International Journal Of Stroke[JOURNAL]
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200 papers
Single versus dual antiplatelet therapy for stroke prevention in patients with first-ever embolic stroke of undetermined source.
Lee M, Kim C, Sohn JH … +4 more , Sung JH, Kim Y, Im HJ, Lee SH
Int J Stroke · 2025 Nov · PMID 41195864 · Publisher ↗
BACKGROUND: This study aims to evaluate the efficacy and safety of dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT) for patients with a first-ever embolic stroke of undetermined source (ESUS). M...
BACKGROUND: This study aims to evaluate the efficacy and safety of dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT) for patients with a first-ever embolic stroke of undetermined source (ESUS). METHODS: We assembled a multicenter cohort and a propensity score-matched (PSM) subset to compare DAPT with SAPT. The primary outcome was a composite of recurrent ischemic stroke, myocardial infarction, or all-cause death, and the safety outcome was major bleeding. Follow-up extended to 3 years (median, 2.6 years). We used Cox proportional hazards models to complement time-stratified (piecewise) analyses and restricted mean survival time (RMST). RESULTS: In the total cohort (n = 1675), DAPT was associated with a lower hazard of the composite outcome (adjusted hazard ratio (HR) = 0.56, 95% confidence interval (CI) = 0.44-0.70). Stroke recurrence and mortality were likewise reduced, while myocardial infarction events were infrequent. There was no significant difference in major bleeding between groups (e.g. incidence-rate ratio ≈1.0; p > 0.05). The annual incidence rate for the composite was 5.5%/year with DAPT versus 10.1%/year with SAPT. Time-stratified analyses revealed that the ischemic benefit was most pronounced between 6 and 12 months and appeared to persist thereafter. Bleeding, however, showed only a numerical increase beyond 1 year without statistical significance. RMST differences favored DAPT from 1 year onward and increased over 1000 days. CONCLUSION: In this ESUS cohort, DAPT was associated with fewer ischemic events and no increased major bleeding. The benefit was most evident at 6-12 months and was sustained over a longer follow-up period.
Safety and tolerability of Rinvecalinase Alfa (DM199) for acute ischemic stroke (ReMEDy1).
Campbell BC, Kasner SE, Lista AD … +14 more , Volpi JJ, Kleinig TJ, Cordato D, Dewey HM, Choi PM, Garcia-Esperon C, Sahathevan R, Wijeratne T, Wong AA, Ghia D, Cloud GC, Giuffre M, Bath PM, ReMEDy1 Investigators
Int J Stroke · 2026 Jul · PMID 41195862 · Full text
BACKGROUND: Rinvecalinase alfa (DM199), a recombinant form of human tissue kallikrein-1 (KLK1), aims to promote local vasodilation to ischemic brain and enhance collateral blood flow. The ReMEDy1 trial tested the safety...
BACKGROUND: Rinvecalinase alfa (DM199), a recombinant form of human tissue kallikrein-1 (KLK1), aims to promote local vasodilation to ischemic brain and enhance collateral blood flow. The ReMEDy1 trial tested the safety and tolerability of rinvecalinase alfa in ischemic stroke. METHODS: ReMEDy1 was a phase II, randomized, double-blind, placebo-controlled, study conducted at 13 Australian sites. Ninety-two patients with NIH Stroke Scale (NIHSS) 6-25 were enrolled within 24 h of ischemic stroke onset. Patients were randomized 1:1 to receive rinvecalinase alfa (1 µg/kg intravenous infusion followed by 3 µg/kg subcutaneously every 3 days for 22 days) or placebo. The primary outcome was safety, assessed by adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included changes in NIHSS, modified Rankin Scale (mRS), and Barthel Index (BI) at Days 22 and 90. Post hoc analyses excluded patients who underwent endovascular therapy (EVT). RESULTS: The median age was 72, NIHSS 10, and onset-to-randomization was 19.5 h. SAEs were reported in 20/47 (43.5%) rinvecalinase alfa patients and 14/45 (31.1%) placebo patients. Most patients experienced at least one AE; the most common in the rinvecalinase alfa group were constipation (60.9%), oral candidiasis (23.9%), and nausea (17.4%). Stroke-in-evolution by Day 90 occurred in 0 (0%) rinvecalinase alfa patients versus 6 (13.3%) placebo patients; 4/6 (66.7%) placebo patients with stroke-in-evolution died. No significant differences were observed in secondary efficacy outcomes at Day 90. Post hoc analyses in patients not treated with EVT suggested a tendency toward improved excellent global outcomes with rinvecalinase alfa. CONCLUSIONS: Rinvecalinase alfa appeared to be safe and generally well-tolerated in ischemic stroke patients, with potential efficacy in reducing stroke progression. Further studies are needed to confirm efficacy and long-term benefits in patients without EVT. REGISTRATIONS: https://www. CLINICALTRIALS: gov/study/NCT03290560.
Frailty index changes before and after stroke: Findings from four cohorts covering 18 countries.
Wang C, Qian X, Zhao X … +3 more , Jin M, Jia C, Jia F
Int J Stroke · 2026 Jul · PMID 41195860 · Publisher ↗
BACKGROUND: Frailty is a dynamic predictor of adverse stroke outcomes, but its bidirectional relationship with stroke-how frailty progresses before and after stroke-remains underexplored. AIMS: This study aims to examine...
BACKGROUND: Frailty is a dynamic predictor of adverse stroke outcomes, but its bidirectional relationship with stroke-how frailty progresses before and after stroke-remains underexplored. AIMS: This study aims to examine longitudinal frailty index (FI) trajectories in individuals with and without stroke, and changes in frailty trajectories within individuals before and after a stroke event across four international longitudinal studies. METHODS: This prospective cohort study analyzed data from four longitudinal cohorts: China Health and Retirement Longitudinal Study (CHARLS), English Longitudinal Study of Ageing (ELSA), Health and Retirement Study (HRS), and Survey of Health, Ageing and Retirement in Europe (SHARE). Frailty progression was assessed using validated FI scores. Incident strokes were identified through self-reported doctor diagnoses. Linear mixed models were used to evaluate changes in FI before and after stroke. RESULTS: Among the 73,961 participants, 4374 (5.9%) incident stroke events were identified. Compared to stroke-free individuals, stroke survivors exhibited an observable increase in FI prior to the stroke event (e.g. CHARLS: β = 0.016/year, 95% confidence interval (CI): 0.014-0.017). A sharp increase in FI occurred during the incident stroke event (HRS: β = 0.078, 95% CI: 0.074-0.083), followed by sustained post-stroke acceleration (ELSA: β = 0.019/year, 95% CI: 0.016-0.022). Sensitivity analyses confirmed robustness across cohorts. CONCLUSION: Frailty accelerates significantly both before and after an incident stroke, suggesting a bidirectional relationship between stroke and frailty. Integrating frailty assessment into stroke risk stratification, rehabilitation, and secondary prevention to optimize patient outcomes, particularly in aging populations.Data access statement:The datasets generated and analyzed during the current study are available on the HRS website (https://hrs.isr.umich.edu/), CHARLS (https://charls.pku.edu.cn/en), SHARE (https://share-eric.eu/), and ELSA (https://www.elsa-project).
Is the association of cannabis use and stroke frequency-dependent: A cross-sectional analysis of the NIH all of us research program.
Brown ED, Obeng-Gyasi B, Jeong SW … +6 more , Schneider D, Elsamadicy AA, Luther E, Libman R, Katz JM, White TG
Int J Stroke · 2026 Jul · PMID 41190717 · Publisher ↗
BACKGROUND: The relationship between cannabis use and stroke prevalence remains incompletely characterized, with most studies limited by binary exposure classification. We examined the frequency-dependent association of...
BACKGROUND: The relationship between cannabis use and stroke prevalence remains incompletely characterized, with most studies limited by binary exposure classification. We examined the frequency-dependent association of cannabis use and stroke prevalence by subtype in a large, diverse national cohort. AIMS: Our primary aim was to explore the relationship between cannabis use frequency and the adjusted prevalence of ischemic and hemorrhagic stroke. METHODS: We conducted a cross-sectional analysis of 122,767 adults from the National Institutes of Health (NIH) Research Program who completed lifestyle surveys between 2017-2022. Cannabis use frequency was stratified into five categories: never, once or twice, monthly, weekly, and daily. Ischemic and hemorrhagic stroke diagnoses were identified using International Classification of Diseases (ICD) 9 and 10 codes. Multivariable logistic regression models were adjusted for age, sex, race/ethnicity, obesity, type 2 diabetes, alcohol, and tobacco use. RESULTS: Among 122,767 participants, 2,765 (2.3%) had a history of stroke. After multivariable adjustment, a significant frequency-dependent association was found for ischemic stroke; compared to never-users, "once or twice" use was associated with a 10% increased odds (adjusted odds ratio (aOR) = 1.10, confidence interval (CI) = 0.95-1.26), monthly use with a 3% reduced odds (aOR = 0.97, CI = 0.73-1.29), weekly use with a 45% increased odds (aOR = 1.45, 95% CI = 1.19-1.77), and daily use with a 48% increased odds (aOR = 1.48, 95% CI = 1.26-1.74). In contrast, the odds of hemorrhagic stroke were elevated across all frequencies of cannabis use, with the highest odds observed in monthly users (aOR = 1.74, 95% CI = 1.21-2.51). These subtype-specific associations contributed to an overall increased odds of any stroke for weekly (aOR = 1.39) and daily (aOR = 1.44) users. CONCLUSIONS: In this large, nationally representative study, cannabis use was associated with stroke through two distinct, subtype-specific patterns. Odds of ischemic stroke demonstrated a clear dose-response relationship concentrated among frequent (weekly or daily) users, while odds of hemorrhagic stroke were elevated across all frequencies of use. These findings highlight the need to incorporate detailed cannabis use assessment into routine cerebrovascular risk stratification.
Polygenic risk scores improve stroke risk stratification in Chinese adults: Validation from the Chinese multi-provincial cohort study.
Wang Z, Jia P, Zhou P … +11 more , Qi Y, Sun J, Liu J, Wang M, Deng Q, Hao Y, Yang N, Han L, Liu J, Du J, Yang Z
Int J Stroke · 2026 Jul · PMID 41175054 · Publisher ↗
OBJECTIVE: To validate whether incorporating existing polygenic risk scores (PRSs) derived from East Asian or trans-ancestry populations into clinical risk equations improves stroke risk stratification in Chinese adults....
OBJECTIVE: To validate whether incorporating existing polygenic risk scores (PRSs) derived from East Asian or trans-ancestry populations into clinical risk equations improves stroke risk stratification in Chinese adults. METHODS: Participants from the Chinese Multi-provincial Cohort study with genotyped data (n = 2931) were included. Four well-established PRSs (i.e., PRS-GBMI, PRS-GIGA, PRS-ChinaPAR, and PRS-MEGA) from either the predominantly Chinese or trans-ancestry populations were constructed and evaluated by assessing their associations with stroke and its subtypes. We tested the incremental predictive capability of the four PRSs for the 10- and 20-year risk of stroke and its subtypes after adding PRSs to recalibrated China-PAR stroke risk equations, based on discrimination, calibration, and reclassification. RESULTS: Over a median follow-up period of 28.2 years, 340 stroke events were recorded. Higher PRSs were generally associated with a higher stroke risk, though only the highest quantile group of PRS-GIGA showed statistical significance (hazard ratio (HR): 1.79, 95% confidence interval (CI): 1.05-3.07). Adding PRS-GIGA to the recalibrated China-PAR stroke risk equations (i.e., the base model) yielded a moderate improvement in 20-year stroke risk, with 17.2% (95% CI: 3.8%-30.6%) more participants correctly categorized into their corresponding risk groups. However, for ischemic stroke, adding PRS-GIGA, PRS-ChinaPAR, and PRS-MEGA to the base model could correctly categorize 18.7%-23.8% more participants into their corresponding 10-year risk groups and 27.8%-32.5% more participants into their corresponding 20-year risk groups. Adding PRSs did not improve prediction for hemorrhagic stroke. CONCLUSION: Adding existing PRSs, particularly PRS-GIGA, to clinical risk equations can improve all stroke and ischemic stroke risk stratification in Chinese adults.
Magnitude and temporal dynamics of dementia risk before and after stroke diagnosis.
Huang X, Yang X, Zhu M … +7 more , Diao X, Zhang J, Pan Y, Dai Y, Ma J, Liu Y, Zheng F
Int J Stroke · 2025 Nov · PMID 41175051 · Publisher ↗
BACKGROUND: Stroke is associated with an increased risk of dementia, but the temporal dynamics of dementia risk before and after stroke diagnosis remain uncertain. This study aimed to examine the risk of dementia from 10...
BACKGROUND: Stroke is associated with an increased risk of dementia, but the temporal dynamics of dementia risk before and after stroke diagnosis remain uncertain. This study aimed to examine the risk of dementia from 10 years before through 30 years after stroke diagnosis, compared with non-stroke individuals. METHODS: We performed a case-control study using the UK Biobank data. We identified all participants diagnosed with stroke who had disease occurrence data available in the database. Controls were matched 3:1 for year of birth, sex, and education level. Conditional logistic regression was applied to estimate odds ratios (ORs) for incident dementia across different time windows before and after stroke diagnosis. RESULTS: This study included 24,056 individuals with stroke and 74,136 matched controls. The risk of dementia was higher in individuals with stroke compared to non-stroke controls in each time window before stroke diagnosis, with ORs ranging from 1.43 (95% confidence interval (CI): 1.02-2.01, = 0.040) in 5-10 years before diagnosis to 5.11 (95% CI: 4.06-6.41, < 0.001) in 1 year immediately before stroke. Within the first year after stroke diagnosis, the risk of incident dementia was the highest (OR: 6.39, 95% CI: 5.20-7.87, < 0.001). Similar results have been observed across sexes and different age groups. CONCLUSIONS: Participants who developed stroke had a higher risk of dementia beginning a decade before stroke onset, with risk peaking in the year around the diagnosis of stroke. These findings suggest the importance of prevention strategies at much earlier stages in individuals who are at risk of developing stroke and dementia.
Lost to follow-up in randomized clinical trials on long-term patient management following stroke: A cross-sectional survey.
Du P, Qin M, Liu Y … +6 more , Pang X, Wang S, Li Y, Gao J, Xu Z, Zhang C
Int J Stroke · 2026 Jul · PMID 41137200 · Publisher ↗
BACKGROUND: Although long-term stroke management is critically important, poor patient adherence to follow-up appointments threatens the validity of clinical trials. This cross-sectional survey aimed to identify contribu...
BACKGROUND: Although long-term stroke management is critically important, poor patient adherence to follow-up appointments threatens the validity of clinical trials. This cross-sectional survey aimed to identify contributing factors and potential consequences of lost to follow-up (LTFU) in long-term stroke management trials. METHODS: We searched Medline, Embase, Web of Science, Cochrane library, and Scopus from inception to 20 August 2024 for randomized controlled trials of multimodal post-stroke care initiated within 1 year of stroke. Data on general trial and methodological characteristics were extracted. Univariable random-effects meta-regression analyses were performed to identify LTFU predictors. Furthermore, we assessed how assumptions about LTFU affected effect estimates for significant binary primary outcomes. RESULTS: Among 58 eligible reports (27,575 patients and 3349 caregivers), six trials (10.3%) did not specify patient LTFU, while 8 of 17 caregiver-inclusive trials (47.1%) omitted LTFU reporting of caregivers. The median follow-up was 12 months (interquartile range (IQR): 6-12), with LTFU rates of 9.0% (IQR: 3.2-15.4%) for patients and 14.0% (IQR: 6.8-20.7%) for caregivers. Higher LTFU odds correlated with a higher proportion of females (odds ratio (OR): 2.93, 95% confidence interval (CI): 1.30-9.29) and older age (OR: 3.05, 95% CI: 1.38-9.07). Trials involving multidisciplinary rehabilitation teams showed lower LTFU (OR: 0.05, 95% CI: 0.01-0.26). When assuming different event rates for LTFU patients, 0-14.3% of significant results were no longer significant. CONCLUSION: Overall, approximately 10% of stroke trials on long-term patient management still did not report LTFU. Identified potential risk factors may provide targets to improve the continuity of stroke management within these trial settings. Attention to patient management is critical for ensuring valid trial conclusions.
A novel rendezvous approach between mobile stroke units and EMS improves timely thrombolysis in rural areas.
Wu X, Li J, Fu T … +12 more , Wang H, Zhang W, Fan P, Wu F, Wang L, Yang F, Jiao X, Li L, Zhang F, Liu S, Ji X, Guo X
Int J Stroke · 2026 Jul · PMID 41137198 · Publisher ↗
BACKGROUND: Mobile stroke units (MSUs) improve outcomes in acute ischemic stroke (AIS), but their effectiveness is constrained by limited service radii. Integrating a rendezvous strategy with emergency medical services (...
BACKGROUND: Mobile stroke units (MSUs) improve outcomes in acute ischemic stroke (AIS), but their effectiveness is constrained by limited service radii. Integrating a rendezvous strategy with emergency medical services (EMS) may extend the operational reach of MSUs in rural areas. AIM: We evaluated whether a novel rendezvous approach between MSUs and EMS could enhance thrombolysis efficiency for rural AIS patients in a larger service area. METHODS: We conducted a single-center, pragmatic, non-randomized, operationally allocated comparative study in Suzhou, Anhui, from 1 January to 31 December 2024. When a suspected stroke call originated from a remote location, a nearby conventional ambulance was dispatched. Subsequently, the MSU was dispatched via an EMS call, met the EMS at a predetermined midway point en route to the stroke center, and treated the patient when MSU was available. Inclusion criteria were: age ⩾ 18 years; onset location ⩾ 20 km from the MSU center; and onset-to-call time ⩽ 4 h. Patients with a final diagnosis of cerebral ischemia were analyzed based on transport method (MSU rendezvous vs EMS only). The primary outcome was the thrombolysis rate; secondary outcomes included time metrics, 90-day functional prognosis, and incidence of symptomatic intracranial hemorrhage (sICH). Propensity score matching (PSM) was used to balance baseline characteristics. RESULTS: A total of 307 patients with AIS were included; the median age was 72 years (IQR, 63-79), and 192 (62.50%) were male. One hundred ninety-three patients were transferred through rendezvous transport, and 114 patients were transferred through EMS-only. The median distance from onset location to hospital in the rendezvous transport group was 39.00 km (24.23 miles) (IQR 30.00-47.00 km), with a maximum of 68.00 km (42.25 miles). Compared with EMS-only transfers, patients transferred through rendezvous transport had a nearly 3-fold increase in thrombolysis rates (68.90% vs 17.50%, < 0.001), reduced dispatch-to-door time by 12.5 min, door-to-needle time by 46 min, and onset-to-needle time by 60 min (all < 0.001). In addition, in terms of clinical outcomes, patients in the rendezvous group had lower median 90-day modified Rankin Scale scores (2.0 (1.0-3.0) vs 3.0 (1.5-5.0), < 0.001). These findings remained consistent after PSM. CONCLUSION: Our study demonstrates that the novel MSU-EMS rendezvous approach significantly improves thrombolysis rates and functional outcomes, serving as a viable strategy to expand acute stroke care to remote populations.Data access statement:Data collected for the study may be made available from the corresponding author to others upon reasonable request.
Incidence and outcome of pediatric moyamoya disease in the Republic of Korea: A nationwide study.
Kim S, Lee JS, Phi JH … +6 more , Lee JY, Kim JW, Park JS, Choi JP, Lee J, Kim SK
Int J Stroke · 2025 Oct · PMID 41137197 · Publisher ↗
BackgroundMoyamoya disease (MMD) is a rare cerebrovascular disorder for which nationwide epidemiological data on the pediatric population are limited. In Korea, the majority of published epidemiologic data on MMD entaile...
BackgroundMoyamoya disease (MMD) is a rare cerebrovascular disorder for which nationwide epidemiological data on the pediatric population are limited. In Korea, the majority of published epidemiologic data on MMD entailed brief study periods and were published many years ago. Moreover, the majority of prior epidemiological studies on MMD have not examined the clinical outcomes associated with cerebral revascularization.AimsTo provide a comprehensive analysis of the recent epidemiological trends and cerebrovascular outcomes associated with pediatric moyamoya disease in Republic of Korea.MethodsA retrospective cohort study was conducted using the Korean National Health Insurance Database, analyzing 4,323 pediatric patients diagnosed with MMD between 2006 and 2021. Prevalence and incidence were assessed in all 4,323 patients, and cerebrovascular outcomes were analyzed in 3,656 of these patients. Patients were categorized into surgical and non-surgical groups, with surgical techniques including indirect bypass (IB), direct bypass (DB), and combined bypass (CB). To evaluate year-to-year variations, linear regression analyses were performed to identify and quantify temporal trends for all measured outcomes.ResultsThe mean observation period for the subjects was 10.3 years, with 12.1 years for the non-surgical group and 9.7 years for the surgical group. The prevalence of pediatric MMD increased from 9.3 to 24.8 per 100,000 between 2006 and 2021. Concurrently, the incidence rate has remained stable at approximately 2.0 per 100,000 since 2010. The surgical rate among prevalent cases has exhibited a gradual increase and has remained at approximately 88% since 2018. Furthermore, the case event rate for stroke has exhibited a downward trend over time, and a statistically significant reduction in hemorrhagic stroke was observed.ConclusionsIn Korea, the prevalence rate of MMD continues to rise, while the incidence rate remains stable despite a reduction in absolute case numbers, reflecting demographic shifts and improved survival. The mortality rate among pediatric MMD patients remained unchanged; however, the incidence of hemorrhagic stroke was found to have decreased. Further multi-institution-based cohort studies are needed to clarify long-term cerebrovascular outcomes in this population.
Intravenous thrombolysis in patients with acute ischemic stroke and cerebral microbleeds: Results from the ENCHANTED trial.
Zhou Z, Ge Y, Yoshimura S … +12 more , Torii-Yoshimura T, Sakamoto Y, Liu X, Carcel C, Chen X, Liu L, Parsons M, Mair G, Lindley RI, Wardlaw J, Anderson CS, Delcourt C
Int J Stroke · 2026 Jun · PMID 41131698 · Publisher ↗
OBJECTIVE: To determine associations between cerebral microbleeds (CMBs) and intracerebral hemorrhage (ICH) as well as functional recovery after thrombolysis in participants of the Enhanced Control of Hypertension and Th...
OBJECTIVE: To determine associations between cerebral microbleeds (CMBs) and intracerebral hemorrhage (ICH) as well as functional recovery after thrombolysis in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: ENCHANTED recruited acute ischemic stroke (AIS) patients eligible for thrombolytic therapy from 111 clinical centers in 13 countries. We included those with T2*-weighted or susceptibility-weighted brain magnetic resonance imaging within 6 h after AIS. Associations between CMB (primary predictor), burden (0, 1, 2-4, or ⩾5 CMBs), and location (deep, lobar, mixed) and any ICH (primary outcome), symptomatic intracerebral hemorrhage (sICH), 90-day disability or death (modified Rankin scale (mRS) score 2-6), and other unfavorable functional outcomes (mRS 3-6, 6, and shift) were explored in logistic regression models and in a stratification by alteplase dose. RESULTS: Of 311 eligible AIS participants, 111 (35.7%) had CMB(s) and this was not associated with an increase in any ICH (adjusted odds ratio = 1.49, 95% confidence interval (CI) = 0.87-2.54) or sICH (2.05, 0.92-4.56). However, the presence of CMB(s) was associated with 90-day disability or death (1.75, 1.04-2.94) and other unfavorable functional outcomes. Comparable associations were seen between CMB burden (defined as ordinally categorical; any ICH 1.16 (0.90-1.50), mRS 2-6 1.44 (1.11-1.87)) or mixed deep-lobar distribution (any ICH 1.42 (0.61-3.29), mRS 2-6 3.66 (1.48-9.05)) and these outcomes. There were no differences in associations between CMB presence/burden/distribution and outcomes between two different alteplase doses ( > 0.087). CONCLUSION: In ENCHANTED, CMB(s) was associated with 90-day unfavorable function recovery but not with a significantly increased likelihood of ICH in post-intravenous thrombolytic AIS. Low-dose alteplase may not offer a better profile for AIS with CMB(s).Data access statement:Individual de-identified participant data used in this analysis will be shared by request from any qualified investigator via the Research Office of The George Institute for Global Health.
Thrombocytopenia as a predictor of hematoma expansion and mortality in intracerebral hemorrhage.
Wilson M, Incontri D, Vu S … +11 more , Heistand E, Marchal J, Marchina S, Wang JY, Lazar A, Carolina Alonso Ramirez A, Saadah L, Andreev A, Carvalho F, Selim M, Lioutas VA
Int J Stroke · 2026 Jun · PMID 41131697 · Publisher ↗
BACKGROUND AND AIMS: There is limited data regarding the association between thrombocytopenia and outcomes of patients with intracerebral hemorrhage (ICH). We investigated whether thrombocytopenia predicts hematoma expan...
BACKGROUND AND AIMS: There is limited data regarding the association between thrombocytopenia and outcomes of patients with intracerebral hemorrhage (ICH). We investigated whether thrombocytopenia predicts hematoma expansion and hospital mortality in ICH. METHODS: This was a retrospective cohort analysis of consecutive patients with spontaneous ICH admitted to a tertiary hospital from 2010 to 2024. We tested the association between baseline thrombocytopenia (platelet count < 150 × 10/L) at the time of the index ICH and both hematoma expansion (absolute increase > 6 mL or relative increase > 33%) and hospital mortality using multivariable logistic regression. Secondary analyses were undertaken to compare outcomes between patients with moderate-to-severe thrombocytopenia (platelet count < 100 × 10/L) and mild thrombocytopenia (platelet count 100-149 × 10/L) and between patients with thrombocytopenia who received platelet transfusion vs no transfusion. RESULTS: We included 1002 patients (median (IQR) age, 73 (61-82); 448 females (44.7%) of whom 168 (16.8%) had thrombocytopenia). At baseline, patients with thrombocytopenia had lower Glasgow Coma Scale (GCS) scores (12 (6-15) vs 14 (9-15) P < 0.001), larger median hematoma volumes (21.4 mL (7.8-56.1) vs 15.3 mL (4.9-43.9), P = 0.004), more intraventricular hemorrhage (IVH) (84/168 (50.0%) vs 320 (38.4%), P = 0.005), and higher ICH scores (2 (1-3) vs 1 (0-3), P < 0.001) compared to those without thrombocytopenia. Hematoma expansion was more frequent in patients with thrombocytopenia (62/136 (45.6%) vs 233/738 (31.5%), P = 0.002); however, no association was present in adjusted analysis (adjusted odds ratio (OR) 1.28 (95% CI, 0.82-2.00), P = 0.269). With exclusion of platelet transfusion as a covariate from the adjusted model, thrombocytopenia was associated with hematoma expansion (OR 1.77 (95% CI, 1.20-2.59), P = 0.004). Thrombocytopenia was independently associated with hospital mortality (77/168 (45.8%) vs 199/834 (23.9%); OR 2.09 (95% CI, 1.24-3.53), P = 0.006). Among patients with thrombocytopenia, a platelet count < 100 × 10/L was associated with more hematoma expansion in univariable (26/44 (59.1%) vs 36/92 (39.1%), P = 0.030) but not multivariable analysis (OR 1.66 (95% CI, 0.58-4.80), P = 0.348). Platelet transfusion predicted hematoma expansion in univariable (23/33 (66.7%) vs 40/103 (38.8%), P = 0.006) but not multivariable analysis (OR 2.74 (95% CI, 0.86-8.75), P = 0.090). CONCLUSIONS: Our findings suggest that both thrombocytopenia and platelet transfusions may be risk factors for hematoma expansion in ICH. Further study is needed to clarify the independent contributions of thrombocytopenia and platelet transfusions toward hematoma expansion and clinical outcome.Data access statement:Data available upon reasonable request.
Addressing sex and gender differences in stroke risk and management: A scientific statement from the World Stroke Organization.
Carcel C, Sandset EC, Ali M … +16 more , Allende Echanez MI, Mosconi MG, de Souza AC, Dalli LL, Venturelli PM, Sakamoto Y, Nasreldein A, Yu AY, Walter S, Lannin NA, Drummond A, Caso V, Alladi S, Bushnell CD, Reeves MJ, Gall S
Int J Stroke · 2026 Mar · PMID 41131690 · Publisher ↗
This World Stroke Organization Scientific Statement highlights how sex and gender differences shape stroke risk, treatment, care, and research. Estrogen confers a relative protection before menopause, with risk increasin...
This World Stroke Organization Scientific Statement highlights how sex and gender differences shape stroke risk, treatment, care, and research. Estrogen confers a relative protection before menopause, with risk increasing thereafter. Beyond shared cardiovascular determinants (hypertension, atrial fibrillation, and diabetes), women face sex-specific risks-hypertensive disorders of pregnancy, menopause, and hormone therapy, with clear implications for stroke prevention and management. Despite comparable efficacy of acute and secondary stroke therapies in women and men, women are less likely to receive timely acute treatment and often experience delays in recognition and access. The statement recommends gender-responsive prevention and care pathways; systematic consideration of pregnancy-related and menopausal factors; and public and professional education to improve stroke symptom recognition and purposeful inclusion of women across the research continuum. By integrating evidence from epidemiology, acute care, and secondary prevention, this statement provides clear and timely guidance for reducing inequities and shaping future research and policy to achieve equitable stroke care globally.
Left atrial occlusion in intracerebral hemorrhage with atrial fibrillation, herpes zoster, and stroke, improving stroke outcomes in China, and Cerebrolysin as a treatment for acute stroke.
Markus HS
Int J Stroke · 2025 Oct · PMID 41126602 · Publisher ↗
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Outcomes of patent foramen ovale closure in patients over 60 years with cryptogenic stroke: A systematic review and meta-analysis.
Jazayeri SB, Phan C, Ghozy S … +12 more , Ravichandran S, Maleki AH, Dumitrascu OM, Agrawal K, Modir R, Hemmen T, Poli S, Zuern CS, Trabattoni D, Meyer D, Meyer B, Shahripour B
Int J Stroke · 2026 Jun · PMID 41099439 · Full text
BACKGROUND: In younger patients (<60 years) with cryptogenic stroke (CS) presumed to be patent foramen ovale (PFO)-related, the standard approach involves transcatheter PFO closure combined with antithrombotic therapy. H...
BACKGROUND: In younger patients (<60 years) with cryptogenic stroke (CS) presumed to be patent foramen ovale (PFO)-related, the standard approach involves transcatheter PFO closure combined with antithrombotic therapy. However, due to their exclusion from randomized clinical trials (RCTs), no formal recommendations exist for patients ⩾60 years. This study had two objectives (1) to compare the efficacy and safety of PFO closure versus antithrombotic therapy alone (ATA) exclusively in older patients (⩾60 years) and (2) to assess the outcomes of PFO closure in patients ⩾ 60 years versus < 60 years. METHODS: We searched PubMed, Embase, Web of Science, and ScienceDirect databases to obtain articles in all languages from January 2004 until July 2025. The primary outcome was risk of recurrent stroke during follow-up. Secondary outcomes were risk of new-onset atrial fibrillation (AF), all-cause mortality, and in-hospital complications. PROSPERO registration ID: CRD420250652870. RESULTS: Only one RCT (post hoc evaluation of the DEFENSE-PFO trial) and 11 observational studies were included. In patients aged ⩾ 60 years, risk of recurrent stroke was lower when PFO was closed compared with ATA (5.48% vs 10.05%, respectively, hazard ratio (HR) = 0.56, 95% confidence interval (CI) = 0.45-0.80, p < 0.001, I = 45.6%). All-cause mortality was also lower for PFO closure versus ATA (1.73% vs 7.59%, respectively, HR = 0.41; 95% CI = 0.19-0.90, p = 0.02; I = 43.8%). There was no difference between PFO closure and ATA in risk of new-onset AF (HR = 1.13, 95% CI = 0.53-2.44, p = 0.74). Compared with patients < 60 years, individuals ⩾ 60 years who underwent PFO closure had a higher risk of recurrent stroke (2.94% vs 1.04%, respectively, HR = 3.47; 95% CI = 1.61-7.48; p = 0.001), new-onset AF (4.86% vs 1.01%, respectively, HR = 4.12; 95% CI = 1.90-8.95; p < 0.001), and all-cause mortality during follow-up (8.32% vs 0.39%, respectively, HR = 8.24; 95% CI = 3.49-19.46; p < 0.0001). In-hospital complications after PFO closure were comparable between two age groups. Due to insufficient data, we were not able to perform a subgroup analysis based on anatomic features of PFO, antithrombotic regimen, or occluder devices. CONCLUSION: Based on available data, which is predominantly derived from observational studies, PFO closure is associated with a reduced risk of recurrent stroke compared to ATA in patients over 60 years. However, these findings are subjected to limitations, including the potential for selection bias, unmeasured confounding, and insufficient long-term follow-up. Furthermore, long-term randomized trials are essential to definitively confirm efficacy and establish clinical guidelines for PFO closure in this older population.
Association of total and moderate-to-vigorous physical activity with stroke risk: A dose-response meta-analysis of 2,639,086 participants from 14 international prospective cohort studies.
Li Z, Zhang Z, Zhang Y … +7 more , Zhang C, Li X, Tian C, Liang J, Ma T, Huang W, Lei J
Int J Stroke · 2026 Apr · PMID 41099436 · Publisher ↗
BACKGROUND: Stroke is the second leading cause of death and third leading cause of disability globally. The dose-response relationship between physical activity (PA), particularly moderate-to-vigorous physical activity (...
BACKGROUND: Stroke is the second leading cause of death and third leading cause of disability globally. The dose-response relationship between physical activity (PA), particularly moderate-to-vigorous physical activity (MVPA), and stroke risk remains unclear, with limited sex-specific evidence. AIMS: To examine the dose-response associations of total PA and MVPA with stroke risk, considering sex and subtype differences. METHODS: A systematic review and dose-response meta-analysis of prospective cohort studies published between 2013 and 2024, with follow-up durations ranging from 4.9 to 17.9 years, were conducted. PA exposures were standardized to MET-hours per week (MET-h/wk), and incident stroke was the primary outcome. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using random-effects models. Dose-response associations were assessed using restricted cubic spline models. Analyses stratified by sex and subtype were performed when available. RESULTS: Fourteen cohorts (n = 2,639,086) were included. Total PA showed a nonlinear inverse association with stroke risk: each 10 MET-h/wk increment reduced risk by 1% up to 130 MET-h/wk, corresponding to a 13% maximum reduction, after which benefits plateaued. MVPA exhibited an L-shaped association (P < 0.001), with the greatest benefit (19% reduction) at 19 MET-h/wk, followed by a gradual increase in risk. Sex-stratified analysis revealed a J-shaped pattern in females (optimal 10-15 MET-h/wk; 18% reduction). For males, the HR was 0.89 (95% CI: 0.70-1.13), and a nonlinear model could not be established due to limited data. In ischemic stroke, dose-response patterns paralleled those for total stroke. CONCLUSIONS: The study found a significant dose-response relationship between total PA and MVPA with stroke risk. Optimal prevention was observed at 130 MET-h/wk for total PA and 19 MET-h/wk for MVPA. Evidence in males and for hemorrhagic stroke remains limited and warrants further study.
Free water, perivascular spaces, and diffusivity along perivascular spaces dynamics after recent small subcortical infarcts and their associations with cognition.
Qiu T, Hong H, Xu X … +7 more , Xu Y, Zhang L, Wang Y, Huang P, Dai S, Li F, Luo X
Int J Stroke · 2026 Jun · PMID 41099419 · Publisher ↗
BACKGROUND AND PURPOSE: The pathophysiological mechanisms underlying cognitive changes following recent small subcortical infarcts (RSSIs) remain incompletely understood. In this study, we aimed to investigate alteration...
BACKGROUND AND PURPOSE: The pathophysiological mechanisms underlying cognitive changes following recent small subcortical infarcts (RSSIs) remain incompletely understood. In this study, we aimed to investigate alterations in brain fluid dynamics-including interstitial fluid (ISF) and perivascular space (PVS) abnormalities-using magnetic resonance imaging (MRI)-based markers, and examined their associations with cognitive outcomes. METHODS: In this prospective single-center study, patients with RSSIs underwent comprehensive neuropsychological evaluations and multimodal MRI assessments at 3-7 days, 3-6 months, and 1, 2, and 3 years post-stroke. Three MRI-derived proxies of brain fluid dynamics were assessed: free water (FW) fraction, reflecting the ISF fraction; and PVS volume and diffusion tensor imaging analysis along the PVS (DTI-ALPS), both reflecting PVS dynamics. Relative metrics (FW, PVS, and DTI-ALPS) were calculated as (ipsilesional - contralesional)/contralesional values, to quantify hemisphere-specific changes associated with RSSI. Comparative analyses of MRI-derived proxies of brain fluid dynamics were performed between ipsilesional and contralesional hemispheres both cross-sectionally and longitudinally. The associations between these markers and cognitive performance were examined using linear regression and mixed-effects models, with false discovery rate (FDR) corrections for multiple comparisons. RESULTS: The study included 66 RSSI patients (mean age: 57.15 ± 7.35 years; 80.3% male). Baseline comparisons revealed significantly higher PVS volume ( = 0.004) and lower DTI-ALPS ( = 0.018) in the ipsilesional hemisphere compared with the contralesional side. While FW did not differ significantly between hemispheres ( = 0.858), the perilesional regions showed significantly higher FW compared with the corresponding contralesional regions ( < 0.05). Furthermore, baseline lower relative PVS was associated with attention improvement (β = 0.513, P = 0.004). Longitudinal analysis revealed bilateral FW increase ( = 0.025) and DTI-ALPS decline ( = 0.016), with no significant interhemispheric differences. However, no significant correlations were observed between relative FW, PVS, and DTI-ALPS slopes and cognitive trajectories (all P > 0.05). CONCLUSION: Our findings demonstrate RSSIs are associated with disrupted MRI-derived proxies of brain fluid dynamics, characterized by increased ISF and PVS dysfunction in the ipsilesional hemisphere. Baseline PVS volume is correlated with cognitive changes in RSSI patients, highlighting the potential of early PVS-targeted interventions to prevent post-stroke cognitive impairment.
Long-term recovery of disabling ischemic stroke: Five-year follow-up of a prospective cohort study.
Jiang YY, Jiang Y, Cheng S … +5 more , Meng X, Li H, Gu HQ, Li ZX, Wang YJ
Int J Stroke · 2026 Apr · PMID 41099400 · Publisher ↗
BACKGROUND: Research on long-term functional recovery after stroke remains limited. This study aims to investigate the long-term functional recovery among ischemic stroke patients with functional disabilities in China. M...
BACKGROUND: Research on long-term functional recovery after stroke remains limited. This study aims to investigate the long-term functional recovery among ischemic stroke patients with functional disabilities in China. METHODS: This prospective cohort study used data from the China National Stroke Registry III, which had 15,166 patients consecutively enrolled across 201 hospitals in China between August 2015 and March 2018. We included 4086 patients with disabling ischemic stroke at discharge (the modified Rankin Scale (mRS) score of ⩾2) after excluding 19 patients (0.47%) lost to follow-up by the 5-year endpoint, and our final cohort included 4067 patients. The main outcome was 5-year functional recovery, defined as a ⩾1-point reduction in the mRS score between discharge and 5-year follow-up. Multivariable Cox proportional hazards regression models were used to determine the factors of recovery. RESULTS: Among 4067 patients, the mean ± SD age was 63.3 ± 11.5 years, and 1416 (34.8%) were female. The functional recovery rate was 86.8% within 5 years (n = 3531/4067). In multivariable analysis, older age (adjusted hazard ratio (aHR) 0.86, (95% CI 0.84-0.89)), current alcohol use (aHR 0.91, (95% CI 0.83-0.99)), history of stroke (aHR 0.88, (95% CI 0.81-0.95)), higher National Institutes of Health Stroke Scale score at discharge (aHR 0.96, (95% CI 0.95-0.97)), and stroke recurrence (aHR 0.88, (95% CI 0.81-0.96)) were independently associated with reduced likelihood of 5-year functional recovery. Patients with small artery occlusion (aHR 1.11, (95% CI 1.01-1.22)), without atrial fibrillation (aHR 1.31, (95% CI 1.09-1.58)), and discharged with anticoagulant medication (aHR 1.35, (95% CI 1.06-1.71)) were independently associated with increased likelihood of 5-year functional recovery. CONCLUSION: In this cohort study of patients with disabling ischemic stroke, long-term functional recovery rates were high, and key factors associated with recovery outcomes were identified, which may help guide personalized rehabilitation strategies.
Microvascular brain damage in middle-aged women with a history of migraine with aura and/or ischemic stroke.
Weerd NV, Wilms AE, van Os HJ … +8 more , Holswilder G, Linstra KM, van Zwet EW, van den Maagdenberg AM, MaassenvandenBrink A, Kruit MC, Terwindt GM, Wermer MJ
Int J Stroke · 2026 Jun · PMID 41090699 · Full text
BACKGROUND: Both patients with migraine with aura (MA) and patients with ischemic stroke have an increased risk of white matter hyperintensities (WMH) indicating structural microvascular brain damage. It is unclear wheth...
BACKGROUND: Both patients with migraine with aura (MA) and patients with ischemic stroke have an increased risk of white matter hyperintensities (WMH) indicating structural microvascular brain damage. It is unclear whether other signs of microvascular damage are also more abundant in these patients, and whether patients with both conditions are more severely affected. METHODS: We included middle-aged women with a history of MA, ischemic stroke, or both, as well as age-matched female control participants without any neurological disease, from two cross-sectional MRI studies (CREW and WHISPER). We assessed WMH, enlarged perivascular spaces, cerebral microbleeds, lacunes, cortical superficial siderosis, parenchymal volume, and cortical atrophy, according to STRIVE criteria. A total small vessel disease (SVD) burden score was determined. We performed regression analyses to assess the association between a history of MA, stroke, or both and the different MRI markers, adjusted for vascular risk factors. RESULTS: We included 207 women (mean age: 51 years): 39 with MA, 67 with stroke, 62 with both MA and stroke, and 39 controls. MA was not associated with increased microvascular damage compared with controls. Stroke patients had more cerebellar WMH (OR = 7.9, 95% CI = 0.9-73.6), more cortical atrophy (β = 0.2, 95% CI = 0.0-0.4), and a lower parenchymal volume (β = -16.1, 95% CI = -30.7 to -1.4) than controls. There was no difference in the frequency of any of the SVD markers on 3 Tesla (3T)-MRI in patients with stroke with or without migraine. CONCLUSION: In our study, markers of microvascular cerebral damage were infrequent in middle-aged women with MA and healthy controls, while stroke was associated with more cerebellar WMH, decreased parenchymal volume, and cortical atrophy. We found no (supra-)additive effect of a history of migraine on the extent of microvascular brain damage in women with stroke.
Effect of drug-coated balloon in patients with severe vertebral artery origin stenosis: A multicenter randomized controlled trial.
Luo J, Jiang C, Wang H … +20 more , Peng R, Wang T, Kuai D, Liang G, Wang F, Wang S, Xu C, Chen W, Deng J, Hu X, Wan S, Li B, Yin B, Du Y, Cheng G, Wan J, Chen X, Wang Y, Jiao L, DCB-VAOS Trial Investigators
Int J Stroke · 2026 Mar · PMID 41067866 · Publisher ↗
BACKGROUND: Vertebral artery origin stenosis (VAOS) is a common cause of posterior circulation ischemic events, and endovascular treatment serves as an alternative treatment. However, conventional endovascular treatment...
BACKGROUND: Vertebral artery origin stenosis (VAOS) is a common cause of posterior circulation ischemic events, and endovascular treatment serves as an alternative treatment. However, conventional endovascular treatment methods are related to high risk of restenosis. It is unclear whether the drug-coated balloon (DCB) can reduce restenosis risk of VAOS. METHODS: This was a prospective, multicenter, randomized trial conducted from 6 January 2020 to 1 October 2023 in China. Symptomatic patients with severe VAOS were randomly allocated in a 1:1 ratio to undergo either DCB or bare-metal stent (BMS) and followed up for 12 months. The primary safety endpoint was the incidence of transient ischemic attack, stroke, or death related to target vessel within 30 days post-procedure. The primary efficacy endpoint was the rate of 12-month restenosis. RESULTS: A total of 179 patients were enrolled with 91 in the DCB group and 88 in the BMS group. No significant difference was observed in the rates of transient ischemic attack, stroke, or death related to target vessel within 30 days between the DCB and BMS groups (0 (0.0%) vs. 1 (1.1%); P = 0.49). The 12-month restenosis rate was significantly lower in the DCB group compared to the BMS group (10/76 (13.2%) vs. 27/76 (35.5%); risk ratio = 0.37; 95% confidence interval = 0.19 to 0.71; P = 0.001). CONCLUSION: This trial demonstrated that DCB may reduce restenosis risk in symptomatic patients with severe VAOS compared to BMS. REGISTRATION: URL: https://clinicaltrials.gov (unique identifier: NCT03910166).
Prevalence of cervical fibromuscular dysplasia among aneurysmal subarachnoid hemorrhage patients.
Rietkerken S, Dankbaar JW, Spiering W … +1 more , Ruigrok YM
Int J Stroke · 2026 Apr · PMID 41058079 · Publisher ↗
BACKGROUND AND OBJECTIVES: Fibromuscular dysplasia (FMD) is a vascular disorder affecting medium-sized arteries, including the extracranial cervical arteries, and can lead to aneurysmal subarachnoid hemorrhage (aSAH). We...
BACKGROUND AND OBJECTIVES: Fibromuscular dysplasia (FMD) is a vascular disorder affecting medium-sized arteries, including the extracranial cervical arteries, and can lead to aneurysmal subarachnoid hemorrhage (aSAH). We aimed to determine the prevalence of cervical FMD in aSAH patients and assess whether cervical FMD in these patients is associated with more severe aneurysmal disease and internal carotid artery (ICA) elongation. METHODS: We retrospectively reviewed computed tomography angiography (CTA) scans acquired on admission in a consecutive series of aSAH patients (2019-2024). The prevalence of FMD in the extracranial segments of the ICA and vertebral arteries (VAs) was determined. In addition, differences in aneurysm size, number of aneurysms, rebleeding rates, and ICA elongation were assessed between patients with and without FMD using logistic regression, adjusting for potential confounders. RESULTS: Cervical FMD was identified in 40 of 485 aSAH patients (prevalence 8.3%, 95% confidence interval (CI) = 6.0-11.1%). aSAH patients with FMD were older, more frequently women, and more likely to have hypertension than those without FMD. We found no statistically significant differences in aneurysm size, number of aneurysms, rebleeding rates, or ICA elongation. DISCUSSION: We report a high prevalence (8.3%) of cervical FMD among aSAH patients, but no clear differences in aneurysm severity and ICA elongation compared to those without. Given the high prevalence, we recommend routine screening for cervical FMD in aSAH patients on CTA (or another angiography modality). If FMD is suspected, full-body CTA (or other angiographic modality) should be considered for further vascular assessment.
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