Abstract Background and aims We investigated whether intravenous thrombolysis (IVT) before endovascular treatment (EVT) reduces the occurrence of infarcts in new territory (INT) and evaluated the clinical relevance of INT. Methods Individual participant data meta-analysis of six randomized clinical trials comparing IVT + EVT versus EVT alone. Imaging from all trials was centrally adjudicated by trained evaluators. INT was defined as an infarct on follow-up imaging in a vascular territory not hypoperfused during acute treatment. Mixed-effects logistic regression models with study-stratified intercepts and random study effects were used to assess the association between treatment allocation and INT, and between INT, functional outcomes, and safety outcomes. Results Evaluable imaging was available for 2024/2313 (88%) participants (1010 EVT alone; 1014 IVT + EVT). INT occurred in 265 (13%) and was less frequent after IVT + EVT compared with EVT alone (113 [11%] vs 152 [15%]; OR 0.71, 95% CI 0.55–0.92). INT was associated with worse functional outcomes at 90 days, including lower odds of improved modified Rankin Scale scores (adjusted common OR 0.57, 95% CI 0.45–0.72) and lower rates of functional independence (42% vs 52%; adjusted OR 0.61, 95% CI 0.46–0.79). INT was also associated with higher rates of symptomatic intracranial hemorrhage. Conclusions INT occurred in 13% of participants with large-vessel occlusion stroke undergoing EVT, and was associated with worse outcomes. Participants randomized to IVT + EVT had lower rates of INT, though this did not translate to improved functional outcome in our data. Conflict of interest Roman Rohner: nothing to disclose. Fabiano Cavalcante: nothing to disclose. Jianmin Liu: nothing to disclose. Yongwei Zhang: nothing to disclose. Kentaro Suzuki: nothing to disclose. Raul Nogueira: nothing to disclose. Peter Mitchell: nothing to disclose. Dr Roos reports stock holdings in Nicolab. Dr Fischer reports grants from Stryker to other; grants from Schweizerische Herzstiftung; grants from Penumbra, Inc, to other; grants from SNSF; compensation from phenox, Inc, for end point review committee services; grants from Medtronic to other; grants from phenox, Inc, to other; grants from Rapid Medical, Ltd, to other; grants from Boehringer Ingelheim; grants from Stryker to other; and grants from Medtronic to other. Dr Gralla reports compensation from Johnson & Johnson Health Care Systems, Inc, for consultant services and compensation from Medtronic USA, Inc, for other services.

Abstract Background and aims Brain frailty, reflected by structural brain changes on CT, has been linked to heterogeneity in stroke presentation and recovery. In ESCAPE-NA1, CT-based brain frailty markers were associated with higher baseline stroke severity and poorer 90-day outcomes after thrombectomy. We aimed to validate these associations in the HERMES collaboration and determine whether brain frailty modifies thrombectomy treatment effects. Methods We performed a pooled analysis of individual patient data from the HERMES collaboration. Brain frailty imaging markers were assessed on baseline non-contrast CT. Associations with baseline National Institutes of Health Stroke Scale (NIHSS) score and 90d-modified Rankin Scale (90d-mRS) were evaluated using multivariable regression, and interaction with thrombectomy effect analyzed. Results Among 1,730 patients in the pooled HERMES dataset, baseline NIHSS was higher in patients with white matter disease (WMD, adjusted β = 0.54, 95%CI:0.01-1.08) and medial temporal atrophy (adjusted β = 0.39, 95%CI 0.02-0.76). Greater brain frailty was associated with lower odds of favorable 90d-mRS, including for WMD (aOR 0.62, 95%CI 0.50–0.77), global cortical atrophy (GCA; aOR 0.65, 0.55–0.78), medial temporal atrophy (OR 0.70, 0.60–0.80), posterior atrophy (aOR 0.69, 0.58–0.83), and cerebral small vessel disease (CSVD) burden (aOR 0.74, 0.64–0.86). EVT treatment effect modification for 90d-mRS was observed for GCA (P = 0.036) and presence of lacunes (P = 0.034, Figure 1). Conclusions CT-based brain frailty markers are associated with higher baseline stroke severity and worse 90d functional outcome. Thrombectomy remained beneficial across brain frailty strata, but treatment benefit was smaller for patients with greater atrophy and CSVD burden, particularly lacunes. Conflict of interest All authors: nothing to disclose.

Abstract Background and aims Multiple randomized control trials have shown that thrombectomy for ischemic stroke resulting from large vessel occlusion (LVO) reduces disability and is cost effective. There remains uncertainty whether thrombectomy for patients with pre-stroke disability (modified Rankin Score/mRS3-4) is similarly effective, as prior meta-analysis (n=14) included cases of mRS2 among those classified as pre-stroke disability. This study aimed to meta-analyse the outcomes of thrombectomy for LVO in those with moderate disability (mRS3-4). Methods We searched Pubmed, Medline and Clinicaltrials.gov using search terms "stroke", "large vessel occlusion", "disability", "prestroke disability", or "pre-stroke disability" on 4/1/2026. From 384 studies, we included those with >90 patients or if there were extractable data on cases with mRS3-4. Analyses were conducted in R using the meta and metafor packages. Results Of 27 studies, two duplicates were excluded. In the remaining 25 studies, 5084/60199 patients with a pre-stroke disability (10.6%, 95% CI 7.8-13.7, I2=99.3%) received thrombectomy. Mean age was 81.0±2.8years. The majority were female 64.9% (95% CI 61.8-67.9%, I2=97.2%). Return to baseline occurred in 27.3% (95% CI 23.2-31.5%, I2=98.9%) and symptomatic intracerebral hemorrhage occurred in 6.5% (95% CI 5.5-7.7%, I2=94.8%). Mortality was 39.5% (95% CI 34.0-45.1%, I2=99.4%). Conclusions The proportion of patients with pre-stroke disability treated by thrombectomy in LVO registries remains low while a modest proportion of the patients returned to baseline following thrombectomy. Surprisingly a large proportion of patients in registries were female, reversing trends seen previously. The high heterogeneity (I2) suggests a large variation in results, and further work in the form of a trial is needed. Conflict of interest Jason Vuong: nothing to disclose, Shaloo Singhal: nothing to disclose, Michael Valente: nothing to disclose, Angelos Sharobeam: nothing to disclose, Lubna Shakhatreh: nothing to disclose, Andy Lim: nothing to disclose, Peter Mitchell: nothing to disclose, Bernard Yan: nothing to disclose, Henry Ma: nothing to disclose, Thanh Phan: nothing to disclose.

Abstract Background and aims Recent trials showing benefit of reperfusion therapy despite large ischemic cores and minimal perfusion mismatch have challenged the traditional infarct-versus-no-infarct dichotomy and support a more graded view of ischemic injury. This study investigates how the severity of white- and grey-matter injury within an infarct relates to functional outcomes. Methods This analysis of the Post-Reperfusion-pathophysiology-in-Acute-Ischemic-StrokE (PRAISE) multicentre observational study included adults with anterior circulation large-vessel-occlusion ischemic stroke who underwent 24-hour follow-up MRI post-thrombectomy. Segmented diffusion lesions were subdivided into white- and grey-matter components and overlaid on apparent diffusion coefficient (ADC) and mean kurtosis (MK) maps. Severe injury fractions, calculated for total, white-, and grey-matter lesion components as the proportion of voxels in the infarct lesion that exhibited values beyond the 1st (ADC) and 99th (MK) percentile voxel value of the contralateral homologous region, were tested in logistic regression models (age, lesion volume, NIHSS) to assess independent associations with 90-day functional independence (mRS 0-2). Results In 63 patients analyzed (median age 72yo, 57% male, 60.32% mRS 0-2), white-matter severe injury fraction was independently associated with outcome for both ADC and MK metrics, with each 1% increase associated with lower odds of functional independence (ADC: aOR 0.95, 95%CI 0.91-0.99, p=0.040; MK: aOR 0.96, 95%CI 0.92-0.99, p=0.043). In contrast, no significant association was found for grey-matter fractions. Conclusions Greater white-matter severity of injury within an infarct is associated with poor functional outcome, underscoring the importance of white-matter integrity in post-stroke recovery and supporting a graded and tissue-specific approach to infarct assessment. Conflict of interest Samantha Rivet: Nothing to disclose. Christopher Steward: Nothing to disclose. Valerian Altersberger: Nothing to disclose. Leonid Churilov: Nothing to disclose. Peter Mitchell: Nothing to disclose. Vincent Thijs: Nothing to disclose. Patricia Desmond: Nothing to disclose. Vijay Venkatraman: Nothing to disclose. Stephen Davis: Nothing to disclose. Bruce Campbell: Nothing to disclose. Felix Ng: Nothing to disclose.

OBJECTIVE:The benefit of intravenous thrombolysis (IVT) before endovascular treatment (EVT) in patients with acute ischemic stroke due to large vessel occlusion (LVO) who present directly to EVT-capable centers remains uncertain, and the effect may differ according to underlying stroke etiology. We assessed whether the benefit of IVT plus EVT versus EVT alone varied by stroke etiologies (large-artery atherosclerosis, cardioembolism, or other/undetermined). METHODS:We performed an individual participant data meta-analysis of 6 randomized controlled trials (RCTs) that compared IVT plus EVT to EVT alone in patients with LVO within 4.5 hours of stroke onset or time last known well. The heterogeneity of treatment effect was assessed using ordinal logistic regression models with interaction terms for stroke etiology and treatment in the intention-to-treat population, followed by subsequent mixed-effects meta-analysis. An additional analysis was performed to assess whether the treatment effect of IVT plus EVT differed by atrial fibrillation status. RESULTS:Among 2,313 eligible patients from 6 RCTs, 1,160 were randomized to the IVT plus EVT group and 1,153 to the EVT alone group. Median age was 71 years (interquartile range [IQR] = 62-78 years), and 44.3% of patients were women. Stroke etiology was classified as cardioembolism in 977 of 2,313 patients (42%), large artery atherosclerosis in 430 (19%), and other or unknown/undetermined in 906 (39%). No evidence of treatment effect modification by stroke etiologies on the association between IVT and 90-day functional outcome was observed (P for interaction = 0.60). For patients with other/undetermined stroke etiology, IVT plus EVT was associated with better 90-day functional prognosis (adjusted common odds ratio for a lower level of disability = 1.34, 95% confidence interval [CI] = 1.05-1.69). No treatment effect modification by stroke etiology was found for safety outcomes. No treatment effect heterogeneity by atrial fibrillation was found for all outcomes. INTERPRETATION:Among patients with LVO presenting directly to EVT-capable centers, stroke etiologies do not modify the overall efficacy or safety of IVT before EVT. The isolated benefit observed in the other/undetermined subgroup requires confirmation. ANN NEUROL 2026;100:180-190.

Abstract Background and aims Whether prior intravenous thrombolysis (IVT) modifies outcomes after endovascular thrombectomy (EVT) remains uncertain. We conducted a one-stage individual participant data meta-analysis of six randomized trials from the Improving Reperfusion Strategies in Ischemic Stroke (IRIS) collaboration to evaluate EVT with versus without IVT across imaging–clinical profiles. Methods Patients with anterior-circulation large-vessel occlusion were randomized to EVT alone or IVT+EVT. Profiles were defined by ASPECTS, NIHSS, and a prespecified simple imaging–clinical equation (ASPECTS + 0.2×NIHSS) reflecting imaging–clinical discordance. The primary outcome was 90-day mRS shift analyzed using mixed-effects ordinal logistic regression with a trial random intercept, adjusted for age, atrial fibrillation, occlusion site, and onset-to-randomization time. Interaction tests evaluated effect heterogeneity across strata. Results Of 2312 randomized patients, 2270 were analyzed (1129 EVT alone). Across ASPECTS strata, EVT alone showed no clear overall advantage, with no significant interaction across ASPECTS or ASPECTS–NIHSS groups. Restricted cubic splines supported two knots (13 and 15) for the equation, defining three strata. Treatment-effect heterogeneity was observed across equation strata (P-interaction=0.04): 0–13 OR 0.99 (95% CI 0.83–1.17), 13–15 OR 1.40 (1.01–1.96; p=0.04), and 15–18 OR 0.81 (0.31–2.11). Conclusions Overall, functional outcomes did not differ consistently between EVT alone and IVT+EVT across ischemic injury or clinical severity profiles. However, patients with intermediate imaging–clinical discordance (equation 13–15) showed a trend favoring EVT alone, suggesting that a simple profile-based approach may help inform rapid, individualized bridging decisions when only limited information is available. Conflict of interest nothing to disclose Table 1 - belongs to Results Table 2 - belongs to Conclusions

Suboptimal clinical outcomes are common after ischemic stroke with large vessel occlusion despite current reperfusion treatment with intravenous thrombolysis and mechanical thrombectomy. Targeting residual distal arterial and microvascular occlusions with intraarterial thrombolysis has recently gained substantial interest as an adjunct to improve cerebral tissue perfusion. While recent trials provide promise in selected patients with anterior-circulation stroke, further high-quality, large-scale studies and pooled individual-patient analyses are needed. This review summarizes the evolving role of intraarterial thrombolysis over the past 3 decades and projects potential developments.

Background: We investigate whether the NIHSS at 24 hours could serve as an alternative primary outcome measure in acute ischemic stroke trials, and whether combining 90-day modified Rankin Score (mRS) and 24-hour NIHSS in a hierarchical outcome could enhance detection of treatment effect, using EVT as an exemplary study intervention. Methods: Post-hoc analysis from the HERMES collaboration that pooled data from 7 randomized controlled EVT trials. Validity of 24-hour NIHSS as a surrogate outcome for 90-day mRS was assessed in a causal mediation model (Figure 1). A 7-point ordinal NIHSS score was generated by grouping 24-hour NIHSS, including death as a separate category (“ordinal” NIHSS). EVT effect sizes and sample sizes required for detecting EVT benefit with 80% power were compared when using granular 24-hour NIHSS, ordinal 24-hour NIHSS, 90-day mRS, and hierarchical outcome (win-ratio) that combines 90-day mRS and 24-hour NIHSS. Subgroup analyses were performed in patients with baseline NIHSS<10 and ≥25. Results: A total of 1720 patients were included. Median 90-day mRS in the EVT/control arms was 3.0(IQR:1.0-4.0)/4.0(IQR:2.0-5.0) and median 24-hour NIHSS was 9.0(IQR:3.0-17.0)/14.0(IQR:7.5-19.0), see Figure 2. 24-hour NIHSS mediated the association between EVT and 90-day mRS and met the criteria for a surrogate outcome. Effect sizes were highest and sample sizes required to detect EVT benefit smallest for the win ratio approach (228), followed by 90-day mRS(240) and ordinal 24-hour NIHSS(242), see Table 1. In subgroup analyses of patients with baseline NIHSS<10 and≥25, ordinal 24-hour NIHSS resulted in the highest effect size/ smallest sample size. Conclusion: 24-hour NIHSS may be a valid surrogate outcome for 90-day mRS in acute ischemic stroke patients undergoing EVT, with a similar EVT effect size compared to 90-day mRS. It could potentially enhance detection of EVT benefit in patient subgroups with very low or very high baseline NIHSS. Combining 90-day mRS and 24-hour NIHSS in an ordered hierarchical could improve detection of EVT treatment effect compared to 90-day mRS.

BackgroundWhether bridging thrombolysis with tenecteplase is beneficial compared with thrombectomy alone in patients who had a stroke with large-vessel occlusion remains unclear.MethodsThis is a causal inference study of observational data from the trials SWIFT DIRECT and EXTEND-IA TNK Parts 1 and 2 applying target trial emulation. We compared patients receiving thrombectomy alone to patients receiving tenecteplase 0.25 mg/kg or 0.40 mg/kg before thrombectomy. The primary outcome was functional independence (modified Rankin Scale (mRS) of 0–2) at 90 days. Secondary outcomes included improvement over the full ordinal mRS scale, freedom of disability (mRS 0–1), mortality and occurrence of symptomatic intracranial haemorrhage. The average causal treatment effect was estimated via inverse probability of treatment weighting and G-Computation. We calculated standardised risk differences (SRDs) and adjusted (common) ORs (a(c)ORs).ResultsOf 377 patients included in the target trial, 187 received thrombectomy alone and 190 tenecteplase before thrombectomy. Tenecteplase before thrombectomy did not increase the probability of patients achieving functional independence (SRD 0.04 (95% CI –0.06 to 0.13)) but resulted in a significant improvement in the mRS overall (acOR 1.56 (95% CI 1.07 to 2.23)) and in a higher probability of freedom from disability (SRD 0.10 (95% CI 0.01 to 0.20)). The probability for improvement of functional outcomes was further increased in patients treated within 140 min after onset (ordinal mRS acOR 1.63 (95% CI 1.04 to 2.56)). No significant differences in safety outcomes were observed between the two groups.ConclusionTenecteplase before thrombectomy compared with thrombectomy alone did not increase the probability of functional independence but resulted in significant improvement over the full mRS scale. This improvement was most evident in patients treated early.

Background and ObjectivesAlthough previous trials have established the efficacy and safety of endovascular thrombectomy (EVT) in large ischemic core strokes, most of them excluded patients with extracranial internal carotid artery (e-ICA) occlusion. We aimed to compare outcomes in patients with e-ICA occlusion and large ischemic core infarcts treated with EVT vs medical management (MM).MethodsThis was a secondary analysis of the SELECT2 trial, a randomized controlled trial conducted at 31 international sites. Adult patients with proximal intracranial anterior circulation large ischemic strokes, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3-5 on noncontrast CT or ischemic core >= 50 mL on CT-perfusion/magnetic resonance-diffusion imaging, and concomitant e-ICA occlusion were selected. The primary outcomes were the distribution of modified Rankin Scale (mRS) score at 90-day follow-up and symptomatic intracranial hemorrhage (sICH).ResultsAmong 352 enrolled patients, 62 (17.6%) with e-ICA occlusions were included. Of those 62 patients, 37 received EVT (median [interquartile range (IQR)] age, 65 [58-71] years; 15 women [38.5%]) and 25 received MM (median [IQR] age, 66 [61-71] years; 7 women [28%]). ASPECTS (EVT: 5 [3-5] vs MM: 5 [4-5]) and ischemic core volume (EVT: 100 [69-134] mL vs MM: 103 [78-135] mL) were similar between groups. The successful reperfusion rate with EVT was 64.9%. Patients receiving EVT demonstrated significantly better functional outcomes (adjusted generalized odds ratio 2.51; 95% CI 1.43-4.39; p = 0.001) and a higher proportion of patients achieving 90-day independent ambulation (EVT: 37.8% vs MM: 8%; adjusted relative ratio [aRR] 4.58; 95% CI 1.18-17.79; p = 0.037) and functional independence (EVT: 21.6% vs MM: 8%; aRR 2.16; 95% CI 0.53-8.83; p = 0.285). Furthermore, no heterogeneity of EVT benefit was observed by the presence or absence of e-ICA occlusion (p-interaction = 0.248). There were no sICH or parenchymal hemorrhage type 2 events in either group, and mortality was similar in the 2 groups (aRR 0.75; 95% CI 0.39-1.45; p = 0.388).DiscussionAmong patients with e-ICA occlusions and large ischemic core stroke, EVT was associated with better functional outcomes without significant safety concerns when compared with MM. Our findings suggest that EVT in these patients is beneficial, while the optimal treatment of the extracranial carotid occlusion remains unclear.Trial Registration InformationName of the trial: SELECT2 trial. Registration number: ClinicalTrials.gov Identifier: NCT03876457. Date of registration submission: August 3, 2019. Date of first patient enrollment: November 10, 2019.Classification of EvidenceThis study provides Class II evidence that for patients with large core acute ischemic stroke and concomitant e-ICA occlusion, EVT is associated with better functional outcome at 90 days compared with MM alone.

Oxygen Extraction Fraction (OEF) is a critical measure of a tissue's metabolic state post-ischemic stroke. This study investigated OEF changes in stroke-affected tissue compared to healthy tissue, post-reperfusion. OEF maps generated from gradient echo MRI images of 87 ischemic stroke patients at three time points after successful Endovascular Thrombectomy (EVT) were analysed in a prospective longitudinal multicentre study. Regions of interest (ROIs) delineating the infarct areas and corresponding mirror regions were drawn. The MR-derived OEF index values were obtained from the ROIs and compared using Wilcoxon signed rank tests. The cross-sectional comparison of OEF index values revealed lower values in the infarct areas than the corresponding contralateral areas at all three time points after successful EVT, presented as median (interquartile range) [24-72 hours: 20.84 (17.56-26.82)% vs 27.56 (23.22-31.87)%; 3 months: 27.37 (23.28-30.35)% vs 32.55 (28.00-35.81)%; 12 months: 24.38 (22.35-29.77)% vs 29.39 (25.86-34.04)%, p < 0.001 for all three time points]. Longitudinally, relative OEF index values increased gradually over time [24-72 hours: 0.81 (0.67-0.87); 3 months: 0.86 (0.79-0.95); 12 months: 0.88 (0.75-0.95)]. The findings revealed that following successful EVT, OEF in infarct tissue improves over time, indicating potential tissue recovery.Trial registration name and URL: Post-Reperfusion Pathophysiology in Acute Ischemic Stroke https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12624000629538.

BACKGROUND AND OBJECTIVES:Although previous trials have established the efficacy and safety of endovascular thrombectomy (EVT) in large ischemic core strokes, most of them excluded patients with extracranial internal carotid artery (e-ICA) occlusion. We aimed to compare outcomes in patients with e-ICA occlusion and large ischemic core infarcts treated with EVT vs medical management (MM). METHODS:This was a secondary analysis of the SELECT2 trial, a randomized controlled trial conducted at 31 international sites. Adult patients with proximal intracranial anterior circulation large ischemic strokes, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3-5 on noncontrast CT or ischemic core ≥50 mL on CT-perfusion/magnetic resonance-diffusion imaging, and concomitant e-ICA occlusion were selected. The primary outcomes were the distribution of modified Rankin Scale (mRS) score at 90-day follow-up and symptomatic intracranial hemorrhage (sICH). RESULTS:Among 352 enrolled patients, 62 (17.6%) with e-ICA occlusions were included. Of those 62 patients, 37 received EVT (median [interquartile range (IQR)] age, 65 [58-71] years; 15 women [38.5%]) and 25 received MM (median [IQR] age, 66 [61-71] years; 7 women [28%]). ASPECTS (EVT: 5 [3-5] vs MM: 5 [4-5]) and ischemic core volume (EVT: 100 [69-134] mL vs MM: 103 [78-135] mL) were similar between groups. The successful reperfusion rate with EVT was 64.9%. Patients receiving EVT demonstrated significantly better functional outcomes (adjusted generalized odds ratio 2.51; 95% CI 1.43-4.39; p = 0.001) and a higher proportion of patients achieving 90-day independent ambulation (EVT: 37.8% vs MM: 8%; adjusted relative ratio [aRR] 4.58; 95% CI 1.18-17.79; p = 0.037) and functional independence (EVT: 21.6% vs MM: 8%; aRR 2.16; 95% CI 0.53-8.83; p = 0.285). Furthermore, no heterogeneity of EVT benefit was observed by the presence or absence of e-ICA occlusion (p-interaction = 0.248). There were no sICH or parenchymal hemorrhage type 2 events in either group, and mortality was similar in the 2 groups (aRR 0.75; 95% CI 0.39-1.45; p = 0.388). DISCUSSION:Among patients with e-ICA occlusions and large ischemic core stroke, EVT was associated with better functional outcomes without significant safety concerns when compared with MM. Our findings suggest that EVT in these patients is beneficial, while the optimal treatment of the extracranial carotid occlusion remains unclear. TRIAL REGISTRATION INFORMATION:Name of the trial: SELECT2 trial. Registration number: ClinicalTrials.gov Identifier: NCT03876457. Date of registration submission: August 3, 2019. Date of first patient enrollment: November 10, 2019. CLASSIFICATION OF EVIDENCE:This study provides Class II evidence that for patients with large core acute ischemic stroke and concomitant e-ICA occlusion, EVT is associated with better functional outcome at 90 days compared with MM alone.

Importance:For patients with acute ischemic stroke due to anterior circulation large vessel occlusion and presenting directly to endovascular treatment (EVT)-capable centers, intravenous thrombolysis (IVT) before EVT raises concerns about intracranial hemorrhage (ICH), but details are not well understood. Objective:To determine the frequency and subtypes of ICH in patients treated with IVT plus EVT vs EVT alone and to determine the association between various ICH subtypes and patient functional outcomes. Data Sources:PubMed and MEDLINE were searched from database inception through March 9, 2023. Study Selection:Randomized clinical trials comparing EVT alone with IVT plus EVT for anterior circulation large vessel occlusion stroke were included. Data Extraction and Synthesis:Individual participant data were extracted following the Preferred Reporting Items for Systematic Review and Meta-Analyses of independent participant data (PRISMA-IPD) reporting guidelines. Data were pooled using a random-effects model. Data were analyzed between April 2024 and February 2025. Main Outcomes and Measures:The primary outcomes were ICH and its subtypes according to the Heidelberg Bleeding Classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], parenchymal hematoma type 2 [PH2], and others; symptomatic or asymptomatic ICH), which were evaluated using a mixed-model approach with multinomial or binary regression. Results:The analysis involved 2313 participants (1160 allocated to the IVT plus EVT group vs 1153 to EVT alone; median [IQR] age, 71 [62-78] years; 1025 female participants [44%]) from 6 studies. Any ICH occurred in 768 of 2261 participants (34%). IVT was associated with an increased rate of any ICH (411 of 1133 [36%] vs 357 of 1128 [32%]; adjusted odds ratio [OR], 1.23; 95% CI, 1.02-1.49; P = .03) and a higher rate of any parenchymal hematoma (PH1 or PH2) (82 of 1133 [7%] vs 61 of 1128 [5%]; adjusted OR, 1.54; 95% CI, 1.02-2.34; P = .04). Compared with participants without ICH, asymptomatic ICH (adjusted common OR, 0.55; 95% CI, 0.46-0.65) and symptomatic ICH (adjusted common OR, 0.08; 95% CI, 0.05-0.13) were both associated with worse functional outcomes, and there was a graded association of ICH radiologic patterns and patient outcomes. Conclusions and Relevance:In this individual participant data meta-analysis, compared with EVT alone, IVT plus EVT modestly increased the risk of ICH, notably any parenchymal hematoma. Although ICH was associated with worse functional outcomes, this effect may be offset by IVT's benefit in final successful reperfusion and early reperfusion.

Background To rapidly predict outcomes of candidate for endovascular thrombectomy in time‐sensitive situations with limited clinical information, we propose a simple but balanced approach, integrating National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early CT Score (ASPECTS). Methods This study utilized data from 2 independent registries to investigate the associations of NIHSS scores and ASPECTS with clinical outcomes of patients with stroke with large vessel occlusion in the anterior circulation who underwent endovascular thrombectomy and to evaluate the accuracy of a novel clinical‐imaging equation in predicting these outcomes. The primary outcome was functional independence. Results A total of 2128 patients were included. Of these, 1052 (49.4%) achieved functional independence. ASPECTS, NIHSS scores, and age were identified as key predictors across all basic parameters. Clinical‐imaging equations (with and without age adjustment, defined as ASPECTS−0.5×NIHSS−age×0.2 and ASPECTS−NIHSS×0.5) were developed. These equations exhibited superior discriminative ability (C statistic, 0.71 [95% CI, 0.68–0.74], 0.68 [95% CI, 0.65–0.70]) compared with traditional methods in the validation cohort. The prediction probability of functional independence by quartiles of clinical‐imaging equation with age adjustment (≤−15.5, −15.5 to −12, −15.5 to −12, >−9.5) was 32% (95% CI, 17%–47%), 51% (95% CI, 43%–59%), 63% (95% CI, 58%–69%), and 77% (95% CI, 65%–90%) in the validation cohort. Conclusions By integrating ASPECTS and NIHSS scores, our clinical‐imaging equations improved rapid prediction of endovascular thrombectomy outcomes in time‐sensitive situations such as patient transfers from primary stroke centers or in mobile stroke units, where clinical information is limited.

Background Robust collateral circulation has been linked with better reperfusion and clinical outcomes. It remains unclear how individual assessments of collateral circulation may be translated into clinical practice. Methods The pooled Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) angiography dataset was analyzed by a centralized, independent imaging core blinded to other clinical data. Conventional angiography was acquired immediately prior to endovascular therapy. Collaterals were graded with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) system and associated with baseline patient characteristics, reperfusion, and day 90 modified Rankin Score (mRS). Both 90-day all-cause mortality and day 90 mRS were modeled via multivariable logistic regression. Results Angiography was available in 376/605 (62%) patients. Baseline ASPECTS (Alberta Stroke Program Early CT Score) (p=0.043), history of diabetes mellitus (p=0.048), site of occlusion (p<0.001), and degree of subsequent Thrombolysis in Cerebral Infarction (TICI) reperfusion (p<0.001) were associated with collateral grades. ASITN collateral grade was strongly associated with ordinal mRS from baseline to 90 days in an unadjusted analysis (p<0.001). Multivariable regression demonstrated that collateral status is a strong determinant of mRS outcome in the presence of other predictors (OR=1.37 per grade, 95% CI [1.05 to 1.74], p=0.018). By comparing ORs, 1 unit of ASITN was determined to be approximately equivalent to 4.5 points of NIHSS, 11 years of age, 1.5 points of ASPECTS, or 100 min less delay from onset to puncture, in terms of impact on mRS. Conclusions Individual collateral physiology may contribute significantly to reperfusion success and clinical outcomes after acute ischemic stroke. Building a consensus for the role of angiographic collateral assessment in the allocation of adjuvant reperfusion therapies may help galvanize a precision medicine approach in stroke.

Importance For patients with acute ischemic stroke due to anterior circulation large vessel occlusion and presenting directly to endovascular treatment (EVT)-capable centers, intravenous thrombolysis (IVT) before EVT raises concerns about intracranial hemorrhage (ICH), but details are not well understood. Objective To determine the frequency and subtypes of ICH in patients treated with IVT plus EVT vs EVT alone and to determine the association between various ICH subtypes and patient functional outcomes. Data Sources PubMed and MEDLINE were searched from database inception through March 9, 2023. Study Selection Randomized clinical trials comparing EVT alone with IVT plus EVT for anterior circulation large vessel occlusion stroke were included. Data Extraction and Synthesis Individual participant data were extracted following the Preferred Reporting Items for Systematic Review and Meta-Analyses of independent participant data (PRISMA-IPD) reporting guidelines. Data were pooled using a random-effects model. Data were analyzed between April 2024 and February 2025. Main Outcomes and Measures The primary outcomes were ICH and its subtypes according to the Heidelberg Bleeding Classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], parenchymal hematoma type 2 [PH2], and others; symptomatic or asymptomatic ICH), which were evaluated using a mixed-model approach with multinomial or binary regression. Results The analysis involved 2313 participants (1160 allocated to the IVT plus EVT group vs 1153 to EVT alone; median [IQR] age, 71 [62-78] years; 1025 female participants [44%]) from 6 studies. Any ICH occurred in 768 of 2261 participants (34%). IVT was associated with an increased rate of any ICH (411 of 1133 [36%] vs 357 of 1128 [32%]; adjusted odds ratio [OR], 1.23; 95% CI, 1.02-1.49; P = .03) and a higher rate of any parenchymal hematoma (PH1 or PH2) (82 of 1133 [7%] vs 61 of 1128 [5%]; adjusted OR, 1.54; 95% CI, 1.02-2.34; P = .04). Compared with participants without ICH, asymptomatic ICH (adjusted common OR, 0.55; 95% CI, 0.46-0.65) and symptomatic ICH (adjusted common OR, 0.08; 95% CI, 0.05-0.13) were both associated with worse functional outcomes, and there was a graded association of ICH radiologic patterns and patient outcomes. Conclusions and Relevance In this individual participant data meta-analysis, compared with EVT alone, IVT plus EVT modestly increased the risk of ICH, notably any parenchymal hematoma. Although ICH was associated with worse functional outcomes, this effect may be offset by IVT's benefit in final successful reperfusion and early reperfusion.