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Stroke: Vascular and Interventional Neurology

Ovid Technologies (Wolters Kluwer Health)

Preprints posted in the last 30 days, ranked by how well they match Stroke: Vascular and Interventional Neurology's content profile, based on 13 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Pre-procedural testing using patient-specific models is associated with high training fidelity and improved procedural efficiency in endovascular aneurysm treatment

Hofmeister, J.; Bernava, G.; Rosi, A.; Brina, O.; Reymond, P.; Muster, M.; Lovblad, K.-O.; Machi, P.

2026-04-24 radiology and imaging 10.64898/2026.04.23.26351592 medRxiv
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Background: Even 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. Methods: We 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. Results: A 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. Conclusion: PPT 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.

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Safety and Efficacy of Bridging Intravenous Thrombolysis Versus Direct Endovascular Therapy in Acute Ischemic Stroke Treated in the 6- to 24-Hour Time Window: A Propensity Score-Matched Analysis

Chen, Y.; Law, Z. K.; Zhou, X.; Dai, Q.; Xiang, S.; Xiao, X.; Ma, J.; Feng, M.; Peng, W.; Zhou, S.; Chen, L.; Zhou, Y.; Lai, Y.; Yeo, L.; An, S.; He, Y.; Pan, S.-Y.

2026-04-23 neurology 10.64898/2026.04.21.26351431 medRxiv
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Abstract Objective: To 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. Methods: This 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 6, NIHSS 6, and pre-stroke mRS 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. Results: Of 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). Conclusion: In 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.

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Mortality and Morbidity in Anterior Versus Posterior Circulation aSAH: A Systematic Review and Meta-Analysis.

Tripurari, S. S.; Nayak, R.; A, R.; Nair, S.; Nair, R.; Huchche, A. M.; M, S. S.; Kunikatta, V.

2026-04-02 neurology 10.64898/2026.03.31.26349908 medRxiv
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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.

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Global Research Architecture and Evolution of Neuroendoscopy for Intracranial Hemorrhage: A Bibliometric Analysis

Duan, Z.; Huang, M.; Peng, Z.; Tu, T.

2026-03-30 neurology 10.64898/2026.03.27.26349582 medRxiv
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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.

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Ethnic Disparities in Acute Stroke Presentation and Reperfusion Therapy in a Dutch Comprehensive Stroke Center

Lee, Y. X.; Hurkmans, P. V.; Arwert, H. J.; Vliet Vlieland, T. P.; van den Wijngaard, I. R.; hofs, d.; Jellema, K.

2026-04-26 neurology 10.64898/2026.04.23.26351631 medRxiv
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Objective: To 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. Methods: In 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. Results: A 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). Conclusion: Patients 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.

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Variation in Haemostasis and VTE Prophylaxis in Elective Adult Cranial Neurosurgery: A Global Survey of Perioperative Practice

Pandit, A. S.; Chaudri, T.; Chaudri, Z.; Vasilica, A. M.; Dhaliwal, J.; Sayar, Z.; Cohen, H.; Westwood, J. P.; Toma, A. K.

2026-04-16 surgery 10.64898/2026.04.14.26350905 medRxiv
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Background Venous 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. Methods An 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. Results Of 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. Conclusion Peri-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.

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High-resolution disconnectome predicts outcome and response to thrombectomy in basilar artery occlusion

Authamayou, B.; Marnat, G.; Matsulevits, A.; Munsch, F.; Lavielle, A.; Courbin, N.; Foulon, C.; Chen, B.; Micard, E.; Gory, B.; L'Allinec, V.; Bourcier, R.; Naggara, O.; Lauze, E.; Boulouis, G.; Lapergue, B.; Eker, O.; Sibon, I. P.; Thiebaut de Schotten, M.; Tourdias, T.

2026-04-21 radiology and imaging 10.64898/2026.04.20.26350998 medRxiv
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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.

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Platelet Function Test-Guided Antiplatelet Therapy Reduces Recurrent Stroke in Atherothrombotic and Lacunar Infarction

Nakayasu, S.; Hayashi, H.; Goda, R.; Maeda, M.; Yoshioka, N.; Kobayashi, S.; Ogino, E.; Horikawa, F.; Murai, N.

2026-04-07 neurology 10.64898/2026.04.06.26350274 medRxiv
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Bakground and Purpose Antiplatelet resistance is a recognized risk factor for recurrent ischemic stroke, yet evidence supporting platelet function test?guided antiplatelet therapy modification in stroke prevention remains limited. We investigated whether VerifyNow-guided antiplatelet therapy modification reduces recurrent ischemic stroke in patients with atherothrombotic or lacunar infarction. Methods This retrospective observational study enrolled consecutive patients with atherothrombotic or lacunar infarction at a single center (April 2023-March 2025). Of 302 patients, 243 were analyzed: 122 in the modified group, whose antiplatelet agent was selected based on VerifyNow Aspirin Reaction Units and P2Y12 Reaction Units, and 121 in the unmodified group, whose agent was empirically selected. The mean follow-up period was 1.62 {+/-} 0.61 years. In the modified group, when both aspirin and clopidogrel showed inadequate inhibition, prasugrel or cilostazol was selected. The primary endpoint was recurrent ischemic stroke; the secondary endpoint was intracranial hemorrhage. Cox proportional hazards models with inverse probability weighting were used to adjust for confounders. Results Recurrent ischemic stroke occurred in 1 patient (0.8%) in the modified group versus 8 (6.6%) in the unmodified group (log-rank P=0.018). After adjustment, the modified group had a significantly lower risk of recurrent stroke (HR, 0.10; 95% CI, 0.012-0.84; P=0.033). Intracranial hemorrhage occurred in 0 (0%) and 1 (0.8%) patients, respectively. Conclusions In Japanese patients with atherothrombotic or lacunar infarction, VerifyNow-guided antiplatelet therapy modification was associated with a significantly lower incidence of recurrent ischemic stroke without increased hemorrhagic risk. Given the single-center retrospective design and small sample size, validation in a multicenter randomized controlled trial is warranted.

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Real-time prospective (shadow mode) validation of an AI-based clinical decision support system for predicting 3-month functional outcome in acute stroke: the VALIDATE study protocol

Rubiera, M.; Bendszus, M.; Leker, R. R.; Hilbert, A.; Werren, I.; Lopez-Ramos, L. M.; Ayesta, M.; Nguyen, T. N. Q.; Bonekamp, S.; Sala, V.; Jubran, H.; Meza, C.; Shalabi, F.; Schwartzmann, Y.; Cano, D.; von Tottleben, M.; Kelleher, J.; Frey, D.

2026-04-27 neurology 10.64898/2026.04.26.26350937 medRxiv
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Introduction Despite the proven benefits of reperfusion therapies in acute ischemic stroke, treatment decisions in the hyperacute phase remain complex and are rarely supported by individualized outcome predictions. Artificial intelligence (AI)-based clinical decision support systems (CDSS) offer potential real-time prognostic estimates, but prospective evidence of their feasibility and performance in routine clinical workflows is limited. Our aim is to prospectively evaluate real-time feasibility, usability, and predictive performance of an AI-based CDSS (VALIDATE-CDSS) for individualized outcome prediction in acute stroke care. Methods and analysis Prospective, multicenter, observational study enrolling consecutive patients with acute ischemic stroke presenting to three tertiary stroke centers. Clinical management will follow standard practice at the discretion of treating physicians. In parallel, a dedicated researcher will collect patient data in real time and input them into the VALIDATE-CDSS using a mobile application, operating in shadow mode without influencing clinical decisions. The system will generate individualized predictions of 3-month functional outcome (modified Rankin Scale) for four treatment strategies (intravenous thrombolysis, endovascular thrombectomy, combined therapy, or no reperfusion) at three sequential time points: baseline clinical data, non-contrast CT, and CT angiography. The primary outcome is the real-world feasibility and usability of the VALIDATE-CDSS in the hyperacute stroke workflow. Secondary outcomes include predictive performance, agreement between model-suggested and actual treatments, incremental value with increasing data availability, and assessment of potential bias across predefined subgroups. This study will provide prospective real-world evidence on the implementation and clinical potential of AI-based decision support for personalized treatment selection in acute ischemic stroke Ethics and dissemination Patient enrollment began after approval from the ethics committees of all participating centers. Results will be disseminated through peer-reviewed open-access journals and conference presentations. Following open science principles, anonymized data and metadata will be made publicly available in the Zenodo repository upon study completion. Trial registration: ClinicalTrials.gov (NCT05622539).

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A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study of Chuanzhi Tongluo Capsule in Acute Ischemic Stroke (CONCERN): Study Rationale and Design

Yang, D.; Li, G.; Song, J.; Shi, X.; Xu, X.; Ma, J.; Guo, C.; Liu, C.; Yang, J.; Li, F.; Zhu, Y.; Zi, W.; Ding, Q.; Chen, Y.

2026-04-23 neurology 10.64898/2026.04.20.26351260 medRxiv
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Abstract Background: Acute ischemic stroke (AIS) remains a significant cause of disability worldwide. Current treatments, primarily intravenous thrombolysis (IVT), are limited by narrow time windows and reperfusion injury, leading to suboptimal outcomes for many patients. Chuanzhi Tongluo (CZTL), a traditional Chinese medicine, has been preliminarily recognized as a novel cerebral protection agent in animal models. Objectives: This trial investigates the efficacy and safety of CZTL capsule in patients with AIS who are not eligible for IVT or who experience early neurological deterioration after IVT. Methods and design: The CONCERN trial is an investigator-initiated, prospective, multicenter, double-blind, parallel-control, randomized clinical study in China. An estimated 1,208 eligible participants will be consecutively randomized to receive CZTL capsule therapy or placebo in 1:1 ratio across approximately 70 stroke centers in China. All enrolled patients are orally administered 2 capsules of CZTL or placebo 3 times a day together with antiplatelet agents for 3 months. Outcomes: The primary endpoint is an excellent functional outcome, defined as a score of 0 or 1 on the mRS at 90 days. Lead safety endpoints included 90-day mortality and symptomatic intracranial hemorrhage within 48 hours. Conclusions: Results of CONCERN trial will determine the clinical efficacy and safety of the traditional Chinese medicine CZTL capsule in the treatment of AIS patients. Trial registry number: ChiCTR2300074147 (www.chictr.org.cn).

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Inflammatory Biomarkers & Interpretable ML for SAP Risk Stratification in AIS Patients Undergoing Bridging Therapy

Wang, X.-Y.; Li, M.-M.; Zhao, S.-M.; Jia, X.-Y.; Yang, W.-S.; Chang, L.-L.; Wang, H.-M.; Zhao, J.-T.

2026-04-17 neurology 10.64898/2026.04.15.26350997 medRxiv
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Stroke-associated pneumonia (SAP) is a common, severe complication in acute ischemic stroke (AIS) patients receiving bridging therapy (intravenous thrombolysis + mechanical thrombectomy), worsening prognosis and increasing mortality. Current SAP prediction models rely heavily on subjective clinical factors, limiting accuracy. This study developed an interpretable machine learning (ML) model combining inflammatory biomarkers to stratify SAP risk in AIS patients undergoing bridging therapy. We retrospectively enrolled AIS patients who received bridging therapy, collected baseline clinical data and inflammatory biomarkers, and constructed ML models (including XGBoost, random forest) with SHAP analysis for interpretability. The model integrating inflammatory biomarkers achieved excellent predictive performance (AUC=0.XX, 95%CI: XX-XX), outperforming traditional clinical models. SHAP analysis identified key biomarkers driving SAP risk, enhancing model transparency. This interpretable ML model provides an objective, accurate tool for SAP risk stratification in AIS patients, helping clinicians identify high-risk individuals early and implement targeted interventions to improve outcomes.

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The Gut-Vascular Axis in Intracranial Aneurysm Rupture: A Systematic Review and Meta-analysis of Human Microbiome Evidence

Fahim, F.; Hemmati, M.; Heshmaty, S.; Sharvirani, A.; Shahini, A.; Hosseini, A.; Hosseini Marvast, S. M.; Mojtahedzadeh, A.; Konarizadeh, M.; Dorisefat, F.; Maham, N.; Omranisarduiyeh, A.; Oveisi, S.; Fadaei Juibari, F.; Malekipour Kashan, B.; Sharifi, G.; Zali, A.

2026-04-07 neurology 10.64898/2026.04.05.26350207 medRxiv
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Background Intracranial aneurysm rupture is the leading cause of spontaneous subarachnoid hemorrhage and is associated with substantial mortality and long term neurological disability. Emerging evidence suggests that the gut microbiome may influence vascular inflammation and endothelial integrity through immune and metabolic pathways, yet human evidence linking gut microbial alterations to intracranial aneurysm remains fragmented and inconsistent. Objective This systematic review and meta analysis aimed to synthesize available human evidence on the association between gut microbiome alterations and intracranial aneurysm formation or rupture, with a primary focus on microbial dysbiosis and differences in gut microbial alpha diversity. Methods This study was conducted according to PRISMA 2020 guidelines and the protocol was prospectively registered in PROSPERO (CRD420261360785). A comprehensive search of PubMed, Scopus, Web of Science, Embase, and Cochrane CENTRAL was performed from database inception until April 1, 2026, with additional screening of grey literature sources. Observational human studies evaluating gut microbiome characteristics in patients with intracranial aneurysm were included. Mendelian randomization (MR) studies investigating genetically predicted microbial taxa and aneurysm outcomes were also reviewed. Random effects meta analysis using standardized mean differences (SMD) was performed for alpha diversity outcomes. MR taxa reported in at least two independent studies were quantitatively synthesized using inverse variance weighting of log odds ratios. Results The systematic search identified 396 records. After removal of duplicates and eligibility screening, 20 studies met inclusion criteria, including 12 observational clinical studies and 8 Mendelian randomization analyses. Meta analysis of three microbiome sequencing studies demonstrated significantly reduced gut microbial alpha diversity in patients with ruptured intracranial aneurysms compared with controls. Sensitivity analyses confirmed the robustness of pooled estimates. In addition, MR evidence identified several microbial taxa, including Ruminococcus1, Bilophila, Fusicatenibacter, and Porphyromonadaceae, as potentially protective factors against aneurysm related outcomes. Across observational studies, gut dysbiosis was frequently associated with inflammatory pathways and alterations in microbial metabolites implicated in vascular dysfunction. Conclusion Current human evidence suggests a potential association between gut microbiome dysbiosis and intracranial aneurysm pathophysiology, particularly in relation to aneurysm rupture. Reduced microbial diversity and specific microbial taxa may influence vascular inflammation and aneurysm wall stability. However, existing evidence remains limited and heterogeneous. Large prospective cohorts and mechanistic studies are required to clarify causal relationships and evaluate whether microbiome targeted interventions could contribute to aneurysm risk stratification or prevention strategies.

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The efficacy and safety of argatroban with clopidogrel versus aspirin with clopidogrel for acute minor ischemic stroke (ACAP): study protocol for a multicenter, randomized controlled trial

Zhang, H.; Ma, X.; Xiao, Y.; Liao, G.; Kong, N.; Qin, T.; Huang, M.; Yin, Z.; Chen, W.; Wu, J.; Xian, J.; Fu, J.; Xie, F.; Jin, C.; Liao, Z.; Liang, W.; Lin, L.; Xian, W.; Nguyen, T. N.; Wang, D.; Zhong, W.

2026-03-31 neurology 10.64898/2026.03.30.26349790 medRxiv
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Background: Previous studies have shown the benefit of dual antiplatelet therapy (DAPT) for acute minor ischemic stroke. Argatroban, is a thrombin inhibitor and is primarily used in patients with acute ischemic stroke experiencing early neurological deterioration. There is no study about the benefit of antiplatelet plus anticoagulant in this population. We aim to study the difference between the combination of argatroban and clopidogrel and DAPT in the outcomes of patients with acute minor ischemic stroke (AMIS, NIHSS <5) presenting within 72 hours after onset. Methods: Argatroban combined with clopidogrel versus aspirin combined with clopidogrel in Stroke (ACAP study) is an investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded endpoint evaluation conducted at four centers in China. This trial will randomize 464 eligible patients with minor ischemic stroke of NIHSS 5 (232 in each arm) within 72 hours of the last known well to receive intravenous argatroban with clopidogrel (treatment group) or aspirin plus clopidogrel (control group). The primary outcome is the proportion of patients achieving excellent outcome, defined as a score of 0-1 on the modified Rankin scale, at 90 days. Conclusions: The ACAP trial will provide important data on the role of intravenous argatroban in patients with acute minor ischemic stroke presenting within 72 hours of last known well.

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Trans-Aqueduct Access to the Third Ventricle for Delivery of Medical Devices: A Feasibility Study

Haines, M. H.; Ronayne, S. M.; Pickles, K.; Begg, D. A.; Hurley, P. J.; Ferraccioli, M.; Desmond, P.; Opie, N. L.

2026-04-21 neurology 10.64898/2026.04.14.26348906 medRxiv
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This research demonstrates that the trans-aqueduct approach is a feasible, minimally invasive access pathway to the third ventricle, offering a potential route to the deep brain for therapeutic technologies. Further pre-clinical investigation is required to thoroughly evaluate physiological tolerance, trauma risk, and the long-term implications of intraventricular implantation. The third ventricle is a high-value site for neuromodulation due to its proximity to deep-brain targets, including the subthalamic nucleus (STN) and globus pallidus internus (GPi). This study defined the anatomical pathway; and evaluated the technical feasibility of retrograde access to the third ventricle via the cerebral aqueduct using minimally invasive interventional techniques. Evaluation was conducted in three phases using human MRI datasets (n=16; mean age 48.4 years) and cadaveric specimens (n=6; mean age 88.2 years). Phase 1 involved morphometric MRI analysis of the aqueduct and ventricles. Phase 2 tested trans-aqueduct access on cadaver specimens via fluoroscopically guided guidewires and catheters. Phase 3 utilized direct anatomical dissections on cadaver specimens (n=3) to morphometrically measure the third ventricular cavity and its relationship to deep-brain nuclei. Measurements across the sample groups showed a mean aqueduct diameter of 1.6 mm (SD=0.14). Third ventricle dimensions averaged 27.6 mm (ventral-dorsal), 19.9 mm (caudal-cranial), and 5.7 mm (lateral). Successful access to the third ventricle was achieved in 83% (5/6) of cadaveric specimens. The optimal technical configuration utilized a 0.018'' angled-tip guidewire and 5-6 Fr catheters; the aqueduct accommodated diameters up to 2.0 mm with minimal resistance. The STN and GPi were localized within 5-20 mm of the ventricular volumetric centroid. The trans-aqueduct approach is a technically feasible, minimally invasive pathway for accessing the third ventricle. This route offers a potential alternative for the delivery of therapeutic neurotechnologies. Further research is required to assess physiological tolerance, trauma risk, and the long-term safety of intraventricular implantation.

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Prognosis of stroke subtypes in whole population health systems data: a matched cohort study

Hosking, A.; Iveson, M. H.; Sherlock, L.; Mukherjee, M.; Grover, C.; Alex, B.; Parepalli, S.; Mair, G.; Doubal, F.; Whalley, H. C.; Tobin, R.; Wardlaw, J. M.; Al-Shahi Salman, R.; Whiteley, W. N.

2026-04-20 neurology 10.64898/2026.04.17.26351150 medRxiv
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Background Outcome 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. Methods We 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. Results From 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 ischaemic stroke; 14,103 with cortical ischaemic 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]). Conclusions NLP 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.

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CTA versus TOF-MRA for circle of Willis segmentation: Implications for hemodynamic modelling

Vikström, A.; Zarrinkoob, L.; Johannesdottir, M.; Wahlin, A.; Hellström, J.; Appelblad, M.; Holmlund, P.

2026-04-11 cardiovascular medicine 10.64898/2026.04.10.26350583 medRxiv
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Modelling of hemodynamics in the circle of Willis (CoW) depends on vascular segmentation, which may vary based on imaging modality. Computed tomography angiography (CTA) is commonly used in clinic but involves radiation and injection of contrast agents, whereas magnetic resonance angiography (MRA) offers a non-invasive alternative. This study aims to compare CoW morphology and modelled cerebral perfusion pressure of CTA and MRA segmentations, validating if MRA can replace CTA in modelling workflows. CTA and time-of-flight MRA (TOF-MRA) of the CoW was performed in 19 patients undergoing elective aortic arch surgery (67{+/-}7 years, 8 women). The CoW was semi-automatically segmented based on signal intensity thresholding. A TOF-MRA threshold was optimized against the CTA segmentation, using the CTA as reference standard. Computational fluid dynamics (CFD) modelling with boundary conditions based on subject-specific flow rates from 4D flow MRI simulated cerebral perfusion pressure in the segmented geometries. A baseline simulation and a unilateral brain inflow simulation, i.e., occlusion of a carotid, were carried out. Linear mixed models indicated there was no effect of choice of modality on either average arterial lumen area (CTA - TOF-MRA: -0.2{+/-}1.3 mm2; p=0.762) or baseline pressure drops (0.2{+/-}1.9 mmHg; p=0.257). In the unilateral inflow simulation, we found no difference in pressure laterality (-6.6{+/-}18.4 mmHg; p=0.185) or collateral flow rate (10{+/-}46 ml/min; p=0.421). TOF-MRA geometries can with signal intensity thresholding be matched to produce similar morphology and modelled cerebral perfusion pressure to CTA geometries. The modelled pressure drops over the collateral arteries were sensitive to the segmentation regardless of modality.

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Instantaneous Wave-Free Ratio-Guided vs Angiography-Guided Coronary Artery Bypass Grafting: 36-Months Graft Patency and Clinical Outcomes of a Randomized Trial

Ordiene, R.; Unikas, R.; Benetis, R.; Jakuska, P.; Ciaponiene, I.; Ivanauskiene, A.; Jankauskas, A.; Aldujeli, A.; Plisiene, J.; Kabosis, T.; Punjabi, P. P.; Davies, J. E.; Krivickas, Z.

2026-04-03 cardiovascular medicine 10.64898/2026.04.01.26350013 medRxiv
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Background: Coronary artery bypass grafting (CABG) to physiologically non-significant coronary artery stenosis may result in graft failure due to competitive native flow. We evaluated whether an instantaneous wave-free ratio (iFR)-guided revascularization strategy improves graft patency and clinical outcomes compared to conventional angiography-guided CABG. Methods: In this prospective, randomized, single-blinded trial, patients with multivessel disease and at least one angiographically intermediate stenosis (50%-75%) were randomized to either CABG guided by angiography alone or angiography supplemented with iFR assessment groups. The primary endpoint was graft patency (occlusion or hypoperfusion of the graft) evaluated by coronary computed tomography angiography (CCTA) at 2, 12, and 36 months. Results: At 36 months, 78% of the patients completed follow-up. Left internal mammary artery (LIMA)-to-left anterior descending (LAD) artery graft patency was significantly higher in the iFR-guided group than in the angiography-guided group (80.5% vs. 56.8%; absolute risk difference, 23.7% [95% CI, 3.7%-43.8%]; RR, 1.42 [95% CI, 1.03-1.95]; P = 0.03). Saphenous vein graft patency also improved with iFR guidance (90.2% vs. 70.3%; P = 0.046). Major adverse cardiac and cerebrovascular events (MACCE) were similar between groups (28% vs. 20%; RR, 1.40 [95% CI, 0.69-2.85]; P = 0.48). Conclusions: iFR-guided CABG advocates significantly improved mid-term graft patency compared with angiography-guided CABG by optimizing surgical target selection and reducing competitive flow.

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Left Ventricular Geometry Improves Prediction of Sex-Specific Post-TAVR Remodeling in Aortic Stenosis

Goraya, S. A.; Lauwers, P.; Javadikasgari, H.; Rouhollahi, A.; Homaei, A.; Masoumi, S.; Zancanaro, E.; Rezaeitaleshmahalleh, S.; Ayers, B. C.; Hirji, S.; Alkhouli, M.; Jassar, A. S.; Aganj, I.; Sabe, A.; Nezami, F. R.

2026-03-31 surgery 10.64898/2026.03.30.26349680 medRxiv
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Background: Women with severe aortic stenosis (AS) are diagnosed later and experience poorer outcomes than men, partly because clinical approaches rely on 2D, valve-centric thresholds derived from male-predominant cohorts that underutilize information from 3D left ventricular (LV) geometry. We hypothesize that a sex-specific computational framework integrating statistical shape analysis (SSA) of pre-TAVR CT with machine learning would improve prediction of 1-year LV mass regression (LVMR). Objective: To develop a computational framework leveraging 3D LV geometry and evaluate whether it improves sex-specific prediction of 1-year LVMR after TAVR. Methods: We studied 339 patients with severe AS who underwent TAVR from 2013 to 2020 and had pre-TAVR CT and 1-year post-TAVR echocardiography. LV geometries were segmented into digital twins, and shape modes predictive of LVMR were extracted using SSA and partial least squares. These modes were incorporated into support vector regression models and compared with conventional echocardiographic predictors, including pre-TAVR LVEF, LVMI, and E/A ratio. Performance was assessed using RMSE and R^2. Results: After one year, 65% of patients showed positive LVMR, with median regression of approximately 10%; regression was significant overall and within each sex (p<0.001) and similar between sexes (p=0.99). Predictive shape modes differed by sex (p<0.01), with women showing more localized variation and men broader geometric gradients. Sex-specific shape modes outperformed general modes and clinical metrics, particularly in women (R^2=0.80, RMSE=0.09 vs. R^2=0.59, RMSE=0.13; clinical-only baseline R^2=0.16, RMSE=0.22). In men, sex-specific modes also performed strongly (R^2=0.89, RMSE=0.08). Conclusion: In severe AS, 3D LV geometry predicts post-TAVR reverse remodeling more accurately than conventional metrics and may improve risk stratification, particularly in women.

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Virtual Spectral Decomposition with Dendritic Binary Gating Detects Pancreatic Cancer Tissue Transformation on Standard CT: Multi-Institutional Validation Across Three Independent Datasets with a 3.8-Year Pre-Diagnostic Detection Window

Chandra, S.

2026-04-12 oncology 10.64898/2026.04.08.26350418 medRxiv
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Background. Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of approximately 12%, largely because it is typically diagnosed at an advanced stage. CT-based computational methods for early detection exist but rely on black-box deep learning or large texture feature sets without tissue-specific interpretability. Methods. We developed Virtual Spectral Decomposition (VSD), which applies six parameterized sigmoid functions S(HU) = 1/(1+exp(-alpha x (HU - mu))) to standard portal-venous CT, decomposing each pixel into tissue-specific response channels for fat (mu=-60), fluid (mu=10), parenchyma (mu=45), stroma (mu=75), vascular (mu=130), and calcification (mu=250). Dendritic Binary Gating identifies structural content per channel using morphological filtering, enabling co-firing analysis and lone firer identification. A 25-feature signature was extracted per patient. Three independent datasets were analyzed: NIH Pancreas-CT (n=78 healthy), Medical Segmentation Decathlon Task07 (n=281 PDAC, paired tumor/adjacent tissue), and CPTAC-PDA from The Cancer Imaging Archive (n=82, multi-institutional, with DICOM time point tags). The same six sigmoid parameters were used across all datasets without retraining. Results. VSD achieved AUC 0.943 for field effect detection (healthy vs cancer-adjacent parenchyma) and AUC 0.931 for patient-stratified tumor specification on MSD. On CPTAC-PDA, VSD achieved AUC 0.961 (6 features) and 0.979 (25 features) for distinguishing healthy from cancer-bearing pancreas on scans obtained prior to pathological diagnosis. All significant features replicated across datasets in the same direction: z_fat (d=-2.10, p=3.5e-27), z_fluid (d=-2.76, p=2.4e-38), fire_fat (d=+2.18, p=1.2e-28). Critically, VSD severity did not correlate with days-from-diagnosis (r=-0.008, p=0.944) across a range of day -1394 to day +249. Patient C3N-01375, scanned 3.8 years before pathological diagnosis, had VSD severity 1.87, well above the healthy mean of 0.94 +/- 0.33. The tissue transformation signature was temporally stable, indicating an early, persistent tissue state rather than a progressively worsening process. Conclusions. VSD with Dendritic Binary Gating detects a stable pancreatic tissue composition signature on standard CT that is present years before clinical diagnosis, validated across three independent datasets without parameter adjustment. The six sigmoid channels map to biologically meaningful tissue components through a fully transparent interpretability chain. The temporal stability of the signal implies a detection window of 3-7 years, consistent with known PanIN-3 microenvironment transformation timelines. VSD functions as a single-scan screening tool applicable to any abdominal CT performed during the pre-clinical window.

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Post-Discharge Anti-Seizure Medication Use Improves Post-Stroke Survival: An Emulated Target Trial in Older Adults

Sankaranarayanan, M.; Donahue, M. A.; Brooks, J. D.; Sun, S.; Newhouse, J. P.; Blacker, D.; Haneuse, S.; Hernandez-Diaz, S.; Moura, L. M. V. R.

2026-04-20 neurology 10.64898/2026.04.17.26351149 medRxiv
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ObjectiveLevetiracetam is commonly prescribed for seizure prophylaxis after acute ischemic stroke (AIS) and often continued beyond discharge. While its short-term effectiveness for preventing post-stroke seizures is established, it is unclear whether prolonged use improves survival, particularly in older adults. We estimated the effect of continued levetiracetam use on 90-day mortality among Medicare beneficiaries after AIS. MethodsUsing Traditional Medicare claims data (2008-2021), we identified beneficiaries aged [&ge;]66 years hospitalized for AIS who initiated outpatient levetiracetam within 90 days of discharge. After one month of continued post-stroke use of levetiracetam (start of follow-up), we compared 90-day mortality between patients with a new levetiracetam dispensation within a 14-day grace period post-follow up and those without one. We performed cloning, censoring and weighting to address immortal time bias and estimated standardized mortality risks, risk differences, and 95% confidence intervals (CI). ResultsAmong 3,212 eligible beneficiaries, 1,779 (55.4%) received a new levetiracetam dispensation within the 14-day grace period. Median age was 76 years (IQR 70-83); 57.8% were female. After adjustment for demographics, hospitalization characteristics, timing of initiation, and comorbidities, continued use was associated with lower 90-day mortality than discontinuation (53 vs 62 deaths per 1,000; risk difference -9 per 1,000; 95% CI: (-12,-5)). The reduction was observed primarily among patients aged [&ge;]75 years. SignificanceAmong older Medicare beneficiaries who initiated levetiracetam after AIS, continued outpatient use was associated with modestly lower 90-day mortality, particularly in those aged [&ge;]75 years. These findings suggest potential benefits of levetiracetam continuation beyond the immediate post-stroke period.