StrokePub Date : 2025-09-19DOI: 10.1161/STROKEAHA.125.052121
Aaron Rodriguez-Calienes, Nagheli Borjas, Sai Sanikommu, Fabian A Chavez-Ecos, Martha I Vilca-Salas, Pedro B Rodrigues, Cristian Morán-Mariños, Dileep R Yavagal, Negar Asdaghi, Santiago Ortega-Gutierrez
{"title":"Endovascular Thrombectomy Versus Best Medical Therapy for Large Vessel Occlusion Stroke Beyond 24 Hours: A Systematic Review and Meta-Analysis.","authors":"Aaron Rodriguez-Calienes, Nagheli Borjas, Sai Sanikommu, Fabian A Chavez-Ecos, Martha I Vilca-Salas, Pedro B Rodrigues, Cristian Morán-Mariños, Dileep R Yavagal, Negar Asdaghi, Santiago Ortega-Gutierrez","doi":"10.1161/STROKEAHA.125.052121","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.052121","url":null,"abstract":"<p><strong>Background: </strong>The benefit of endovascular thrombectomy (EVT) beyond 24 hours from last known well in acute ischemic stroke remains uncertain. Although some slow progressors may retain salvageable tissue, supporting evidence in this ultra-late window comes mainly from small observational studies.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Central up to February 2025 for studies comparing EVT and best medical therapy in patients with acute ischemic stroke treated >24 hours from last known well. Eligible studies reported functional independence (90-day 0-2 modified Rankin Scale score), excellent clinical outcome (90-day 0-1 modified Rankin Scale score), symptomatic intracranial hemorrhage, or 90-day mortality. Pooled unadjusted and adjusted odds ratios (ORs) with 95% CIs were calculated using random-effects meta-analyses. Subgroup analyses were performed by study design, stroke severity, imaging modality, and occlusion territory. Statistical heterogeneity was assessed using the I² statistic and the Cochran <i>Q</i> test, and the certainty of evidence (CoE) was assessed using the Grading of Recommendation, Assessment, Development, and Evaluation approach.</p><p><strong>Results: </strong>Ten observational studies (3 prospective and 7 retrospective) comprising 1871 patients (EVT: 866; best medical therapy: 1009) were included. EVT was associated with significantly higher odds of functional independence (8 studies; adjusted OR, 4.62 [95% CI, 3.30-6.47]; <i>I</i>²=0%; low CoE) and excellent clinical outcome (2 studies; adjusted OR, 5.68 [95% CI, 2.49-12.97]; <i>I</i>²=0%; very-low CoE). EVT increased the risk of symptomatic intracranial hemorrhage (4 studies; adjusted OR, 9.54 [95% CI, 3.78-21.07]; <i>I</i>²=0%; low CoE), but 90-day mortality did not differ significantly between groups (4 studies; adjusted OR, 0.63 [95% CI, 0.30-1.31]; <i>I</i>²=41.2%; very-low CoE). All subgroup analyses aligned with the main findings.</p><p><strong>Conclusions: </strong>Our results revealed that EVT was associated with improved functional outcomes without an increase in 90-day mortality, despite a higher symptomatic intracranial hemorrhage risk. Given the limited CoE and overall study quality, ongoing randomized trials are essential to confirm these findings and guide patient selection in the ultra-late time window.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087162","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}
StrokePub Date : 2025-09-19DOI: 10.1161/STROKEAHA.125.051488
Anna Richardt, Liisa Verho, Aino Korhonen, Kirsi Rantanen, Hannele Laivuori, Mika Gissler, Minna Tikkanen, Karoliina Aarnio, Petra Ijäs
{"title":"Stroke Recurrence and Pregnancy Outcomes in the Subsequent Pregnancies After Maternal Ischemic Stroke.","authors":"Anna Richardt, Liisa Verho, Aino Korhonen, Kirsi Rantanen, Hannele Laivuori, Mika Gissler, Minna Tikkanen, Karoliina Aarnio, Petra Ijäs","doi":"10.1161/STROKEAHA.125.051488","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.051488","url":null,"abstract":"<p><strong>Background: </strong>Maternal ischemic stroke (IS) might affect the course of subsequent pregnancies. We aimed to study stroke recurrence, other complications, and the implementation of secondary prevention in subsequent pregnancies of women with a prior maternal IS.</p><p><strong>Methods: </strong>Women diagnosed with IS during pregnancy or puerperium in Finland during the years 1987 to 2016, and the data of subsequent pregnancies were collected from the Medical Birth Register and Hospital Discharge Register. Diagnoses were verified from medical records. Three matched controls without a maternal stroke were identified for each case.</p><p><strong>Results: </strong>Data on subsequent pregnancies were available for 90 patients with maternal IS after excluding patients who died within 1 year. Patients with maternal IS less frequently had at least 1 subsequent pregnancy (38.9% versus 51.7%; age-adjusted odds ratio, 0.55 [95% CI, 0.32-0.93]), and more frequently, multiple induced abortions (adjusted odds ratio, 6.24 [95% CI, 1.12-34.88]) than controls. Three women had a recurrent maternal IS or transient ischemic attack (8.6%). Patients with maternal IS more commonly had diabetes during pregnancy (29.1% versus 13.6%; adjusted odds ratio, 2.77 [95% CI, 1.17-6.59]) and hypertensive disorders of pregnancy than controls (12.7% versus 4.5%; adjusted odds ratio, 3.57 [95% CI, 1.02-12.51]). In the first subsequent pregnancy, perinatal deaths were more common in patients with maternal IS compared with controls (5.9% versus 0%; <i>P</i>=0.042). Most women used antithrombotic medication (87.9%) in the first subsequent pregnancy, but this declined in later pregnancies. The use of other secondary preventive medications was uncommon both before and during pregnancy.</p><p><strong>Conclusions: </strong>Although most pregnancies proceed without complications, the subsequent pregnancies of women with a prior maternal IS are high-risk pregnancies that require careful planning and surveillance. They are frequently complicated with diabetes and hypertensive disorders of pregnancy, and the recurrence of IS or transient ischemic attack is notable.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087282","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}
StrokePub Date : 2025-09-19DOI: 10.1161/STROKEAHA.125.051020
Loraine Mania-Pâris, Antonio Vitobello, Hana Safraou, Frédéric Tran Mau-Them, Yannis Duffourd, Sophie Nambot, Ange-Line Bruel, Anne-Sophie Denommé-Pichon, Gauthier Duloquin, Yannick Béjot, Laurence Faivre, Christel Thauvin-Robinet, Quentin Thomas
{"title":"Systematic Genetic Assessment in Young Patients With Cryptogenic Stroke: The ES-EASY project.","authors":"Loraine Mania-Pâris, Antonio Vitobello, Hana Safraou, Frédéric Tran Mau-Them, Yannis Duffourd, Sophie Nambot, Ange-Line Bruel, Anne-Sophie Denommé-Pichon, Gauthier Duloquin, Yannick Béjot, Laurence Faivre, Christel Thauvin-Robinet, Quentin Thomas","doi":"10.1161/STROKEAHA.125.051020","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.051020","url":null,"abstract":"<p><strong>Background: </strong>Up to 15% of strokes occur in young adults, with more cryptogenic cases, raising the possibility of rare causes, such as genetic diseases. Although available in everyday practice, genetic analyses are usually reserved for patients with evocative personal or family history. We aimed to assess the interest of systematic genetic analyses in young adults with cryptogenic stroke and estimate the true frequency of genetic disorders in such patients.</p><p><strong>Methods: </strong>We conducted a retrospective observational cohort study with additional prospective genetic testing. We screened all patients under 50 admitted to Dijon University Hospital stroke unit between 2018 and 2021. Those already genetically tested during etiological work-up were included in a first cohort (cohort 1). Among the remaining patients, those with unexplained intracerebral hemorrhage or stroke (ie, cryptogenic stroke), or a stroke subtype known to have monogenic forms, were offered exome sequencing to form cohort 2. Monogenic diagnoses were defined by likely pathogenic/pathogenic variants according to American College of Medical Genetics and Genomics criteria.</p><p><strong>Results: </strong>Among 305 patients with stroke screened, 24 had prior genetic testing (cohort 1) with exome sequencing, genome sequencing, gene panels or targeted gene analyses, leading to a molecular diagnosis in 8 (33%). Of the remaining 281 patients, 71 met eligibility criteria and 35 consented to the study (cohort 2). Exome sequencing identified pathogenic variants in 4 of them (11%). The overall diagnostic yield of genetic tests was 20.3% (12/59 patients tested across both cohorts). In total, monogenic causes explained 3.9% (12/305) of all young stroke cases. Notably, most diagnosed patients (66%) had no family history of stroke. Genetic cardiopathies and conditions conferring increased cardiovascular risk factors accounted for 50% of diagnoses.</p><p><strong>Conclusions: </strong>Genetic analyses should be considered in all unexplained strokes or in stroke subtypes with known genetic forms (eg, Moya Moya syndrome, cardiopathy, small vessel disease), even without an evocative family history.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087344","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":"Experimental Ischemic Stroke-Induced Alpha-Synuclein Pathology Enhances Endothelial Inflammatory Response and Impairs Angiogenesis.","authors":"Tizibt Ashine Bogale, Domenico Mercurio, Alessia Valente, Serena Seminara, Gaia Faustini, Francesca Longhena, Aurora Bianchi, Stefania Mitola, Arianna Bellucci, Stefano Fumagalli, Marina Pizzi","doi":"10.1161/STROKEAHA.125.052265","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.052265","url":null,"abstract":"<p><strong>Background: </strong>α-Syn (alpha-synuclein) increases and oligomerization contributes to ischemic brain damage. Nevertheless, the exact mechanisms of ischemia-induced α-Syn pathology after stroke are understudied. In this exploratory and hypothesis-testing study, we specifically investigated how ischemia-induced α-Syn pathology impacts vascular inflammation and angiogenesis.</p><p><strong>Methods: </strong>Transient focal cerebral ischemia was induced in C57BL/6J wild-type and C57BL/6S mice with spontaneous deletion of α-Syn. In total, 72 mice were randomized to receive sham (12) or ischemia (60), with 1:1 allocation to genotype. Ischemic mice were included if presenting ≥3 intraischemic focal deficits. Experimental end points were 48 hours (acute phase) and 7 days (subacute phase) of reperfusion. Sensorimotor assessment, elevated plus maze, and survival analysis were stroke outcome readouts. Brain samples were collected for quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry. In vitro ischemia in brain microvascular endothelial cells was used to investigate the direct effect of extracellular α-Syn.</p><p><strong>Results: </strong>In vivo, cerebral ischemia induced α-Syn 2.5-fold change gene expression, 2.7- to 3.2-fold-change protein oligomerization with apparent localization around cortical ischemic vessels. Improved subacute functional recovery linked to better survival was observed in C57BL/6S α-Syn null (87% to end point) versus C57BL/6J (45%) ischemic mice. The α-Syn null mice had reduced expression of <i>ICAM-1</i>, <i>MMP-9</i>, and vascular permeability factors, associated with less infiltrating leukocytes and juxta-vascular microglia in the acute phase. In the subacute phase, they showed upregulated proangiogenic factors (<i>VEGF-A</i>, <i>VEGFR-2</i>, <i>Angpt-2</i>, and <i>IL-6</i>) and angiogenic vessels. In vitro, brain microvascular endothelial cells upregulated <i>ICAM-1</i>, <i>IL-6</i>, and <i>VEGFR-2</i> expression when exposed to recombinant α-Syn at the beginning of ischemia and to a larger extent when α-Syn was preconditioned for 18 hours in hypoxia.</p><p><strong>Conclusions: </strong>These findings indicate that ischemia-triggered pathological α-Syn leads to worse outcome in stroke mice by promoting endothelial inflammatory response and immune cell infiltration during the acute phase and by limiting angiogenesis in the subacute phase.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081423","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}
StrokePub Date : 2025-09-18DOI: 10.1161/STROKEAHA.125.052558
Lilou Crinière-Boizet, Marguerite Watrin, Grégoire Braux, Maxime Gauberti, Gwendoline Le Du, Jean Bouchart, Estelle Laporte, Marion Garnier, Marion Boulanger, Emmanuel Touzé, Ahmad Nehme, Romain Schneckenburger
{"title":"Incidence and Prognosis of Acute Convexity Subarachnoid Hemorrhage in Sporadic Cerebral Amyloid Angiopathy: A Population-Based Study.","authors":"Lilou Crinière-Boizet, Marguerite Watrin, Grégoire Braux, Maxime Gauberti, Gwendoline Le Du, Jean Bouchart, Estelle Laporte, Marion Garnier, Marion Boulanger, Emmanuel Touzé, Ahmad Nehme, Romain Schneckenburger","doi":"10.1161/STROKEAHA.125.052558","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.052558","url":null,"abstract":"<p><strong>Background: </strong>Cerebral amyloid angiopathy (CAA) is a common cause of acute convexity subarachnoid hemorrhage (cSAH). We aimed to report the incidence and prognosis of cSAH secondary to CAA in a population-based cohort.</p><p><strong>Methods: </strong>The Normandy Stroke Study prospectively identified people with SAH in Caen Normandy Metropole (France). This analysis included participants with a first-ever cSAH that met the Boston 2.0 criteria for probable CAA and occurred between May 15, 2017, and December 31, 2023. The incidence of cSAH secondary to CAA was determined in individuals aged ≥50 years after standardization to the 2013 European population. The cumulative risk of subsequent intracerebral hemorrhage was calculated with death as a competing event.</p><p><strong>Results: </strong>Among 193 participants with a first-ever SAH, 27 (14.0%) had a cSAH, and 18 (9.3%) met the Boston 2.0 criteria for probable CAA (mean age 79 years, 66.7% women). Among these, 17 (94.4%) were aged ≥70 years, and 16 (88.9%) presented with transient neurological symptoms. The standardized incidence of cSAH secondary to CAA was 1.7 per 100 000 person-years (95% CI, 1.0-2.7) at ages ≥50 years. Three-year cumulative risks were 30.0% (95% CI, 10.2-53.0) for intracerebral hemorrhage and 21.8% (95% CI, 0.0-41.2) for death.</p><p><strong>Conclusions: </strong>Acute cSAH secondary to CAA remains a rare event at the population level. The high risk of intracerebral hemorrhage during follow-up underscores the importance of accurately identifying cSAH, particularly in people aged ≥70 years presenting with transient neurological symptoms.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081369","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":"<i>CYP2C19</i> Genotype and Efficacy of Clopidogrel Initiated Between 24 to 72 Hours for Ischemic Stroke.","authors":"Yun Chen, Lingling Jiang, Ying Gao, Weiqi Chen, Hongyi Yan, Tingting Wang, Yingying Yang, Dongxiao Yao, Dandan Liu, Yuesong Pan, Yilong Wang","doi":"10.1161/STROKEAHA.125.052167","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.052167","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to investigate the clinical outcomes of clopidogrel-aspirin therapy initiated between 24 and 72 hours from the symptom onset among patients with minor stroke or transient ischemic attack stratified by <i>CYP2C19</i> loss-of-function allele status.</p><p><strong>Methods: </strong>This was a prespecified secondary analysis of the INSPIRES trial (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis), which was a randomized clinical trial conducted across 222 centers in China from September 2018 to October 2022. Two loss-of-function alleles (<i>CYP2C19*2</i>, <i>CYP2C19*3</i>) and 1 gain-of-function allele (<i>CYP2C19*17</i>) were genotyped in the INSPIRES study. Patients with <i>CYP2C19</i> loss-of-function allele carriers were patients with either <i>CYP2C19*2</i> or <i>CYP2C19*3</i>. All participants were randomized to receive clopidogrel-aspirin or aspirin treatment, and those started treatment between 24 and 72 hours from the symptom onset were included in this study. The primary efficacy outcome was new stroke within 90 days. The primary safety outcome was moderate-to-severe bleeding. Cox proportional hazards models were performed to estimate the interaction between treatment assignment and <i>CYP2C19</i> loss-of-function allele status for the primary outcomes.</p><p><strong>Results: </strong>Among 5003 patients, 2911 (58.2%) patients were loss-of-function carriers, and 2092 (41.8%) patients were noncarriers. Relative to aspirin alone, clopidogrel-aspirin reduced the rate of new stroke in the noncarriers (hazard ratio, 0.67 [95% CI, 0.49-0.91]; <i>P</i>=0.01) but not in the carriers (hazard ratio, 0.96 [95% CI, 0.73-1.25], <i>P</i>=0.74; <i>P</i>=0.09 for interaction). For the safety outcome, moderate-to-severe bleeding did not vary significantly between the carriers (hazard ratio, 1.83 [95% CI, 0.68-4.95]; <i>P</i>=0.23) and noncarriers (hazard ratio, 2.07 [95% CI, 0.62-6.88], <i>P</i>=0.23; <i>P</i>=0.88 for interaction).</p><p><strong>Conclusions: </strong>Clopidogrel-aspirin treatment presented a priority to aspirin in reducing the risk of new stroke in <i>CYP2C1</i>9 loss-of-function noncarriers when administered between 24 and 72 hours after stroke onset. These findings supported the necessity of <i>CYP2C19</i> genotyping in the choice of antiplatelet therapy with an extended treatment window to 72 hours.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635749.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081627","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}
StrokePub Date : 2025-09-18DOI: 10.1161/STROKEAHA.125.051997
Katharine Scrivener, Elisha Ball, Catherine Dean, Joanne Glinsky, Louise Ada, Petra Graham, Johannah Campbell, Karen Felton, Natasha Lannin
{"title":"High-Dose Walking Booster Program Is Feasible for People After Stroke: A Phase II Randomized Trial.","authors":"Katharine Scrivener, Elisha Ball, Catherine Dean, Joanne Glinsky, Louise Ada, Petra Graham, Johannah Campbell, Karen Felton, Natasha Lannin","doi":"10.1161/STROKEAHA.125.051997","DOIUrl":"https://doi.org/10.1161/STROKEAHA.125.051997","url":null,"abstract":"<p><strong>Background: </strong>Maintaining walking ability in the long term after a stroke is challenging. Furthermore, access to ongoing physiotherapy is limited. This trial determined the feasibility of a clinical trial of a high-dose walking booster program (HiWalk) and measured clinical outcomes.</p><p><strong>Methods: </strong>A multisite, assessor-blinded pilot and feasibility randomized trial was conducted in Australia (June 2023 to July 2024). Participants had a stroke 6 months to 8 years prior and could walk unaided at 0.4 m/s to 1.0 m/s. The experimental group received HiWalk plus usual care, while the control group received usual care alone. HiWalk was group-based motor training to improve walking, 43 hours over 3 weeks. Feasibility outcomes included recruitment and retention. Clinical outcomes included walking speed (preferred and fast over 5 m, fast over 6 minutes), and self-efficacy at 1 and 6 months.</p><p><strong>Results: </strong>Eighty-two individuals were screened, and 47 participated: age 58 (SD, 16), time poststroke 2.7 years (SD, 2.1), and baseline fast walking speed 0.9 m/s (SD, 0.4). Feasibility outcomes: the HiWalk trial was feasible in terms of recruitment (refusal rate 27%), retention at 1 month (98%), adherence (mean 91% [SD 13] attendance once commenced), safety (minor adverse events 0.4/wk), and measurement (98% of data collected at 1 month). Clinical outcomes: at month 1, there was a beneficial effect on a 30-point self-efficacy scale (MD, 3.0 [95% CI, 0.1-5.9]). However, despite a small positive mean effect of HiWalk on fast walking speed (MD, 0.05 m/s [95% CI, -0.09 to 0.19]), there were no other significant between group differences. Exploratory analysis suggests the effect on walking speed for those not undertaking rehabilitation was 0.24 m/s (95% CI, 0.06-0.43) more than for those who were.</p><p><strong>Conclusions: </strong>The HiWalk booster program was a feasible way to deliver mobility training in the community after stroke. Benefits in clinical outcomes were found for the subgroup of participants no longer undertaking rehabilitation. Therefore, future research should target this subpopulation.</p><p><strong>Registration: </strong>URL: https://www.anzctr.org.au; Unique identifier: ACTRN12623000316606p.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081364","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}
StrokePub Date : 2025-09-17DOI: 10.1161/STROKEAHA.125.052998
Paul M Wechsler, Heidi Sucharew, David J Robinson, Robert J Stanton, Yasmin N Aziz, Charles Prestigiacomo, Stacie L Demel, Paul Horn, Thomas C Maloney, Brady J Williamson, Lily Wang, Vivek J Khandwala, Shantala Gangatirkar, Mary Gaskill-Shipley, Mary Haverbusch, Thomas Tomsick, David Wang, Rebecca S Cornelius, Daniel Woo, Joseph P Broderick, Dawn O Kleindorfer, Brett M Kissela, Matthew L Flaherty, Eva A Mistry, Achala Vagal, Pooja Khatri
{"title":"Projecting US Population Eligibility for Minimally Invasive Surgical Evacuation of Intracerebral Hemorrhage.","authors":"Paul M Wechsler, Heidi Sucharew, David J Robinson, Robert J Stanton, Yasmin N Aziz, Charles Prestigiacomo, Stacie L Demel, Paul Horn, Thomas C Maloney, Brady J Williamson, Lily Wang, Vivek J Khandwala, Shantala Gangatirkar, Mary Gaskill-Shipley, Mary Haverbusch, Thomas Tomsick, David Wang, Rebecca S Cornelius, Daniel Woo, Joseph P Broderick, Dawn O Kleindorfer, Brett M Kissela, Matthew L Flaherty, Eva A Mistry, Achala Vagal, Pooja Khatri","doi":"10.1161/STROKEAHA.125.052998","DOIUrl":"10.1161/STROKEAHA.125.052998","url":null,"abstract":"<p><strong>Background: </strong>Minimally invasive surgical evacuation improved outcomes for patients with acute, spontaneous, lobar intracerebral hemorrhage (ICH) in the ENRICH trial (Early Minimally Invasive Removal of ICH). We determined the percentage of patients with ICH in a US population-based study eligible for minimally invasive surgical evacuation and projected the annual number of patients with ICH in the United States in 2020 eligible for this therapy.</p><p><strong>Methods: </strong>We ascertained adults (aged ≥18 years) with acute (<24 hours from last known well), spontaneous ICH in Greater Cincinnati/Northern Kentucky in 2015. Cases were identified by the <i>International Classification of Diseases</i> codes, clinical data abstracted, and physician adjudicated. Location and volume of ICH were centrally adjudicated by neuroradiologists. We applied ENRICH trial criteria to calculate conservative and liberal estimates of the percentage of patients with (1) all ICH at any location and (2) lobar ICH eligible for minimally invasive surgical evacuation. We extrapolated our estimates to the 2020 US adult population using 2020 US census data.</p><p><strong>Results: </strong>We identified 196 patients in Greater Cincinnati/Northern Kentucky in 2015 with acute, spontaneous ICH. After applying all criteria, 2.0% (n=5) of all patients with acute ICH (5.1%; n=5 lobar ICH) were eligible for minimally invasive surgical evacuation. The most common exclusion criteria were ICH volume <30 mL (60%) and prestroke modified Rankin Scale score >1 (52%). In liberal estimates, 2.6% to 3.6% (n=4-7) of all patients with acute ICH (4.1%-7.1% of lobar ICH) were eligible. We projected 1066 to 1848 patients of an estimated 72 283 adult patients with ICH in the United States in 2020 met eligibility criteria.</p><p><strong>Conclusions: </strong>Approximately 2% to 4% of patients with ICH in our population were eligible for minimally invasive surgical evacuation based on ENRICH criteria, which extrapolates to 1066 to 1848 patients with ICH in the United States annually. Future research is needed to determine whether indications for effective surgical therapy for ICH can be expanded.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076095","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":"Fetal Hypoxia Suppresses TRPC6 and Impairs Cerebral Autoregulation in Neonatal Rats.","authors":"Xiang-Qun Hu, Rui Song, Chiranjib Dasgupta, Arlin B Blood, Lubo Zhang","doi":"10.1161/STROKEAHA.125.052524","DOIUrl":"10.1161/STROKEAHA.125.052524","url":null,"abstract":"<p><strong>Background: </strong>Cerebrovascular pressure autoregulation is the physiological mechanism that maintains cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure. It is a vital protective mechanism of the brain during fluctuations in arterial blood pressure that is particularly volatile in newborn infants. Yet, much remains unknown of the mechanisms underlying CBF autoregulation in the infant brain.</p><p><strong>Methods: </strong>Time-dated pregnant Sprague-Dawley rats were randomly divided into the normoxic control group and continuous hypoxic exposure group (10.5% oxygen) from day 15 to 21 of gestation. Rat pups were raised in normoxic conditions after birth. We tested the hypothesis that TRPC6 (transient receptor potential canonical channel 6) plays a key role in CBF autoregulation in the neonatal brain using postnatal days 12 to 14 rat pups. Blood pressure and CBF were measured. TRPC6 and Ca<sub>V</sub>1.2 expression and activity were assessed.</p><p><strong>Results: </strong>We demonstrated that TRPC6 functions as a mechanosensor to stretch the cell membrane and modulates Ca<sub>V</sub>1.2 activity of the middle cerebral artery in the neonatal rat brain. Fetal hypoxia downregulated TRPC6 expression/activity, TRPC6-Ca<sub>V</sub>1.2 coupling, and CBF autoregulation in the neonate. The loss-of-function approach using TRPC6 knockdown by siRNA and pharmacological TRPC6 inhibition recapitulated the effect of fetal hypoxia on the impairments of CBF autoregulation in neonatal pups.</p><p><strong>Conclusions: </strong>Our findings provide novel insights into the mechanism of CBF autoregulation in newborn brains and highlight a critical role of TRPC6 dysfunction in impaired cerebral autoregulation and heightened vulnerability to brain injury that is observed in the infant exposed to fetal hypoxia.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076129","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}
StrokePub Date : 2025-09-17DOI: 10.1161/STROKEAHA.124.049972
Benedict C Kupper, Martin F Reiner, Laura Werlen, Stefanie Aeschbacher, Pratintip Lee, Meret Allemann, Giorgio Moschovitis, Thomas Lüscher, Giovanni G Camici, Nicolas Rodondi, Luise Adam, Pascal B Meyre, Leo H Bonati, Tim Sinnecker, Michael Kühne, Stefan Osswald, David Conen, Jürg H Beer
{"title":"Plasma β-Thromboglobulin Is Inversely Associated With Cerebral Microbleeds in Atrial Fibrillation.","authors":"Benedict C Kupper, Martin F Reiner, Laura Werlen, Stefanie Aeschbacher, Pratintip Lee, Meret Allemann, Giorgio Moschovitis, Thomas Lüscher, Giovanni G Camici, Nicolas Rodondi, Luise Adam, Pascal B Meyre, Leo H Bonati, Tim Sinnecker, Michael Kühne, Stefan Osswald, David Conen, Jürg H Beer","doi":"10.1161/STROKEAHA.124.049972","DOIUrl":"https://doi.org/10.1161/STROKEAHA.124.049972","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers may increase the understanding of the pathophysiology of brain lesions in newly evaluated atrial fibrillation. BTG (β-thromboglobulin) is released from platelet alpha granules upon activation, reflecting platelet activation and destruction. We assessed the association of plasma BTG with cerebral microbleeds (CMBs) and ischemic brain lesions using brain magnetic resonance imaging (bMRI) in patients with atrial fibrillation.</p><p><strong>Methods: </strong>BTG was analyzed using the Luminex assay. CMBs and ischemic brain lesions were detected by standardized bMRI of 1724 patients from the Swiss-Atrial Fibrillation cohort, a prospective, national, multicenter cohort study that enrolled patients between 2014 and 2017. For this cross-sectional analysis, associations of BTG with bMRI lesions were evaluated by logistic and linear regression analyses using 2 models. The first model was adjusted for age and sex, and the second model was additionally multivariable-adjusted for a large number of clinical characteristics, including coronary artery disease, hypertension, diabetes, chronic kidney disease, history of heart failure, major bleeding, as well as concomitant platelet inhibitor, and anticoagulation therapy.</p><p><strong>Results: </strong>Mean age at baseline was 72.5 years (SD, 8.4), and 27.3% were female. On bMRI, CMBs were found in 369 patients (21.4%) and cerebral infarcts in 635 (36.8%). After multivariable adjustment, a 1-unit increase of log-transformed plasma BTG was associated with 25% lower odds of having CMBs (odds ratio, 0.75 [95% CI, 0.59-0.96]). However, BTG was not associated with the presence of large noncortical or cortical infarcts (odds ratio, 0.85 [95% CI, 0.66-1.09]) or small noncortical infarcts (odds ratio, 1.06 [95% CI, 0.83-1.35]).</p><p><strong>Conclusions: </strong>In patients with atrial fibrillation, the platelet-specific biomarker BTG was inversely and independently associated with CMBs on bMRI. Low-grade platelet activation may improve vascular integrity.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":8.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076089","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}