECTS of 0-5, before inter-hospital transfer. The primary outcome was functional outcome at 3 months, assessed using the modified Rankin Scale (mRS). Results Among the 333 patients enrolled in LASTE, 157 were included in this analysis; 80 received MM alone and 77 underwent EVT plus MM. Median age was 73 years, NIHSS score 20, and symptoms onset-to-PSC imaging time 120 minutes. PSC imaging was MRI in 99% of cases, showing ASPECTS 0-2 in 56% and 3-5 in 44%. Median time from PSC imaging to comprehensive center admission was 145 minutes. EVT resulted in better functional outcomes than MM alone (generalized odds ratio, 1.71; 95%CI 1.21-2.41; P = 0.002). Death at 3-month (relative risk, 0.73; 95%CI 0.50-1.05; P = 0.08) and symptomatic hemorrhagic transformation (relative risk, 1.85; 95%CI 0.64-5.26; P = 0.24) was similar across groups. Conclusions These findings support consideration of inter-hospital transfer for EVT in AIS-LVO patients with a large ischemic core admitted in PSC in the early time-window. Conflict of interest The authors have nothing to disclose.

OBJECTIVE:Brain-predicted age difference (BrainAGE) is a neuroimaging biomarker reflecting brain health, with potential implications for post-stroke recovery. However, training robust BrainAGE models requires large, diverse datasets, often restricted by privacy and regulatory concerns. This study evaluates the performance of federated learning (FL) for BrainAGE estimation in ischemic stroke patients treated with mechanical thrombectomy, and investigates its association with clinical phenotypes and functional outcome. METHODS:We used pre-treatment FLAIR brain images from 1674 stroke patients across 16 hospital centers. We implemented standard machine learning and deep learning models for BrainAGE estimates under three data management strategies: centralized learning (pooled data), FL (local training at each site), and single-site learning. We reported prediction errors and examined associations between BrainAGE and vascular risk factors (e.g., diabetes mellitus, hypertension, smoking), as well as functional outcome at three months post-stroke. Logistic regression evaluated BrainAGE's predictive value for this outcome, adjusting for age, sex, vascular risk factors, stroke severity, time between MRI and arterial puncture, prior intravenous thrombolysis, and recanalization outcome. RESULTS:While centralized learning yielded the most accurate predictions, FL consistently outperformed single-site models. BrainAGE was significantly higher in patients with diabetes mellitus across all models. Comparisons between patients with good and poor functional outcome, and multivariate predictions of these outcome showed the significance of the association between BrainAGE and post-stroke recovery. CONCLUSION:FL enables accurate age predictions without data centralization. The strong association between BrainAGE, vascular risk factors, and post-stroke recovery highlights its potential for personalized prognostic modeling in stroke care.

Background and Purpose Whether perfusion-diffusion mismatch modifies treatment effect of mechanical thrombectomy (MT) for large strokes is poorly known. To address this question, we conducted a post hoc secondary analysis of the Large Stroke Therapy Evaluation (LASTE) randomized controlled trial (RCT). Methods The LASTE RCT compared MT plus best medical treatment (BMT) to BMT alone in patients with large infarct (Alberta Stroke Program Early CT Score 0–5) in the 0–7-hour timewindow. This secondary analysis was restricted to patients with available baseline MR perfusionweighted imaging. We investigated the potential heterogeneity of MT treatment according to the presence of perfusion-diffusion mismatch, defined as a mismatch ratio ≥1.2, calculated as the time-to-maximum >6 seconds cerebral volume divided by ischemic core volume. The primary outcome was better functional outcome (favorable shift in the distribution of modified Rankin Scale [mRS] at 90 days, analyzed using generalized odds ratio [GenOR]). Results A total of 102/324 patients were included, among whom 55 (54%) had a perfusiondiffusion mismatch. No significant treatment effect heterogeneity by diffusion-perfusion mismatch was observed for the primary outcome (GenOR for better functional outcome: 1.70 [95% confidence interval, CI, 0.95 to 3.05] and 1.04 [95% CI, 0.57 to 1.87] in patients with and without mismatch, respectively; ratio of GenORs: 1.63 [95% CI, 0.71 to 3.74]; P for heterogeneity=0.24) or for the secondary efficacy and safety outcomes. Conclusions Our study found no evidence of heterogeneity of treatment effect with respect to benefit or safety in patients with unrestricted infarct size at baseline treated with MT by presence of perfusion-diffusion mismatch. An individual participant-data meta-analysis of RCT is needed for definitive conclusions.

BACKGROUND:Comparative data on tenecteplase versus alteplase in patients aged ≥80 years undergoing bridging therapy before thrombectomy are limited. METHODS:We retrospectively analyzed two prospective cohorts of patients aged ≥80 years with anterior circulation large-vessel occlusion treated with bridging intravenous thrombolysis: the multicenter TETRIS registry (tenecteplase) and a single comprehensive stroke center (alteplase). Propensity score matching (1:1, 11 covariates, caliper 0.2 SD logit) was performed, with overlap weighting as sensitivity analysis; matched dichotomous outcomes were analyzed by conditional logistic regression and generalized estimating equations clustered on the matched pair. Because treatment was completely confounded with center and data source, analyses compare cohorts rather than isolate a drug effect. The primary outcome was modified Rankin Scale (mRS) ≤3 at 90 days. Secondary outcomes included substantial early neurological improvement (ENI: ≥8-point NIHSS improvement or NIHSS ≤1 at 24 h), complete early neurological recovery (NIHSS = 0 at 24 h), early reperfusion (eTICI 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS:Among 720 eligible patients, 278 matched pairs were analyzed. The primary outcome (mRS ≤3) occurred in 48.0% of tenecteplase- versus 43.5% of alteplase-treated patients (OR 1.20, 95% CI 0.86-1.67); an excellent outcome (mRS 0-2: 27.6% vs 27.0%), the ordinal mRS shift (common OR 1.06), early reperfusion (16.9% vs 16.5%), substantial ENI (40.2% vs 34.9%), sICH (3.7% vs 4.4%), and 90-day mortality (30.2% vs 30.2%) did not differ. Complete early neurological recovery (NIHSS = 0 at 24 h) was more frequent with tenecteplase (10.3% vs 2.6%; OR ≈4.3), but this difference was confined to the single NIHSS value 0, reversed at NIHSS = 1, left no trace in any 90-day endpoint, and was nullified by modest unmeasured confounding (E-value for the lower confidence bound ≈2-3). CONCLUSIONS:In patients aged ≥80 years undergoing bridging therapy, tenecteplase and alteplase were associated with similar 90-day functional outcomes and similar safety. An isolated 24-hour complete-recovery signal favoring tenecteplase is hypothesis-generating and vulnerable to ascertainment bias, given complete confounding of treatment with center. Dedicated randomized data in this age group are warranted.

BACKGROUND:Intra-arterial thrombolysis (IAT) following successful mechanical thrombectomy (MT) in patients with anterior circulation large-vessel occlusion (LVO) improves cerebral tissue reperfusion and consequently clinical outcome, but has to be validated in non-Asian populations. We hypothesised that IAT with alteplase versus no IAT leads to a better clinical outcome in patients with anterior circulation LVO stroke who have successful angiographic recanalisation. STUDY DESIGN:Intra-Arterial thrombolysis after SUCCESSful angiographic recanalization in acute large-vessel occlusion stroke of the anterior circulation (IA-SUCCESS) trial is a phase 3 investigator-initiated, multicentre, randomised, open-label, blinded-endpoint (PROBE) clinical trial with a health economic evaluation conducted in France. Patients with acute ischaemic stroke due to anterior circulation LVO within 24 h of stroke onset and successful angiographic reperfusion (defined as extended Thrombolysis in Cerebral Infarction score 2b-3) after intravenous thrombolysis alone, MT alone or both will be randomised in two balanced parallel groups (1:1) to receive either IAT with alteplase (0.225 mg kg-1 and a maximum of 20 mg) injected in the ipsilateral internal carotid artery or no IAT. A total of 626 patients will be included. STUDY ENDPOINTS:The primary outcome is the functional outcome on the modified Rankin Scale at 90 (±15) days. Standard secondary clinical outcomes are assessed at 24 (±6) h, 5-7 days, 90 (±15) days and 12 (±1) months. Safety outcomes include mortality at 90 (±15) days and intracranial haemorrhage. SUMMARY:The IA-SUCCESS trial will provide high-quality randomised data on the clinical efficacy and safety of intra-arterial alteplase following successful angiographic recanalisation in European patients with ischaemic stroke due to anterior circulation LVO intended for MT. TRIAL REGISTRATION:ClinicalTrials.gov NCT06768138.

BACKGROUND:Endovascular thrombectomy (EVT) has demonstrated benefits in patients with ischemic stroke and large-vessel occlusions, but its efficacy and safety in patients with the largest baseline infarcts (Alberta Stroke Program Early Computed Tomography Score [ASPECTS] 0-2), remain controversial. This study aimed to evaluate the efficacy and safety of EVT in early presenting patients with ASPECTS 0 to 2 compared with medical care alone. METHODS:This post hoc analysis of the multicenter, randomized LASTE trial ([Large Stroke Therapy Evaluation]; patients ≤80 years, ASPECTS 0-5, proximal anterior circulation large-vessel occlusion, randomization within 6.5 hours of last known well) evaluated the subgroup with ASPECTS 0 to 2, representing those with large baseline infarcts without an upper size limit, randomized to receive EVT plus medical care or medical care alone. Primary outcomes included the distribution of the modified Rankin Scale score at 90 days. Secondary outcomes included mortality, infarct volume growth at 24 hours, the incidence of symptomatic intracranial hemorrhage and modified Rankin Scale score at 180 days. The LASTE trial was conducted and reported in accordance with the CONSORT guidelines (Consolidated Standards of Reporting Trials). RESULTS:Median age was 72 years and 55.8% were women. Among the 181 patients with ASPECTS 0 to 2 (median core volume 156 mL [25th-75th percentiles, 121-204 mL]), at 90 days after randomization, EVT improved functional outcomes (generalized odds ratio, 1.81 [95% CI, 1.32-2.47]) and reduced mortality (38.4% versus 59.6%; relative risk, 0.64 [95% CI, 0.47-0.89]), which translated predominantly into an increase in the proportion of modified Rankin Scale score of 0 to 3 in the EVT group (31.4% versus 8.5%; relative risk, 3.69 [95% CI, 1.77-7.68]). A significant reduction in infarct growth volume was observed in the EVT group compared with medical care (mean difference, -70.3 mL [95% CI, -94.2 to -46.3]). Rates of symptomatic intracranial hemorrhage were 12.9% versus 4.5%, respectively (relative risk, 2.85 [95% CI, 0.94-8.60]). CONCLUSIONS:EVT improves functional outcomes and reduces mortality in patients with ASPECTS 0 to 2. These findings support the concept that in patients aged <80 years presenting within early time window (6.5 hours) with unlimitedly large infarct (predominantly selected using magnetic resonance imaging), the infarct size in isolation should not be used to disqualify patients from endovascular treatment. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03811769.

BACKGROUND AND PURPOSE:The optimal anesthetic regimen for the endovascular treatment (EVT) of stroke due to large-vessel occlusion remains unclear. Patients with large infarct cores on initial imaging constitute a specific subpopulation. The aim of this study was to investigate the impact of the anesthesia type during EVT on outcomes in this subpopulation. MATERIALS AND METHODS:Data were extracted from the multicenter, randomized, controlled LASTE trial (n = 30 centers in France and Spain) that compared EVT plus best medical treatment versus best medical treatment alone in patients with a large infarct core (ASPECTS = 0-5). In this post hoc analysis, only patients who underwent EVT were included. We defined 2 study groups: general anesthesia (GA) and conscious sedation and/or local anesthesia (CS-LA). The primary end point was the functional outcome, assessed with the mRS at 3 months. Secondary end points included early neurologic status, infarct extension at day 1, symptomatic intracranial hemorrhage, and mortality. End points were investigated using univariate and multivariate analyses adjusted for prespecified confounders. RESULTS:For this post hoc analysis, we included 159 patients: 45 in the GA group and 114 in the CS-LA group. The functional outcome at 3 months was not different between groups: median mRS score = 5; interquartile range [IQR]: 3-6 in the GA group and 4; IQR: 3-6 in the CS-LA group (adjusted OR =0 .78; 95% CI, 0.52-1.18). However, in the GA group, the NIHSS score significantly worsened between admission and day 1 (mean difference = -3.8 [-6.6 to -1.0]; P = .007), infarct volume extension was more severe (mean difference: -26.5 mL [-50.2 to -2.9]; P = .028), and parenchymal hematoma was more frequently detected. Between-group differences in early neurologic improvement, symptomatic intracranial hemorrhage, and mortality were not significant. CONCLUSIONS:In this post hoc analysis of the LASTE trial data, we detected potential signals of a GA detrimental effect in patients with large infarct cores on baseline imaging. Larger studies are necessary to confirm this finding.

BACKGROUND:Patients with extensive ischaemic change are often excluded from endovascular thrombectomy. We aimed to synthesise the evidence from recent trials in these patients by performing a systematic review and individual patient data meta-analysis to estimate treatment benefit, including within clinical and imaging subgroups. METHODS:In this systematic review and meta-analysis, we searched PubMed and Embase for randomised trials published between March 1, 2018, and March 1, 2025, that evaluated efficacy and safety of endovascular thrombectomy compared with medical management in patients with large-core ischaemic stroke (based on an Alberta Stroke Program Early CT Score [ASPECTS] of ≤5 or estimated ischaemic core ≥50 mL) presenting within 24 h of onset. Individual patient-level data from all eligible trials were obtained. A central imaging core laboratory readjudicated ASPECTS and reanalysed ischaemic core volume. A two-stage meta-analysis with random-effects model was used to evaluate the distribution of 90-day modified Rankin Scale (mRS) scores (the primary outcome) using adjusted pooled generalised odds ratios (aGenORs). Missing data were handled by multiple imputation. Safety outcomes were all-cause mortality within 90-day follow-up and neurological worsening within 24-48 h of randomisation, reported as adjusted pooled relative risk (aRR); and symptomatic intracerebral haemorrhage within 36 h of randomisation (reported as risk difference). Subgroup analyses based on clinical and imaging characteristics were done, including subgroups defined by ischaemic core volume, ASPECTS, and time window from onset to randomisation. The meta-analysis was registered with PROSPERO (CRD420251058584). FINDINGS:We included 1886 patients (944 assigned to endovascular thrombectomy and 942 assigned to medical management) from six trials. Baseline characteristics were similar between treatment groups. At day 90, the distribution of mRS scores was improved in patients in the endovascular thrombectomy group (median score 4 [IQR 3-6]; n=940) versus those in the medical management group (5 [4-6]; n=931; aGenOR 1·63 [95% CI 1·42-1·88], p<0·0001). The endovascular thrombectomy group also had reduced mortality (292 [31·1%]) compared with the medical management group (347 [37·3%]; aRR 0·82 [95% CI 0·70-0·97], p=0·022). No significant differences were observed in symptomatic intracranial haemorrhage (ten [1·1%] of 944 vs nine [1·0%] of 942 patients; pooled unadjusted risk difference -0·17 percentage points [95% CI -1·01 to 0·67], p=0·69) or neurological worsening (197 [22·0%] of 896 patients vs 161 [17·9%] of 899; aRR 1·19 [0·87-1·62], p=0·27). Improved functional outcomes with endovascular thrombectomy were consistent across clinical and imaging subgroups, except for those with an estimated ischaemic core volume of 150 mL or greater, in whom point estimates favoured endovascular thrombectomy, particularly in the early time window (0-6 h), but wide 95% CIs limited interpretation. INTERPRETATION:Endovascular thrombectomy was associated with improved functional outcomes and reduced mortality versus medical management in patients with large-core ischaemic stroke presenting within 24 h of onset. With the exception of very extensive ischaemic changes (core volume ≥150 mL) presenting beyond 6 h, where evidence remains limited, benefit was sustained across ASPECTS and ischaemic core strata for patients presenting up to 24 h after onset. FUNDING:None.

Accurate delineation of acute ischemic stroke lesions in MRI is a key component of stroke diagnosis and management. In recent years, deep learning models have been successfully applied to the automatic segmentation of such lesions. While most proposed architectures are based on the U-Net framework, they primarily differ in their choice of loss functions and in the use of deep supervision, residual connections, and attention mechanisms. Moreover, many implementations are not publicly available, and the optimal configuration for acute ischemic stroke (AIS) lesion segmentation remains unclear. In this work, we introduce ISLA (Ischemic Stroke Lesion Analyzer), a new deep learning model for AIS lesion segmentation from diffusion MRI, trained on three multicenter databases totaling more than 1500 AIS participants. Through systematic optimization of the loss function, convolutional architecture, deep supervision, and attention mechanisms, we developed a robust segmentation framework. We further investigated unsupervised domain adaptation to improve generalization to an external clinical dataset. ISLA outperformed two state-of-the-art approaches for AIS lesion segmentation on an external test set. Codes and trained models will be made publicly available to facilitate reuse and reproducibility.

BACKGROUND:Endovascular thrombectomy (EVT) is now the standard treatment for patients with large cerebral infarcts. However, the benefit of intravenous thrombolysis before EVT (IVT+EVT) in this setting is uncertain. METHODS:We conducted a post hoc analysis of the Large Stroke Therapy Evaluation (LASTE) trial, which randomized patients with large infarcts (Alberta stroke program early CT score (ASPECTS) ≤5) to EVT plus medical care or medical care alone. Among those assigned to EVT, patients were divided into two groups: IVT+EVT and EVT alone. The main outcome was the shift analysis of the 3 month modified Rankin Scale (mRS) score. Safety outcomes included parenchymal hemorrhage (PH) and symptomatic intracranial hemorrhage (sICH). RESULTS:Among 159 patients allocated to EVT, 55 received IVT+EVT and 104 EVT alone. Patients in the IVT+EVT group had lower National Institutes of Health Stroke Scale (NIHSS) scores (median 19 (IQR 17-22) vs 22, (19-24) p=0.003), were less often anticoagulated (3.6% vs 27.9%, p<0.001) and shorter onset-to-imaging time (median 148 (91-280) vs 200 (123-311); P=0.024). Both groups had similar rates of ASPECTS 0-2 (50.9% vs 55.8%; P=0.56). There was no significant difference in 3 month functional outcome between IVT+EVT and EVT alone (generalized OR 1.22 (95% CI 0.85 to 1.74); P=0.28) or sICH (RR 1.72 (95% CI 0.65 to 4.48); P=0.27). Pre-EVT recanalization was higher in the IVT+EVT group (RR 15.1 (95% CI 1.9 to 117.9); P<0.001). Mortality rates did not differ significantly. DISCUSSION:In patients with very large infarcts, IVT+EVT was not associated with better functional outcome than EVT alone, despite higher pre-EVT recanalization rates. Safety outcomes were comparable. Randomized trials are warranted to clarify the role of IVT in this high-risk population. TRIAL REGISTRATION NUMBER:NCT03811769.

INTRODUCTION:Acute ischaemic strokes (AIS) due to proximal anterior cerebral artery (ACA) occlusions are rare. Their clinical outcomes following medical management alone have been scarcely described. PATIENTS AND METHODS:We conducted a retrospective, multicentre, international study of consecutive AIS due to isolated proximal ACA occlusion (A1 or A2 segment) admitted within 6 h of symptom onset and treated with best medical management alone (ie, without endovascular therapy), across 23 centres in France and Switzerland. The primary outcome was poor functional outcome, defined as a mRS score > 2 at 3 months or failure to return to baseline mRS if the pre-stroke mRS was > 2. Associations between baseline clinical/radiological variables and outcome were evaluated in multivariable logistic regression analyses. Associations between outcome and key radiological follow-up variables such as recanalisation and haemorrhagic transformation were also analysed. RESULTS:Ninety-five patients were included in the study: median age was 76 (IQR, 66-87), baseline NIHSS score was 10 (IQR, 5-15) and occlusion site was A1 in 8 (8%) and A2 in 87 (92%). Intravenous thrombolysis was administered in 76 (80%) cases. Poor functional outcome was observed in 47 (49%) patients. Among baseline variables, older age (adjusted odds ratio [aOR] per 5-year increase = 1.25; 95% CI, 1.10-1.55; P = .028) and higher NIHSS score (aOR = 1.20, 95% CI, 1.07-1.34; P < .001) were independently associated with poor outcome. Lack of recanalisation at 24 h was also independently associated with poor outcome (aOR = 14.5, 95% CI, 1.1-188.7, P = .04). Poor outcome was higher in patients with than in those without haemorrhagic transformation (73% vs 42%, P = .03) in univariable analysis, but not in multivariable analysis adjusting for age and NIHSS score (aOR = 2.3, 95% CI, 0.5-11.5, P = .32). DISCUSSION AND CONCLUSION:Nearly half of AIS patients with isolated proximal ACA occlusion treated with medical management alone had poor 3-month functional outcomes. Older age, high NIHSS at admission and lack of recanalisation at 24 h were associated with poor outcome. These results underscore the need to investigate therapeutic strategies aimed at enhancing early arterial recanalisation to improve recovery in this population.

Importance:In patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), the benefit of intravenous thrombolysis (IVT) administered beyond 4.5 hours from the last time known well before endovascular therapy (EVT) is uncertain. Recently, the TIMELESS trial failed to demonstrate a benefit of IVT in this setting, but this trial focused on patients directly admitted to comprehensive stroke centers (CSCs) with fast access to EVT. Objective:To assess the efficacy and safety of IVT initiated beyond 4.5 hours in patients with AIS-LVO initially admitted to primary stroke centers (PSCs) and subsequently transferred to a CSC for EVT, allowing substantial time for the IVT to take effect. Design, Setting, and Participants:This multicenter retrospective cohort study was conducted between January 2020 and December 2024, with 3-month follow-up, at 20 French PSCs. All consecutive patients with AIS-LVO admitted beyond 4.5 hours from the last time they were known well in the PSC and subsequently transferred to a CSC for EVT, with or without IVT administered prior to transfer, were eligible for inclusion. Data analysis was performed between May 2025 and July 2025. Main Outcomes and Measures:The primary outcome was the 3-month modified Rankin Scale score, analyzed in the ordinal approach. Propensity score with overlap weighting (PSOW) balanced covariates between patients treated with IVT vs those without. Results:A total of 584 patients were included, among whom 309 patients (52.9%) were female. Median (IQR) age was 71 (61-81) years, median (IQR) baseline National Institutes of Health Stroke scale score was 15 (10-19), median (IQR) time from last known well to PSC imaging was 10.5 (6.9-14.0) hours, and 232 patients (39.7%) received IVT before transfer. Advanced brain imaging (magnetic resonance imaging or computed tomography [CT] with CT-perfusion) was performed at the PSC in 544 patients (93.2%). IVT use before transfer was independently associated with a shift toward better 3-month outcomes (PSOW-common odds ratio [OR], 1.97; 95% CI, 1.33-2.92; P = .001) and higher odds of recanalization during transfer (PSOW-OR, 8.69; 95% CI, 3.16-23.87; P < .001) compared with those without. The rate of any intracerebral hemorrhage and symptomatic intracerebral hemorrhage were similar between groups. Conclusions and Relevance:In this multicenter cohort study, IVT initiated beyond 4.5 hours prior to interhospital transfer for EVT was associated with higher rates of recanalization during transfer and improved 3-month functional outcomes, without safety concerns. These findings offer encouraging support for clinical trials evaluating IVT in the late time window before interhospital transfer.

Importance Evidence regarding efficacy and safety of thrombectomy in acute ischemic stroke (AIS) due to medium or distal vessel occlusions (MDVOs) is lacking. Objective To evaluate the benefit of thrombectomy, in addition to medical treatment over medical treatment alone, in patients with an AIS related to a primary and isolated MDVO. Design, Setting, and Participants Randomized clinical trial conducted at 22 stroke centers in France from November 2021 to April 2025, with planned enrollment of 488 patients. The trial has been stopped after the planned interim analysis on the recommendation of the data and safety monitoring board for futility and increased rate of symptomatic intracranial hemorrhage with thrombectomy. Eligible adult patients had an AIS due to a primary MDVO within 8 hours of symptom onset or within 24 hours of last seen well if no hyperintense signal was present on fluid-attenuated inversion recovery imaging. Intervention Thrombectomy in addition to medical treatment (n = 123) or medical treatment alone (n = 121). Main Outcomes and Measures The primary end point was a good clinical outcome at 3 months, defined as a modified Rankin Scale score of 0 to 2, assessed by an independent, blinded assessor. Secondary end points included mortality rate at 3 months and adverse and serious adverse events. Results Of the 244 patients randomized (median age, 75 years [IQR, 67-81]; 56% male; median National Institutes of Health Stroke Scale score, 8 [IQR, 6-12]), 100 of the 123 patients in the thrombectomy group (81%) received thrombectomy and none of the 121 patients in the control group received thrombectomy; 217 (89%) completed follow-up. At 3 months, 72 of 116 patients (62%) in the thrombectomy group had a good clinical outcome vs 81 of 119 patients (68%) in the control group (odds ratio, 0.73 [95% CI, 0.40-1.31]; P = .29; adjusted absolute difference, −6.8% [95% CI, −19.4% to 5.7%]). The incidence of symptomatic intracranial hemorrhages was higher among the 100 patients who actually received thrombectomy than in those who did not (11% vs 3%, P = .008), as was incidence of subarachnoid hemorrhages (13% vs 2%, P < .001) and embolus migration (5% vs 1%, P = .04). Mortality rate did not significantly differ between the 2 groups (6% vs 8%; P = .49). Conclusions and Relevance Thrombectomy did not lead to a higher rate of good clinical outcome at 3 months compared with medical treatment alone in patients with acute ischemic stroke related to an MDVO. Hemorrhagic complications were more frequent after thrombectomy. Trial Registration ClinicalTrials.gov Identifier: NCT05030142

Over a third of minor stroke patients experience post-stroke cognitive impairment (PSCI), but no validated tools exist to identify at-risk patients early. This study investigated whether disconnection features derived from infarcts and white matter hyperintensities (WMH) could serve as markers for short- and long-term cognitive decline in first-ever minor ischemic stroke patients. First-ever minor ischemic stroke patients (NIHSS ≤ 7) were prospectively followed at 72-h, 6 months, and 36 months post-stroke with cognitive tests and brain MRI. Infarct and WMH volumes were semi-automatically assessed on DWI and FLAIR sequences. Bayesian tract-based disconnection models estimated remote pathological effects of infarcts and WMH. Associations between disconnection features and cognitive outcomes were analyzed using canonical correlation analyses, adjusted for age, education, and multiple comparisons. Among 105 patients (31% female, mean age 63 ± 12 years), infarct volume averaged 10.28 ± 17.10 cm 3 and predominantly involved the middle cerebral artery territory (83%). WMH burden was higher in frontal periventricular white matter. Infarct-based features did not significantly relate to PCSI. However, a WMH-derived disconnection factor, involving commissural and frontal tracts, and the right superior longitudinal fasciculus, was significantly associated with PSCI at 6 months (OR = 9.96, p value = 0.02) and 36 months (OR = 12.27, p value = 0.006), particularly in executive/attention, language, and visuospatial domains. This factor, unrelated to WMH volume, outperformed demographic and clinical predictors of PSCI. WMH-induced disconnection may be associated with short- and long-term PSCI in minor stroke. Routine MR-derived features could identify at-risk patients for rehabilitation trials.

BACKGROUND:Management of large cerebellar infarctions with potential malignant evolution is highly heterogeneous across physicians, and recommendations rely on low-evidence studies. AIM:We aimed to perform a systematic review and meta-analysis on patients with large cerebellar infarction undergoing neurosurgery, to study mortality and functional outcome, according to neurosurgical technique. SUMMARY OF REVIEW:We searched on PubMed and Embase according to pre-defined selection criteria and we assessed their quality according to a predefined risk of bias scale. Our primary outcomes were mortality and functional outcome rates. Favorable outcome was defined as a modified Rankin scale of 0-2, a Glasgow Outcome Scale of 4-5, or a Barthel Index > 90%. Pooled rates were obtained using random effect model and heterogeneity was quantified using I2 statistics. Among 27 included studies (including 1173 patients), we studied the 662 patients undergoing neurosurgery. All studies were retrospective and observational; there was no randomized clinical trial (RCT). The median selection bias score was 5 (IQR, 4-6). Mortality rate was estimated at 18% [95% CI, 13-24%], I2 58%. Among survivors, 64% achieved a favorable functional outcome [95% CI, 51-77%], I2 82%. Study design and heterogeneity in patients' characteristics limited a meaningful comparison of mortality and functional outcome according to neurosurgical techniques. CONCLUSION:High-quality evidence on neurosurgical treatment for large cerebellar infarctions remains limited. Our systematic review and meta-analysis, despite moderate risk of bias, suggest that neurosurgery may reduce mortality and improve functional outcomes. These findings support its potential benefit, but RCTs are needed to confirm effectiveness and evaluate best surgical technique.

BACKGROUND AND OBJECTIVES:Cerebrovascular reserve (CVR) is a key physiological mechanism allowing the brain to adapt to fluctuating perfusion, particularly relevant in the management of neurovascular disorders such as idiopathic (iMM) and syndromic moyamoya (sMM). Although 99m Tc-HMPAO SPECT with acetazolamide is commonly used for CVR assessment, it faces limitations including low spatial resolution, artifacts, and variability in interpretation. This study primarily aims to evaluate a novel, semiautomated, and more objective method for interpreting HMPAO SPECT in CVR assessment. As a secondary objective, the method is applied to a cohort of patients who underwent revascularization surgery for iMM or sMM. METHODS:A retrospective analysis was performed on prospectively collected data from a tertiary neuroscience center, including 20 adult patients with iMM (n = 9) or sMM (n = 11). Clinical and imaging data were reviewed. 99m Tc-HMPAO SPECT images were assessed independently by 2 nuclear medicine physicians blinded to clinical details. Images were registered to T1-weighted MRI and overlaid with an arterial territory atlas. Territories classified as healthy by experts were defined as true negatives; all others as altered. Statistical comparisons were made using Student's t-tests with false discovery rate correction. RESULTS:Among the 20 patients (12 females), patients with sMM were older and had more cardiovascular risk factors. The proposed method significantly discriminated between altered and healthy perfusion territories. Compared with expert interpretation, the method demonstrated specificities of 93% (iMM) and 92% (sMM), with negative predictive values of 80% and 75%%, respectively. CONCLUSION:Although 99m Tc-HMPAO remains a validated modality for CVR assessment, its interpretation is operator-dependent. The proposed semiautomated method offers high specificity and greater objectivity, supporting its integration into clinical workflows. Further multicenter validation is warranted.

BACKGROUND:Whether perfusion 'mismatch' modifies the effect of endovascular thrombectomy (EVT) in patients with large core ischemic stroke remains uncertain. METHODS:We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review and meta-analysis of randomized controlled trials (RCTs) enrolling patients with large infarcts and reporting outcomes by perfusion mismatch status, defined as a mismatch ratio ≥1.2 and a mismatch volume ≥10 mL. A Mantel-Haenszel fixed-effect model was used to pool ORs for three 90-day outcomes: independent ambulation (modified Rankin Scale (mRS) score 0-3, primary outcome), good outcome (mRS score 0-2), severe disability or death (mRS score 5-6). We tested for interaction to assess whether the effect of thrombectomy differed according to mismatch status. RESULTS:Three RCTs met the inclusion criteria, totaling 863 patients, of whom 113 (13%) had no perfusion mismatch (47% from LASTE). There was no significant interaction between mismatch status and EVT efficacy across any of the outcomes. In the mismatch subgroup, EVT significantly improved outcomes compared with medical therapy (mRS 0-3: OR=2.14, 95% CI 1.57 to 2.90; mRS score 0-2: OR=3.22, 95% CI 2.14 to 4.85; mRS score 5-6: OR=0.66, 95% CI 0.50 to 0.89; all I² = 0%). In the no-mismatch subgroup, OR values were not significant for both mRS score 0-3 (OR=2.32, 95% CI 0.84 to 6.38) and mRS score 5-6 (OR=0.73, 95% CI 0.34 to 1.57); OR for mRS score 0-2 was neutral (OR=1.00, 95% CI 0.15 to 6.55). CONCLUSIONS:No interaction was found between mismatch status and EVT effect. However, in patients without mismatch, effect estimates were non-significant for EVT. Additional data are needed to better assess treatment benefit in this subgroup.

BACKGROUND AND OBJECTIVES:There is uncertainty about whether patients with an anterior circulation large vessel occlusion (LVO) and a low NIH Stroke Scale (NIHSS) score (≤5) benefit from endovascular therapy (EVT) in the late time window (6-24 hours). We compared the clinical outcomes of these patients receiving EVT with those receiving medical management (MM). METHODS:The CT for Late Endovascular Reperfusion multinational cohort study was conducted at 66 sites across 10 countries from January 2014 to May 2022. This subanalysis included consecutive patients with late-window stroke due to an anterior circulation LVO, defined as occlusion of the internal carotid artery or proximal middle cerebral artery (M1/M2 segments), and a baseline NIHSS score ≤5 who received EVT or MM alone. The primary end point was a 90-day ordinal shift in the modified Rankin Scale (mRS) score. Secondary outcomes were 90-day excellent outcome (defined as mRS scores 0-1 or return to baseline mRS score in patients with a prestroke mRS score >1) and favorable outcome (defined as mRS scores 0-2 or return to baseline mRS score in patients with prestroke mRS score >2). Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. We used ordinal and binary logistic regression models to test for outcome differences. RESULTS:Among 5,098 patients, 318 patients were included (median [interquartile range] age 67 [56-76] years; 149 [46.9%] were female; baseline NIHSS score was 4 [2-5]). A total of 202 patients (63.5%) received EVT and 116 MM (36.5%). There was no difference in favorable 90-day ordinal mRS score shift (adjusted common odds ratio [OR] 0.77, 95% CI 0.45-1.32), excellent outcome (adjusted OR 0.86, 95% CI 0.49-1.50), or favorable outcome (adjusted OR 0.72, 95% CI 0.35-1.50) in the EVT group compared with MM. Symptomatic intracranial hemorrhage risk (adjusted OR 3.40, 95% CI 0.84-13.73) and mortality at 90 days (adjusted OR 2.44, 95% CI 0.60-10.02) were not statistically different between treatment groups. DISCUSSION:In patients with an anterior LVO and low NIHSS score in the 6-24-hour time window, there was no statistical difference in disability outcomes or intracranial bleeding risk between patients treated with EVT compared with MM. The retrospective and observational design limits our findings. Ongoing randomized controlled trials will provide further insight. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that in adult patients with anterior circulation LVO and low NIHSS score (≤5) presenting in the late time window (6-24 hours), EVT does not improve clinical outcome vs MM. TRIAL REGISTRATION:This study was registered at clinicaltrials.gov under NCT04096248.

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.