Stroke最新文献

{"title":"SIK3-mKO Enhances Myelin Debris Phagocytosis via CD11c Complement Pathway for White Matter Protection Poststroke.","authors":"Leilei Mao, Chenran Wang, Ke Wang, Chenxi Zhong, Ziyu Shi, Yiwen Yuan, Jianan Zheng, Jingjing Wu, Miao He, Zeyu Sun, Yanqin Gao","doi":"10.1161/STROKEAHA.126.056423","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.056423","url":null,"abstract":"<p><strong>Background: </strong>White matter preservation is a rate-limiting factor in neurological recovery after ischemic stroke and depends on efficient clearance of myelin debris by microglia/macrophages. Our prior work demonstrated that microglia/macrophage-specific SIK3 (salt-inducible kinase) knockout (SIK3-mKO) promotes an anti-inflammatory subset, enhances myelin phagocytosis, and limits white matter injury, yet the downstream molecular mechanisms remain undefined. Here, we elucidate a previously unrecognized signaling axis underlying these protective effects.</p><p><strong>Methods: </strong>SIK3-mKO mice (SIK3^Flox+/+;CX3CR1^CreER) were generated via tamoxifen-induced Cre recombination. Transient focal cerebral ischemia was induced by 60-minute transient middle cerebral artery occlusion. Neurological outcomes were assessed via Garcia, rotarod, foot-fault, and adhesive-removal tests. Immunofluorescence, flow cytometry, single-cell RNA sequencing, real-time quantitative polymerase chain reaction, ex vivo myelin phagocytosis assay, magnetic resonance imaging, and compound action potential recordings were used to characterize microglia/macrophage polarization, myelin phagocytic capacity, white matter integrity, and nerve conduction function.</p><p><strong>Results: </strong>In the acute phase poststroke, SIK3-mKO selectively upregulated CD11c and its upstream complement initiator component 1q in anti-inflammatory microglia/macrophage subsets. Within the 400 to 800 µm peri-infarct zone, SIK3-mKO elevated the proportion of CD11c⁺ microglia/macrophage by 15.1% and C1q⁺ microglia/macrophage by 15.8% relative to wild-type controls. This CD11c-component 1q axis enhanced myelin debris clearance by 19.0% while constraining pathological engulfment of intact myelin, representing a balanced functional switch that mitigates severe demyelination. Conversely, myeloid-CD11c silencing using AAV-<i>Itgax</i> shRNA partially reversed SIK3-mKO-conferred protection. CD11c knockdown reduced anti-inflammatory microglia/macrophage proportions by 9.7%, attenuated physiological phagocytosis and lowered debris clearance efficiency by 7.5%, reduced MBP (myelin basic protein)-positive myelin preservation by 10.0%, and ultimately impaired white matter preservation and neurological recovery.</p><p><strong>Conclusions: </strong>We identify the SIK3-CD11c-component 1q axis as a novel pathway that orchestrates microglia/macrophage phagocytic homeostasis and preserves white matter integrity after ischemic stroke. These findings clarify SIK3 signaling in microglia/macrophage and highlight the CD11c-centered complement cascade as a promising therapeutic target for restoring white matter integrity in poststroke neurorepair.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Resolution Disconnectome Predicts Outcome and Response to Thrombectomy in Basilar Artery Occlusion.","authors":"Benjamin Authamayou, Gaultier Marnat, Anna Matsulevits, Fanny Munsch, Audrey Lavielle, Nadège Corbin, Chris Foulon, Bailiang Chen, Emilien Micard, Benjamin Gory, Vincent L'Allinec, Romain Bourcier, Olivier Naggara, Eliot Lauze, Grégoire Boulouis, Bertrand Lapergue, Omer Eker, Igor Sibon, Michel Thiebaut de Schotten, Thomas Tourdias","doi":"10.1161/STROKEAHA.126.056382","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.056382","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Acute basilar artery occlusion causes devastating strokes. Despite the benefit of endovascular treatment, the optimal management remains controversial in specific subgroups, particularly 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 could improve outcome prediction and identify responders to recanalization compared with conventional metrics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a secondary analysis of a prospective multicenter stroke registry in France, including consecutive patients (2017-2024) with basilar artery occlusion and admission magnetic resonance imaging. Ultra-high-resolution diffusion magnetic resonance imaging was acquired in 2 healthy participants to build normative tractograms with optimized posterior fossa quality. Patient infarcts delineated on diffusion-weighted imaging were projected onto these tractograms to estimate disconnected fiber volume. The primary outcome was 90-day modified Rankin Scale score (0-3 versus 4-6). Predictive performance of disconnected fiber volume was compared with baseline National Institutes of Health Stroke Scale (NIHSS), infarct volume, and posterior circulation Alberta Stroke Program Early Computed Tomography Score using logistic regressions and area under the receiver operating characteristic curves. Ordinal regressions tested associations between dichotomized disconnection status and the full modified Rankin Scale spectrum, stratified by recanalization status. Analyses were repeated in patients with an NIHSS score ≤10.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 201 patients (median age, 70; NIHSS score, 10), 97 (48.3%) had a poor outcome. Despite a small median infarct volume (4.75 mL), disconnected fiber volume was substantial (median 25.15 mL). Disconnected fiber volume achieved an area under the receiver operating characteristic curves of 0.84, outperforming NIHSS score (0.67; &lt;i&gt;P&lt;/i&gt;&lt;0.0001), infarct volume (0.75; &lt;i&gt;P&lt;/i&gt;=0.00059), and posterior circulation Alberta Stroke Program Early Computed Tomography Score (0.76; &lt;i&gt;P&lt;/i&gt;=0.0127). Patients without significant disconnection had better outcomes across the full modified Rankin Scale spectrum (odds ratio, 0.12 [95% CI, 0.065-0.204]) and derived greater benefit from successful recanalization (odds ratio, 0.33 [95% CI, 0.15-0.70]). In patients with an NIHSS score ≤10 (n=102), disconnected fiber volume remained the strongest predictor (area under the receiver operating characteristic curves of 0.83).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Disconnected fiber volume derived indirectly is a robust prognostic marker of basilar artery occlusion outcomes that outperforms conventional predictors and may support future treatment decisions after prospective validation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Registration: &lt;/strong&gt;URL: https://clinicaltrials.gov; Uniqu","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vessel Wall MRI in Pediatric Arterial Ischemic Stroke: Diagnostic Utility and Prognostic Value.","authors":"Paul Cazier, Manoëlle Kossorotoff, Olivier Naggara, Kylian Gonnet, Volodia Dangouloff-Ros, Nathalie Boddaert, Charles-Joris Roux","doi":"10.1161/STROKEAHA.126.056262","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.056262","url":null,"abstract":"<p><strong>Background: </strong>Vessel wall magnetic resonance imaging (VW-MRI) is a promising tool for evaluating intracranial arteriopathies in pediatric non-neonatal arterial ischemic stroke, but its diagnostic and prognostic roles remain underexplored. This study assesses the utility of VW-MRI in identifying arteriopathy subtypes and predicting clinical and radiological outcomes in children.</p><p><strong>Methods: </strong>We conducted an ancillary retrospective study using the national KidClot cohort and the stroke database at Necker-Enfants Malades Hospital (Paris). Children with arterial ischemic stroke who underwent VW-MRI within 3 months of onset and follow-up MRI at least 18 months later were included. Stroke causes were assessed according to the Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation, and intracranial arterial vessel wall enhancement (VWE) was evaluated. Analyses focused on the focal cerebral arteriopathy (FCA) subgroup, comparing VWE-positive and VWE-negative patients and assessing correlations with clinical factors, imaging metrics, and outcomes. Categorical variables were compared using the χ²/Fisher exact test, qualitative/ordinal variables using the Mann-Whitney <i>U</i> test, and correlations were assessed using the Spearman rank correlation coefficient (ρ).</p><p><strong>Results: </strong>From 193 children, 67 were included (median age, 4.1 years, interquartile range, 2.0-9.8; 61.1% male). Causes were FCA (42%, 28/67), bilateral cerebral arteriopathy (5%, 3/67), aortic/cervical arteriopathy (12%, 8/67), cardioembolic (7%, 5/67), other (22%, 15/67), and multifactorial (12%, 8/67). In FCA, 75% (21/28) showed concentric VWE, correlating with stenosis severity (ρ=0.31; <i>P</i>=0.001). VWE-positive patients with FCA had a higher initial focal cerebral arteriopathy severity score (median 5 versus 3; <i>P</i>=0.046) than VWE-negative patients, but no statistically significant differences were found in other evaluated factors, including initial Pediatric National Institutes of Health Stroke Scale (median 8.5 versus 8; <i>P</i>=0.5) and 12-month Pediatric Stroke Outcome Measure (median 0.5 versus 1; <i>P</i>=0.8).</p><p><strong>Conclusions: </strong>VW-MRI detects inflammatory arterial changes in pediatric FCA. However, its prognostic value is limited, suggesting enhancement reflects acute inflammation rather than long-term trajectory.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Metabolites Are Biomarker Candidates for Stroke Risk Prediction: Results From the BiomarCaRE Project.","authors":"Christian Schulte, Francisco M Ojeda, Märit Jensen, Ferdinand Seum, René Riedel, Jukka Kontto, Giovanni Veronesi, Marco Mario Ferrario, Allan Linneberg, Torben Joergensen, Christian Gieger, Barbara Thorand, Mahir Karakas, Licia Iacoviello, Daniela Börnigen, Dylan Aissi, Mark Woodward, Renate B Schnabel, Simona Costanzo, Hugh Tunstall-Pedoe, Wolfgang Koenig, Kari Kuulasmaa, Veikko Salomaa, Stefan Blankenberg, Tanja Zeller","doi":"10.1161/STROKEAHA.125.053290","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.053290","url":null,"abstract":"<p><strong>Background: </strong>Stratification of stroke risk remains challenging, but metabolomic profiling offers the potential to detect new biomarkers and to improve early risk assessment of incident stroke. The objective of this study was to evaluate the association between circulating metabolites and the incidence of stroke in a case-cohort study conducted across several large population-based European cohorts.</p><p><strong>Methods: </strong>Following the case-cohort design, a subset of 10 299 individuals, including all individuals with incident stroke, was selected from the original cohort of >70 000 individuals. The case-cohort design used a random subsample of the selected population cohorts, supplemented with cases not sampled in this random subcohort. A total of 141 circulating metabolites were measured from serum samples of the selected individuals, and associations of these metabolites with risk of incident stroke were estimated and compared with those of classic risk factors (sex, age at examination, systolic blood pressure, total cholesterol, body mass index, diabetes, daily smoking status, and antihypertensive treatment). Associations with time to stroke were assessed using weighted Cox proportional hazards models adjusted for the classic risk factors. Hazard ratios (HRs) for the log-transformed metabolites were reported per 1 SD increase.</p><p><strong>Results: </strong>Of the 70 195 individuals in the original cohort, 1516 (2.2%) experienced incident strokes during a median follow-up time of 8.9 years (interquartile range, 4.4-14.7). Median age was 56.8 years (interquartile range, 49.5-62.4), and 39.5% were female. Six of the 141 metabolites (2 diacyl-phosphatidylcholines, 2 lyso-phosphatidylcholines, 1 hydroxysphingomyelin, and glutamic acid) remained significantly associated with incident stroke after correction for multiple comparisons (adjusted HRs [95% CIs] per SD: lyso-phosphatidylcholines a C18:2 HR, 0.88 [95% CI, 0.82-0.93], lyso-phosphatidylcholines a C17:0 HR, 0.88 [95% CI, 0.83-0.94], hydroxysphingomyelin C14:1 HR, 0.90 [95% CI, 0.85-0.94], diacyl-phosphatidylcholines C34:1 HR, 1.10 [95% CI 1.05-1.16], diacyl-phosphatidylcholines C32:1 HR, 1.14 [95% CI, 1.08-1.21], glutamic acid HR, 1.23 [95% CI 1.11-1.37]). The strengths of these associations were similar to those for classic cardiovascular risk factors (C statistics for 10-year prediction ranging from 0.782 to 0.785 for metabolites compared with 0.781 to 0.792 for classic cardiovascular risk factors).</p><p><strong>Conclusions: </strong>Among 10 299 individuals from the general European population, we identified 6 metabolites from 4 different metabolite classes that were associated with future risk of stroke. The application of specific circulating metabolites may improve early stroke risk prediction before the onset of potentially irreversible cerebrovascular pathological processes.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inpatient Rehabilitation and Major Adverse Cardiovascular Events After Ischemic Stroke.","authors":"Abdulaziz T Bako, Elizabeth F Larkin, Thomas Potter, Alan Pan, Farhaan S Vahidy","doi":"10.1161/STROKEAHA.126.055755","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.055755","url":null,"abstract":"<p><strong>Background: </strong>Acute ischemic stroke (AIS) survivors are at high risk of major adverse cardiovascular events (MACE), highlighting the need to identify modifiable secondary prevention targets. We assessed whether postacute discharge destination is associated with 1-year MACE risk among AIS survivors.</p><p><strong>Methods: </strong>In this retrospective cohort study, adult AIS survivors were identified from the state inpatient and emergency department databases of 5 US states (2016-2019) and categorized by discharge destination: home, inpatient rehabilitation facility (IRF), or skilled nursing facility (SNF). Other destinations were excluded. The primary outcome was 1-year MACE, defined as recurrent stroke, acute myocardial infarction, systemic embolism, or vascular death. Multivariable Cox models, adjusted for demographic and clinical factors, were used to evaluate the association between discharge disposition and MACE risk. Fine-Gray models were used for nonfatal secondary outcomes, and restricted mean survival time analyses were used to estimate absolute risk. Effect modification by age (<65 versus ≥65 years) was examined. Confounder-adjusted number-needed-to-be-exposed was estimated by marginal standardization.</p><p><strong>Results: </strong>Among 213 511 AIS survivors (median age, 71 years), 16 237 (7.6%) experienced MACE within 1-year. MACE incidence was lowest after IRF discharge (6.6%) versus home (7.6%) or SNF (8.3%). In adjusted analyses, IRF discharge was associated with lower MACE risk versus home (adjusted hazard ratio, 0.88 [95% CI, 0.83-0.93]) and SNF (0.84 [95% CI, 0.79-0.89]). The association persisted across age strata but was more pronounced in patients <65 years (<i>P</i>_interaction=0.014). Restricted mean survival time analyses indicated that IRF discharge was associated with 3.47 and 3.87 additional MACE-free days versus home and SNF discharge, respectively (both <i>P</i><0.001). Adjusted number-needed-to-be-exposed were 115 (95% CI, 80-207) for IRF versus home and 87 (95% CI, 64-136) for IRF versus SNF.</p><p><strong>Conclusions: </strong>Postacute IRF discharge is associated with a lower 1-year MACE risk after AIS, highlighting the postacute care setting as a potentially modifiable system-level target for secondary prevention of long-term vascular outcomes.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148919995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Recanalization After Tenecteplase or Alteplase in Distal and Medium Vessel Occlusion Strokes: An Observational Cohort Study.","authors":"Nicolas Chausson, Joseph Benzakoun, Sofia Vargas-Ibarra, Yann L'Hermitte, Wagih Ben Hassen, Didier Smadja, Guillaume Turc","doi":"10.1161/STROKEAHA.125.054734","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.054734","url":null,"abstract":"<p><strong>Background: </strong>Intravenous thrombolysis remains the standard treatment for distal and medium vessel occlusion (DMVO) strokes. However, unlike large vessel occlusions, whether tenecteplase achieves higher early successful recanalization rates than alteplase in DMVO strokes remains uncertain.</p><p><strong>Methods: </strong>This single-center observational cohort study included consecutive patients with magnetic resonance imaging (MRI)-confirmed DMVO stroke treated at Centre Hospitalier Sud-Francilien, France, according to an institutional thrombolysis protocol specifying alteplase (0.9 mg/kg, 2016-2018) or tenecteplase (0.25 mg/kg, 2018-2023), with follow-up MRI 1 to 2 hours after intravenous thrombolysis. Patients intended for endovascular thrombectomy or without diagnostic-quality follow-up MRI were excluded. Recanalization was blindly assessed using a modified Arterial Occlusion Lesion scale designed for MRI and DMVO. Early successful recanalization was defined as ≥50% recanalization on early follow-up MRI (grade ≥2b), and substantial early infarct growth, assessed using a semiautomatic segmentation technique, was defined as a ≥0.5 mL and ≥20% increase in lesion volume. Propensity-score weighting accounted for baseline imbalances, including age, sex, vascular risk factors, baseline National Institutes of Health Stroke Scale score, occlusion site, and time period (2020-2023 versus 2016-2019).</p><p><strong>Results: </strong>Of the 319 included patients, 159 were treated with tenecteplase and 160 with alteplase. Median baseline National Institutes of Health Stroke Scale was 3 (1-7) in the tenecteplase group versus 4 (1-7.5) in the alteplase group, while M2 occlusions accounted for 54.1% versus 43.8% of cases. Early successful recanalization, assessed at a median postintravenous thrombolysis time of 80 (70-94) minutes, occurred in 72 (45.3%) and 53 (33.1%) patients treated with tenecteplase and alteplase, respectively (propensity-score weighting-odds ratio, 1.59 [95% CI, 1.15-2.20]; <i>P</i>=0.005). Substantial early infarct growth was observed in 42 (26.8%) and 64 (40.5%) patients, respectively (propensity-score weighting-odds ratio, 0.49 [95% CI, 0.35-0.69]; <i>P</i><0.0001).</p><p><strong>Conclusions: </strong>Compared with alteplase, tenecteplase-treated patients with DMVO had higher early successful recanalization and a lower risk of substantial early infarct growth, supporting its preferential use in this setting.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT05635786.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arterial Spin Labeling Hemodynamic Indices Relate to Cognitive and Small Vessel Disease Trajectories Over 11 Years.","authors":"W Hudson Robb, Ava M Santner, Panpan Zhang, Darcie S Kim, T Bryan Jackson, Niranjana Shashikumar, Kimberly R Pechman, Yukti Vyas, Dandan Liu, L Taylor Davis, Timothy J Hohman, Angela L Jefferson","doi":"10.1161/STROKEAHA.125.054879","DOIUrl":"10.1161/STROKEAHA.125.054879","url":null,"abstract":"<p><strong>Background: </strong>Hemodynamic insufficiency may contribute to the development of neuroimaging signs of cerebral small vessel disease (SVD). The arterial spin labeling (ASL) spatial coefficient of variation (ASL-sCoV) is a proxy marker of arterial transit time and may better capture SVD-related hemodynamic disturbances compared with ASL-derived cerebral blood flow. We investigated ASL-derived hemodynamic indices in relation to cognition and neuroimaging markers of SVD over an 11-year follow-up period.</p><p><strong>Methods: </strong>Participants without dementia or stroke were enrolled in the Vanderbilt Memory and Aging Project, a longitudinal observational cohort study in Nashville, TN. Participants underwent serial multimodal 3T brain magnetic resonance imaging to quantify SVD burden and neuropsychological assessment from 2012 to 2024 (4.9±3.5 years mean follow-up). Pseudo-continuous ASL assessed cerebral blood flow and ASL-sCoV in total gray matter. Baseline ASL-sCoV and cerebral blood flow were individually related to the cross-sectional burden and longitudinal trajectory of each SVD neuroimaging marker (white matter hyperintensities, enlarged perivascular spaces, cerebral microbleeds, and lacunar infarcts) and cognitive performances using linear and linear mixed-effects regression models. Models were adjusted for demographics, cognitive status, Framingham Stroke Risk Profile (minus age), <i>apolipoprotein E</i>-ε4 status, intracranial volume (for SVD outcomes), and follow-up time (for longitudinal models).</p><p><strong>Results: </strong>Among participants (n=667, 68±9 years, 18% mild cognitive impairment, 51% female), higher ASL-sCoV was cross-sectionally associated with SVD markers, including white matter hyperintensities and enlarged perivascular spaces (<i>p</i>_FDR-values<0.006). Higher baseline ASL-sCoV was associated with a faster longitudinal increase in the burden of white matter hyperintensities (<i>p</i>_FDR=0.03) and accelerated decline in executive function, information processing, language, and visuospatial performances (<i>P</i><0.05). Gray matter cerebral blood flow was not associated with SVD burden or cognition cross-sectionally (<i>p</i>_FDR-values>0.05) or longitudinally (<i>p</i>_FDR-values>0.06).</p><p><strong>Conclusions: </strong>ASL-sCoV may serve as an important hemodynamic measure for identifying perfusion deficits tied to SVD burden and progression. Readily derived from existing ASL data sets, ASL-sCoV could provide substantial insight into the longitudinal clinical consequences of SVD.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13564205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility-Weighted Analysis of the Modified Rankin Scale: An Updated Review of Methods, Challenges, and Future Directions.","authors":"Paul M Wechsler, Joseph P Broderick, Jeffrey L Saver, Eva A Mistry","doi":"10.1161/STROKEAHA.126.056638","DOIUrl":"https://doi.org/10.1161/STROKEAHA.126.056638","url":null,"abstract":"<p><p>The utility-weighted approach to analyzing the modified Rankin Scale (mRS) is increasingly being utilized in acute stroke clinical trials. This analytic approach assigns a patient-centered utility weight-the desirability or value of a health state to patients-to each level of the mRS. The utility-weighted-mRS analysis converts the mRS from a scale reflecting only the rank order of functional outcome after stroke into one that quantifies the value of each poststroke mRS health state from patients' perspectives. The ability of the utility-weighted-mRS analysis to capture the unequal difference in patient health-related quality of life between each level of the mRS makes it an appealing patient-centered end point for acute stroke clinical trials. However, several concerns have historically raised skepticism regarding its value as a trial end point. Unfamiliarity with how utility weights are derived and used poses challenges to its use for shared decision-making between patients and clinicians. There are valid concerns that social, geographic, and demographic factors that differ between countries influence the mRS utility weights, so that use of uniform weights across all settings mildly reduces the precision of utility quantification, particularly in multinational stroke clinical trials. This narrative review aims to provide the clinical and research stroke community with a practical overview of key methodology in the utility-weighted-mRS analysis to aid in its interpretation, considers the advantages and challenges of using the utility-weighted-mRS analysis, and suggests future areas of study.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Determinants of Health in Early to Mid-Adulthood and Risk of Early-Onset Stroke.","authors":"Nathaniel Fleming, Christina Dintica, Alexander Arynchyn, Donald M Lloyd-Jones, Daniel Lackland, Kristine Yaffe","doi":"10.1161/STROKEAHA.126.055839","DOIUrl":"10.1161/STROKEAHA.126.055839","url":null,"abstract":"<p><strong>Background: </strong>Despite increasing incidence of stroke among younger adults, the associations of social determinants of health (SDOH) and stroke among younger adults are not well known. This study investigates the associations between SDOH from early adulthood and stroke in a prospective longitudinal cohort.</p><p><strong>Methods: </strong>We studied participants enrolled in the CARDIA study (Coronary Artery Risk Development in Young Adults). Participants aged 18 to 30 years were enrolled in 1985 and followed through 2022. We investigated longitudinal, time-varying measures of SDOH classified into 5 distinct domains: economic (6 measures), education (1 measure), healthcare (4 measures), neighborhood (2 measures), and social/community (5 measures). The outcome was incident stroke or transient ischemic attack. We evaluated associations between individual SDOH and stroke using unadjusted Cox models. We then evaluated whether a greater cumulative number of adverse SDOH domains (each represented by 1 exposure selected by empirical techniques) was associated with stroke risk after adjustment for demographics.</p><p><strong>Results: </strong>Among the 5114 participants (54.5% were female; baseline age, 25 years; and median follow-up, 37.9 years), 146 individuals experienced stroke or transient ischemic attack, all of which occurred <65 years. Household income (hazard ratio [HR], 1.24 per $10 000 lower [95% CI, 1.11-1.39]), education (HR, 0.93 per greater year [95% CI, 0.87-0.99]), neighborhood deprivation (HR, 1.21 [95% CI, 1.02-1.43]), and lacking health insurance (HR, 1.49 [95% CI, 1.05-2.11]) were associated with stroke risk. Those experiencing 2 adverse SDOH domains (HR, 1.65 [95% CI, 0.91-2.97]) or <u>≥</u>3 adverse domains (HR, 2.00 [95% CI, 1.09-3.66]) had progressively higher stroke risk (<i>P</i>_trend=0.005). In interaction analyses, the association between income and stroke appeared stronger in Black participants (<i>P</i>_interaction=0.02) and women (<i>P</i>_interaction=0.02).</p><p><strong>Conclusions: </strong>In this young cohort followed through midlife, SDOH spanning several domains were associated with stroke risk. We also observed a dose-dependent response with the number of adverse SDOH domains experienced. Our results suggest that SDOH experienced throughout adulthood are relevant to future stroke risk.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":11.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Perivascular Space Morphometry Reflects Shared Familial Microvascular Architecture and Neuropsychiatric Influences.","authors":"Alexandra Morozova, Maria Del C Valdés Hernández, Roberto Duarte Coello, Heather C Whalley, Andrew McIntosh, Anca-Larisa Sandu Giuraniuc, Gordon D Waiter, Christopher J McNeil, J Douglas Steele, Jennifer A Macfarlane, Alison D Murray, Joanna M Wardlaw","doi":"10.1161/STROKEAHA.126.055378","DOIUrl":"10.1161/STROKEAHA.126.055378","url":null,"abstract":"<p><strong>Background: </strong>Brain perivascular spaces (PVS) are emerging magnetic resonance imaging markers of microvascular function and waste metabolite clearance. Although PVS enlargement has been linked to aging and vascular risk, it remains unclear whether PVS morphometry reflects shared familial microvascular characteristics and how these are shaped by individual vascular, physiological, and neuropsychiatric factors. We investigated whether PVS morphometry captures these familial characteristics in addition to individual determinants.</p><p><strong>Methods: </strong>We analyzed 1183 participants from the Stratifying Depression and Resilience Longitudinally family-based cohort, including 324 individuals with first-degree relatives. Automated magnetic resonance imaging segmentation quantified PVS volume, count, density, and median length in the centrum semiovale and basal ganglia. Linear mixed-effects models assessed associations with age, hypertension, hair cortisol, depressive symptom scores, and hand grip strength while accounting for familial clustering.</p><p><strong>Results: </strong>In 1050 individuals (59.5% female; mean age, 59.3±10.1 years), PVS burden increased with age (PVSvolume%ROI, β=0.18 [95% CI, 0.11-0.26]; <i>P</i><0.0001), current depressive symptoms across both regions (PVS density: centrum semiovale, β=0.092 [0.023-0.16]; <i>P</i>=0.009; BG, β=0.11 [0.043-0.18]; <i>P</i>=0.002; largely robust to false discovery rate correction), and with higher hair cortisol (PVS count β=0.08 [0.003-0.15]; <i>P</i>=0.041; borderline after false discovery rate correction) and weaker grip strength (PVSvolume%ROI β=-0.09 [-0.16 to -0.02]; <i>P</i>=0.013), in the centrum semiovale. Familial clustering was significant for PVS volume (β=0.22 [0.096-0.52]; <i>P</i>=0.013) and median length (β=0.28 [0.16-0.49]; <i>P</i>=0.0003), independent of other factors.</p><p><strong>Conclusions: </strong>PVS morphometry reflects shared familial microvascular phenotypes and neuropsychiatric influences beyond hypertension, highlighting both familial and individual determinants of PVS burden and morphology. These findings support PVS morphometry as a neuroimaging marker of cerebral microvascular health.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":"2768-2779"},"PeriodicalIF":11.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}