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Stroke represents one of the most significant global health challenges of the 21st century, with 11.9 million people experiencing stroke annually and a disproportionate burden falling on low- and middle-income countries, where 87% of stroke deaths and 89% of disability occur. Despite stroke being highly preventable-with 84% of the burden attributable to modifiable risk factors-and the availability of treatments that have proven to reduce the rate of death or disability, including stroke units, thrombolysis, and thrombectomy, these interventions remain inaccessible to most of the world's population. Advocacy-systematic efforts to influence policy, practice, and resource allocation through evidence-based engagement with decision-makers-has achieved notable successes such as establishing stroke units globally. However, individual advocacy efforts face structural limitations in addressing global stroke challenges. The Global Stroke Action Coalition (GSAC) was formed in 2024 as a coordinated, multi-sectoral initiative convened by the World Stroke Organization, uniting scientific, civil societies, and industry partners to transcend these limitations. The Coalition leverages established infrastructure and expertise to create a unified advocacy force capable of commanding attention from global health leaders. Centered around five strategic priorities-integrating stroke into national non-communicable disease (NCD) strategies, developing National Stroke Action Plans, securing funding commitments, implementing monitoring systems, and including survivors in policy development-the Coalition successfully utilized the 2025 UN High-Level Meeting on Non-Communicable Diseases to further elevate the position of stroke on the global agenda. Key achievements include securing ministerial commitments from 10 countries and launching the "Every Minute Counts" campaign. The Coalition's coordinated approach demonstrates that systematic, evidence-based advocacy can transform stroke care delivery globally, providing a framework for sustained collaboration across sectors and regions essential for meeting Sustainable Development Goal targets and reducing the devastating burden of stroke worldwide.
BackgroundThere is a well-established association between atrial fibrillation and an increased risk of ischaemic stroke, new evidence however suggests that atrial tachycardia (AT) may also contribute to this risk. Through cardiac remodelling pathways and physiological changes, a multi-faceted risk of stroke exists. Our review suggests there is an increased risk of ischaemic stroke in the presence of AT and additionally a greater risk of developing overt AF after these events. There are however many inconsistencies within the studies including ambiguity surrounding AHRE definitions, control for anticoagulation and concurrent AF episodes that are not often reported. Further research is warranted to better define atrial high-rate episodes to further characterise this relationship. Whilst there is clinical direction for anticoagulation in patients with AF, there are no standardised indications for intermediate durations of AHREs and oral anticoagulation is largely determined on an individual basis. Given this gap within clinical practice, we performed a review of the literature to explore if a relationship between episodes of AT and ischemic stroke exists, excluding those with a history of prior AF.AimsTo systematically review and meta-analyse the association between device-detected atrial tachycardia/AHREs and (i) risk of ischaemic stroke and (ii) progression to clinical AF, excluding patients with a prior history of AF.Summary of reviewA systematic review was conducted according to PRISMA guidelines (PROSPERO CRD42022337209). MEDLINE, EMBASE, and Cochrane databases were searched to 10 March 2025. Nine studies (n = 5,099 patients) met inclusion criteria. Overall, 33.7% experienced at least one AHRE, and 2.5% developed a thromboembolic event during follow-up. Meta-analysis of six studies demonstrated a 2.6-fold increased risk of ischaemic stroke in patients with AHREs (pooled HR 2.59, 95% CI 1.54-3.64; I² = 0%). A second meta-analysis demonstrated a 4.5-fold increased risk of progression to AF (pooled effect size 4.51, 95% CI 1.50-7.51; I² = 73.1%). Amongst the reviewed studies, definitions of AHRE duration and rate varied substantially.ConclusionsDevice-detected AHREs are associated with a significantly increased risk of ischaemic stroke and progression to clinical AF in patients without prior AF. While the magnitude of stroke risk is lower than that reported for overt AF, AHREs represent a clinically meaningful risk marker. Standardised definitions and burden thresholds are required to guide anticoagulation strategies and optimise stroke prevention.
Stroke patients are prone to gastrointestinal dysfunction, with a significantly higher risk of fecal incontinence (FI), which severely affects their quality of life. We investigated the incidence and associated risk factors of FI in stroke patients. Stroke patients who met the inclusion and exclusion criteria were consecutively recruited at one university medical center from January 2022 to December 2024. FI occurred in 220 of 1359 stroke patients (16.19%). Logistic regression analysis revealed that age, gender, cognitive impairment, National Institutes of Health Stroke Scale (NIHSS) admission score, antibiotic use, and gavage feeding were closely associated with FI incidence in stroke patients. Subsequently, a systematic review and meta-analysis of observational studies followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Studies were included if they reported the incidence or risk factors of FI in stroke patients. Subgroup analyses were conducted according to the stage of stroke and survey site. The forest plot showed that the incidence of post-stroke FI was 24.42% (95% confidence interval (CI) = 15.11-33.72). On subgroup analysis, the incidence of FI was 25.73% (95% CI = 14.61-36.86) in the acute stage and 15.99% (95% CI = 9.32-22.67) in the rehabilitation stage. Meanwhile, the incidence of FI in the hospital-based stroke patients was 25.31% (95% CI = 11.37-39.26), which was higher than that in the community-dwelling stroke patients (15.14%, 95% CI = 2.26-28.02). The incidence of post-stroke FI is relatively high. Age, gender, cognitive impairment, NIHSS score, antibiotic use, and gavage feeding are closely associated with FI occurrence in stroke patients.
Endovascular thrombectomy (EVT) is the standard of care for large-vessel occlusion stroke. Medium distal vessel occlusions (MDVO) account for 25-40% of acute ischemic stroke cases, but recanalization rates with intravenous thrombolysis (IVT) are often less than 50%. Recent randomized trials have failed to show better outcomes after EVT versus best medical management in MDVO stroke. The main research question of the study: Is the addition of EVT to IVT associated with benefits or harm when treating patients with MDVO stroke? We performed a retrospective observational study of patients in the Safe Implementation of Treatments of Stroke International Stroke Treatment Registry (SITS-ISTR) 2016-2023, treated with IVT or IVT + EVT for occlusion of the anterior cerebral artery (ACA), posterior cerebral artery (PCA) or distal middle cerebral artery (MCA; M3 and more distal). Only patients with available occlusion data from computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) were included. Patients with M2 occlusions or those treated with EVT only were excluded. Outcomes were acute post-treatment hemorrhage, 3-month modified Rankin Scale (mRS) score, and death at 3 months. Propensity score matching was performed due to baseline imbalances (age, National Institutes of Health Stroke Scale [NIHSS], and occlusion site). Of 2198 included patients, 295 (13%) were treated with IVT + EVT, and 1903 (87%) received IVT alone. IVT + EVT patients were younger (73 vs. 75) and had higher median NIHSS: 10 (interquartile range [IQR]: 6-15) versus 8 (5-12), p < 0.001. More IVT + EVT patients were functionally independent (mRS 0-1) before stroke at 91.8% versus 83.0% (p < 0.001). For the IVT + EVT group, PCA occlusion was the most common (n = 179, 60.7%), and distal MCA (n = 1140, 59.9%) in the IVT group. After propensity score matching, IVT + EVT was associated with worse 3-month outcomes compared to IVT alone: mRS 0-1 (35.8% vs. 47.0%, p = 0.016, mRS 0-2 52.4% vs. 63.4%, p = 0.017, and death 21.4% vs. 11.8%, p = 0.005). Symptomatic intracerebral hemorrhage rates were higher in the IVT + EVT group according to European Collaborative Stroke Study II (ECASS II): 6.5% versus 2.4%, p = 0.043, but were similar according to National Institute of Neurological Disorders and Stroke (NINDS): 8.2% versus 4.2%, p = 0.095, and Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS-MOST): 0.6% versus 1.2%, p = 0.825. IVT + EVT for MDVO was associated with worse functional outcomes compared to IVT alone. Our results support recent publications but should be interpreted with caution due to the retrospective observational design, warranting further RCTs.
Rehabilitation has been identified by the World Stroke Organization (WSO) as a key priority to reduce the global burden of stroke. Global access to rehabilitation is inconsistent and is particularly limited in low-and-middle-income countries. Progress in rehabilitation has not been as well evidenced as progress in acute care. The WSO certification program, which commenced in 2021, focuses on acute interventions. A rehabilitation certification program, applicable in both inpatient and outpatient rehabilitation settings, has been developed to complement the acute certification program to address global implementation of evidence-based stroke care. To develop globally applicable, evidence-based, stroke rehabilitation recommendations and performance metrics for use in a stroke rehabilitation certification program. Strong recommendations were extracted from high-quality stroke rehabilitation Clinical Practice Guidelines, systematic reviews and syntheses of clinical practice guidelines, and from the defining criteria of the International Stroke Recovery and Rehabilitation Alliance (ISRRA) Centers of Clinical Excellence. The WSO Rehabilitation Implementation Committee led the development of the recommendations and invited input from three international, multidisciplinary consultation groups. Group 1 compared strong recommendations from the Australia/New Zealand Living Guidelines with other international guidelines to identify consistent, high-quality recommendations. Group 2 mapped recommendations from global guideline syntheses against the Australia/New Zealand Living Guidelines. Group 3 reviewed and adapted the ISRRA Center of Clinical Excellence recommendations. Recommendations were consolidated through consensus meetings involving representatives from each workgroup, including people from high, upper-middle, and lower-middle-income countries. Strong recommendations that were consistent across teams, alongside additional recommendations based on certainty of evidence, anticipated risk versus benefit, and relevance across settings, were included as patient-level recommendations in the implementation certification program. Service-level recommendations were generated through consensus or derived from existing guidelines. An implementation manual, outlining "what," "who," and "how," as well as indicators to demonstrate performance of each recommendation, was developed to support clinical implementation and to facilitate assessment for certification. The criteria were piloted between November 2024 and September 2025 at 15 centers in six upper- and lower-middle-income countries (three continents) and subsequently refined. Expectations (mandatory or recommended) for each level of certification (Minimal, Essential and Advanced) were set post-pilot through rating strength of evidence, a series of group discussions and review of pilot data.ResultsFifty-five recommendations were included. Nine recommendations address service-level indicators, and 46 address patient-level indicators. Service-level indicators address defining features of rehabilitation services that are not apparent in individual patient medical record audits. Patient-level indicators address management of swallowing impairment, nutrition and hydration, information provision and goal setting, amount and timing of rehabilitation, exercise and motor rehabilitation, visual function, communication, mood and cognition, management of complications, and discharge planning and support. An implementation manual complements the recommendations to guide clinical care and consistent assessment.ConclusionsThe WSO rehabilitation recommendations and performance metrics incorporate the most current evidence and have been refined following pilot-testing. The recommendations are globally relevant and support both resource-limited and high-income settings in participating in the rehabilitation certification program to advance international stroke rehabilitation delivery.
Randomized trials have shown that endovascular thrombectomy improves functional outcomes in patients with acute ischemic stroke and large infarct. However, there is continued debate about the generalizability of these results to routine clinical practice. To investigate whether functional outcomes reported in the randomized TENSION trial can be achieved in routine clinical practice. TENSION was a prospective, multicenter, randomized trial that enrolled patients with acute ischemic stroke and large infarct at 41 centers across Europe and Canada. Patients were randomized to endovascular thrombectomy or best medical treatment. The main inclusion criteria of TENSION were defined as pre-stroke mRS 0-2, randomization within 11 hours of symptom onset, occlusion of the intracranial ICA or M1 segment of the MCA, ASPECTS 3-5, and baseline NIHSS score 0-25. Patients from the thrombectomy arm of TENSION (TENSION-RCT) were compared to patients from the German Stroke Registry meeting the main inclusion criteria of TENSION (TENSION-GSR) using 1:1 propensity score matching. Primary outcome was the 90-day mRS score (shift analysis). Of 308 patients who met the inclusion criteria, 198 were matched (median age, 74 [IQR, 64-81]; 98 [49.5%] female; median 90-day mRS, 5 [IQR, 3-6]). There was no significant shift in 90-day mRS scores between TENSION-RCT and TENSION-GSR (acOR, 1.19; 95% CI, 0.70-2.02; p = 0.52). The proportions of independent ambulation (90-day mRS 0-3; 33.3% vs 31.3%, p = 0.76) and severe disability or death (90-day mRS 5-6; 50.5% vs 52.5%, p = 0.78) did not differ between TENSION-RCT and TENSION-GSR. Functional outcomes of the TENSION thrombectomy arm are achievable within comprehensive stroke centers in Germany. These findings support endovascular thrombectomy for acute ischemic stroke with large infarct and its broad implementation in routine care. The data that support the findings of this study are available upon reasonable request after approval of the steering committees of the TENSION trial and the GSR-ET.
Most stroke trials conventionally use outcome measures that reflect a single point of concern, such as functional outcomes or neurological improvement. Such a focus has a limited capacity to reflect the holistic nature of clinical reality, where multiple facets of health are of importance.Other clinical areas are increasingly embracing alternative approaches that better reflect the multifaceted nature of health outcomes, driven by the development of Win Statistics methodology. These methods compare the outcomes for all possible pairs of patients from the treatment versus control group and summarise the treatment effect as a combination of proportions of such comparisons where the person from the treatment group has a better/worse outcome when compared to the person in the control group. In this context, "better outcome" is defined holistically, based on information collected across multiple health facets (e.g. mortality, symptom reduction and quality of life).Such approaches are highly applicable to stroke research. They are a direct extension of "Tournament Methods" that are already used to analyse modified Rankin Scale data, and several stroke trials have already adopted this new approach to better reflect the multifaceted nature of stroke. Despite this, there is little guidance available to stroke researchers who wish to make use of the approach. This article provides a review of how to effectively use Tournament Methods to reflect the multifaceted nature of stoke.We review how Tournament Methods may be used to estimate treatment effects that simultaneously consider multiple clinical outcomes.We describe methods that have been used within stroke to combine multiple clinical outcomes for Tournament Methods analysis, provide an overview of the effect size measure estimates commonly used to summarise treatment effects, and discuss both available statistical methods and software for the analysis, visualisation and reporting of Win Statistics. We provide practical recommendations for conducting and reporting statistical analyses under the Tournament Methods approach using published stroke trials as illustrative examples. We further present newly developed point-and-click software that provides easy access to statistical codes for conducting Tournament Methods analyses and facilitates the use of our recommendations.
Randomized trials have demonstrated that early anticoagulation after acute atrial fibrillation-associated ischemic stroke is safe and non-inferior to delayed initiation. Whether anticoagulation should be delayed in people with larger infarcts is uncertain. To investigate whether ischemic stroke infarct volume, measured precisely by segmentation, modifies the treatment effect of early anticoagulation with a direct oral anticoagulant (DOAC). We did a prespecified secondary analysis of OPTIMAS (NCT: 03759938), a randomized, parallel-group, open-label trial with blinded outcome assessment which randomized people with acute ischemic stroke and atrial fibrillation to early initiation of any licensed DOAC, within 4 days of onset, or delayed initiation 7-14 days from onset. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage (ICH), and systemic arterial embolism within 90 days. A central neuroimaging laboratory determined infarct volume using diffusion-weighted magnetic resonance imaging (MRI) using a validated deep learning segmentation model; on computed tomography (CT), infarcts were segmented manually. We modeled infarct volume as a continuous variable using restricted cubic splines and tested for an interaction with treatment allocation in mixed effects logistic regression. We included 3572 participants (mean age = 78 ± 10 years, 45% female), 98.6% of the main trial population. The effect of early versus delayed anticoagulation did not vary with infarct volume (pinteraction = 0.18). Rates of the primary outcome were 17/568 (3.0%) and 12/599 (2.0%) for early versus delayed initiation with infarcts of 0-5 mL; 6/220 (2.7%) and 11/229 (4.8%) with infarcts of 5-10 mL; 13/258 (4.6%) and 10/283 (3.5%) with infarcts of 10-25 mL; 6/145 (4.1%) and 8/145 (5.5%) with infarcts of 25-50 mL; 1/93 (1.1%) and 7/94 (7.4%) with infarcts of >50 mL; and 14/481 (2.9%) and 10/430 (2.2%) in participants with no infarct visible on clinically acquired brain imaging. Corresponding odds ratios and 95% confidence intervals were 1.52 (0.71-3.20), 0.55 (0.20-1.51), 1.29 (0.55-3.00), 0.74 (0.25-2.21), 0.13 (0.02-1.11), and 1.25 (0.55-2.86), respectively. There were no increased rates of symptomatic ICH with respect to anticoagulation timing for those with large infarcts (>25 mL); there were 3/238 (1.3%) events in the early group and 5/239 (2.1%) in the delayed group. The treatment effect of early anticoagulation with a DOAC in acute ischemic stroke associated with atrial fibrillation was not modified by infarct volume. Adverse outcomes were not increased with early anticoagulation in people with larger infarcts. Our results provide no evidence that anticoagulation initiation should be delayed beyond 4 days on the basis of infarct size.
Adverse non-motor outcomes are common after stroke, yet their true prevalence and prognosis remain uncertain, partly due to substantial methodological heterogeneity across studies. We aim to undertake a comprehensive synthesis of the available evidence on adverse non-motor outcomes after stroke. First, we aim to examine prevalence across study settings (hospital-based versus population-based cohorts) and to evaluate the influence of outcome definitions, measurement instruments (validated versus non-validated), stroke type (ischaemic stroke, intracerebral haemorrhage, or mixed), and duration of follow-up. Second, we aim to identify study-level characteristics associated with adverse outcomes. We searched PubMed, MEDLINE, EMBASE, Scopus, Web of Science, and PsycINFO via Ovid (1st January 1999 - 30th November 2025) for prospective cohorts reporting 11 non-motor outcomes: anxiety, depression, apathy, fatigue, sleep disturbance, social participation, pain, bladder, bowel, and sexual dysfunction. Pooled prevalence according to study setting (hospital versus population) was estimated using random-effects models; outcome definitions and measures were synthesised using descriptive statistics, and meta-regression analysis was used to identify associated factors. The quality of all included studies was assessed with the Newcastle-Ottawa Scale. A total of 357 prospective cohort studies, (247 541 participants; mean age 64 years; 247 male-predominant studies) were included, with a follow-up between 30 days to 10 years after stroke with median follow-up 6 months [IQR 3-12]. Half of the studies were hospital based 181/352 (51%). Of the included studies, 195 (55%) included participants with ischaemic stroke, 148 (42%) included participants with ischaemic stroke or intracerebral haemorrhage, while only 10 (3%) included participants with intracerebral haemorrhage. Across all analysis heterogeneity ranged I2 41%-99%. We found no significant differences in the prevalence of adverse non-motor outcomes between hospital versus population settings, except, bowel dysfunction was more frequently reported in population-based studies (61%, 95% Cl 54%-67% vs 47%, 95% Cl 37%-58%, p=0.005). Non-validated outcome measures were used in 156/352 studies (44.3%). Studies using non-validated outcome measures showed higher pooled prevalence of anxiety (34%, 95% Cl 29%-40%, vs 25%, 95% Cl 20%-33%, p<0.001), apathy (32%, 95% Cl 27%-36, vs 22%, 95% 13%-41%, p=0.005), sleep disturbance (62%, 95% Cl 54%-73%, vs 51%, 95% Cl 44%-58%, p<0.001), and bowel dysfunction (56%, 95% Cl 43%-69% vs. 49%, 95% Cl 38%-60%, p=0.027). Majority of studies 207/352 (59%), were conducted within 30 days to 6 months after stroke, whereas only 41/352 (12%) examined non-motor outcomes beyond 2 years post-stroke. Older age (>60 years), stroke due to ICH, and use of non-validated outcome measures were significantly associated with a higher prevalence of adverse non-motor outcomes across multiple domains. Non-motor outcomes are highly prevalent after stroke in hospital and population settings. However, we found methodological limitations across included studies, including limited evidence on non-motor outcomes after ICH, poor characterisation of stroke type, frequent use of non-validated outcome measures, and few studies assessing outcomes beyond two years after stroke. Our findings indicate an urgent need for long-term, methodologically rigorous studies of non-motor outcomes after stroke to enable consistent assessment, inform life after stroke pathways, and improve clinical care.
Individuals without stenotic large-artery atherosclerosis (LAA) are an important subgroup of the patients who suffer transient ischemic attack (TIA) or ischemic stroke (IS), and they are commonly treated with dual antiplatelet therapy (DAPT). Stenotic LAA is a marker of higher vascular risk, and current guideline-defining trials did not prospectively evaluate if negative LAA status modifies the effect of DAPT. Moreover, platelet activation may not contribute as much towards future stroke risk after excluding stenotic LAA, leaving uncertainty regarding the applicability of this treatment amongst populations without this marker. We aimed to evaluate the efficacy and safety of DAPT compared with monotherapy for patients who suffered a TIA or IS without stenosis of 50% or more on vessel imaging. We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to November 2025 for publications in English. We included randomized controlled trials comparing short-term (up to 90 days) DAPT to single antiplatelet therapy after a TIA or IS with outcome data available for the groups without 50% or more stenosis on vessel imaging. Data was pooled using random-effects for non-rare outcomes and Bayesian models for rare outcomes. The primary outcome was a new ischemic or hemorrhagic stroke. We also analyzed ischemic and hemorrhagic stroke individually, moderate and severe bleeding, any bleeding, all-cause death, functionality and a composite vascular outcome. 8 publications met the eligibility criteria. DAPT was associated with a reduction in new stroke, with a relative risk of 0.80 (95% CI 0.65 to 0.98; p = 0.04, I² = 25.5%). Trial sequential analysis showed a substantial risk of type I error, and a sensitivity analysis restricted to studies that included only high-risk TIA or mild IS found no significant benefit. There was an increase in moderate and severe bleeding (odds ratio of 2.70, 95% Bayesian Credible Interval 1.28 to 4.85) and no differences in functionality and mortality. Heterogeneity in trial methodology and populations may limit interpretation of our findings, but sensitivity analyses evaluating the impacts of DAPT duration and region of trial conduction on new stroke did not show significant effects, although they are hindered by the small number of studies. In patients with TIA or IS with a negative assessment of stenotic atherosclerosis on any vessel imaging, the benefit of DAPT is unclear, particularly for individuals with high-risk TIA and mild IS, while there is an increased risk of bleeding. Further trials are required to clarify if DAPT is truly beneficial for these patients.
There is a growing recognition of the importance of engaging with people with lived experience (PWLE) to support research relevance and impact. However, there is little specific guidance for stroke recovery and rehabilitation researchers about how best to engage with PWLE of stroke in research, who face additional barriers to engaging due to common post-stroke sequelae including communication and cognitive difficulties, sensory and perceptual impairments, emotional wellbeing, and fatigue. The aim of this roundtable was to develop recommendations to support researchers to engage with PWLE of stroke in primary and secondary research conducted in laboratory, clinical, health system, or community settings. We convened an interdisciplinary, international taskforce comprising researchers and lived experience experts (n = 16) to create recommendations to support researchers to engage with PWLE of stroke meaningfully and respectfully. Guided by priorities and key gaps identified by taskforce members, and underpinned by gray and published literature, we formed discrete workgroups to develop consensus-based recommendations and guidance documents addressing common barriers to engagement in stroke research. The recommendations and guides were reviewed, and consensus was reached during a 2-day hybrid in-person/online meeting of the taskforce. These were further refined through consultation with international experts in research engagement. We created the EMBED (Engaging Meaningfully to Build research with people with lived experience to drive improvements in stroke research) framework, consisting of five consensus recommendations: Select the engagement approach; Identify people to engage with; Embed accessible and inclusive ways of working; Support and strengthen accessibility and inclusivity; and Report accessibility and inclusivity. Ten guidance documents provide practical support to researchers to engage with PWLE of stroke in all research settings. The EMBED framework provides researchers with pragmatic and structured support to engage with PWLE in stroke research.
Cerebral small vessel disease (SVD) is a major cause of ischemic stroke, intracerebral hemorrhage, and dementia. Despite its importance, there are few studies of its prevalence and how cerebral SVD varies across the world, different age ranges, sexes, and magnetic resonance imaging (MRI) parameters. SVD can be estimated using MRI neuroimaging markers, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), and perivascular spaces (PVS). This study aimed to document the global prevalence of SVD based on population-based or large community-based MRI studies and to determine how SVD prevalence varies by region, mean age, and sex. With SVD neuroimaging markers being the standard to assess SVD prevalence, we aimed to investigate how different MRI acquisition parameters may influence its prevalence. In this systematic review and meta-analysis, articles were searched from the Ovid MEDLINE and EMBASE databases between 1 January 2000 and 31 March 2024, without language restrictions. Title and abstract screening, full-text review, and data extraction were performed by at least two independent reviewers. The prevalence of SVD, subject demographic information, and MRI acquisition parameters were extracted. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). Of 14,582 studies identified, 246 studies spanning 40 countries were included in the systematic review. In the meta-analysis, 85 studies (88 cohorts) from 17 regions (n = 1,562,765) were included. The quality of studies was high (mean score 7.67 out of 8, ranging between 5 and 8). The pooled prevalence of moderate-to-severe WMH was 18.9%, and the pooled mean of WMH volume was 4.4 mL. Pooled prevalences of lacunes, cerebral microbleeds (CMBs), and moderate-to-severe perivascular spaces (PVS) were 11.2%, 10.3%, and 22.6%, respectively. A lower lacune prevalence (7.3% vs 13.3%; adjusted OR (aOR) [95% confidence interval (CI)]: 0.45 [0.30-0.68]) but higher PVS prevalence (30.9% vs 19.6%; aOR [95% CI]: 12.15 [2.12-69.46]) was found in Europe compared with Asia. A higher mean age of the studies was associated with a higher prevalence of most SVD markers, except for PVS. There was an overall trend of more lacunes and CMBs in males. MRI field strength, sequence used, and slice thickness could potentially influence the reported SVD prevalence, especially for WMH volume and CMB count. There was high heterogeneity in the studies (>95%) that was not resolved by performing analyses stratified by Global Burden of Disease (GBD) regions, age groups, study design, or MRI parameters. This systematic review and meta-analysis based on large MRI studies demonstrated that SVD is a common health problem affecting about one-fifth of the adult population. SVD prevalence differs in regions separated by geographical regions. SVD prevalence is higher with increasing age. There is an overall trend of more lacunes and CMBs in males. WMH volume and CMB are SVD markers prone to the variability of MRI acquisition parameters, and a harmonised SVD scanning protocol should be used. More studies from middle- and low-income regions would benefit the estimation of a truly global prevalence of SVD.
Stroke is the second leading cause of death and the third leading cause of disability worldwide, with global economic costs exceeding US $890 billion annually and a projected 50% rise in deaths between 2020 and 2050. So far, stroke has been addressed within the World Health Organization (WHO) Global Noncommunicable Disease (NCD) Action Plan 2023-2030 and the Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031, but until now, no World Health Assembly resolution has been specifically dedicated to stroke. To present the first WHO Resolution specifically dedicated to stroke (EB158/CONF./9), describe its content and significance, and analyze its implications for global public health. This article presents and analyzes resolution EB158/CONF./9-"Reducing the burden of stroke: strengthening prevention, acute care, rehabilitation and health-system readiness", as advanced by the WHO Executive Board at its 158th session on 3 February 2026 and adopted by the Member States in the Seventy-ninth World Health Assembly.Key content of the resolution:In February 2026, the 158th session of the WHO Executive Board advanced the first WHO resolution dedicated to stroke, proposed by Egypt and co-sponsored by Chile, Georgia, Palestine, Paraguay, and Tunisia, and adopted by Member States at the Seventy-ninth World Health Assembly. The resolution frames stroke as a continuum of care and sets out 16 operative actions for Member States (OP1), organized under three categories: (1) primary interventions across the prevention spectrum; (2) acute care and rehabilitation; and (3) surveillance and data; all underpinned by a health-system strengthening approach. A further eight requests to the Director-General (OP2) provide WHO's mandate to act, covering normative guidance, technical support, monitoring, research, medicine access, regional cooperation, and progress reporting.Public health implication:The resolution establishes a comprehensive stroke action plan across the full continuum of care. Its legacy will depend not on its adoption in Geneva but on whether political commitment is matched by sustained implementation, investment, robust monitoring, and accountability grounded in stroke-specific indicators.
Climate change poses an escalating threat to global brain health and is increasingly linked to stroke incidence, outcomes, and inequities in prevention and treatment. This World Stroke Organization scientific statement summarizes current evidence on the associations between stroke and the environmental variables exacerbated by climate change, with a focus on risk and outcomes. We systematically identified and reviewed published studies assessing associations between stroke and environmental variables, including extreme temperatures, temperature variability, humidity, barometric pressure, wildfires, dust and sandstorms, and compound weather events. Air pollution, unrelated to wildfire exposure, was excluded, as a subsequent statement will focus on this. Paired reviewers screened titles and abstracts. Full texts were evaluated for study design, sample size, geographic context, and strength of evidence, with attention to impacts on vulnerable populations where data were available. Study type, exposure assignment, and strength of evidence were further confirmed by a team member with Master's level qualification in epidemiology. Most of the included studies were based on ecological designs. Cold exposure, temperature variability, and extreme thermal events were most consistently associated with increased stroke risk. Although cold effects were generally stronger than heat effects, heat effects have been increasing over time. Increased stroke incidence was also associated with low or varying barometric pressure, rapid humidity shifts, and exposure to wildfire smoke, dust, and sandstorms, particularly among older adults and those in low- and middle-income countries. Compound weather events, such as concurrent heat and humidity extremes, showed additive or synergistic effects on stroke incidence and mortality. Despite heterogeneity in definitions and methods and most evidence supporting associations rather than proving causation, the overall direction of evidence across exposures was positive, coherent, and biologically plausible. Advancing mitigation efforts that reduce greenhouse gas emissions is essential, since limiting further climate change directly decreases the environmental drivers of stroke risk and protects long-term population brain health, along with broader climate-related health risks. Stroke professionals and organizations can meaningfully contribute through local, regional, and global advocacy. Climate-related environmental variables already meaningfully increase stroke risk and exacerbate existing health inequities. To further counter these trends, stroke prevention and care systems should integrate climate risk awareness, patient education, and early-warning mechanisms into clinical practice and health system planning. Priority areas include targeted protection for vulnerable groups, standardized exposure metrics, longitudinal surveillance, systematized education on climate change's impact on brain health, and expansion of research in underrepresented regions. Strengthening global collaboration and embedding climate resilience into stroke systems of care are critical for reducing both stroke-related morbidity and the wider health impacts of a climate-impacted world. This scientific statement has been reviewed and approved by the WSO Executive.
We aimed to explore whether the benefits of tenecteplase within 4.5 to 24 h would be modified by the infarct growth rate (IGR). This study is a secondary analysis of the Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-III (TRACE-III) trial, a Phase 3, multicenter, prospective, open-label, randomized, blinded-outcome-assessment trial. In the TRACE-III trial, patients with large-vessel occlusion at 4.5 to 24 h without thrombectomy were enrolled at 58 centers in China and randomly assigned to receive 0.25 mg/kg tenecteplase or standard medical treatment. Of these, patients with witnessed stroke onset time were analyzed. The IGR was calculated as baseline ischemic core volume divided by time since onset. The primary outcome was the modified Rankin Scale (mRS) 0-1 at 90 days. The treatment effect of tenecteplase versus standard medical treatment was assessed in two groups based on the median IGR cut point. A multiplicative interaction term for IGR*treatment was used to test for effect modification. In 292 eligible patients, the median IGR was 1.4 ml/h. A total of 146 patients with IGR < 1.4 ml/h were classified as ultraslow IGR (Tenecteplase, 70; Standard medical treatment, 76), and 146 patients with IGR ⩾ 1.4 ml/h were classified as slow IGR (Tenecteplase, 73; Standard medical treatment, 73). The rate of no disability (mRS ⩽ 1) was significantly increased with tenecteplase in slow progressors (34.2% vs 15.1%; OR = 2.94, 95% CI 1.32 to 6.55; P = 0.009). The functional status was similar in ultraslow progressors (mRS 0-1: 37.1% vs 35.5%; OR = 1.07, 95% CI 0.55 to 2.11; P = 0.84). A P value for the interaction between IGR and treatment was 0.06. The incidence of sICH and mortality did not differ significantly between the two treatment regimens in the IGR groups. Patients with late-window ischemic stroke who are not eligible for endovascular thrombectomy may derive greater benefit from tenecteplase compared with standard medical treatment among those with relatively faster infarct growth, although this finding should be considered exploratory.
Randomized trials support early initiation of direct oral anticoagulants (DOACs) after atrial fibrillation (AF)-related ischemic stroke, but patients with breakthrough ischemic stroke occurring despite ongoing anticoagulation have been largely under-represented. We evaluated the effectiveness and safety of early versus delayed DOAC initiation after breakthrough ischemic stroke. We performed a target trial emulation comparing early versus delayed DOAC initiation in patients with breakthrough ischemic stroke. Treatment strategies were prespecified using severity-adapted timing thresholds based on baseline National Institutes of Health Stroke Scale (NIHSS) scores. The study population was drawn from the retrospective arm of the international, multicenter Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulant (ASPERA) study and included patients with AF who experienced an ischemic stroke while receiving continuous anticoagulation. To emulate random assignment and avoid immortal time bias, a cloning-censoring-weighting approach with inverse probability weighting was applied. Primary outcomes were 90-day new ischemic events and moderate-to-severe bleeding. Risk ratios (RRs), absolute risk differences (RDs), and hazard ratios (HRs) were estimated using weighted regression and Cox models. Among 833 patients (median age = 81 years), 336 were assigned to early and 497 to delayed DOAC initiation. At 90 days, early initiation was associated with a lower risk of new ischemic events (RR = 0.44, 95% CI = 0.21-0.90; RD = -3.64%, 95% CI = -6.40 to -0.87; HR = 0.43, 95% CI = 0.21-0.91). Moderate-to-severe bleeding occurred less frequently with early initiation (RR = 0.10, 95% CI = 0.01-0.76). Early initiation was also associated with lower 90-day all-cause and vascular mortality. A Net Early Benefit Score integrating ischemic and bleeding risks was positive across all NIHSS strata. In patients with breakthrough ischemic stroke, early severity-adapted DOAC initiation was associated with lower risks of recurrent ischemic events and mortality at 90 days without an increase in major bleeding. These findings support early anticoagulation initiation in this high-risk population.
Venous thrombosis and venous thromboembolism (VTE) are important, yet under-recognized causes and complications of stroke. They may complicate acute stroke as deep venous thrombosis or pulmonary embolism (DVT/PE), contribute causally to ischemic stroke through paradoxical embolism from a patent foramen ovale (PFO), or present directly as cerebral venous thrombosis (CVT). Despite shared pathophysiological features and overlapping antithrombotic strategies, these conditions are typically considered separately, fragmenting evidence and limiting the exchange of concepts. We therefore convened experts across both fields to examine these conditions under a unifying venous theme.Thirty-two stroke and thrombosis clinicians and researchers identified research priorities across three domains: prevention of VTE after stroke, secondary prevention after PFO-related stroke, and acute and long-term management of CVT. Structured discussions were guided by the PICO (Population, Intervention, Comparison, Outcome) framework, followed by a Delphi survey to establish consensus.Priority questions centred on the balance between thrombosis prevention and bleeding risk and the optimal timing, duration, and choice of DVT/PE prophylaxis after stroke; the optimal antithrombotic strategy for patients awaiting or forgoing PFO closure; and, for CVT, the role of endovascular therapy in severe disease and the optimal duration of secondary prevention (Graphical Abstract). Across domains, the group prioritized pragmatic and platform trial designs, integration with international registries to address the rarity of CVT, and patient-oriented outcomes that extend beyond functional recovery.By considering these venous conditions together and bridging stroke neurology and thrombosis medicine, this work defines priority questions to address persistent evidence gaps, harmonize practice, and improve patient-centered outcomes.
The benefit of adjunctive intra-arterial alteplase treatment following near-complete to complete reperfusion (expanded thrombolysis in cerebral infarction (eTICI) scale of 2c to 3) by mechanical thrombectomy for acute large vessel occlusion stroke remains controversial. The study aimed to explore whether intra-arterial alteplase was associated with improved outcomes in patients with eTICI 2c/3 after thrombectomy compared with standard treatment. This post hoc analysis used data from the PEARL (Intra-arterial Alteplase for Acute Ischemic Stroke After Mechanical Thrombectomy) randomized controlled trial conducted at 28 sites in China. Patients with anterior circulation large-vessel occlusion who achieved eTICI 2c/3 reperfusion after mechanical thrombectomy were included. Patients were randomized to intra-arterial alteplase or standard medical treatment. The primary outcome was the distribution of modified Rankin Scale (mRS) scores at 90 days. Safety outcomes included intracranial hemorrhage and symptomatic intracranial hemorrhage within 36 h and mortality at 90 days. Of 324 randomized patients in the PEARL trial, 136 were included in this analysis, with 65 assigned to intra-arterial alteplase and 71 to standard medical treatment. Compared with standard medical treatment, intra-arterial alteplase was associated with a favorable shift in 90-day functional outcome (common odds ratio, 2.07 [95% confidence interval (CI), 1.10-3.92]; P = 0.02). Rates of intracranial hemorrhage (adjusted risk ratio, 1.06 [95% CI, 0.62-1.83]; P = 0.82), symptomatic intracranial hemorrhage within 36 h (adjusted risk ratio, 0.29 [95% CI, 0.03-2.82]; P = 0.29), and mortality at 90 days (adjusted hazard ratio, 0.97 [95% CI, 0.29-3.28]; P = 0.96) did not differ significantly between groups, although the number of safety events was low. Among patients in the PEARL trial who achieved near-complete to complete reperfusion after mechanical thrombectomy, adjunctive intra-arterial alteplase was associated with improved functional outcomes at 90 days. Owing to the small sample size of this study, a pooled analysis of intra-arterial alteplase in patients with eTICI 2c/3 is needed to confirm these results. Clinicaltrials.gov identifier: NCT05856851.
Despite major advances in the prevention and treatment of stroke, many stroke trials have yielded neutral or modestly positive results due to multiple factors, including patient heterogeneity, small treatment effects, inadequate statistical efficiency, and in some settings limited biological efficacy or insufficient early-phase validation of interventions. This review summarizes emerging methodological innovations relevant to contemporary stroke trials, including group sequential methods, adaptive design (response-adaptive randomization, sample size re-estimation, enrichment strategies), Bayesian designs, and master protocol frameworks (basket, umbrella, and platform trials). We also discuss advances in outcome assessment, including hierarchical composite endpoints analyzed using the win ratio, ordinal and utility-weighted analyses of the modified Rankin Scale, and the growing role of patient-reported outcomes in capturing patient-centered benefits across the recovery continuum. Finally, we highlight stroke-specific methodological challenges and outline future opportunities enabled by advances in imaging, digital health, and data-driven approaches. Together, these innovations have the potential to improve the efficiency, interpretability, and clinical relevance of stroke trials, provided they are implemented within rigorously pre-specified protocols that preserve trial integrity and valid statistical inference.
Increasing knowledge about stroke may reduce its burden. We examined the effect of the Stroke RiskometerTM mobile phone application (the App) on stroke knowledge in a randomized controlled trial (RCT). This was a pre-specified secondary outcome analysis in a phase III, prospective, participant and outcome assessor-blinded, two-arm RCT in Australia and New Zealand. Participants were recruited between 2021 and 2023, aged 35-75 years, with ⩾2 stroke risk factors and no cardiovascular disease history. Participants were randomized after assessment of stroke risk factors and knowledge to the intervention group (IG-received risk factor assessment by email and links to the App), and the usual care group (UCG-received risk factor assessment with links to generic information by email). Stroke knowledge was measured at baseline, 3, 6, and 12 months using six validated questions (total score 0 (low knowledge) to 19 (high knowledge)). We used linear and logistic mixed-effects modeling to assess differences in the level of overall stroke knowledge and domains (description, warning signs, risk factors, management) between IG and UCG at each time point. Effect modification of the intervention with age, sex, level of education, ethnicity, socioeconomic status (SES), and country was assessed. There were 862 participants (mean age: 58.1 years (standard deviation (SD): 10.8), 63.0% female, 61.6% tertiary educated, 73.3% European, and 14.7% most disadvantaged area-level SES) randomized to IG (n = 429) and UCG (n = 433). Dropouts (IG/UCG) were as follows: 7.9%/4.8% at 3 months, 3.0%/1.8% at 6 months, and 13.5%/9.0% at 12 months. The time-IG interaction showed a statistically significantly increased overall stroke knowledge (β = 0.50, 95% confidence interval (CI) = 0.02, 0.97) compared with UCG at 6 months only. The intervention effect was stronger in tertiary educated, non-European, and non-Indigenous ethnic groups, and the least disadvantaged SES group. For domains, IG was more likely to correctly identify stroke risk factors (odds ratio (OR) = 1.92, 95% CI = 1.09, 3.39) at 3 months, compared with UCG. The Stroke RiskometerTM App modestly improved stroke knowledge compared with UCG at 6 months but lacks evidence for retaining knowledge at 12 months. As knowledge can drive behavior change, the App may be a tool to enhance primary stroke prevention. ACTRN12621000211864.