Stroke: Vascular and Interventional Neurology

BackgroundEven for experienced operators, endovascular treatment of unruptured intracranial aneurysms involves intraoperative uncertainty that may lead to adjustments in strategy, prolong the procedure, and potentially cause inefficiency and device waste. This study aimed to evaluate whether pre-procedural testing (PPT) of endovascular treatment using patient-specific models was associated with increased operator confidence and perceived clinical utility, including improvements in procedural efficiency and reduced resource waste. MethodsWe enrolled a cohort of patients who underwent PPT before endovascular treatment for complex unruptured intracranial aneurysms and compared their outcomes with a control group treated without PPT. The primary outcome was the Training Fidelity Score, a composite of three operator-reported Likert items defined a priori. Secondary outcomes included perceived clinical utility, intraoperative strategy changes, procedural time, radiation exposure, device waste and safety. ResultsA total of 85 patients met the inclusion criteria (PPT=40; control=45). The Training Fidelity Score was high across the PPT group (median, 4.33/5). Perceived clinical utility was high and further increased significantly after the procedure. A significant reduction was observed in intraoperative strategy changes, with no changes recorded in the PPT group, compared to 6/45 in the control group (RR 0.09; p=0.027). Reductions in treatment time, radiation exposure and device waste were also noted. ConclusionPPT using patient-specific models was associated with increased operator confidence, fewer intraoperative strategy changes, improved procedural efficiency, and reduced device waste without compromising safety. These findings support its use in pre-interventional preparation, but require prospective multicenter validation.

Background: Three-dimensional visualization and quantitative analysis of cerebral arteries on 3DRA are central to endovascular treatment planning, device selection, and cerebrovascular research. Manual segmentation is time-consuming and operator-dependent, yet no open-source deep learning model has been prospectively validated for this task on 3DRA. Methods: A nnUNet v2 model was trained for binary cerebral artery segmentation on 400 consecutive 3DRA acquisitions from three angiographic systems, comparing four configurations across architectures and loss functions. The best-performing configurations were prospectively validated on 40 patients using a dual approach: quantitative metrics (DSC, clDice, HD95, ASD, Precision, Recall), and blinded expert qualitative evaluation by two interventional neuroradiologists assessing 12 arterial segments, a global quality score, and clinical usability across 40 test cases. Results: The ensemble model achieved median DSC 0.917, clDice 0.932, and HD95 1.494 mm. Global quality scores were significantly lower for nnUNet v2 than for expert segmentations (median 4 vs 5, p<0.001), but nnUNet v2 segmentations were rated clinically usable in 88-90% of cases versus 95-98% for expert segmentations, without significant difference on the binary usability criterion. A consistent proximal-to-distal quality gradient was identified, with comparable scores at proximal arteries and the largest differences at distal arterial segments. Conclusion: nnUNet v2 with topology-aware training provides clinically usable cerebral artery segmentations on 3DRA, prospectively validated through both quantitative metrics and structured expert qualitative assessment, and represents a reproducible open-source foundation for endovascular and research applications.

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.

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.-

Background and Purpose: Hemorrhagic transformation (HT) is a serious complication of endovascular thrombectomy (EVT), yet dedicated prediction models for young adults are lacking. We aimed to develop and externally validate a simplified risk score for HT in young adults with acute ischemic stroke undergoing EVT. Methods: This multicenter retrospective study included patients aged 18 to 49 years with acute anterior circulation large vessel occlusion who underwent EVT. The primary outcome was any HT within 24 hours after EVT. Multivariable logistic regression was used to identify independent predictors of HT, from which the NO?PAIN Score was derived. External validation was performed in an independent cohort of 138 patients. Results: Among 598 patients in the derivation cohort, HT occurred in 176 (29.4%). Five independent predictors were identified: admission NIHSS, number of thrombectomy passes, atrial fibrillation, alcohol consumption, and mTICI grade. The mTICI grade demonstrated a non-linear, inverted U-shaped relationship with HT risk, peaking at partial recanalization. The NO-PAIN Score showed acceptable discrimination in both the derivation (C-index, 0.737; optimism-corrected C-index, 0.748) and external validation cohorts (C-index, 0.726), with satisfactory calibration. Conclusions: The NO-PAIN Score is a simple risk prediction tool for HT after EVT in young adults with acute anterior circulation large vessel occlusion. It may assist in individualized risk stratification in this population.

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.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke associated with higher morbidity and mortality. Posterior circulation aneurysms are considered to have worse prognosis than anterior circulation aneurysms due to anatomical location, hemorrhage severity, and treatment complexity. We aimed to determine whether aneurysm location independently influences clinical outcomes following aSAH Methods: PubMed, Scopus, Embase, and Web of Science were searched from January 2000 to December 2025 for studies reporting outcomes in anterior or posterior circulation aSAH. The outcome analysis included mortality, functional recovery (modified Rankin Scale [mRS] 0-2 and 3-6 at 6 months and 1 year), hydrocephalus, delayed cerebral ischemia (DCI), and symptomatic cerebral vasospasm. Pooled proportions and subgroup comparisons were performed using random-effects meta-analysis (DerSimonian-Laird method). Publication bias was evaluated using contour-enhanced funnel plots and Egger's test. Results: Nineteen analytic entries from 18 studies (anterior: n = 1,625; posterior: n = 986; total N = 2,611) were included. Pooled mortality was 13% (95% CI: 10%-17%; I2 = 84.6%), with no significant difference between the anterior (14%; 95% CI: 10%-20%) and posterior (11%; 95% CI: 7%-18%) circulation subgroups (p = 0.437). Good functional outcome was 60% at 6 months (95% CI: 51%-67%) and 55% at 1 year (95% CI: 46%-64%), with no location-based differences. Hydrocephalus (35% vs 35%; p = 0.979) and DCI (17% vs 17%; p = 0.939) were comparable between subgroups. Symptomatic cerebral vasospasm was the only outcome differing significantly by location, occurring more frequently in anterior circulation aSAH (24% vs 11%; {chi}2 = 5.59; p = 0.018). Conclusion: Aneurysm location does not independently determine mortality, functional recovery, hydrocephalus, or DCI following aSAH. Symptomatic cerebral vasospasm was the only location-specific outcome. Admission neurological grade (World Federation of Neurosurgical Societies [WFNS]), rather than vascular territory, appears to be the primary determinant of mortality. Aneurysm location alone should not guide prognostic decisions or limit aggressive treatment.

BACKGROUNDEarly prognostic stratification of aneurysmal subarachnoid hemorrhage (aSAH) is clinically important. We developed and temporally validated an admission-based prediction model for 90-day outcomes in a cohort of patients with aSAH. METHODSConsecutive treatment-eligible patients with aSAH, managed at a single center between January 2021 and December 2025, were retrospectively analyzed. Patients treated from 2021-2023 and 2024-2025 comprised the development and temporal validation cohorts, respectively. Prediction models were developed using admission variables, including age, pre-morbid modified Rankin Scale (mRS) score, World Federation of Neurosurgical Societies grade, modified Fisher grade, and intracerebral hemorrhage on initial computed tomography. The primary outcome was a 90-day mRS score of 0-3. A sensitivity model was constructed for 90-day mRS scores of 0-2. RESULTSA total of 245 patients were included (development cohort: 160; validation cohort: 85); 107 patients were aged [&ge;] 70 years. For mRS 0-3, the model demonstrated good discrimination in both the development and validation cohorts (area under the curve [AUC]: 0.917 and 0.868), while mRS 0-2 had corresponding AUCs of 0.920 and 0.840, respectively. Among patients aged [&ge;] 70 years, the validation AUCs were 0.842 and 0.768 for mRS scores of 0-3 and 0-2, respectively. Calibration was acceptable overall but less stable in older patients. CONCLUSIONSIn an aSAH cohort with a substantial proportion of older patients, an admission-based five-variable model provided 90-day outcome prediction with good discrimination on temporal validation. This tool may facilitate early risk stratification at admission, pending multicenter external validation. CLINICAL PERSPECTIVEO_ST_ABSWhat is New?C_ST_ABSO_LIWe developed and temporally validated a simple admission-based prediction model for 90-day functional outcomes after aneurysmal subarachnoid hemorrhage in a contemporary, consecutive, single-center cohort comprising a substantial proportion of older patients. C_LIO_LIBased on five readily available admission variables, the model showed good discrimination in both the overall population and the subgroup aged [&ge;] 70 years, with additional support for clinical utility from decision curve analysis and an exploratory external assessment in an independent published cohort. C_LI What are the Clinical Implications?O_LIAdmission-based prediction may support early prognostic estimation, family counseling, and initial risk stratification at admission when treatment-related information is unavailable. C_LIO_LIBecause the cohort comprised treatment-eligible patients who received active aneurysm treatment, the model was intended for prognostic estimation rather than for guiding treatment allocation or withdrawal decisions. C_LI

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.

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. Carotid webs (CaWs) are shelf-like protrusions in carotid bifurcation recognized as a potential cause of ischemic stroke. However, their impact on wall-based hemodynamic metrics (TAWSS, OSI, RRT) in distinguishing from normal bifurcations remains unclear. Methods. Carotid geometries were reconstructed from CT angiography in patients with CaWs, classified as symptomatic (with ischemic stroke) or asymptomatic (incidentally detected), and controls with normal bifurcations. Influence of three blood viscosity models (Newtonian, Carreau-Yasuda, Casson) was evaluated. Metrics were quantified using a Gaussian-weighted spatial averaging method and compared between groups. Results. CFD simulations were performed in 22 CaW cases (16 symptomatic, 6 asymptomatic) and 6 normal bifurcations. Simulations predicted recirculation corresponding to delayed contrast clearance on DSA. Viscosity models had minimal influence on flow patterns (<2% differences). CaWs showed greater inter-patient variability than normal bifurcations, but overlap remained (e.g., TAWSS 3.39 (2.72-8.96) vs 4.18 (3.09-4.56) Pa, p = 0.858). Symptomatic CaWs showed lower TAWSS and higher OSI and RRT than asymptomatic CaWs (TAWSS 3.39 vs 6.63 Pa), although did not reach statistical significance (p > 0.25). Conclusion. Symptomatic CaWs show lower shear stress and stronger oscillations than asymptomatic CaWs. However, wall-based hemodynamic metrics alone may not distinguish CaWs from normal carotid geometries.

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

Objective: Neuroendoscopy has emerged as a crucial minimally invasive strategy for the treatment of intracranial hemorrhage (ICH). This bibliometric analysis aims to systematically delineate the global research architecture and evolution of neuroendoscopic ICH research over the past two decades. Methods: Relevant publications were retrieved from the Web of Science Core Collection using a reproducible search strategy. Bibliometric tools were applied to analyze contributions from countries, institutions, authors, publications, keywords and journals, enabling the construction of a comprehensive knowledge map and evolutionary framework of this field. Results: A total of 403 articles were identified, involving 2128 authors from 555 institutions across 43 countries. The publication trajectory exhibited fluctuating growth, reflecting the dynamic interplay between clinical demand and technological maturation. China contributed the highest publications and citation impact, followed by the US, jointly anchoring the global influence of the field. The research keywords have evolved from ?intracerebral hemorrhage? and ?initial conservative treatment? to ?augmented reality.? Thematic evolution analysis revealed a clear progression from early emphasis on operative feasibility, safety, and perioperative outcomes toward more rigorous evidence appraisal and the refinement of context-specific clinical indications, accompanied by continuous technological innovation. Conclusion: These findings collectively position neuroendoscopy as a cornerstone of modern ICH management, reshaping clinical strategies toward precision, minimal invasiveness, and multimodal intervention. Future progress will depend on strengthened international collaboration to generate high-quality evidence that supports patient stratification. The integration of emerging technologies, including advanced endoscopic robotics, is expected to further accelerate the translational and clinical landscape of neuroendoscopic ICH therapy.

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.

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: 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

ObjectiveThe JAK2 V617F mutation increases the risk of thrombosis in patients with myeloproliferative neoplasms (MPNs). However, it remains unclear whether individuals who carry the JAK2 V617F mutation without MPN also have an increased risk of stroke. MethodsWe prospectively tested for the JAK2 617F mutation in consecutive patients with acute ischemic stroke or transient ischemic attack (TIA) admitted between January 2020 and September 2024. Patients with overt MPN or abnormal blood counts were excluded. We used allele-specific PCR to detect the mutations. ResultsIn total, 921 patients (median age, 77 years; 557 men (62%); TIA, 32 patients) were enrolled in this study. Among them, 11 patients (1.2%; median age, 72 years; 8 male) tested positive for the JAK2 V617F mutation. There were no significant differences in clinical background, including age, sex, BMI, comorbidities, or history of thrombosis, between the positive and negative groups. The blood count and coagulation parameters did not differ significantly between the two groups. Among the 11 patients in the positive group, 9 had embolic stroke and 2 had thrombotic stroke. Embolic stroke of undetermined source (ESUS) was more frequently observed in the positive group than in the negative group (45 vs. 13%; p=0.002). Stroke severity and outcomes did not differ between the two groups. DiscussionApproximately 1% of patients with acute ischemic stroke or TIA carry the JAK2 V617F mutation despite normal blood counts. Of the 11 mutation-positive patients, nine (82%) exhibited embolic imaging features and five (45%) met the ESUS criteria, whereas other clinical characteristics did not differ significantly from the mutation-negative group.

BackgroundCarotid artery stenosis may contribute to cognitive impairment through chronic hypoperfusion and subclinical ischemic injury. Although carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce stroke risk, their cognitive effects remain unclear. We conducted a systematic review and meta-analysis to evaluate cognitive outcomes after these interventions. MethodsFollowing PRISMA guidelines, we searched PubMed, Embase, Web of Science, and the Cochrane Library from January 2000 to November 2025. Eligible studies reported cognitive outcomes after CEA or CAS, either alone or in direct comparison. Random-effects meta-analyses were performed for Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) outcomes. Single-arm studies were analyzed using standardized mean change, and head-to-head studies using mean difference. Outcomes were stratified by intervention type and follow-up interval (0-6 months and >6 months). Domain-specific cognitive outcomes were summarized qualitatively. Risk of bias was assessed using RoB-2, ROBINS-I, and the Newcastle-Ottawa Scale. ResultsSixty-eight studies including 4,659 patients met inclusion criteria; 27 contributed to meta-analysis and 41 to qualitative synthesis. MMSE showed no significant early change after either intervention, while CAS showed significant improvement at >6 months. MoCA improved significantly after both CEA and CAS at early and late follow-up, although heterogeneity was high. Head-to-head analyses found no significant difference between CEA and CAS for MMSE or MoCA, but these comparisons were limited by small sample sizes. Domain-specific outcomes were mostly stable, with improvements most often reported in memory, attention, executive function, and processing speed. ConclusionsCarotid revascularization may be associated with improved cognitive outcomes, particularly on MoCA, but results are heterogeneous and largely observational. Comparative evidence does not show a clear cognitive advantage of CEA or CAS. Future studies should use standardized cognitive testing and adequately powered direct comparisons.

BackgroundVenous thromboembolism (VTE) remains a major cause of perioperative morbidity in cranial neurosurgery, yet clinical practice varies widely, and formal guidelines are inconsistent. Understanding internationally sampled neurosurgical practice is essential for informing consensus and future trials. MethodsAn international, 2-stage cross-sectional, internet-based survey was conducted. Practising neurosurgeons performing elective adult cranial surgery were eligible. Descriptive statistics were used to summarise practice. Responses covered patterns of pre-operative haemostasis decision making, use and timing of mechanical and/or chemical prophylaxis, use of perioperative imaging prior to anticoagulation, and frequency of clinical assessment for VTE. Associations with geographical income status, subspecialty, and years post-certification were statistically tested. Practice heterogeneity was quantified and contextual influence was summarised using mean effect sizes across stratifying variables in order to determine domains of true equipoise. ResultsOf 585 responses, 456 (78%) met criteria for inclusion: representing 322 units across 78 countries (71% high-income). Thirteen per cent reported no departmental VTE plan; 23% followed no guidelines and 12% used multiple. Routine pre-operative testing almost universally included haemoglobin/platelets/haematocrit, with fibrinogen more common in high-income settings. Compared with high-income country respondents, low- and middle-income respondents reported higher haemoglobin transfusion thresholds (>90 g/dL; p<0.001) and shorter antiplatelet interruption (p[&le;]0.03), and less frequent outpatient VTE assessment (p<0.001). Mechanical prophylaxis was common (TEDs 81%, IPC 62%), typically started pre-or intra-operatively. Among those completing the chemoprophylaxis section (n=310), 57% required a CT or MRI scan before LMWH which was then initiated on average 31.4 hours after surgery. 1% of respondents did not routinely use LMWH. Many clinical decisions demonstrated statistical equipoise ie. high heterogeneity with low contextual influence. ConclusionPeri-operative haemostasis and VTE prophylaxis practices in adult elective cranial neurosurgery vary substantially worldwide, with some decisions reflecting geographical or socioeconomic differences and many others reflecting true clinical equipoise rather than contextual determinants. By mapping contemporary real-world practice across diverse health-system contexts, this study provides a necessary empirical foundation for rational trial design and future guideline development.