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Stroke: Vascular and Interventional Neurology

Ovid Technologies (Wolters Kluwer Health)

Preprints posted in the last 90 days, ranked by how well they match Stroke: Vascular and Interventional Neurology's content profile, based on 14 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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Temporal and Geographic Variation in Outcomes After Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis

de Oliveira Manoel, A. L.; Msheik, A.; Zampieri, F. G.; Peralta, R.; Al Rumaihi, G.; Al-Thani, H.; Suarez, J. I.

2026-07-02 neurology 10.64898/2026.06.29.26356892 medRxiv
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Background: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains associated with high mortality and severe disability, yet contemporary outcomes may differ substantially from historical estimates. We performed a systematic review and meta-analysis to evaluate long-term outcomes after poor-grade aSAH and assess temporal, geographic, and treatment-related factors associated with prognosis. Methods: PubMed/MEDLINE, Embase, Cochrane Central, Scopus, and Google Scholar were searched from inception through March 2026. Studies enrolling consecutive adults with poor-grade aSAH (World Federation of Neurosurgical Societies grades IV-V, Hunt-Hess grades IV-V, or equivalent) reporting mortality and/or functional outcomes at 3 months were included. To minimize survivorship bias, studies excluding untreated patients or patients dying before aneurysm treatment were excluded. Random-effects meta-analyses of proportions were performed using generalized linear mixed models. Prespecified subgroup analyses and exploratory meta-regression analyses evaluated temporal, geographic, and treatment-related factors associated with outcomes. Results: Forty-two studies including 7,726 patients from 16 countries across 4 continents were included. The pooled favorable functional outcome rate was 27.2% (95% CI, 23.9%-30.8%), whereas pooled overall mortality was 53.3% (95% CI, 49.0%-57.5%). Pre- and post-treatment mortality were 25.9% and 33.9%, respectively. Aneurysm treatment rate was 72.0% (95% CI, 65.6%-77.7%). Favorable outcomes improved over time from 13.5% (95% CI, 7.0%-24.3%) in the 1980s to 33.7% in the 1990s but plateaued thereafter. In exploratory meta-regression analyses, higher aneurysm treatment rates were independently associated with improved favorable functional outcome (0.134 log-odds increase per 10% increase in treatment rate; p = 0.01) and lower mortality (-0.224 log-odds per 10% increase in treatment rate; p < .001). Publication year was associated with lower mortality (p = 0.03) but not favorable outcome. Geographic region, country income group, and the proportion of grade V patients were not independently associated with outcomes. Conclusions: Mortality after poor-grade aSAH remains high, but approximately one-third of patients achieved favorable outcome. Higher aneurysm treatment rates were independently associated with improved functional outcomes and lower mortality.

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Quantitative Prognostic Modeling in Aneurysmal Subarachnoid Hemorrhage: Multicenter Validation of the eSAH Score

Salman, S.; Graf von Moy, C.; Haidenberger, F.; Ahmed, M.; Foettinger, F.; Sharma, R.; Gutierrez-Aguirre, S.; de Toledo, O.; Patel, V.; Yujia-Wei, D.; Rezai Jahromi, B.; Brandmeir, N.; Lakkaraju, K.; Ombada, M.; Aguilar-Salinas, P.; Miller, D.; Erickson, B.; Hanel, R.; Tawk, R.; Byrne, R.; Freeman, W. D.

2026-07-21 neurology 10.64898/2026.07.18.26358390 medRxiv
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Background: aneurysmal subarachnoid hemorrhage (aSAH) is neurological emergency associated with substantial mortality and disability. Current grading systems such as the modified Fisher Scale (mFS) and World Federation of Neurological Societies (WFNS) score, rely on semiquantitative and examination based assessments. Hence, they demonstrate limited predictive precision. The enhanced subarachnoid hemorrhage (eSAH) score is a simplified quantitative model integrating age, Glasgow Coma Scale (GCS), and cisternal subarachnoid hemorrhage volume (SAHV) to predict clinical outcomes after aSAH. Methods: We performed a retrospective multicenter cohort study that included 1088 patients across three tertiary-care centers the United States. Predictive performance for unfavorable functional outcome, in-hospital mortality and delayed cerebral ischemia (DCI) was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). Comparative analyses were performed and compared to the WFNS and mFS grading systems. Results: the eSAH score demonstrated excellent discrimination for unfavorable functional outcome at discharge ( AUC 0.89 ) and in-hospital mortality (AUC 0.87). The DCI subscore demonstrated good discriminatory performance for predicting DCI (AUC 0.77). Compared with conventional grading systems, this was superior to both the WFNS (AUC 0.75) and the mFS ( AUC 0.70). increasing eSAH scores were additionally associated with progressively higher rates of mortality and unfavorable functional outcomes. Conclusion: the eSAH score demonstrates strong external validity, reproducibility and superior predictive performance compared with conventional grading systems in a large multicenter cohort. These findings support the clinical utility of quantitative hemorrhage burden integration for early risk stratification in patients with aSAH.

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Association of biological sex with clinical outcomes following STA-MCA bypass in atherosclerotic cerebrovascular disease

Iqbal, M. A.; Alsolivany, J.; Ferdowssian, K.; Mertens, R.; Sprünken, E. D.; Wessels, L.; Vajkoczy, P.; Acker, G.; Hecht, N.

2026-07-20 surgery 10.64898/2026.07.17.26358368 medRxiv
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Background: Sex differences in cerebrovascular disease are established determinants of outcome in acute stroke care and vascular interventions, but evidence in cerebrovascular bypass surgery remains limited. This study examined whether biological sex was associated with outcome after superficial temporal artery to middle cerebral artery (STA-MCA) bypass in patients with atherosclerotic cerebrovascular disease (ACVD). Methods: We retrospectively screened adults undergoing extracranial-to-intracranial (EC-IC) bypass (2012?2025) and included ACVD patients treated by STA-MCA bypass with available follow-up. The primary outcome was modified Rankin Scale (mRS) at latest follow-up, analyzed using proportional odds regression. Multivariable models adjusted for age, preoperative mRS, and vascular comorbidities. Cerebrovascular reserve capacity (CVRC) was analyzed in a subgroup. Results: A total of 140 patients (30.7% female) were included. Disease morphology varied by sex, with more multivessel (65.1% vs. 47.4%) and stenotic disease (39.5% vs. 20.6%) in females and more isolated internal carotid artery occlusion in males (43.3% vs. 16.3%). The 30-day risk of symptomatic ischemic stroke was higher in females than in males (9.3% vs. 1.0%). A similar pattern was observed at follow-up (median 13.5 months), with ischemic events predominating in females (16.3% vs. 7.2%) and hemorrhagic events occurring exclusively in males (5.2%). Female sex was independently associated with worse functional outcome (OR 2.59, 95% CI 1.28?5.30, p=0.008). Preoperative mRS was the strongest determinant of outcome (OR 4.30, 95% CI 3.07?6.18, p<0.001). Adjusted analysis detected no significant association between CVRC and outcome (OR 0.80, 95% CI 0.24?2.70, p=0.721). Conclusions: Female sex was independently associated with worse functional outcome after STA-MCA bypass, independent of preoperative functional status, hemodynamic impairment and cardiovascular comorbidities. These findings identify sex as a clinically relevant determinant of outcome in cerebrovascular bypass surgery and should be considered in future risk stratification and trial design.

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Beyond Binary Vasospasm: A Continuum Model Relating Severity and Distribution to Perfusion Deficits After Aneurysmal SAH

Thaler, C.; Meyer, L.; Tokareva, B.; Geest, V.; Kniep, H. C.; Heitkamp, C.; Dührsen, L.; Meyer, H. S.; Bester, M.; Fiehler, J.; Schlicht, F.

2026-07-18 neurology 10.64898/2026.07.16.26358285 medRxiv
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Background: Cerebral vasospasm is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with delayed cerebral ischemia (DCI) and unfavorable outcome. While CTA-based vasospasm grading is frequently used, its relationship with actual cerebral perfusion remains incompletely understood. This study investigates the association between vasospasm severity and distribution and territorial perfusion deficits. Methods: In this retrospective single-center study, 513 CT examinations (CTA and CT perfusion) from 194 patients with aSAH were analyzed. Vasospasm was graded per vessel segment using the CTA Vasospasm Score, and perfusion deficits were assigned to corresponding vascular territories (left/right anterior circulation, posterior circulation). Vasospasm distribution was further classified by severity and multifocality. Associations between vasospasm score and perfusion deficits were assessed using a generalized linear mixed model with binomial distribution, adjusting for Hunt & Hess grade, modified Fisher score, and days since hemorrhage. Results: Vasospasm was detected in 79.3% of examinations, and a perfusion deficit in at least one territory was present in 62.6%. The proportion of perfusion deficits increased progressively with both vasospasm severity and multifocality, ranging from 21.7-25.0% in the absence of vasospasm to 81.2-82.2% in severe multifocal vasospasm. The CTA Vasospasm Score was significantly associated with perfusion deficits in all territories (OR 1.36-1.50), with stronger associations in the anterior than posterior circulation. Conclusion: Vasospasm severity and distribution are strongly associated with perfusion deficits, supporting a continuum model of ischemic risk. However, the substantial proportion of perfusion deficits occurring independent of vasospasm suggests additional microcirculatory mechanisms not captured by CTA. CT perfusion should be considered complementary to CTA, particularly in clinically deteriorating or non-assessable patients.

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IL-10 Overexpression Improves Cerebral Microcirculation and Attenuates Cerebral Vasospasm After Experimental SAH

Nogami, K.; Ishii, H.; Demura, M.; Nakamura, T.; Loc, N. D.; Takarada-Iemata, M.; Tsunekawa, Y.; Nitahara-Kasahara, Y.; Okada, T.; Kamide, T.; Nakada, M.; Hori, O.

2026-08-29 pathology 10.64898/2026.08.25.747167 medRxiv
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BACKGROUND: Subarachnoid hemorrhage (SAH) induces inflammatory responses and subsequent immune cell activation, which may contribute in cerebral vasospasm, microcirculatory impairment and poor neurological outcomes. Although cerebral vasospasm has traditionally been considered a major cause of delayed cerebral ischemia after SAH, therapies targeting angiographic vasospasm have not consistently improved functional outcomes. Early inflammatory responses may contribute to microcirculatory impairment, cerebral vasospasm, and subsequent neurological injury. Herein, we investigated whether interleukin-10 (IL-10), an anti-inflammatory cytokine, improves these outcomes in an experimental SAH model. METHODS: Mice received intramuscular injections of either an adeno-associated virus encoding IL-10 (AAV/IL-10) vector or an AAV expressing green fluorescent protein (AAV/GFP) vector (control). India ink angiography was performed to assess the diameter of the sphenoidal segment of the middle cerebral artery (MCA), the total length of the visible cortical arteries, and cortical staining intensity, as indices of cerebral vasospasm, microcirculatory impairment, and cerebral perfusion, respectively. Perivascular inflammatory cell infiltration and cytokine levels were assessed using immunohistochemistry and ELISA. We also evaluated the therapeutic efficacy of the AAV/IL-10 vector when administered immediately after SAH induction. RESULTS: IL-10 overexpression significantly improved neurological outcomes after SAH and was associated with attenuated cerebral vasospasm and microcirculatory impairment, as well as preservation of cerebral perfusion. It also significantly reduced neutrophil and macrophage infiltration around the internal carotid artery and attenuated SAH-induced elevations in IL-6 and matrix metalloproteinase-3 levels. Mice treated with the AAV/IL-10 vector immediately after SAH induction showed significant improvements in neurological scores and cerebral perfusion. CONCLUSIONS: AAV-mediated IL-10 overexpression improves neurological outcomes after SAH, likely by attenuating inflammatory responses, cerebral vasospasm, and microcirculatory impairment. These findings suggest that IL-10-based anti-inflammatory therapy is a promising therapeutic strategy for SAH.

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Impact of Operator Technique Preference on Thrombectomy Reperfusion Outcomes

Yelam, T.; Martins, P. N.; Dolia, J.; Batista dos Reis, S.; Grossberg, J. A.; Pabaney, A. H.; G Nogueira, R.; Al-Bayati, A. R.; Haussen, D. C.

2026-07-04 neurology 10.64898/2026.07.01.26357084 medRxiv
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ABSTRACT Background: Randomized trials have shown comparable reperfusion rates among stent-retriever, contact-aspiration, and combined thrombectomy techniques. We aim to evaluate the association between operator device-selection preference and procedural performance metrics. Methods: Retrospective analysis of prospective data from a comprehensive stroke center. Preferred technique was defined as a technique used in >50% of an operator's thrombectomies. Main exposure: proportion of usage of a given technique by operators in a certain period; primary endpoint: rate of first-pass effect(FPE). Results: 1405 patients fit inclusion criteria. The first time period(2019- mid 2022/n=839) included 4 operators(3 experienced/1 starting practice), with CoT being overall used in 58.9%, SR in 24.4%, and CA in 16.7%. The second( mid 2022-2024/n=566) included 4 total operators(2 experienced/2 starting), with CA reaching 48.2%, CoT 39.8% and SR 12.0%. The distribution of techniques varied between intra-/inter-operators and most(75.0%) had a preferred technique. The technique with the highest FPE rate was never the most used technique. The chances of operators achieving FPE were not dependent on the previous cumulative success for a given technique. Increasing case volume was associated with higher FPE on average, but the learning rate differed by technique and only contact aspiration had a significant learning curve. The parenchymal hemorrhage rates were comparable for individual operators regardless of technique. Conclusion: Neurointerventionists tended to rely on a preferred technique, which did not necessarily lead to superior reperfusion outcomes. The cumulative success with a given technique did not increase the likelihood of attaining FPE in subsequent cases. Among new operators, a learning curve for contact aspiration was observed.

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Time Metrics of Acute Stroke Pathways for Mechanical Thrombectomy in Indonesia: A Descriptive Study on Two Tertiary Major Hospitals

Permana, A. P.; Ronoatmodjo, S.; Gunawan, K.; Nugroho, S. W.; Kurniawan, M.; Rasyid, A.; Mulyana, R. M.; Syahrul, S.; Arpandy, R. A.; Hidayat, Y. A. S.; Ilato, K. F.; de Liyis, B. G.; Hasanah, N. A.; Adisasmita, A. C.

2026-07-16 neurology 10.64898/2026.07.14.26358067 medRxiv
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Background: Mechanical thrombectomy (MT) is a time-sensitive reperfusion treatment for acute ischemic stroke caused by large-vessel occlusion. Workflow time metrics for MT remain poorly characterized in Indonesia, where stroke burden is substantial. This study describes pre-hospital and in-hospital time-interval metrics for MT across two major tertiary hospitals in Jakarta and evaluates institutional trends over a nine-year period. Methods: We conducted a retrospective descriptive study of consecutive patients undergoing MT at dr. Cipto Mangunkusumo National General Hospital (RSCM) and Prof. Dr. dr. Mahar Mardjono National Brain Center Hospital (RSPON) from 2017 to 2025. Pre-hospital and in-hospital time-interval metrics were reported as median (interquartile range [IQR]) and stratified by institution. Results: Among 330 registered patients, 71 were excluded due to incomplete data, leaving 259 in the final cohort (RSCM n=38; RSPON n=221). The pooled cohort had a mean age of 58.12 {+/-} 11.09 years; 63.71% were male. Hypertension was the most prevalent vascular risk factor (53.67%). Median door-to-CT time was 9 minutes (IQR 18), door-to-decision 101 minutes (IQR 100), and door-to-groin puncture 272 minutes (IQR 152). Total ischemic time (onset-to-groin puncture) was 468 minutes (IQR 294). MT volume increased substantially over the study period, particularly after 2022 at RSPON, which also demonstrated progressive improvement in in-hospital workflow times. RSCM showed increasing delays in later years, consistent with institutional congestion at a general multispecialty center. Conclusions: Early brain imaging was achievable at both centers; however, post-imaging delays particularly in CT-to-groin intervals, represent the dominant in-hospital bottleneck. Future quality-improvement efforts should prioritize decision-making, team mobilization, and pre-hospital coordination to reduce total ischemic time and improve access to reperfusion therapy.

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Interventional Rescue Therapy for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: 10-Year Experience

Kissling, C.; Petutschnigg, T.; Nasiri, D.; Goldberg, J.; Bervini, D.; Dobrocky, T.; Piechowiak, E. I.; Murek, M.; Müller, M. D.; Schucht, P.; Schefold, J. C.; Raabe, A.; Z'Graggen, W. J.

2026-08-31 neurology 10.64898/2026.08.25.26361378 medRxiv
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Background: Evidence regarding delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) remains sparse. We aimed to identify its predictors and occurrence and evaluate its role in ischemic stroke and functional outcome under treatment with interventional rescue therapy (IRT). Methods: This retrospective single-center study included 628 adults with aSAH from 2014?2023. The primary endpoint was occurrence of refractory DCI (= refractory despite induced hypertension) treated with at least one IRT. Multivariable models evaluated refractory DCI, new ischemic stroke, and poor functional outcome (mRS 3?6) at 6?12 months. Results: Among 628 included patients, 61 who died within 3 days were excluded from DCI analysis; 166/567 (29%) developed refractory DCI. Younger age (OR = 0.98; P<0.001), female sex (OR = 0.57; P=0.007), and higher WFNS grade (OR = 1.18; P=0.011) were independently associated with refractory DCI. Earlier first IRT was associated with longer DCI duration (IRR = 0.88; P<0.001) and more required IRTs (IRR = 0.91; P<0.001). IRT was performed later than day 14 in 29/166 patients (17.5%); none was older than 70 years. Refractory DCI was associated with new ischemic stroke (OR = 4.68; P<0.001) and poor functional outcome (OR = 2.37; P<0.001); earlier first IRT was associated with poor outcome within the refractory DCI subgroup (OR = 0.86; P=0.03). Outcomes after 1?2 IRTs did not differ from those without refractory DCI (P=0.4), whereas ?3 IRTs were associated with poor outcome (P=0.04). Conclusions: Refractory DCI affected 29% of aSAH patients, predominantly younger women and patients with poorer initial neurological status, and extended beyond day 14 in nearly 20% of affected patients, none of whom was older than 70 years. Refractory DCI and earlier onset were associated with poorer radiological and functional outcomes. The absence of a detected outcome difference after 1?2 IRTs suggests that favorable outcomes may remain achievable despite refractory DCI.

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A Prospective Evaluation of Clinical Outcomes in Acute Ischemic Stroke after Endovascular Treatment Using Transcranial Doppler (PRECISE-TCD): Study Protocol

Srisilpa, S.; Robinson, A.; Sabo, R.; Reavey-Cantwell, J.; Rivet, D. J.; Roy, A.; Mainali, S.; Falcao, D.; Srivastava, T.; Sarwal, A.

2026-07-29 neurology 10.64898/2026.07.27.26359066 medRxiv
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Endovascular thrombectomy (EVT) improves outcomes in acute ischemic stroke caused by large vessel occlusion. Despite successful recanalization, early neurological deterioration (END) remains frequent and predicts poor outcomes. Disturbances in cerebral autoregulation may contribute to END, yet reliable bedside predictors are limited. Transcranial Doppler (TCD) provides noninvasive bedside assessment of cerebral blood flow velocities and may identify hemodynamic patterns associated with post-EVT deterioration. PRECISE-TCD is a prospective, single-center observational study enrolling 180-300 patients undergoing EVT for anterior circulation large vessel occlusion at a tertiary academic medical center. TCD examinations will be performed as soon as feasible after EVT, daily through 72 hours, and near END events. Hemodynamic parameters including peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (MFV), and pulsatility index (PI) will be measured in bilateral MCA, ACA, PCA, carotid siphon, vertebrobasilar, and ophthalmic artery territories. The primary outcome is the association between TCD-derived parameters and END within 72 hours, defined as an increase of [&ge;]4 points in total NIHSS score, an increase of [&ge;]1 point in NIHSS subcategory 1a, radiologic evidence of intracranial hemorrhage within 72 hours, or any neurological change prompting emergent head CT at clinician discretion. Secondary outcomes include NIHSS at 24 hours and discharge, discharge disposition, and modified Rankin Scale (mRS) at 90 {+/-} 10 days after hospital discharge. Joint models for longitudinal and time-to-event data will determine the association between TCD parameter trajectories and time to END. Unsupervised clustering will identify TCD-based hemodynamic phenotypes using vessel velocities, pulsatility indices, hemispheric asymmetry measures, collateral flow, and temporal trajectory patterns. We hypothesize that abnormal post-EVT hemodynamic phenotypes will correlate with END and hemorrhagic transformation. Identifying such signatures may support development of TCD-guided, individualized blood pressure strategies to reduce secondary injury after reperfusion and inform future interventional trials. The study is registered at ClinicalTrials.gov (NCT07013396).

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Safety of Tenecteplase in Pediatric Arterial Ischemic Stroke

Lee, S.; International Pediatric Stroke Study, ; Sun, L. R.; Pediatric Neurocritical Care Research Group, ; Lee-Eng, J.; Barry, D.; Wilson, J. L.; Harrar, D. B.; Torres, M.; Galardi, M. M.; Hassanein, S. M.; Barry, M. M.; Rivkin, M. J.; Guilliams, K.; Amlie-Lefond, C.

2026-07-22 neurology 10.64898/2026.07.20.26358531 medRxiv
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Background: Recent AHA guidelines recommend the use of IV Tenecteplase (TNK) in adult stroke patients, but there is minimal safety and dosing data on TNK in pediatric patients. We performed a safety surveillance study aiming to evaluate risk of symptomatic intracranial hemorrhage (ICH) in children who received TNK for suspected acute ischemic stroke (AIS). Methods: This was a prospective observational cohort surveillance study analyzing responses from a monthly email survey sent to members of two large international pediatric stroke and neurocritical care research consortia querying recent use of TNK in children. Limited demographic, clinical, and outcome data were collected. A Bayesian beta-binomial model for risk of symptomatic ICH with IV TNK was fit using a prior distribution based on the risk level in adults. Results: Between February 2023-June 2026, 44 children received TNK for suspected AIS. Most patients (n=37, 84.1%) were adolescents; no children under 5 received TNK. Twelve patients (27.3%) were ultimately diagnosed with a stroke mimic. Symptomatic ICH was not reported in any children who received IV TNK; 3 had asymptomatic ICH on follow-up imaging. One patient received intra-arterial TNK and experienced symptomatic ICH. No other major bleeding events were reported. Conclusions: IV TNK is being administered to pediatric patients with suspected stroke in clinical practice, and may be safe in older children with AIS. Rigorous prospective studies are needed to better assess risk and outcomes in this unique population.

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The Psychological Footprint of Unruptured Intracranial Aneurysm Discovery

Renedo, D.; Chen, H.; Sheth, K. N.; Gandhi, D.; Malhotra, A.; Matouk, C. C.

2026-08-31 neurology 10.64898/2026.08.25.26361377 medRxiv
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Background: Unruptured intracranial aneurysms (UIAs) are increasingly identified incidentally, and management balances rupture risk against treatment risk. UIA diagnosis has been linked to psychological distress, but psychotropic medication initiation after UIA discovery has not been compared across the full UIA management spectrum. Methods: We conducted a retrospective cohort study using IBM MarketScan claims (CCAE, MDCD, and MDCR; 2009-2023) among adults with a UIA diagnosis, continuous enrollment for 365 days before and after the index date, and no SAH/rupture on or before the index date. We compared the prevalence of 6 mental-health diagnoses before versus after UIA discovery and used adjusted logistic regression to examine psychotropic medication initiation within 365 days by management strategy (untreated observation as the reference). Results: Among 54,945 patients (untreated, 78.5%; endovascular, 11.3%; clipping, 3.0%; other/uncertain, 7.2%), prevalence of every mental-health diagnosis was higher after UIA discovery, most for depression (+4.6 percentage points) and anxiety (+4.5 points). Medication initiation was most common for benzodiazepines (8.7%). Endovascular treatment was associated with higher adjusted odds of benzodiazepine (aOR, 1.21), SSRI (aOR, 1.20), and sedative-hypnotic (aOR, 1.25) initiation.Surgical clipping demonstrated the broadest association, with higher odds across 5 of 6 classes, including benzodiazepines (aOR, 1.71) and sedative-hypnotics (aOR, 1.86). Benzodiazepines had the lowest 1-year persistence (10.5%) despite being the most commonly initiated class. Findings were consistent across sensitivity analyses, with the exception of the increase in panic disorder, which was no longer observed after applying a 30-day post-index lag. Conclusions: Mental-health diagnoses and psychotropic medication initiation increased after UIA discovery, and medication initiation was most pronounced among patients treated with surgical clipping. These findings support psychological assessment as part of aneurysm management regardless of strategy.

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ICH-CARE: ICH-integrated Care for Accelerated Response to Hemorrhage Using a Phased Approach.

Salman, S.; English, S.; Mooney, L.; Miller, D.; Ng, L.; Kramer, C.; Ombada, M.; Tawk, R.; Freeman, W. D.

2026-07-21 neurology 10.64898/2026.07.18.26358392 medRxiv
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Introduction: Intracerebral hemorrhage (ICH) carries higher morbidity and mortality than ischemic stroke. Recent studies have demonstrated improved patient outcomes by applying ultra-early bundled interventions including blood pressure management, coagulopathy reversal, and osmotic therapy. Effective strategies to deliver these ultra-early treatment options are currently being explored. On December 19th, 2022, the Mayo Clinic Comprehensive Stroke Center (CSC) launched the "ICH Phases'' communication system to accelerate ICH patient care. Objective: To evaluate adherence to the AHA/ASA guidelines in acute ICH care following the implementation of our novel-tiered paging system. Methods: We retrospectively reviewed patients admitted with spontaneous ICH during 2024 and 2025. We excluded traumatic cases. We extracted clinical data such as time to imaging, documentation of ICH score, blood pressure control, reversal of anticoagulation, venous thrombo-embolism (VTE) prophylaxis and discharge disposition. Results: Among 67 patients, 68.7% underwent CT imaging within 25 minutes. We documented the ICH score within 6 hours in 82.9% of patients. Nearly 94.7% of patients with SBP>140 mm Hg received antihypertensive therapy, yet only 18% reached target BP within 60 minutes. We completed the reversal of anticoagulation within 120 minutes in 75% of patients. VTE prophylaxis was initiated within 24 hours in 91% of patients. Discussion: Our novel system demonstrated adherence to the AHA/ASA guidelines, and time sensitive benchmarks in neuroimaging, reversal of anticoagulation, and VTE prophylaxis. Early BP control remains a challenge, that highlights the discrepancy between guidelines and real-ground implementation. Conclusion: A novel tiered paging system is effective for enhancing early ICH care. Such a holistic system remains critical for sustained improvement in quality of care.

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From CHESS to CHECKMATE: A Practical Score for Predicting Shunt Dependency Following Subarachnoid Hemorrhage

Salman, S.; Haidenberger, F.; Ahmad, M.; Rezai Jahromi, B.; Albaramony, N.; Patel, V.; Peel, J.; Ombada, M.; Gutierrez-Aguirre, S.; de Toledo, O.; Aguilar-Salinas, P.; Tawk, R.; Byrne, R.; Hanel, R.; Rabinstein, A.; Freeman, W. D.

2026-07-21 neurology 10.64898/2026.07.18.26358389 medRxiv
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Objective: Shunt-dependent hydrocephalus is a common and costly complication of aneurysmal subarachnoid hemorrhage (aSAH), affecting up to 28% of survivors. Existing prediction tools, including the Chronic Hydrocephalus Ensuing from SAH Score (CHESS), have limited discriminative accuracy. We developed the CHECKMATE score, a clinically practical tool to improve prediction of ventriculoperitoneal shunt dependency after aSAH. Methods: In this multicenter retrospective cohort of 486 patients with aSAH from Mayo Clinic (January 1, 2006-December 31, 2021), we used multivariable logistic regression and machine learning to identify independent predictors of ventriculoperitoneal shunt placement. The CHECKMATE score was derived from 5 weighted variables: symptomatic hydrocephalus (10 points), intraventricular hemorrhage (5 points), SAH volume greater than 10 mL (3 points), neutrophil-to-lymphocyte ratio greater than 12 (2 points), and 10-year incremental age thresholds starting at older than 60 years (1 point each). Results: Of 486 patients (mean age, 56.3 years; 64.6% female), 137 (28.2%) required ventriculoperitoneal shunt placement. The CHECKMATE score achieved an area under the curve of 0.808 (compared to 0.737 for CHESS), with a sensitivity of 0.85, specificity of 0.67, and negative predictive value of 0.92 at the optimal cutoff of 14 points. Conclusions: The CHECKMATE score outperforms CHESS for predicting ventriculoperitoneal shunt dependency after aSAH and is easily used at the bedside. Its high negative predictive value helps identify low-risk patients who may benefit from earlier external ventricular drain weaning and shorter hospital stays.

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Intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis for acute medium vessel occlusion (MeVO-TNK): Study rationale and design

Deng, G.; Liu, C.-C.; Wang, Y.-H.; Ao, D.-H.; Huang, H.; Xie, Y.; Zhang, Y.; Kong, Q.-Q.; Lan, L.-N.; Li, P.-X.; Qin, T.-T.; Li, G.; Xu, S.-B.; Luo, X.

2026-06-18 neurology 10.64898/2026.06.16.26355640 medRxiv
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Background The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra-arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand-alone IAT remains undefined. Aim To preliminarily evaluate the efficacy and safety of intra-arterial tenecteplase (IA-TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA-TNK dosing strategy. Design The MeVO-TNK trial is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging-confirmed MeVO will be randomized 1:1 to receive either IA-TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra-arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety. Outcomes The primary efficacy outcome is final infarct volume measured at 72{+/-}24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0-1, 0-2 and 0-3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours. Conclusions This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand-alone IA-TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

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Clinical Characteristics and Predictors of Delayed Cerebral Ischemia in High-Altitude Aneurysmal Subarachnoid Hemorrhage

Song, Z.; Hu, C.; Wujin, D.; Duoji, Y.; Chang, X.; Cao, X.; Ren, Z.; Wu, G.

2026-06-23 neurology 10.64898/2026.06.19.26356110 medRxiv
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Background and Purpose-Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular event, with delayed cerebral ischemia (DCI) representing its most feared complication. High-altitude environments induce profound cerebrovascular adaptations, yet no study has systematically examined aSAH outcomes in chronically hypoxic populations. We characterized clinical features and identified DCI predictors among aSAH patients on the Tibetan Plateau. Methods-This single-center retrospective cohort included 256 consecutive aSAH patients admitted at a tertiary neurosurgical center in Tibet (altitude 2,330-4,920 m) between 2013 and 2015. The primary outcome was DCI per consensus criteria. Multivariable logistic regression identified independent predictors; receiver operating characteristic analysis evaluated model performance. Altitude and hemoglobin were specifically evaluated as altitude-related risk factors. Results-DCI occurred in 26 patients (10.2%). In-hospital mortality was 1.6%. Most patients presented with good-grade aSAH (Hunt-Hess I-II, 73.0%; Fisher I-II, 73.1%). On multivariable analysis, only Fisher grade independently predicted DCI (odds ratio, 3.63 [95% CI, 1.14-11.52]; P=0.029). Neither altitude (P=0.697) nor hemoglobin concentration (P=0.858) was associated with DCI risk. The predictive model achieved an area under the curve of 0.812. At 1-year follow-up, 77.8% achieved favorable functional outcomes (modified Rankin Scale 0-2). Conclusions-Fisher grade is the sole independent predictor of DCI in high-altitude aSAH patients, while chronic hypoxia and compensatory hemoglobin elevation do not significantly modify DCI risk. Established sea-level prognostic frameworks remain valid in high-altitude settings, supporting their continued use for clinical risk stratification. Keywords: aneurysmal subarachnoid hemorrhage; high altitude; delayed cerebral ischemia; Fisher grade; Tibetan Plateau; prognosis

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Aortic Valve Level as a Candidate Zone 4/5 Boundary Landmark in Endovascular Aortic Repair

Nishii, T.; Horinouchi, H.; Kotoku, A.; Mori, S.; Ohta, Y.; Fukuda, T.

2026-07-22 radiology and imaging 10.64898/2026.07.20.26358310 medRxiv
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Background: The zone 4/5 boundary has been described as the mid-descending aorta-T6 level, but this correspondence has uncertain anatomic support. Purpose: To determine whether the aortic valve (AV) level approximates the descending aortic midpoint and to compare candidate boundaries relative to the critical segmental artery (CSA) origin. Materials and Methods: This retrospective study included 204 patients who underwent Adamkiewicz artery-specific CT angiography from January 2022 through February 2026. The CSA was defined as the aortic origin of the segmental artery directly or collaterally connected to the Adamkiewicz artery. Along the descending-aortic centerline, the descending aortic midpoint was the point halfway between a site 20 mm distal to the left subclavian artery origin and the celiac artery origin; the AV-level midpoint was the point halfway between the centerline intersections of the left coronary and noncoronary aortic sinus planes. Equivalence between midpoints was tested within a prespecified +/-20-mm margin. Distal CSA classifications were compared using McNemar tests. Results: The study included 204 patients (median age, 72 years [IQR, 59-79 years]; 142 men and 62 women). The mean difference between the AV-level midpoint and descending aortic midpoint was -1.2 mm (90% CI, -3.3 to 0.9 mm; P < .001 for equivalence). The T6 vertebral level was 59.0 mm proximal to the descending aortic midpoint. The CSA origin was distal to the AV-level midpoint and descending aortic midpoint in 96.6% (197/204) and 95.6% (195/204), respectively (P = .68), but distal to the noncoronary aortic sinus plane in 89.7% (183/204; P = .001 versus the AV-level midpoint). Conclusion: The AV-level midpoint approximated the descending aortic midpoint, whereas the T6 vertebral level was more proximal. Fewer critical segmental artery origins were classified as distal to the noncoronary aortic sinus plane than to the AV-level midpoint.

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Dual-phase vessel wall MRI deep learning for identifying composite unstable intracranial aneurysm phenotypes: a multicenter study

Yuan, W.; Wang, Z.; Wu, Q.; He, X.; Tan, J.; Wei, X.; Li, R.; Yin, Y.; Wang, D.; Wang, G.; Chen, T.

2026-08-14 radiology and imaging 10.64898/2026.08.13.26360349 medRxiv
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Objectives: To develop and externally validate a wall-focused deep learning framework for identifying composite unstable intracranial aneurysm phenotypes on dual-phase high-resolution vessel wall imaging (HR-VWI), and to visualize model attention on the aneurysm wall surface. Methods: This retrospective multicenter study included patients with intracranial aneurysms who underwent both non-contrast and contrast-enhanced HR-VWI. Center 1 was used for model development and patient-level five-fold out-of-fold assessment, whereas Centers 2 and 3 served as independent external validation cohorts. For each aneurysm, dual-phase local wall patches and larger spatial context patches were generated. The Wall-Constrained Encoding Network (WCE-Net) extracted mask-constrained local wall features, and a transfer-learning U-Net with Nested Transformers (UNesT) branch extracted spatial context information. Branch outputs were fused by logit-level stacking. Model performance was evaluated using discrimination, calibration, and decision curve analysis. Three-dimensional gradient-weighted class activation mapping (Grad-CAM) responses were projected onto the reconstructed aneurysm wall surface and compared with HR-VWI surface signal intensity. Results: A total of 629 patients with 773 aneurysms were included. The final fusion model achieved areas under the receiver operating characteristic curves (AUCs) of 0.908, 0.857, and 0.855 in Center 1, external Center 2, and external Center 3, respectively. Corresponding Brier scores were 0.119, 0.153, and 0.150. Surface Grad-CAM showed partial spatial overlap between model-attention hotspots and high-signal HR-VWI regions. Conclusions: Dual-phase wall-focused local-context fusion showed feasibility for identifying composite unstable intracranial aneurysm phenotypes across centers. Surface Grad-CAM provided anatomically referenced visualization of model attention.

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Validation and Refinement of PreICH scale to Identify Intracerebral Hemorrhage Versus Large-Vessel Occlusion

Freixa, A.; Mauri-Capdevila, G.; Gallego, Y.; Garcia-Diaz, A.; Nieva, C.; Vicente-Pascual, M.; perez-girona, L.; San Pedro-Murillo, E.; Saureu-Rufach, E.; Mijana, R.; Salvany, S.; Peguera, A.; Pereira, C.; Purroy, F.

2026-07-13 neurology 10.64898/2026.07.07.26357511 medRxiv
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Background and Purpose- Prehospital large-vessel occlusion (LVO) scales identify severe stroke syndromes but may not distinguish LVO from intracerebral hemorrhage (ICH). We aimed to prospectively validate the PreICH scale, with the primary diagnostic objective of differentiating ICH from confirmed LVO, and to explore whether additional hemorrhage-oriented variables could refine its performance. Methods- We conducted a prospective observational study of consecutive stroke-code activations evaluated before neuroimaging by a vascular neurologist. PreICH was calculated prospectively. Patients with calculable PreICH and valid final diagnosis were included. The primary diagnostic cohort comprised confirmed LVO and ICH. Secondary cohorts included ischemic stroke versus ICH and the overall stroke-code cohort, including stroke mimics. Multivariable NIHSS-adjusted models identified variables associated with ICH. A modified PreICH score (mPreICH) was derived post hoc and evaluated as exploratory apparent performance. Results- Among 1012 screened activations, 982 patients were analyzed: 597 ischemic strokes, 91 ICH, and 294 stroke mimics. The LVO-versus-ICH cohort included 144 LVO and 91 ICH. NIHSS and RACE were higher in ICH than in ischemic stroke, but did not differ between LVO and ICH (NIHSS, 13 [IQR, 7-20] versus 15 [5-23], P=0.300; RACE, 5 [2-8] versus 6 [2-8], P=0.435). In the LVO-versus-ICH cohort, PreICH showed an AUC of 0.758 (95% CI, 0.696-0.820), whereas RACE did not discriminate LVO from ICH (AUC, 0.530 [95% CI, 0.453-0.607]). The exploratory mPreICH showed apparent AUCs of 0.835 (95% CI, 0.785-0.884) for ischemic stroke versus ICH and 0.798 (95% CI, 0.740-0.856) for LVO versus ICH. Conclusions- In this prospective stroke-code cohort, severity-based scales distinguished ICH from the overall ischemic stroke population but showed limited ability to differentiate LVO from ICH. An exploratory modified PreICH scale incorporating additional hemorrhage-oriented variables improved apparent discriminative performance, including in the LVO-versus-ICH setting. External validation is required before potential implementation in prehospital decision-making.

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Burr-Hole Intersection of Middle Meningeal Artery Branches and Recurrence in Chronic Subdural Haematoma: a Multicentre Retrospective Cohort Study

Saba, T. M.; Moudgil-Joshi, J.; Pandit, A. S.; Penn, J.; Mallon, D.; Marcus, H. J.; Grover, P.

2026-08-31 surgery 10.64898/2026.08.26.26361348 medRxiv
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Background and Objectives: Recurrence following burr-hole drainage of chronic subdural haematoma (cSDH) occurs in 10-25% of cases, sustained by neovascularisation of the subdural neomembrane supplied by the middle meningeal artery (MMA). MMA embolisation reduces recurrence; whether incidental burr-hole intersection of MMA branches during drainage confers similar benefit is unknown. Methods: We performed a multicentre retrospective cohort study of consecutive adults undergoing burr-hole drainage for cSDH at two UK tertiary neurosurgical centres. Postoperative thin-slice CT was used to classify burr-hole intersection of the underlying MMA groove (no hit, distal-branch hit or main-branch hit) and measure perpendicular burr-hole-to-MMA-groove distance. Co-primary outcomes were radiological recurrence and recurrence requiring intervention. Patient-clustered multivariable logistic regression adjusted for prespecified clinical covariates and treating site. Results: 227 patients (284 operated hemispheres) were included. Radiological recurrence decreased from 34.4% with no branch hit to 22.9% with main-branch intersection, with the gradient confined predominantly to unilateral cSDH. Main-branch intersection was associated with lower adjusted odds of radiological recurrence in unilateral cSDH (adjusted OR 0.30, 95% CI 0.11- 0.81; P = .018), with a similar but non-significant association in the overall cohort (adjusted OR 0.53, 95% CI 0.26-1.07; P = .075). Burr-hole-to-MMA-groove distance demonstrated a more consistent association: in the overall cohort, each 5-mm increase independently increased the odds of radiological recurrence (adjusted OR 1.38, 95% CI 1.04-1.82; P = .025). In unilateral cSDH, each 5-mm increase was independently associated with both radiological recurrence (adjusted OR 1.45, 95% CI 1.03-2.04; P = .034) and recurrence requiring intervention (adjusted OR 1.52, 95% CI 1.05-2.20; P = .027). Conclusion: Main-branch intersection of the middle meningeal artery during routine burr-hole surgery is associated with lower recurrence of unilateral cSDH, while the accompanying burr-hole-to-MMA-groove distance gradient provides biologically plausible support for a dose-response relationship. Together, these findings provide mechanistic rationale for prospective evaluation of intentional neuronavigation-guided MMA targeting (BURR-MMA; NCT07549893).

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Endothelial Microvesicles: A Plasma Biomarker of Futile Recanalization Post Intravenous Thrombolysis in Patients with Stroke

Zhang, H.; Xu, X.; Zhou, Z.; Chen, Y.; Liao, Z.; Wu, J.; Xian, J.; Zhong, W.; Ma, X.

2026-06-29 neurology 10.64898/2026.06.25.26356528 medRxiv
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Investigating futile recanalization indicators is very important. Here, we explored plasma endothelial microvesicles (EMVs) as biomarkers for recombinant tissue plasminogen activator (rtPA)-treated acute ischemic stroke. This study prospectively enrolled 195 acute IS patients who underwent rtPA and measured plasma EMVs levels via fluorescence nanoparticle tracking analysis at baseline, 24 h and 90 days. Early futile recanalization was assessed by transcranial Doppler and the National Institutes of Health Stroke Scale. The ROC curves and corresponding areas under the curve (AUC) of the EMVs were analysed. The plasma EMVs levels at baseline and 24 h were positively related to both early and late futile recanalization. In both the late recanalization and futile recanalization groups, the plasma levels of EMVs significantly increased at 24 h but decreased at 90 days. For early futile recanalization, the baseline and 24-h EMVs AUCs were 0.7 and 0.67, respectively. For late futile recanalization, the AUCs for baseline and 24-h EMVs levels were 0.52 and 0.66, respectively. Collectively, the results imply that the plasma level of EMVs could serve as a surrogate indicator of futile recanalization (both early and late) following rtPA administration in acute IS.