Stroke

Background and Purpose: Futile interhospital transfers, where patients transferred for endovascular thrombectomy (EVT) do not ultimately receive the procedure, represent a critical systemic burden on stroke transfer network. Whether pre-transfer computed tomography angiography (CTA) at the primary stroke center (PSC) reduces futile transfers, and at what workflow cost, remains incompletely characterized. Methods: This retrospective study enrolled 314 acute ischemic stroke patients transferred for potential EVT within the Tainan-Chiayi Stroke Network (October 2021-September 2025). Patients were stratified by CTA timing: pre-transfer (n=66) versus post-transfer (n=248). Workflow time metrics and 90-day functional outcomes were compared. Futile transfers were classified into three categories: preventable over-triage, physiological futility, and gray zone cases. Results: The futile transfer rate was substantially lower in the pre-transfer CTA group (27.3% vs. 66.1%; P<0.001), with post-transfer CTA as the strongest independent predictor of futility (aOR 5.21; 95% CI 2.83-9.60). In the post-transfer CTA group, 40.2% of futile transfers involved conditions identifiable by pre-transfer CTA. Regardless of CTA timing, gray zone cases predominated in both groups (83.3% vs. 47.6%), driven by intracranial atherosclerotic stenosis/ chronic total occlusion, large infarct cores, and medium vessel occlusions. Pre-transfer CTA significantly prolonged PSC door-in-door-out time (140 vs. 88 min; P<0.001) and showed numerical trends toward longer onset-to-EVT time and lower rates of favorable functional outcome. Conclusions: Adopting CTA during the pre-transfer period reduces preventable futile transfers but prolongs PSC processing time. Nevertheless, the persistent gray zone requires strategies beyond imaging alone, and the trade-off between triage precision and transfer efficiency warrants ongoing evaluation across different stroke networks settings.-

BackgroundAcute basilar artery occlusion (BAO) causes devastating strokes. Despite the benefit of endovascular treatment, the optimal management remains sometimes controversial, such as for patients with mild deficits, and would benefit from robust prognostic tools. Given the dense white matter networks within the posterior fossa, we tested whether quantifying disconnections from acute diffusion-weighted imaging (DWI) could improve outcome prediction and responders to recanalization compared with conventional metrics. MethodsWe conducted a secondary analysis from a prospective multicenter stroke registry, including consecutive patients (2017-2024) with BAO and admission MRI. Ultra-high-resolution diffusion MRI was acquired in healthy participants to build normative tractograms with optimized posterior fossa quality. Patient infarcts delineated on DWI were projected onto these tractograms to estimate disconnected fiber volume. The primary outcome was 90-day modified Rankin Scale (mRS) 0-3 vs 4-6. Predictive performance of disconnected fiber volume was compared with baseline NIHSS, infarct volume, and posterior circulation ASPECTS (pc-ASPECTS) using logistic regressions and areas under receiver operating characteristic curves (AUC). Ordinal regressions tested associations across the full mRS spectrum, stratified by recanalization status. Analyses were repeated in patients with NIHSS [&le;]10. ResultsAmong 201 patients (median age 70; NIHSS 10), 97 (48.3%) had poor outcome. Despite small median infarct volume (4.75 mL), disconnected fiber volume was substantial (median 25.15 mL). Disconnected fiber volume achieved an AUC of 0.84, outperforming NIHSS (0.67; p<0.0001), infarct volume (0.75; p=0.00059), and pc-ASPECTS (0.76; p=0.0127). Low disconnected fiber volume predicted better outcomes across the full mRS (OR=0.12 [95% CI, 0.065-0.204]) and greater benefit from successful recanalization (OR=0.33 [95% CI, 0.15-0.70]). In patients with NIHSS [&le;]10 (n=102), disconnected fiber volume remained the strongest predictor (AUC=0.83). ConclusionsDisconnected fiber volume derived indirectly is a robust prognostic marker of BAO outcomes that outperforms conventional predictors and may support future treatment decisions. Registrationhttps://clinicaltrials.gov - NCT03776877.

ObjectiveTo assess ethnic disparities in time to hospital presentation, use of acute reperfusion therapies, and in-hospital treatment times among patients presenting with stroke in a Dutch emergency department. MethodsIn this single-centre observational cohort study, we included patients with a first-ever ischemic stroke between September 2020 and September 2021. Patients were categorized by ethnicity (with or without migration background). Demographic and stroke characteristics were compared between groups. Outcomes included: rates of presentation outside therapeutic time window, acute reperfusion therapy (intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)), and, when applicable, door-to-treatment time (DTTT), with a door-to-needle time (DTNT) and door-to-groin time (DTGT) for IVT and EVT respectively. Univariable and multivariable linear and logistic regression analyses were performed, adjusted for age, sex, and NIHSS at presentation, where appropriate. ResultsA total of 232 patients were included, of whom 62 (26.7%) had a migration background. These patients were younger (66.6 vs 71.2 years) and more frequently had diabetes (27.4% vs 15.9%). Sex distribution was similar (59.7% vs 60.6% male). Stroke etiology differed between groups with less cardio-embolism (4.8% vs 15.3%) and more small vessel disease (69.4% vs 48.2%) among patients with a migration background. These latter patients presented more often outside the therapeutic time window (53.2% vs 37.1%; OR 1.90; 95% CI 1.05-3.45). EVT was less frequently performed in patients with a migration background compared to those without (8.1% vs 22.4%; OR 0.28; 95% CI 0.10-0.75). There were no significant differences in treatment times (DTTT 38min vs 30min, DTNT 35min vs 26min, DTGT 64min vs 54min). ConclusionPatients with a migration background were more likely to present outside the therapeutic time window and had a lower rate of EVT. In order to improve access for these patients, more insight into prehospital and within hospital barriers and facilitators for appropriate management are needed.

BackgroundHemorrhagic transformation (HT) is a frequent and serious complication, occurring in up to 40% of cases after endovascular treatment (EVT) for acute ischemic stroke (AIS). Inflammation has been increasingly recognized as a key factor influencing both stroke pathophysiology and post-treatment complications (such as HT) interacting with endothelial dysfunction to exacerbate vascular injury after EVT. The objective of this study is to evaluate whether systemic inflammatory status predicts HT in AIS patients, and its relationship with endothelial biomarkers in the setting of this complication. MethodsWe retrospectively reviewed a prospective cohort of 229 AIS patients treated with EVT. Demographic, clinical, imaging, and laboratory data were collected. Inflammatory markers included white blood cell subsets and indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-neutrophil ratio (PNR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). Endothelial function was assessed by flow-mediated dilation (FMD) and circulating homoarginine (HArg), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). The main outcome was radiological or symptomatic HT, classified according to ECASS criteria. ResultsHT was observed in 92 patients (40.2%), of whom 35 (36.1% of HT and 15.3% of the total) were symptomatic. In multivariate analysis, independent predictors of HT included higher NIHSS at admission, higher plasma glucose at admission, the use of non-aspiration devices, lower pre-recanalization lymphocyte count, higher pre-recanalization SII and higher NLR levels. Among endothelial function markers, HArg correlated with inflammatory markers, ANC (r = -0.2) and WBC (r = -0.19), and was associated to PH and symptomatic HT, but not with any radiologic HT after AIS. ConclusionsAn altered inflammatory status prior to EVT in AIS patients is associated with an increased risk of developing HT after EVT. Additionally, endothelial dysfunction could participate in the more aggressive forms of this complication.

Background: Immune-mediated mechanisms are increasingly implicated in childhood arterial ischemic stroke (AIS), but the associated inflammatory pathways and how they differ by stroke subtype and outcome remain poorly understood. Understanding immune responses to AIS may identify subtype-specific mechanisms and inform targeted strategies to reduce ischemic injury. Methods: We conducted a prospective cohort study with cross-sectional transcriptomic analysis through the Vascular Effects of Infection in Pediatric Stroke Study Part II (VIPS II) at 22 academic centers in the United States, Canada, and Australia between December 2016 and January 2022. Children aged 28 days to 18 years with centrally confirmed AIS were enrolled within 72 hours of stroke onset, in addition to enrollment of stroke-free well children. Peripheral blood RNA sequencing was performed on samples collected within 72 hours of stroke or at enrollment for controls. Differential gene expression (DGE) and pathway analyses were performed comparing all AIS cases to stroke-free well children. Additional cross-sectional analyses stratified by stroke subtype and neurological outcomes were performed. Results: Transcriptomes were available in 190/205 AIS cases (median age 11.7 years) and 91/100 stroke-free children (11.8 years). Stroke subtypes included 67 definite arteriopathic, 74 probable arteriopathic, 23 cardioembolic, and 26 idiopathic, with similar demographics but smaller infarct size for idiopathic cases. 47 genes (false discovery rate (FDR) <0.05 and log2 fold-change (log2FC)>1) were differentially expressed in AIS versus stroke-free well children, with upregulated pathways reflecting innate immune responses. Stratification by subtype revealed these inflammatory responses occurred after arteriopathic and cardioembolic AIS, but not idiopathic AIS; in sensitivity analyses, these findings were not explained by infarct size. Four immune-related genes were differentially expressed in children with good versus poor neurological outcomes at hospital discharge or 12 months; upregulation of one (Joining Chain; JCHAIN) correlated with poor outcomes at both timepoints. Conclusions: Compared with stroke-free children, children with AIS, particularly arteriopathic and cardioembolic subtypes, have upregulated innate immune pathways, including neutrophil activation and interleukin-1 signaling. Differential expression of immune-related genes also correlated with neurological outcomes. These findings support immune dysregulation as a key feature of early pediatric AIS while highlighting differences across subtypes and clinical outcomes, with implications for targeted immunomodulatory therapies and future biomarker development.

ObjectiveTo compare the safety and efficacy of bridging intravenous thrombolysis (IVT) plus endovascular thrombectomy (EVT) versus direct EVT in patients with acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO) treated within the 6- to 24-hour time window. MethodsThis is a retrospective analysis of prospective EVT registry from 10 comprehensive stroke centers in China and Singapore between 2019 and 2024. Eligible patients had anterior circulation LVO, underwent EVT within 6-24 hours of onset, had ASPECTS [&ge;]6, NIHSS [&ge;]6, and pre-stroke mRS [&le;]2. Patients were stratified into bridging IVT + EVT (IVT group) versus direct EVT alone (non-IVT group). Propensity score matching (1:2 ratio) was performed to balance baseline covariates. The primary outcome was 3-month favorable functional outcome (mRS 0-2). Secondary outcomes included successful recanalization (mTICI 2b-3), symptomatic intracranial hemorrhage (sICH), hemorrhagic transformation (HT) and 3-month mortality. In the matched cohort, binary outcomes were compared using the Cochran-Mantel-Haenszel test. ResultsOf 772 included patients, 110 (14.2%) received bridging IVT and 662 (85.8%) received direct EVT. After propensity score matching, 202 non-IVT patients were matched to 101 IVT patients, with all covariates well-balanced (absolute SMD <0.10). In the matched cohort, bridging IVT was not associated with a significant difference in 3-month favorable outcome (44.55% vs. 47.03%; common OR 0.91; 95% CI 0.56- 1.46), successful recanalization (91.09% vs. 90.10%; OR 1.11; 0.51-2.44), sICH (5.94% vs. 9.41%; OR 0.61; 0.24-1.58), HT (23.76% vs. 23.27%; OR 1.03; 0.57-1.85), or 3-month mortality (15.84% vs. 13.37%; OR 1.22; 0.62-2.37). ConclusionIn this large multicenter propensity score-matched analysis, bridging intravenous thrombolysis before endovascular thrombectomy in the 6- to 24-hour time window was not significantly associated with improved efficacy or increased safety risks compared with direct endovascular therapy alone.

BackgroundHemorrhagic transformation (HT) after endovascular thrombectomy (EVT) is a principal determinant of clinical outcome. Artificial intelligence (AI) algorithms for spontaneous hemorrhage detection exist, but none has been validated for post-procedural HT across multiple imaging modalities. MethodsWe conducted a multicenter diagnostic accuracy study within the Clinical Research Collaboration for Stroke in Korea registry (18 centers, 2022-2023). Patients who underwent EVT and received follow-up NCCT, GRE, or SWI within 168 hours were included. AI-derived hemorrhage volumes were compared against expert-determined ECASS classification. Three-month modified Rankin Scale (mRS) scores were evaluated for volume-outcome association. ResultsAmong 1,490 patients (median age 73; 57.4% male), HT was present in 41.4% and parenchymal hemorrhage (PH) in 11.1%. PH detection sensitivity exceeded 94% across all modalities (NCCT 95.4%, GRE 94.4%, SWI 98.3%), with AUCs of 0.900, 0.943, and 0.953, respectively. AI-derived volume correlated with 3-month mRS (Spearman {rho} = 0.353, P < 0.001); good outcome (mRS 0-2) declined from 61.8% to 6.7% across increasing volume categories. Among ECASS 0 cases, AI-positive patients had significantly worse outcomes than true-negatives (good outcome 48.2% vs 67.2%, mortality 10.7% vs 4.6%, P < 0.001). ConclusionsAI-based hemorrhage quantification provides high detection of clinically significant PH after EVT and demonstrates a dose-response association with functional outcome. AI-derived volume may serve as a continuous prognostic biomarker that identifies at-risk subgroups beyond categorical ECASS grading.

Objectives: Among individuals attending stroke rehabilitation, we aimed to determine the proportion who participated in cardiorespiratory exercise, identify patient characteristics predicting participation, and describe exercise characteristics. Design, setting, and participants: This was an observational cohort study involving all patients admitted to four stroke rehabilitation centres in Ontario, Canada, during March or October 2019, or over 12 months starting in 2021. Main measures: Patient characteristics extracted during chart review included age, sex, marital status, employment status, date of stroke, time post-stroke at admission, length of stay for rehabilitation, past medical history that could affect exercise participation, Functional Independence Measure, Functional Ambulation Category, mobility aid use, Chedoke-McMaster Stroke Assessment, Montreal Cognitive Assessment, National Institutes of Health Stroke Scale, and details describing cardiorespiratory exercise completed. Results: 40.1% of stroke patients participated in cardiorespiratory exercise, with 26.4% having it included in their treatment plan. Diagnosed cardiac disease (OR=0.74), poor left ventricular function (OR=0.09), history of mental health conditions (OR=0.69), lower functional ambulation ability (OR=0.74), and wheelchair use at rehabilitation admission (OR=0.46) were associated with lower odds of participating in cardiorespiratory exercise after stroke (p-values<0.05). Use of a walker or rollator at rehabilitation admission (OR=3.22), having a cardiorespiratory exercise goal (OR=2.13), and longer lengths of stay (OR=1.01) were associated with higher odds of participating in cardiorespiratory exercise after stroke (p-values<0.05). Only 1.5% of patients (N=9/601) who participated in cardiorespiratory exercise completed it with recommended intensity and duration. Conclusion: Improving participation in cardiorespiratory exercise during stroke rehabilitation may require addressing cardiovascular, mental health, and mobility-related barriers.

BackgroundEndovascular thrombectomy (EVT) is the standard of care for acute ischemic stroke caused by large-vessel occlusion. However, the additional benefit of intravenous thrombolysis (IVT) before EVT remains controversial. This systematic review and meta-analysis evaluated the efficacy and safety of bridging therapy (EVT plus IVT) compared with EVT alone. MethodsThis systematic review and meta-analysis was conducted according to PRISMA 2020 and Cochrane Handbook recommendations and prospectively registered in PROSPERO. PubMed, EMbase, Scopus, and the Cochrane Library were searched for randomized controlled trials published between 1st January 2015 and 30th April 2026 comparing EVT plus IVT versus EVT alone in acute ischemic stroke. Random-effects meta-analysis was performed to estimate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Primary outcomes included functional independence at 90 days and successful recanalization. Secondary outcomes included symptomatic intracranial hemorrhage (sICH) and all-cause mortality. ResultsEleven randomized controlled trials involving 4,419 patients were included in the meta-analysis. Compared with EVT alone, bridging therapy was associated with significantly better functional independence at 90 days (OR=1.25; 95% CI: 1.02-1.53). Patients receiving EVT plus IVT also demonstrated a trend toward higher rates of successful recanalization (OR=1.25; 95% CI: 0.95-1.64) and lower 90-day mortality (OR=0.84; 95% CI: 0.67-1.04). The risk of sICH was comparable between the two treatment strategies (OR=1.07; 95% CI: 0.81-1.40). Overall, the certainty of evidence was rated as moderate. ConclusionsBridging therapy before EVT may improve functional outcomes and recanalization without increasing sICH, supporting its use as a reasonable treatment strategy in eligible patients with acute ischemic stroke.

Background: Stroke guidelines recommend intravenous thrombolysis (IVT) within 4.5 hours of symptom onset for patients with minor acute ischemic stroke (AIS) but disabling symptoms. However, such patients are often overlooked for treatment, increasing their risk of stroke-related disability. Tenecteplase is endorsed as an alternative to alteplase for IVT in patients with AIS. More evidence is required regarding its efficacy and safety in the minor stroke population. Methods: This post hoc analysis of the ORIGINAL randomized clinical trial aimed to evaluate the efficacy and safety of tenecteplase versus alteplase in the patient subgroup with minor (National Institutes of Health Stroke Scale [NIHSS] 5) disabling stroke. Primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 at Day 90. Results: Data were analyzed for 299 patients treated with tenecteplase 0.25 mg/kg and 297 patients treated with alteplase 0.9 mg/kg. At Day 90, 86.3% of tenecteplase recipients and 82.8% of alteplase recipients achieved a mRS score of 0 or 1 (risk ratio=1.04 [95% confidence interval 0.971?1.114]; non-significant). No heterogeneity of treatment effect was observed across predefined subgroups according to baseline NIHSS score, time to drug administration, sex, age, presence (yes/no) of atrial fibrillation and diabetes and thrombectomy performed. No statistically significant differences were observed between tenecteplase and alteplase across secondary efficacy and safety outcomes. Conclusions: The comparable efficacy and safety of tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg in the minor stroke population of the ORIGINAL randomized clinical trial suggests that tenecteplase is a suitable alternative to alteplase in this setting. Trial registration: ClinicalTrials.gov NCT04915729 (ORIGINAL randomized clinical trial; https://clinicaltrials.gov/study/NCT04915729). Submitted 4 June 2021. Key words: acute ischemic stroke, alteplase, intravenous thrombolysis, minor stroke, tenecteplase

ImportanceHigh-intensity interval training (HIIT) improves peak oxygen uptake (VO2peak) and walking post-stroke. However, previous HIIT trials have primarily implemented maximal exercise testing, limiting clinical implementation. ObjectiveEvaluate the preliminary efficacy of HIIT, compared to moderate-intensity continuous training (MICT) using a submaximal exercise test. Hypothesis: HIIT will produce greater improvements than MICT in VO2peak, vascular measures, and walking outcomes. DesignThis was a randomized preliminary efficacy trial conducted between July 2023 and December 2025. SettingUniversity of Kansas Medical Center. ParticipantsParticipants with chronic stroke, 20-85 years of age, were randomized to HIIT or MICT. InterventionHIIT and MICT were performed on a total-body recumbent stepper 3 times per week for 4 weeks, with intensity prescribed using peak power output (PPO) to achieve target heart rate zones derived from a submaximal exercise test. HIIT was performed for 25 minutes with 1-minute vigorous-intensity intervals (65-95% PPO) interspersed with 1-minute active recovery intervals. MICT was performed continuously at 45-65% PPO for 25 minutes. Main OutcomesThe primary outcome was change in predicted VO2peak. Secondary outcomes included middle cerebral artery velocity, peripheral vascular function, and arterial stiffness with gait speed and walking endurance as tertiary outcomes. ResultsForty-nine participants (HIIT: n=25, MICT: n=24) were randomized (62.4(12.5) years, 42.9% female), attended 99.5(2.0)% of sessions, and achieved target intensity zones. No study-related serious adverse events occurred. Our results showed no significant between-group differences (p=0.54) for study outcomes. Both groups significantly improved VO2peak (HIIT: +1.13 mL*kg-1*min-1 (95% CI: 0.05-2.21), p=0.04; MICT: +1.58 mL*kg-1*min-1 (95% CI: 0.18-2.97), p=0.03) and with fast gait speed and walking endurance. Peripheral vascular function significantly improved following HIIT. Conclusions and RelevanceHIIT can be safely implemented in individuals with chronic stroke using a submaximal exercise test. Both HIIT and MICT elicited clinically meaningful gains in VO2peak and walking. However, only HIIT led to a significant improvement in peripheral vascular function, suggesting a biologic signal for intensity-dependent vascular adaptation. Trial RegistrationClinicalTrials.gov identifier: NCT05936008. Key PointsO_ST_ABSQuestionC_ST_ABSIn individuals with chronic stroke, does high-intensity interval training (HIIT) improve predicted VO2peak more than moderate-intensity continuous training (MICT)? FindingsIn this randomized clinical trial of 49 participants with chronic stroke, both HIIT and MICT achieved prescribed intensity targets with high adherence and resulted in clinically meaningful improvements in predicted VO2peak and walking outcomes after 4 weeks, with no significant between-group difference in our primary outcome of VO2peak. MeaningThese findings suggest that when aerobic exercise is prescribed to achieve target intensity, both HIIT and MICT produce meaningful improvements in fitness and walking after stroke, supporting the importance of appropriate exercise dosing.

Background: Prospective stroke registries have advanced our understanding of cerebrovascular disease, yet most reduce neuroimaging to categorical variables, forfeiting the multidimensional information inherent in clinical imaging. We describe the CRCS-K Imaging Repository, a prospective multicenter platform that systematically collects all stroke neuroimaging and integrates artificial intelligence (AI)-based automated quantification with clinical and outcome data through a dedicated research platform, AISCAN. Methods: Building upon the Clinical Research Collaboration for Stroke in Korea (CRCS-K), a nationwide prospective registry, all neuroimaging (computed tomography [CT], magnetic resonance [MR], and angiography) performed during index hospitalization of consecutive acute ischemic stroke patients was collected from 18 comprehensive stroke centers. Imaging underwent centralized quality verification, sequence classification, and AI-based quantification. As a proof-of-concept application, we examined the association between pre-treatment imaging modality, treatment workflow efficiency, and functional outcomes in patients receiving intravenous thrombolysis (IVT) or endovascular treatment (EVT). Results: From June 2022 through May 2025, 225,159 imaging sequences were collected from 20,792 patients. AI-based quantification modules converted these into standardized numeric features encompassing ischemic lesion volumes, perfusion parameters, white matter hyperintensity burden, and cerebral microbleed counts. Substantial inter-hospital variation in imaging modality selection was observed, with MR-first workflows ranging from 1.0% to 56.7% across centers. In the proof-of-concept analysis, each additional imaging sequence was associated with prolonged door-to-treatment times for both IVT and EVT. Propensity score overlap-weighted analyses suggested numerically more favorable functional outcomes with CT-based imaging among EVT-treated patients, whereas differences among IVT-treated patients were smaller and less consistent. Conclusions: The CRCS-K Imaging Repository demonstrates the feasibility of large-scale, prospective neuroimaging collection integrated with AI-based quantification and clinical data. The infrastructure enables clinically consequential questions that conventional registries cannot address.

Background and PurposeDespite high rates of macrovascular recanalization, approximately half of patients with large vessel occlusion stroke fail to achieve functional independence after endovascular thrombectomy (EVT). Residual tissue-level perfusion abnormalities on post-procedural CT perfusion (CTP) may indicate futile recanalization and inform selection for adjuvant therapy. We synthesized post-EVT CTP thresholds, summarized acquisition timing, and discussed implications for patient selection in trials of intra-arterial thrombolysis, antithrombotics, and neuroprotection, limited to studies performing perfusion imaging after EVT. MethodsWe searched MEDLINE, EMBASE, and the Cochrane Library (January 2018-April 2026) for studies performing perfusion imaging after EVT, reporting [&ge;]1 quantitative CTP parameter with functional or neurological outcome, and enrolling [&ge;]10 patients; pre-EVT CTP studies were excluded. Functional independence with versus without post-EVT hypoperfusion was pooled using DerSimonian-Laird random-effects. Individual patient data from our prospective Cerebrolysin proof-of-concept cohort (N=18) were integrated. ResultsNine post-EVT perfusion imaging studies (497 patients) met inclusion criteria. Residual hypoperfusion occurred in 21-53% of angiographically successful reperfusions and was associated with lower odds of functional independence (pooled OR 0.23, 95% CI 0.17-0.33; I{superscript 2}=29%). A Tmax >6 s volume <3.5 mL at 30-90 minutes post-EVT was the most consistently validated threshold (OR 3.5, 95% CI 1.6-7.8). In our cohort, an ischemic core (rCBF <30%) of 0 mL versus any detectable residual core was associated with markedly higher odds of independence (OR 27.5, 95% CI 1.0-746 with continuity correction; {rho}=0.77, p=0.003). The optimal CTP acquisition window is 30-120 minutes post-EVT. ConclusionsPost-EVT CTP outperforms modified TICI grading for predicting functional outcome and identifies biologically distinct subgroups for adjuvant therapy selection. Standardized post-EVT CTP at 30-120 minutes, applied with the proposed threshold framework, should be used for eligibility and stratification in future trials of intra-arterial thrombolysis, antithrombotics, and neuroprotection.

Background: The past decade has witnessed rapid growth of clinical-trial programs in Europe and Asia, with randomized clinical trials (RCTs) publications from these regions outpacing those of the U.S. However, limited data exist quantifying their relative influence on practice-defining results. Here, we evaluate these shifts by analyzing geographic origin, funding source, and clinical impact of practice-changing RCTs. Methods: From the 2018 and 2026 American Heart Association/American Stroke Association (AHA/ASA) Acute Ischemic Stroke (AIS) Guidelines, we identified RCTs supporting new recommendations and extracted geographic origin (China/Europe/USA/Other), funding source (government/academic/non-profit vs. industry (private/mixed); NIH vs. non-NIH), and research topic (endovascular therapy (EVT), thrombolysis, imaging, poststroke care, and prehospital and systems of care). Analyses used unweighted, reference-density-weighted, and clinical-impact-weighted strategies. Temporal trends were assessed using the chi-square/Fisher?s exact tests, with Rao-Scott adjusted chi-square tests accounting for weighting. Results: We identified 21 new recommendations (47 RCTs) in 2018 and 45 (89 RCTs) in 2026. In 2018, Europe led (51.1%), followed by the U.S. (31.9%), while China and other regions contributed minimally. By 2026, Europe remained first (36%), China rose to second (29.2%), and the U.S. declined to the smallest share (14.6%), across all weighted analyses (p<0.01). NIH-funded trials declined significantly from 21.3% (unweighted), 27.4% (reference-density-weighted), and 27.3% (clinical-impact-weighted) in 2018 to 4.5%, 4.8%, and 3.4%, respectively in 2026 (p<0.01 across all weighted strategies). Conclusion: In this analysis, we identify a shift away from U.S.-based clinical trials and increasing contributions from China. U.S.-based RCTs fell from the second most cited to the least cited sources of practice-changing recommendations. NIH-funded research fell from nearly one-quarter in 2018 to <5% in 2026, highlighting increasing dependence on non-U.S. studies for U.S.-based care. These findings raise questions about the effectiveness of current AIS research paradigms in the U.S. Keywords: Acute Ischemic Stroke, Endovascular Thrombectomy, Thrombolytic Therapy, NIH Funding

ImportanceMedicare-Medicaid dual eligible beneficiaries experience pronounced disparities in stroke recovery. However, it remains unclear whether inpatient rehabilitation services and outcomes are comparable between dual-eligible beneficiaries enrolled in Medicare fee-for-service (FFS) versus Medicare Advantage (MA) plans. ObjectiveTo compare rehabilitation therapy utilization and associated outcomes among dual-eligible beneficiaries enrolled in FFS versus MA plans with stroke. DesignRetrospective cohort study. SettingInpatient Rehabilitation Facilities (IRF). ParticipantsMedicare beneficiaries admitted to IRF with stroke (n=125,782) between 2017 and 2019. ExposureDual-eligible beneficiaries enrolled in FFS versus MA plans. Main Outcome MeasuresTotal number of minutes of physical and occupational therapy provided within the first 2 weeks of IRF stay, self-care and mobility change scores, and 30-day all-cause hospital readmission. ResultsFor the first 2 weeks of therapy utilization, we did not find significant differences between the four groups. Using the non-dual FFS beneficiaries and low category of change as a reference, we found significantly lower likelihood of achieving high change in self-care scores for the dual FFS (OR=0.73, 95% CI=0.69-0.76), and dual MA (OR=0.93, 95% CI=0.88-0.98). However, non-dual MA patients had a higher likelihood of changes in self-care scores (OR=1.17, 95% CI=1.13-1.22). Similar trends were found for the mobility change scores, compared to non-dual FFS: dual FFS (OR=0.72, 95% CI=0.68-0.75), and dual MA (OR=0.91, 95% CI=0.86-0.96) and non-dual MA (OR=1.16, 95% CI=1.12-1.20). For 30-day readmission risk, dual FFS showed a higher likelihood of readmission (OR=1.19, 95% CI=1.08-1.31), while non-dual MA had a significantly lower likelihood (OR=0.77, 95% CI=0.71-0.83). Conclusions and RelevanceAlthough no differences in rehabilitation therapy utilization for stroke among dual-eligible beneficiaries, they had poorer functional recovery and higher 30-day readmission risk irrespective of FFS vs MA. Whereas non-dual-eligible MA beneficiaries experienced favorable outcomes. These findings underscore the importance of addressing post-IRF discharge needs among disadvantaged populations.

IntroductionDelivering large-bore aspiration catheters through tortuous anatomy remains challenging during mechanical thrombectomy (MT). The Carrier delivery-assist catheter (DAC) was designed to facilitate aspiration catheter navigation, but multicenter data remain limited. We evaluated the efficiency and safety of the Carrier DAC. MethodsWe performed a multicenter retrospective study of prospectively collected data from patients undergoing MT at 15 U.S. Comprehensive Stroke Centers (September 2024-September 2025). Co-primary endpoints were puncture-to-clot engagement time and first-pass effect (FPE; eTICI 2c-3). A pre-specified single-center analysis compared upfront contact aspiration using the Carrier DAC versus standard 0.021'' microcatheter techniques with identical aspiration catheter sizes. ResultsThe multicenter cohort included 211 Carrier-assisted MTs. Median aspiration catheter inner diameter was 0.071'', with super-bore catheters used in 5.7%. Median puncture-to-clot time was 12 minutes, and FPE was achieved in 50.7%. Median puncture-to-reperfusion time was 20 minutes, and mFPE occurred in 74.4%. Parenchymal hematoma and subarachnoid hemorrhage occurred in 11.8% and 6.6%, respectively. Cavernous tortuosity did not affect primary endpoints. The single-center analysis included 242 patients. Carrier use was associated with shorter puncture-to-clot times and numerically higher FPE rates without increased hemorrhagic complications. ConclusionsThe Carrier DAC enables efficient navigation of large-bore aspiration catheters and may reduce procedural time while maintaining procedural safety. Prospective studies are warranted.

BackgroundOutcome after stroke varies according to stroke subtype by location, but healthcare systems data studies do not include subtyping information. We linked natural language processing (NLP) of brain imaging reports to routinely collected data to estimate risk of death and other outcomes after stroke subtypes in a nationwide dataset. MethodsWe applied a previously validated NLP algorithm to all CT and MRI head scan reports in Scotland between 2010 and 2018. We linked the reports to hospital readmissions, prescriptions and death data to identify and characterize people with stroke, and to categorize into deep and cortical ischemic stroke, deep and lobar intracerebral hemorrhage (ICH), subarachnoid hemorrhage, and subdural hemorrhage. We used a matched cohort design, and age- and sex-matched four controls per case who never had a stroke. By subtype, we estimated rehospitalization with stroke, myocardial infarction (MI), cancer, dementia, epilepsy and death, accounting for confounders and competing risk of death. ResultsFrom 785,331 people with a head scan, we identified 64,219 with clinical stroke phenotypes (mean age 73.4yrs, 49.5% male), and subtyped 12,616 with deep ischemic stroke; 14,103 with cortical ischemic stroke; 1,814 with deep ICH; and 1,456 with lobar ICH. There was higher absolute rate of 1-year hospital readmission for lobar compared with deep ICH (4.9% [95%CI 3.9% - 6.1%] vs 3.4% [2.6% - 4.3%]), higher risk of dementia beyond 6 months after lobar ICH compared to controls than for other stroke subtypes (aHR 3.5 [2.3-5.3]); and higher risk of MI within 6 months of cortical ischemic stroke than for other stroke subtypes (aHR 4.6 [3.4-6.3]). ConclusionsNLP of free-text reports linked to coded data successfully subtyped stroke at scale, and we estimated risk of clinically relevant outcomes. Future work should use free text to enable large-scale audit and epidemiology of people with stroke.

BackgroundMoyamoya disease (MMD) is characterized by progressive arterial stenosis and abnormal collateral formation, but the spatial organization of vessel-wall abnormalities remains incompletely understood. MethodsWe combined Xenium in situ spatial transcriptomics and multiplex immunofluorescence in superficial temporal artery samples from patients with MMD and controls, and performed gain- and loss-of-function experiments in human brain microvascular endothelial cells (HBMECs). Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), tube-formation, Transwell migration, and cell scratch assays were used to assess signaling and endothelial phenotypes. ResultsMMD vascular tissue showed intimal hyperplasia, altered spatial cellular architecture, and enrichment of extracellular matrix- and proteoglycan-related programs, with upregulation of sulfatase 1 (SULF1). In HBMECs, SULF1 knockdown reduced, whereas SULF1 overexpression enhanced, vascular endothelial growth factor A165 (VEGF-A165)-induced vascular endothelial growth factor receptor 2 (VEGFR2), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (AKT) phosphorylation, migration, tube formation, and angiogenesis- and adhesion-related gene expression. Heparinase III attenuated the signaling effects associated with SULF1 overexpression. ConclusionThese findings suggest that SULF1-associated extracellular matrix alterations may contribute to local vessel-wall remodeling and enhanced endothelial responsiveness in MMD. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/721514v1_ufig1.gif" ALT="Figure 1"> View larger version (81K): org.highwire.dtl.DTLVardef@143db87org.highwire.dtl.DTLVardef@1a9d9org.highwire.dtl.DTLVardef@1362215org.highwire.dtl.DTLVardef@f7c5a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background. Up to 70% of stroke survivors develop cognitive impairment, yet clinicians lack non-invasive vascular biomarkers that could meaningfully inform risk stratification. Carotid-femoral pulse wave velocity (cfPWV), the gold-standard measurement of central arterial stiffness, is a novel biomarker of vascular aging linked to cognitive impairment. This study evaluated the association between cfPWV and post-stroke cognitive impairment, as measured by the Montreal Cognitive Assessment (MoCA), in individuals [&ge;]6 months post-stroke. Methods. This is a secondary cross-sectional analysis of baseline data from a randomized control trial. Logistic regression analyses examined the association between cfPWV (m/s) and MoCA score at the primary cut point of [&le;]26/30, with secondary cut points of [&le;]24/30 and [&le;]22/30. Models were adjusted for age, sex, systolic blood pressure, type-2 diabetes, National Institutes of Health Stroke Scale (NIHSS) score, and smoking status. Results. Of 82 participants enrolled in the main trial, 68 participants (n = 45 males, age 64.6 {+/-} 9.6 years, 1.8 {+/-} 1.2 years post-stroke) with mild-to-moderate stroke severity (NIHSS median [IQR] = 1 [2]) were included. In the fully adjusted model using the MoCA [&le;]26/30 cut point, each 1 m/s increase in cfPWV was associated with a 35% increase in the odds of post-stroke cognitive impairment (adjusted OR [aOR] = 1.35; 95% CI 1.06, 1.81; p = 0.027; Area Under the Curve [AUC] = 0.77). Consistent associations were observed at the MoCA [&le;]24/30 (aOR = 1.41; 95% CI 1.04, 2.01; p = 0.037; AUC = 0.88) and MoCA [&le;]22/30 (aOR = 1.33; 95% CI 1.03, 1.79; p = 0.039; AUC = 0.82) cut points. Conclusions. Higher cfPWV was independently associated with post-stroke cognitive impairment across clinically referenced MoCA cut points. cfPWV may be a complementary vascular biomarker to support cognitive risk stratification and identify stroke survivors who could benefit from closer monitoring or vascular-targeted intervention.

Background: The Functional Outcome in Patients with Primary Intracerebral Hemorrhage (FUNC) score was initially validated for prediction of functional independence on the Glasgow Outcome Scale (GOS) 90 days after intracerebral hemorrhage (ICH), but recovery often extends beyond three months. Aims: Our objective was to extend the FUNC score for prediction of 12-month functional independence to strengthen its utility for family counseling and research methodology. Methods: We conducted a single-center prospective cohort study enrolling adult patients with primary ICH between February 2009 and January 2018. We calculated FUNC scores at admission and assessed GOS 12 months after ICH. The primary outcome was 12-month functional independence, defined as a GOS score [&ge;]4. We calculated the area under the receiver operating characteristic curve (AUC) of the FUNC score using logistic regression, handling missing GOS with multiple imputation by chained equations. We evaluated score calibration using a calibration curve and the Brier score, and we assessed clinical utility using decision curve analysis. We explored the statistical efficiency gains of using FUNC-based sliding dichotomy thresholds for favorable outcome definitions by running simulations of a clinical trial with 1:1 randomization. We ran 5000 simulations for each sample size (100 to 1000, in increments of 10) and treatment effect (odds ratio of 1.5, 2.0 and 2.5) combination and calculated efficiency gains for each respective treatment effect as the percentage reduction in sample size required to have 80% power using sliding versus fixed dichotomy thresholds. Results: A total of 535 patients were included (median [IQR] age 68 [54-79], 237 [44%] female, median [IQR] NIHSS 16 [6-25], median [IQR] FUNC 8 [6-9]). Overall, 99 of 445 (22%) patients with known 12-month GOS achieved functional independence. The FUNC score had an AUC of 0.79 (95%-CI: 0.75-0.84) for 12-month functional independence. The calibration plot was reasonable, with modest evidence of overestimation at low predicted probabilities, and the Brier score was 0.15. A net benefit was observed across 5-50% threshold probabilities. Sliding dichotomy had an efficiency gain of 27% for a treatment effect of OR=2.0, and a gain of 22% for a treatment effect of OR=2.5. The efficiency gain for a treatment effect of OR=1.5 could not be calculated because the fixed dichotomy did not reach 80% power despite a sample size of 1000 patients. Conclusions: The FUNC score's predictive performance for 12-month functional independence was comparable to its originally validated 3-month discrimination. Following external validation across centers, the FUNC score may be leveraged to counsel families on global measures of long-term functional independence and to implement sliding dichotomy methodology in ICH research.