BACKGROUND:Direct transfer to angiography suite (DTAS) for patients with suspected stroke primarily admitted to an endovascular-capable centre could accelerate in-hospital workflow and improve outcome. We aimed to assess the safety and efficacy of DTAS for patients with acute severe neurological deficit highly suggestive of ischaemic stroke due to a large vessel occlusion (ASND-LVO). METHODS:We did an open-label, multicentre, randomised controlled trial in ten comprehensive stroke centres in France. We enrolled adult patients (age ≤85 years) with ASND-LVO (unilateral motor deficit with a score ≥5 plus a cortical symptom with a score ≥1 based on the National Institues of Health Stroke Scale) admitted within 5 h of symptom onset. Patients were randomly assigned (1:1) with a web-based system to DTAS or conventional pathway (ie, imaging followed by transfer to the angiography suite for endovascular treatment if eligible). The primary outcome was functional independence defined as a modified Rankin Scale score 0 to 2 at 90 days in the intention-to-treat population-ie, all randomly assigned patients in their originally assigned treatment groups, irrespective of diagnosis, imaging findings, or treatments received. Symptomatic intracranial haemorrhage and all-cause mortality at 90 days were the main safety outcomes. This study was registered on ClinicalTrials.gov (NCT03969511). FINDINGS:Between July 9, 2020, and April 18, 2023, 115 patients were randomly assigned to the DTAS group (n=57) or the conventional group (n=58). An interim analysis was done on Sept 27, 2023. The trial steering committee permanently stopped the trial on Dec 1, 2023, for safety reasons after unmasking and analysis of the data. In the intention-to-treat analysis, the risk of symptomatic intracranial haemorrhage was increased in the DTAS group compared with the conventional group (five [15%] of 34 vs zero [0%] of 42; adjusted odds ratio [OR] 11·0 [95% CI 1·28-1406]). All-cause mortality did not differ significantly between groups (ten [18%] of 56 vs six [11%] of 53; adjusted OR 1·65 [95% CI 0·52-5·55]). Functional independence was reached in 20 [36%] of 56 participants in the DTAS group vs 22 [42%] of 53 in the conventional group (adjusted OR 0·73 [95% CI 0·32-1·69]). INTERPRETATION:DTAS for patients with ASND-LVO was associated with an increased risk of symptomatic intracranial haemorrhage without evidence of a beneficial effect on functional outcome at 90 days. However, because the trial was stopped early for safety reasons, the small sample size limits the precision of the effect estimates on the primary outcome and all secondary and safety outcomes. Therefore, further clinical trials are required to firmly conclude on the safety and efficacy of DTAS for patients with suspected acute ischaemic stroke due to a large vessel occlusion. FUNDING:French Ministry of Health and Medtronic.

BACKGROUND AND OBJECTIVES:Hemorrhagic transformation (HT) remains an important issue following ischemic stroke. Efforts have been made to identify predictors of HT, especially imaging features. Among them, the infarct growth rate (IGR) remains underexplored. We investigated the influence of IGR on the risk of subsequent HT in the setting of large vessel occlusion stroke (LVOS) intended for endovascular treatment (EVT) and compared IGR to baseline infarct volume as predictors of HT. METHODS:We conducted a secondary analysis of two merged prospectively collected databases (FRAME 2017-2019 and ETIS 2015-2021). Patients presenting with anterior circulation LVOS, a witnessed symptoms onset, baseline MRI within 24 h after symptoms onset and available day 1 imaging (MRI or CT) were included. Posterior circulation LVOS, medium and distal vessel occlusions of the anterior circulation, tandem occlusions and unknown time of stroke onset were excluded. The primary endpoint was the occurrence of any HT detected on day 1 imaging. Secondary endpoint was the occurrence of parenchymal hematoma (defined as PH1 or PH2). Associations between the IGR and the occurrence of any HT and parenchymal hematoma within 24-h after mechanical thrombectomy were assessed using univariable and multivariable logistic regression models. RESULTS:We included 775 patients (mean age 70.5 years (SD 15.1)). The median of IGR was 8.7 ml per hour (IQR 2.8-24.2). A faster IGR was independently associated with a higher risk of any HT (adjusted OR 1.35; 95% CI 1.16-1.57 per one log unit increase). A faster IGR was also associated with an increased risk of parenchymal hemorrhage in univariate analysis (OR 1.35; 95% CI 1.15-1.58), but the association did not remain significant in multivariable analysis including all the other predictors of parenchymal hemorrhage (adjusted OR 1.16 (95% CI 0.96-1.40) per one log unit increase). ROC analyses revealed that baseline infarct volume significantly better predicted any HT and PH occurrence than the IGR (p = 0.019 and p = 0.029 respectively). CONCLUSION:In patients presenting with anterior circulation LVOS and treated with EVT, the IGR was significantly associated with an increased risk of HT. However, the baseline infarct volume was a stronger predictor of HT than IGR.

INTRODUCTION:Post-stroke depression is a frequent yet underrecognized complication after ischemic stroke. In patients treated with endovascular thrombectomy (EVT), favorable functional recovery may mask psychological distress. METHODS:We conducted a prospective multicenter observational study including consecutive patients with anterior circulation large-vessel occlusion treated with EVT between February 2021 and June 2024. At 3 months, depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D; ≥16 indicating clinically significant symptoms), and additional patient-reported outcomes including anxiety, post-traumatic stress symptoms, fatigue, and subjective cognitive complaints were collected. Baseline clinical and imaging characteristics were recorded. Multivariable logistic regression analyses were performed to identify factors independently associated with depressive symptoms and their relationship with functional outcome. RESULTS:Among 559 patients treated with EVT (mean age 71 years; 49% women), 325 (58.1%) reported clinically significant depressive symptoms at 3 months. Depressive symptoms were observed across the spectrum of functional outcomes and were not independently associated with excellent functional outcome (modified Rankin Scale (mRS) 0-1) or functional independence (mRS 0-2). In contrast, depressive symptoms were strongly associated with anxiety (OR 8.19, 95% CI 2.79 to 24.07), post-traumatic stress symptoms (OR 7.31, 95% CI 1.71 to 33.30), fatigue (OR 2.85, 95% CI 1.70 to 4.77), and cognitive complaints (OR 2.06, 95% CI 1.21 to 3.50). A history of atrial fibrillation was independently associated with depressive symptoms (OR 1.72, 95% CI 1.02 to 2.83). CONCLUSIONS:Depressive symptoms are prevalent after EVT and represent a substantial component of post-stroke morbidity not captured by functional outcome scales, supporting integration of psychological assessment into post-EVT follow-up.

BACKGROUND:Glenzocimab is a humanized fragment of a monoclonal antibody directed against the human platelet glycoprotein VI, which has shown promising features, including thrombus growth inhibition and minimal bleeding risk. The first inpatient study suggested the benefit of glenzocimab with alteplase in subgroups of patients with acute ischemic stroke (AIS) receiving endovascular treatment (EVT), with increased reperfusion rates and decreased risk of symptomatic hemorrhagic transformation. The objective of the GREEN (Glenzocimab for REperfusion in the setting of Endovascular therapy for brain infarctioN) study is to evaluate the efficacy of glenzocimab with EVT compared with EVT plus placebo, with or without intravenous thrombolysis (IVT), on functional outcome. METHODS:GREEN is a multicenter, randomized, double blind, placebo controlled study. Participants presenting with AIS and a large vessel occlusion of the anterior circulation (intracranial internal carotid artery or middle cerebral artery, or both), with symptoms onset within 24 hours, will be randomized to one of two groups: intravenous glenzocimab 1000 mg with standard of care (SoC-EVT±IVT) or SoC (EVT±IVT) plus placebo. The main primary efficacy endpoint is functional outcome (assessed by the modified Rankin Scale score) at 90 days. CONCLUSION:This is the first randomized trial evaluating the efficacy of glenzocimab with EVT. This prospective trial aims to determine whether glenzocimab with EVT improves functional outcome. TRIAL REGISTRATION:ClinicalTrials.gov NCT05559398.

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.

BACKGROUND AND OBJECTIVES:The benefit of IV thrombolysis (IVT) with alteplase before endovascular thrombectomy (EVT) compared with EVT alone has been shown to be limited and time dependent. Data on tenecteplase, its recommended alternative, are limited. We aimed to assess the efficacy and safety of IVT with tenecteplase plus mechanical thrombectomy (TNK + EVT) compared with EVT in patients with large vessel occlusion stroke and determine whether its potential benefit decreases with treatment time. METHODS:We conducted a retrospective pooled analysis of 2 nationwide, real-world registries of patients with anterior circulation large vessel occlusion stroke within 4.5 hours of known symptom onset and with no contraindication to thrombolysis, treated with TNK + EVT (TETRIS) or EVT (ETIS). The efficacy outcome was the 3-month modified Rankin Scale (mRS) score, analyzed in ordinal and dichotomized (mRS score ≤2) approaches. We used propensity score-weighted logistic regression to assess associations between treatment groups and outcomes of interest. RESULTS:Among 1,890 patients who were analyzed (TNK + EVT: n = 798; EVT: n = 1,092; median age 73 years [interquartile range 61-82]; 49.6% women), the median expected onset-to-thrombolysis time was 146 minutes [interquartile range 119-180]. More than half of patients (n = 1,063; 56.2%) were admitted first to a primary stroke center. All baseline characteristics were balanced between treatment groups after overlap weighting. Overall, TNK + EVT was associated with better 3-month functional outcome over the full mRS (weighted common odds ratio [OR] 1.53 [95% CI 1.29-1.82]; p < 0.001) and regarding functional independence (propensity score overlap weighting [PSOW]-OR 1.50 [95% CI 1.23-1.84]; p < 0.001). This benefit did not differ statistically between patients admitted first to a primary or comprehensive stroke center (p-interaction = 0.12). There was no significant effect of the expected onset-to-thrombolysis time on the association between TNK + EVT and better functional outcome (p-interaction = 0.11). There were no significant differences in parenchymal hematoma (PSOW-OR 1.29 [95% CI 0.94-1.79]; p = 0.12) and symptomatic intracerebral hemorrhage (PSOW-OR 1.13 [95% CI 0.69-1.86]; p = 0.61) rates. DISCUSSION:Among patients treated within 4.5 hours of symptom onset, TNK + EVT was associated with better functional outcome than EVT, without safety concerns. This benefit does not seem to be time dependent. These findings support the routine use of tenecteplase before EVT in the early time window. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that, in patients with stroke due to anterior circulation large vessel occlusion, IV tenecteplase plus thrombectomy is associated with better functional outcomes at 3 months compared with thrombectomy alone. TRIALS REGISTRATION INFORMATION:NCT03776877 (ETIS registry) and NCT05534360 (TETRIS registry).

Blood pressure (BP) variability, particularly arterial hypotension during mechanical thrombectomy (MT) for acute ischemic stroke (AIS), has been associated with unfavorable outcomes. This variability in BP is notably present during induction in general anesthesia (GA). This study seeks to assess the effectiveness of a personalized BP management protocol during MT under general GA in mitigating hypotension and its impact on functional outcomes at 90 days. We conducted a monocentric before-after study involving two retrospective cohorts of patients who underwent MT for AIS under GA, before and after implementing the protocol. The protocol aimed to maintain the mean arterial pressure (MAP) within 10

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:The presence of a coincident intracranial aneurysm (CIA) on the target vessel of patients undergoing mechanical thrombectomy (MT) for acute ischemic stroke (AIS) poses challenges, as the benefits and risks of the procedure in this scenario remain unclear. This study aimed to evaluate the efficacy and safety of MT in AIS cases with a CIA on the target vessel. METHODS:We retrospectively analyzed data from 14 stroke centers in France and Switzerland between January 2015 and January 2023. We identified AIS cases with CIA on the target vessel treated with MT. The control population was constituted from the ETIS registry (Endovascular Treatment in Ischemic Stroke), including AIS patients treated with MT in the same centers during the same period, and were matched (1:4) on age (±1 year) and sex. The primary outcome was favorable functional status at 3 months, defined as a modified Rankin Scale (mRS) score ≤2 or equal to pre-stroke mRS. RESULTS:A total of 104 MT-treated patients with at least one CIA on the target vessel and 416 MT-treated patients without CIA were analyzed. Despite an aneurysm rupture occurring in 5.8% of cases, no significant differences were observed in favorable functional outcome at 3 months between the CIA and control groups (42.4% vs 41.0%; adjusted OR 1.20, 95% CI 0.72 to 1.97). Similarly, recanalization rates (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b at end of MT) did not differ significantly (90.0% vs 85.9%; adjusted OR 1.75, 95% CI 0.77 to 3.95). CONCLUSION:MT is an effective option for AIS patients, even with CIA on the target vessel, but the risk of rupture underscores the need for procedural planning. Future studies should further explore size and location criteria to optimize patient selection and orientation.

Abstract Background and aims Mechanical thrombectomy improves functional outcomes in patients with large infarcts (ASPECTS 0–5), but patients aged 80 years or older were excluded from previous randomized studies. This age group accounted for about 32% of thrombectomy procedures in France in 2024. We aimed to assess the impact of thrombectomy in this population. Methods We retrospectively analyzed the ETIS registry, including patients aged 80 years or older with a proximal cerebral vessel occlusion in the anterior circulation and a large infarct (ASPECTS 0–5), admitted between 01/01/2017 and 31/12/2024. Patients were classified according to arterial recanalization after thrombectomy (mTICI ≥2b vs <2b). The primary endpoint was 90-day modified Rankin Scale (mRS). Secondary endpoints included 7-day and 3-month mortality, and symptomatic/asymptomatic intracranial hemorrhage. Results A total of 642 patients were included (median age 85 years; 390 women; median ASPECTS 4), of whom 87.2% (560/642) achieved mTICI ≥2b. Successful recanalization was associated with improved 3-month functional outcome (mRS 0–3; adjusted OR 2,70 ; 95% CI 1,21-6,40 ; p = 0,016) and reduced mortality at day 7 and 3 months (adjusted OR 0,41 ; 95% CI 0,27 – 0,72 ; p < 0,001; adjusted OR 0,44; 95% CI 0,26 – 0,75 ; p = 0,002, respectively), without increased hemorrhagic complications or procedure-related adverse events. Conclusions In patients aged 80 years or older with a proximal cerebral vessel occlusion in the anterior circulation and a large infarct, mechanical thrombectomy is associated with better functional outcomes and lower mortality, without higher risk of hemorrhagic or procedural complications. Conflict of interest Bertrand Lapergue has received fundings by Terumo (outside this work)

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.

Rapidly sorting patients with large vessel occlusion (LVO) ischemic stroke is crucial to ensure efficient transfers to stroke units. Peripheral monocyte subsets (classical Mon1, intermediate Mon2, non-classical Mon3) could be interesting candidate biomarkers in this setting: their profiles in the first hours after stroke symptom onset are unknown.To characterize monocyte subsets in patients admitted to emergency units for acute stroke suspicion.BOOST ("Biomarkers-algOrithm-for-strOke-diagnoSis-and-Treatment-resistance-prediction," NCT04726839) is a prospective multicenter cohort. Adult patients with symptoms suggesting acute stroke within the last 24 hours were included. Blood was collected upon admission before brain imaging. Flow cytometry (FCM) was performed on fresh blood with gating based on CD45/CD14/CD16/CD91 as well as on activation markers (CD62L/CD11b/CD86/HLA-DR/CCR2/ICAM-1/CX3CR1/TF).Of the 298 consecutive patients tested, mean age 64.0 ± 18.7 years, 64 (21.5%) had LVO stroke versus 234 (78.5%) other diagnosis (non-LVO ischemic stroke, cerebral venous thrombosis, intracranial hemorrhage, transient ischemic attack, and stroke mimics). The median time from symptom onset to sampling was 2.3 hours. We found a significantly lower proportion of Mon3 (geometric mean: -47%, p = 0.0093) and a higher proportion of Mon1 (+1.6%, p = 0.0296), suggesting earlier Mon1 mobilization and patrolling Mon3 consumption in LVO patients versus those without. Using linear-mixed-effect model, significant differences in ICAM-1 and HLA-DR expression on monocyte subsets were evidenced between LVO and other patients.This is the first study to evidence monocyte subset differences in LVO versus non-LVO patients at the time of admission, indicating an acute systemic response in LVO. Whether Mon assessment would add value for LVO diagnosis remains to be determined.

BACKGROUND AND PURPOSE:Cryptogenic strokes, accounting for 25%-40% of ischemic strokes, represent a major challenge in secondary prevention due to their uncertain etiology and high recurrence risk. Identifying biomarkers to reliably distinguish cardioembolic (CE) strokes among embolic strokes of undetermined source (ESUS) could help guide therapeutic decisions. Previous studies have indicated thrombus DNA content as a potential biomarker of CE stroke etiology, but direct quantification of fibrin, another key component, has not been adequately explored. METHODS:We analyzed thrombi collected from 186 ischemic stroke patients undergoing endovascular treatment between 2019 and 2023. Thrombi were processed using a quantitative method based on ex vivo tPA-mediated fibrinolysis followed by mechanical homogenization. Stroke etiology was classified according to TOAST criteria: 40% cardioembolic, 24% non-cardioembolic (large artery atherosclerosis or dissection), and 36% ESUS. Biomarker content was correlated with stroke etiology, and the diagnostic performance of DNA and fibrin (D-dimer) content was evaluated. RESULTS:Cardioembolic thrombi contained significantly higher levels of DNA (median [IQR]: 325.3 [177-484] ng/mg) and D-dimer (17.5 [9.1-23.8] μg/mg) compared to non-cardioembolic thrombi (DNA: 128 [76.4-263] ng/mg; D-dimer: 11.4 [6.8-13.2] μg/mg), with no significant differences observed in heme or GPVI content. The combined use of thrombus DNA and fibrin (D-dimer) content provided good discrimination between CE and non-CE thrombi, with an area under the ROC curve of 0.79 (95% CI, 0.70-0.87). CONCLUSION:DNA and fibrin content in thrombi are promising biomarkers for identifying cardioembolic stroke etiology. Prospective studies should evaluate their use in selecting ESUS patients who may benefit from anticoagulant therapy.

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.

Abstract Background and aims The first pass effect (FPE) is associated with improved clinical outcomes in large vessel occlusion (LVO) stroke treated by mechanical thrombectomy. However, the optimal technique to achieve FPE remains unclear, with no demonstrated superiority of direct aspiration (DA), stent retriever (SR), or combined technique (CT). This prospective study Methods We conducted a prospective multicenter study across 14 French centers between April and October 2024. Patients with acute ischemic stroke due to anterior circulation LVO (terminal internal carotid artery or M1 segment of the middle cerebral artery) were included. Clinical, procedural, and follow-up data were collected to compare thrombectomy strategies. The primary endpoint was successful reperfusion (final mTICI ≥2b). All patients were enrolled in the prospective French ETIS registry. Results A total of 248 patients were included: 138 (56%) treated with DA, 5 (2%) with SR, and 105 (42%) with CT. Mean age was 72 years, 42.5% were men, and median baseline NIHSS was 17 (12–20), with no significant differences between groups. No thrombectomy strategy was superior in achieving FPE (DA 54.5%, CT 42.9%, SR 2.6%; p=0.64). FPE was more frequent when the aspiration catheter was blocked against the clot (p=0.047) and when the microcatheter was withdrawn before aspiration (p=0.022). FPE was associated with lower rates of symptomatic intracranial hemorrhage (p=0.004) and better 3-month functional outcome (p=0.017). Conclusions Technical factors such as microcatheter withdrawal and effective catheter–clot interaction appear to enhance FPE. Larger studies are warranted to further optimize thrombectomy techniques. Conflict of interest

BACKGROUND AND OBJECTIVES:The benefit of IV thrombolysis (IVT) before thrombectomy in patients with anterior-circulation large-vessel occlusion (LVO) due to carotid artery dissection (CAD) remains uncertain. We aimed to evaluate the safety and efficacy of IVT in this specific population in clinical practice. METHODS:This study included patients from the Carotid Dissection Thrombectomy vs Medical Treatment collaboration and the Endovascular Treatment in Ischemic Stroke registry with anterior-circulation LVO due to CAD who were treated with thrombectomy, with or without prior IVT. The coprimary outcomes were favorable functional outcome at 3 months (modified Rankin Scale 0-2) and successful reperfusion (thrombolysis in cerebral infarction score ≥2b). The safety end point was symptomatic intracranial hemorrhage (sICH). Inverse probability of treatment weighting was applied to adjust for baseline imbalances, and weighted Poisson regression models were used to estimate adjusted risk ratios (aRRs). RESULTS:A total of 1,091 patients (mean age 53.0 years, 74.0% men) were included, of whom 571 patients received IVT prior thrombectomy and 520 underwent thrombectomy only. IVT before thrombectomy was associated with a higher likelihood of favorable functional outcome (aRR 1.16, 95% CI 1.03-1.30, p = 0.013) and successful reperfusion (aRR 1.34, 95% CI 1.18-1.53, p < 0.001). No association was observed with sICH (aRR 0.69, 95% CI 0.41-1.16, p = 0.161). Subgroup analyses showed that the functional benefit of IVT was pronounced in patients with higher admission NIH Stroke Scale scores (p interaction = 0.039). DISCUSSION:IVT prior thrombectomy was associated with improved functional outcome and higher reperfusion success in patients with anterior-circulation LVO due to CAD, without an increase in sICH. The association with functional outcome was largely driven by patients presenting with higher admission stroke severity. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that IVT before thrombectomy was associated with improved functional outcome and higher reperfusion success in patients with anterior-circulation LVO due to CAD, without an increase in sICH.

Abstract Background and aims Mechanical thrombectomy (MT) is the cornerstone of acute ischemic stroke (AIS) treatment due to large vessel occlusion, yet incomplete recanalization remains a significant challenge. The glycoprotein VI receptor plays a pivotal role in platelet-mediated thromboinflammation, contributing to secondary brain injury. Glenzocimab, a humanized anti-glycoprotein VI antibody fragment, has shown promise in reducing symptomatic intracranial hemorrhage (sICH) and mortality when used in combination with intravenous thrombolysis (IVT) in the ACTIMIS trial. The GREEN trial aimed to evaluate the efficacy of glenzocimab as an adjunct to MT in participants with AIS, providing further insights into its potential role in improving clinical outcomes. Methods GREEN was a randomized, double-blind, multicenter, placebo-controlled, trial conducted across eight stroke centers in France. Participants aged 18 years or older with disabling AIS (NIHSS ≥6) eligible for MT within 0–24 hours of symptom onset were enrolled. Participants were randomly assigned in a 1:1 ratio to receive either glenzocimab (1000 mg intravenous infusion) or placebo, stratified by age, use of IVT, and time to treatment. The primary endpoint was the distribution of modified Rankin Scale (mRS) scores at 90 days, analyzed using ordinal logistic regression. Results Between January 3, 2023, and July 23, 2024,102 participants were randomized, 50 were assigned to glenzocimab and 52 to placebo. The study was terminated after a pre-planned interim analysis. Conclusions The GREEN trial, evaluating glenzocimab as an adjunct therapy to MT in AIS participants with LVO of the anterior circulation, in the 0-24 hour’s time window, was terminated early. Conflict of interest

BACKGROUND AND OBJECTIVES:Despite successful recanalization after mechanical thrombectomy for acute ischemic stroke, a substantial proportion of patients experience early neurologic deterioration or infarct progression. Early blood-brain barrier disruption, visualized on post-contrast fluid-attenuated inversion recovery (pcFLAIR) imaging as hyperintense acute reperfusion marker (HARM) or gadolinium leakage in ocular structures (GLOS), has been proposed as a marker of reperfusion injury, but its determinants and prognostic significance in thrombectomy cohorts remain uncertain. We aimed to evaluate whether HARM and GLOS are associated with poor clinical outcomes after mechanical thrombectomy. Secondary objectives included their association with poor radiologic outcomes and the identification of baseline and procedural predictors. METHODS:We retrospectively analyzed data from the French Endovascular Treatment in Ischemic Stroke (ETIS) registry (2010-2021), including consecutive patients admitted to Versailles and Foch Hospital. All patients underwent mechanical thrombectomy at Foch Hospital and pcFLAIR imaging within 4-48 hours postgadolinium administration. Independent predictors of HARM and GLOS were identified through multivariable logistic regression, and their associations with early neurologic deterioration, poor 3-month functional outcome, infarct growth, and hemorrhagic transformation (HT) outcomes were evaluated. RESULTS:Among 229 patients (mean age 69.7 ± 14.9 years, 52.0% female), HARM was observed in 48.9% and GLOS in 41.9%. Overall, 60.3% of patients had either HARM or GLOS, including 29.3% with both markers, 19.7% with isolated HARM, and 11.4% with isolated GLOS. HARM was independently associated with early neurologic deterioration (adjusted odds ratio [aOR] 3.45; 95% CI 1.33-8.95) and infarct growth (aOR 2.46; 95% CI 1.22-4.95), but not with HT or 3-month functional outcome. GLOS was not independently associated with clinical or radiologic outcomes. Older age, higher creatinine, and a shorter interval between the first and second FLAIR were common predictors of both HARM and GLOS, whereas single-pass recanalization was an independent predictor of HARM only. DISCUSSION:In this large thrombectomy cohort, HARM was independently associated with early neurologic deterioration and infarct progression after thrombectomy, supporting its role as an imaging marker of early blood-brain barrier disruption. GLOS, although frequent, was not independently associated with clinical or radiologic outcomes. Prospective studies with early and serial imaging are required to clarify the prognostic relevance of HARM. TRIAL REGISTRATION INFORMATION:NCT03776877 (ETIS registry).

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.

BACKGROUND:The impact of stent retriever size on mechanical thrombectomy (MT) outcomes remains uncertain. We aim to clarify the influence of stent retriever size on MT outcomes by analyzing data from two national prospective registries. METHODS:A retrospective analysis was performed on data from the French and German MT registries including consecutive patients with anterior circulation large vessel occlusion who underwent Solitaire stent retriever MT with or without additional aspiration. Efficacy outcomes were successful reperfusion and complete reperfusion. Safety outcomes included any intracerebral hemorrhage (ICH) and symptomatic intracerebral hemorrhage (sICH). RESULTS:Complete reperfusion was lower in the 4×20 mm stent retriever group than in the 4×40 mm stent retriever group (47% vs 53%; OR 0.61, P=0.0039). Successful reperfusion did not differ between the 4×20 mm and 4×40 mm stent retriever groups (89% vs 93%; OR 0.69, P=0.25). There was no difference between the 6×30/6×40 mm and 4×20 mm stents, and there was no difference in functional outcomes between the groups. In terms of safety, any ICH was lower in the 4×20 mm group than in the 4×40 mm group (20% vs 36%; OR 0.60, P=0.0095). Symptomatic ICH was lower in the 4×20 mm group than in the 4×40 mm group (5% vs 10%; OR 0.58, P=0.086), but the difference did not reach statistical significance. Mortality was lower in the 4×20 mm than in the 6×40 mm group (26% vs 33%; OR 0.70, P=0.044). When compared according to occlusion location, the results were overall similar. CONCLUSION:This study suggests that longer and larger stent retrievers lead to a higher reperfusion rate but also a higher rate of hemorrhagic complications. Overall, the size of the stent did not affect functional outcomes.