International Journal of Stroke

Leadership development is essential to advancing stroke care globally. The World Stroke Organization (WSO) Future Stroke Leaders Program (FSLP) was established to identify and support global early-career professionals in stroke care worldwide. The program offers structured leadership training, mentorship, and seed funding for implementation projects. Selection criteria prioritize diversity, leadership potential, and institutional support. The article describes the design and implementation of the WSO FSLP and evaluates its contribution to stroke care advancement, professional development, and global collaboration.

This is a descriptive narrative of the WSO FSLP, based on program documentation, participant surveys, and public databases. Programmatic key performance indicators (KPIs) aligned with WSO’s strategic goals were used to track impact.

Among 56 participants in the first two cohorts, selected from over 35 countries, engagement with the WSO FSLP contributed to improved access to and delivery of care by developing stroke services in underserved areas, enhancing publication output, and supporting active involvement in international policy and advocacy efforts. Participants reported career advancement, increased research engagement, and expanded collaborative networks as a direct result of their participation in the program.

The WSO FSLP is a model for developing global stroke leadership. Its impact spans clinical innovation, academic research, and policy influence, guiding implementation. Continued program adaptation to the changing international landscape, alumni engagement, and long-term impact evaluation will help sustain and scale worldwide contributions to stroke care equity.

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.

To examine the dose–response associations of total PA and MVPA with stroke risk, considering sex and subtype differences.

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.

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.

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.

Evidence on the role of herpes-zoster (shingles) vaccination in reducing stroke risk is inconsistent and limited, particularly concerning intracerebral hemorrhage (ICH). We aimed to examine the association between zoster live vaccine (ZVL) and overall stroke, as well as its main subtypes.

We conducted a population-based nested case–control study using the database of Israel’s largest healthcare provider. The underlying cohort consisted of individuals aged 50 years or older, regardless of prior stroke status, from 2015 to 2022, with follow-up through June 2023. Stroke cases diagnosed during follow-up were matched with controls based on age, sex, population sector, and index date. ZVL exposure was defined as the prior filling of a prescription of the vaccine.

Among 37,027 matched case–control pairs, ZVL was associated with significantly reduced odds of stroke, with an adjusted odds ratio (OR) of 0.65 (95% confidence interval (CI), 0.58–0.72) for overall stroke, 0.65 (95% CI, 0.58–0.73) for ischemic stroke, and 0.64 (95% CI, 0.47–0.89) for ICH. The protective association with overall stroke decreased as time since vaccination increased; adjusted OR of 0.56 (0.48–0.65) within the first 2.5 years, 0.71 (95% CI, 0.58–0.87) after 2.5 to 5 years, and 0.81 (95% CI, 0.65–1.01) after 5 years. The association between ZVL and stroke was modified by age and sex, with a stronger association in individuals younger than 65 years (p for interaction = 0.004) and males (p for interaction = 0.031).

ZVL is associated with a reduced risk of both ischemic stroke and ICH. The protective association appears to decrease over time and to be stronger in males and younger individuals.

An in-hospital double-dose influenza vaccination strategy’s effect on preventing major adverse cardiovascular events (MACE) in patients with previous stroke is still uncertain. This study is a prespecified analysis of the vaccine against influenza to avoid cardiovascular events after the Acute Coronary Syndrome (VIP-ACS) trial.

The VIP-ACS trial was a randomized, pragmatic, multicenter, open-label trial with blinded-adjudication endpoints. Adult patients with acute coronary syndrome (ACS) ⩽ seven days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine or a standard-dose vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of all-cause death, myocardial infarction (MI), stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analyzed by the win ratio (WR) method. The secondary endpoint was a hierarchical composite consisting of CV death, MI and stroke (MACE). Patients were followed for 12 months each influenza season.

The trial enrolled 1801 patients (31% female). A total of 67 patients had a history of stroke. There were no significant differences between groups on the primary hierarchical endpoint: 11.4% wins (862 patients) in the double-dose vaccine group versus 12.1% wins (872 patients) in the standard-dose vaccination group (WR: 0.94; 95% CI: 0.72–1.24; p = 0.69) without a history of stroke. However, in-hospital double-dose vaccination favored individuals (34 patients) with previous stroke (WR: 2.62; 95% CI: 1.10–6.25; p = 0.03; 43.9% wins vs 16.8% wins). Results were consistent for hierarchical MACE (WR: 3.01; 95% CI: 1.15–7.88; p = 0.02; 41.3% wins vs 13.7% wins) in favor of in-hospital double-dose vaccination (34 patients).

After an ACS, in-hospital double-dose influenza vaccination prevents hospitalizations and death compared with standard-dose vaccination at 12 months in individuals with previous strokes.

NCT04001504

Using mobile low-field magnetic resonance imaging (MRI) in the emergency department to detect cerebral infarction(s) in patients with minor ischemic stroke (MIS) and transient ischemic attack (TIA) has not yet been thoroughly reported.

We aimed to evaluate the performance of mobile low-field (0.23T) MRI in detecting acute ischemic infarction in MIS or TIA patients within 72 h of symptom onset and compare it to computed tomography (CT) in those scanned within 24 h. We also aimed to analyze predictors of DWI-positive lesions on mobile MRI.

This prospective observational cohort consecutively included patients with MIS (National Institutes of Health Stroke Scale (NIHSS) ⩽ 5) or TIA who underwent mobile low-field MRI within 72 h of symptom onset in the emergency department of a tertiary general hospital. The MRI protocol included localizer, axial T1-weighted fluid-attenuated inversion recovery (FLAIR), axial T2-weighted FLAIR, axial T2-weighted fast spin-echo, hematoma-enhanced inversion recovery (HEIR), and diffusion-weighted imaging (DWI) with apparent diffusion coefficient sequences. The total acquisition time is 10 min 28 s. Two raters, blinded to clinical information and CT findings, interpreted the MRI images for acute infarction. Multivariable logistic regression identified predictors of DWI positivity. The primary outcome was restricted diffusion (acute infarction) on the brain low-field MRI scan. We analyzed patients who underwent head CT scan within 24 h of low-field MRI to compare the detection rates of acute infarction between low-field MRI and head CT.

A total of 974 patients (564 men and 410 women; mean (standard deviation, SD) age, 61.3 (14.9) were enrolled. New ischemic lesions were detected by low-field MRI on the DWI sequence in 37.4% (338 in 974) of patients. Among them, 304 underwent head CT within 24 h of the low-field MRI scan; CT identified new ischemic lesions in only 122 (40.1%) of these. Higher NIHSS score (hazard ratio, 1.36 (95% confidence interval (CI), 1.21–1.54); p < 0.01), longer onset to imaging time (hazard ratio, 1.33 (95% CI, 1.10–1.63); p < 0.01), aphasia (hazard ratio, 2.24 (95% CI, 1.36–3.71); p < 0.01), and hemiplegia (hazard ratio, 2.50 (95% CI, 1.76–3.55); p < 0.01) were independently associated with DWI positivity on mobile low-field MRI. Female sex (hazard ratio, 0.57 (95% CI, 0.42–0.79); p < 0.01) and non-focal symptoms were negatively associated with DWI positivity.

Mobile low-field MRI provides a safe, efficient, and accessible imaging solution for MIS and TIA evaluation in emergency settings and detects more acute infarctions than non-contrast head CT. Higher NIHSS score, longer onset to imaging time and focal clinical features were independently associated with DWI positivity.

We examined the timing of suicide after stroke, the sociodemographic factors associated with the risk of suicide, and whether major depression modified the stroke–suicide association.

We conducted a population-based retrospective cohort study of all adults in Ontario hospitalized for stroke between January 1, 2008, and December 31, 2017, who were matched 1:1 to controls from the general Ontario population on age, sex, neighborhood-level income, rurality, and comorbidities. Suicide, a composite of deliberate self-harm or death by suicide, was ascertained based on hospitalizations and emergency department visits. Cause-specific hazard models were used to evaluate the association between stroke and suicide, and major depression was treated as a time-varying covariate. Cause-specific hazard models evaluated the association between sociodemographic factors and suicide in stroke survivors. The modifying effect of major depression was assessed by adding an interaction term between stroke and major depression.

We included 64,719 matched pairs of patients with stroke and general population controls (45.4% female, mean age 71.4 years). In the 627,774 person-years follow-up, 436 cases and controls had an episode of self-harm or died by suicide, with 203 (67.4%) events in stroke survivors occurring after the first year. Compared to matched controls, stroke survivors had a higher rate of suicide (11.1 vs 3.2 per 10,000 person-years, hazard ratio (HR) 2.87; 2.35–3.51). The association between stroke and suicide did not vary by the presence of major depression (P_{stroke*depression} = 0.51). Suicide rates were elevated in younger stroke survivors (HR_{18–40 vs ⩾ 80 years} 4.34; 2.48–7.61), those living in low-income neighborhoods (HR_{lowest vs highest quintile} 1.88; 1.30–2.70), and those with major depression (HR 12.3; 7.63–19.7).

The elevated rate of suicide after stroke persists beyond one year, highlighting the need for long-term screening for suicidality, especially in younger stroke survivors and those residing in low-income neighborhoods and with major depression after stroke.

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.

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.

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.

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.

Early initiation of neurorehabilitation (NR) at the stroke unit is recommended and has been associated with improved outcomes. However, ensuring a direct, uninterrupted transition to subsequent inpatient NR remains challenging in clinical practice. This study investigates whether direct transfer to inpatient NR is associated with functional recovery at 3-month post-stroke.

This study is based on prospectively collected registry data of all stroke patients discharged with functional dependence (modified Rankin Scale (mRS) 3–5) from five stroke units in Styria, Austria, between 2012 and 2023. All patients received standardized inpatient NR, either immediately after acute stroke care or—due to limited NR bed availability—following interim care on a general neurological ward without specialized rehabilitation. The primary outcome was a ⩾ 1-point mRS improvement from discharge to the 3-month follow-up. Outcome predictors were analyzed using univariable and multivariable methods.

Of 2497 included patients (median age: 74 years; 44.7% female), 740 (29.6%) were directly transferred to NR after stroke unit care, while 1757 patients (70.4%) were not, with a median delay to NR of 8 days. Improvement in mRS during follow-up was observed in 1665 patients (66.7%). In multivariable analysis, direct transfer to NR was independently associated with mRS improvement (adjusted odds ratio 1.57, 95% CI 1.25-1.94) as were younger age, male sex, absence of prior stroke, and lower NIHSS score at discharge.

Direct transition from the stroke unit to inpatient NR is associated with a greater likelihood of functional improvement at 3 months post-stroke. These findings support the value of implementing continuous post-stroke rehabilitation pathways.

Intracranial large artery stenosis (ILAS) is one of the most common causes of stroke worldwide and is associated with the risk for future vascular events. Asymptomatic ILAS is a frequent finding on neuroimaging and shares many risk factors with atherosclerotic vascular disease. Whether asymptomatic ILAS is driven by genetic variants is not well-understood.

This study included 4960 participants from seven geographically diverse population-based cohorts (34% Whites, 16% African Americans, 22% Hispanics, 24% Asians, 5% native Ecuadorians). We defined asymptomatic ILAS as luminal stenosis >50% in any large brain artery using time-of-flight magnetic resonance angiography.

A genome-wide association study revealed one variant in RP11-552D8.1 (rs75615271; odds ratio (OR), 1.22 (1.11–1.33); p = 4.85×10⁻⁸) associated with global ILAS at genome-wide significance (p < 5×10⁻⁸). Gene-based association analysis identified a gene-set enriched in chr1q32 region, including NEK2, LPGAT1, INTS7, DTL, and TMEM206, in global ILAS (p = 1.34 ×10⁻⁷) and anterior ILAS (p = 1.77 ×10⁻⁸).

This study reveals one variant rs75615271 and a gene-set enriched in chr1q32 region associated with asymptomatic ILAS in a multi-population. Further functional studies may help elucidate the role that this variant plays in the pathophysiology of asymptomatic ILAS.

Cerebrovascular diseases (CeVD) and neurodegenerative diseases (NDs) are two major neurological disorders, which are associated with increasing global morbidity and mortality. Population-based studies have indicated a complex link between CeVD and ND. However, the shared genetic etiology between these disease conditions remains less explored.

We conducted genome-wide genetic correlation analysis and investigated the shared genetic architecture through pleiotropy analysis between ND and CeVD, like stroke and its subtypes, to understand shared genetic factors and biological mechanisms. Publicly available large-scale genome-wide association studies (GWAS) summary statistics data of cross-ancestry, European, and South Asian (SAS) ancestry were analyzed using methods implemented in the tools linkage disequilibrium score regression (LDSC), PLeiotropic Analysis under COmposite null hypothesis (PLACO), and Bayesian-based method of colocalization (COLOC).

We detected 116 shared genetic loci consisting of 770 lead pleiotropic single nucleotide polymorphisms (SNPs) (ND-CeVD P-range: 4.81×10⁻⁸ to 4.57×10⁻¹⁶) and 40 shared causal genetic regions (ND-CeVD PP.H4-range: 0.70–0.9, posterior probability of H4 (PP.H4) ⩾ 0.7) between multiple CeVD and ND pairs. The genetic regions near ICA1L, HLA-DQA1, HLA-DRB1, MIR297, and PITX2 genes were identified as highly pleiotropic across multiple CeVD-ND pairs. We report ERGIC1 (5q35.1) for the first time as a shared causal genetic locus between Amyotrophic Lateral Sclerosis and small vessel stroke. The genetic risk score of stroke derived from the SAS population of the GIGASTROKE study was associated with ND (P-range = 2.23×10⁻²⁸ to 0.02), despite a small sample size compared to other ethnic groups, indicating high penetrance.

The shared genetic loci and pathway analysis in this study provide new genes and pathways shared between ND and CeVD, which may help in a better understanding of disease mechanisms in these neurological diseases.

Endothelial inflammation is involved in cerebral small vessel disease (CSVD) pathogenesis. Vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) are biomarkers of endothelial inflammation.

This study investigated the association of VCAM-1 and ICAM-1 with the presence of CSVD and CSVD burden.

This cross-sectional study included community residents from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study. Fasting venous blood was drawn to assay VCAM-1 and ICAM-1. Cognition was assessed by the Montreal Cognitive Assessment (MoCA). Cognitive impairment was defined as MoCA scores < 26. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated in a 3.0T MRI scanner. CSVD burden was rated according to the criteria of Wardlaw’s (score 0–4) and Rothwell’s (score 0–6), and classified into four grades. Presence of CSVD was defined as CSVD burden score ⩾ 1.

This study included 2596 participants with a mean age of 61.2 ± 6.7 years and 50.9% of males. Elevated VCAM-1 was associated with increased odds of presence of CSVD (Rothwell: odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.06–1.26, P = 0.001), higher CSVD burden (Wardlaw: common OR (cOR) = 1.11, 95% CI: 1.02–1.21, P = 0.02; Rothwell: cOR = 1.16, 95% CI: 1.07–1.25, P < 0.001), and presence of cognition-impaired CSVD (Rothwell: OR = 1.15, 95% CI: 1.05–1.25, P = 0.003). VCAM-1 improved net reclassification index and integrated discrimination improvement for the presence of CSVD (Rothwell) and cognition-impaired CSVD (Rothwell). However, ICAM-1 was not associated with CSVD and did not improve prediction of CSVD.

Endothelial inflammation, especially VCAM-1, was associated with the presence of CSVD and higher CSVD burden.

Ischemic stroke remains a leading cause of morbidity and mortality worldwide. Cardioembolic sources account for a significant proportion of these events, necessitating accurate identification of underlying structural heart abnormalities. Traditionally, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been utilized for this purpose, although both have limitations. Cardiac computed tomography (CCTA) has emerged as a potential alternative, offering non-invasive imaging with high sensitivity and specificity for detecting intracardiac thrombi.

This study aimed to evaluate the diagnostic yield of CCTA compared to TTE and TEE in detecting high-risk cardioaortic sources of embolism, including left ventricular (LV) thrombus, left atrial (LA) thrombus, valvular thrombus, and ulcerated aortic plaques, in patients with ischemic stroke.

We conducted a retrospective, single-center cohort study at Mayo Clinic, Rochester, MN, including 426 ischemic stroke patients who underwent CCTA within 30 days of stroke onset between March 2019 and June 2023. We compared the diagnostic yields of CCTA, TTE, and TEE in detecting structural cardiac sources of embolism.

The overall diagnostic yield of CCTA for detecting high-risk cardioaortic sources was 15.5%. Specifically, CCTA identified LV thrombus in 2.3% of patients, LA thrombus in 4.0%, valvular thrombus in 2.8%, and ulcerated aortic plaques in 7.0%. In comparative analysis, CCTA demonstrated a higher yield than TTE (16.0% vs 3.5%, p < 0.001) and a comparable yield to TEE (25.3% vs 20.7%, p = 0.47) in detecting these sources.

CCTA proved to be a viable option for identifying high-risk structural sources of cardioembolism in ischemic stroke patients. Its non-invasive nature, coupled with the ability to perform imaging soon after stroke onset, underscores its clinical utility. However, further prospective and blinded studies are required to validate these findings and fully establish the efficacy of CCTA in this context.

Stroke remains a leading cause of mortality in the United States, with evolving epidemiologic patterns over five decades. This study analyzes stroke mortality trends from 1968 to 2023, focusing on disparities across age, sex, race, and geographic regions.

This population-based descriptive study used national mortality data from CDC WONDER. Stroke deaths among individuals aged ⩾ 25 years were identified using International Classification of Diseases (ICD) codes from 1968 to 2023. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated using US Census data. Temporal trends were analyzed using the Joinpoint regression.

From 1968 to 2023, 8,933,826 stroke deaths occurred. AAMRs declined from 250.6 (95% CI = 249.5 to 251.8) in 1968 to 60.0 (95% CI = 59.7 to 60.3) in 2023, with rapid declines from 1973 to 1981, slower reductions until 2000, and modest rise post-2011. Males consistently had higher AAMRs than females. Among males, AAMR fell from 268.4 (95% CI = 266.5 to 270.3) to 60.5 (95% CI = 60.1 to 61.0), while in females, it declined from 236.8 (95% CI = 235.4 to 238.2) to 58.7 (95% CI = 58.3 to 59.1). Racial disparities persisted, with Black individuals having higher AAMRs than White individuals in 2023 (83.2 vs 58.6). The Southern United States had the highest AAMRs, with recent increases post-2011. In 2022–2023, stroke mortality ranged from 37.3 (95% CI = 36.6 to 37.9) in New York to 92.9 (95% CI = 88.4 to 97.4) in Delaware. Ischemic stroke AAMR declined from 59.9 (95% CI = 59.3 to 60.4) to 12.4 (95% CI = 12.3 to 12.5), with increases observed post-2014. Hemorrhagic stroke AAMR fell from 79.4 (95% CI = 78.7 to 80.0) to 10.0 (95% CI = 9.9 to 10.1), with continued decline from 1997 onward.

Despite long-term declines, stroke mortality has recently increased, particularly among younger adults, racial minorities, and the Southern United States. These findings underscore the need for targeted public health interventions to address disparities.

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.

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.

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.

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.