International Journal Of Stroke[JOURNAL]
Sun
200 papers
Atrial fibrillation detected after stroke: Recent advances and future directions.
Folleco-Insuasty L, Roa-Wandurraga LF, Liberman F … +3 more , Ayan D, Bagur R, Sposato LA
Int J Stroke · 2026 Jul · PMID 42402477 · Publisher ↗
Prolonged cardiac monitoring has made atrial fibrillation (AF) an increasingly common diagnosis after ischemic stroke. Applied to all patients with ischemic stroke, prolonged cardiac monitoring would result in over a mil...
Prolonged cardiac monitoring has made atrial fibrillation (AF) an increasingly common diagnosis after ischemic stroke. Applied to all patients with ischemic stroke, prolonged cardiac monitoring would result in over a million new AF diagnoses per year worldwide. Almost 10 years after the conceptual inception of AF detected after stroke (AFDAS), several patterns are now consistent across studies. AFDAS is a distinct, mechanistically heterogeneous entity that differs from AF known before stroke in its risk-factor profile, cardiac comorbidity, and its lower rate of ischemic stroke recurrence. Its detection is determined primarily by the monitoring method and increases with earlier and longer-duration monitoring. AF identified on a standard electrocardiogram behaves as a high-burden arrhythmia, resembling AF known before stroke, and should be distinguished from the low-burden AF detected by prolonged monitoring. Important questions remain unresolved. It is unproven that detecting more AF, or detecting it earlier, reduces recurrent ischemic stroke. The low-burden arrhythmia that monitoring increasingly identifies appears to carry a lower embolic risk than the high-burden AF for which anticoagulation was established. Whether patients with low-burden, monitor-detected AFDAS derive net benefit from anticoagulation, the contribution of neurogenic mechanisms, and the thresholds of AF burden that should guide treatment are undefined. Future trials should be powered for recurrent stroke as the primary endpoint.
World Stroke Organization (WSO) rehabilitation certification program.
Nolan J, Li Khim K, Gandhi DB … +20 more , Baggio JAO, Thilarajah S, Charalambous M, Stevens EA, Rowe FJ, Bird ML, El Nahas N, Gururaj S, Meier P, Ignacio SD, Pandian JD, Stockley RC, Bernhardt J, Martins S, Mead G, Wu S, Hussein N, Kandasamy T, Savitz SI, Lynch EA
Int J Stroke · 2026 Jul · PMID 42390941 · Publisher ↗
BACKGROUND: 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 i...
BACKGROUND: 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. AIM: To develop globally applicable, evidence-based, stroke rehabilitation recommendations and performance metrics for use in a stroke rehabilitation certification program. METHODS: 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.
Advancing engagement of people with lived experience of stroke in recovery and rehabilitation research: Consensus-based core recommendations from the fourth Stroke Recovery and Rehabilitation Roundtable.
Lynch EA, Bright FAS, Chamberlain S … +14 more , Adebajo A, Campbell P, Chen DT, English CK, Graham ID, Isaksen J, Manning MX, Mohapatra S, Nelson M, Nesbitt K, Rackoll T, Thilarajah S, Zeiler S, Kidd L
Int J Stroke · 2026 Jun · PMID 42359885 · Publisher ↗
RATIONALE: 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 an...
RATIONALE: 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 sequalae 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. METHODS: 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 grey 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. RESULTS: 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; Report accessibility and inclusivity. Ten guidance documents provide practical support to researchers to engage with PWLE of stroke in all research settings. CONCLUSIONS: The EMBED framework provides researchers with pragmatic and structured support to engage with PWLE in stroke research.
The first-ever World Health Organisation (WHO) resolution on stroke, climate change and stroke, and do illicit drugs increase stroke risk.
Markus HS
Int J Stroke · 2026 Jul · PMID 42345328 · Publisher ↗
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Global epidemiology of atrial fibrillation and atrial flutter: An increasing worldwide burden.
Sanchis-Gomar F, Lavie CJ, Lippi G
Int J Stroke · 2026 Jun · PMID 42332406 · Publisher ↗
BACKGROUND: Atrial fibrillation and atrial flutter (AF/AFL) are major contributors to ischemic stroke, heart failure, disability, and mortality worldwide. OBJECTIVE: To provide a descriptive global analysis of AF/AFL bur...
BACKGROUND: Atrial fibrillation and atrial flutter (AF/AFL) are major contributors to ischemic stroke, heart failure, disability, and mortality worldwide. OBJECTIVE: To provide a descriptive global analysis of AF/AFL burden using Global Burden of Disease (GBD) 2023 estimates, with emphasis on incidence, prevalence, deaths, disability-adjusted life years (DALYs), and their distribution by sex, age, and socio-demographic index (SDI). METHODS: We performed a descriptive epidemiological analysis using direct extractions from the Institute for Health Metrics and Evaluation Global Burden of Disease 2023 Results Tool for the cause category "atrial fibrillation and atrial flutter." We assessed incidence, prevalence, deaths, DALYs, and selected rates globally and according to sex, quinquennial age group, and SDI. Temporal trends were examined using available historical series, and the 2023 burden was summarized across major demographic and SDI strata. RESULTS: In 2023, AF/AFL accounted globally for 5,021,980 incident cases, 59,045,058 prevalent cases, 9,265,726 DALYs, and 377,258 deaths. Compared with 1990, the global burden increased substantially in absolute terms. It was substantially higher in older adults, with the highest observed counts of incident and prevalent cases in the 70- to 74-year age group, the highest DALY counts in the 80- to 84-year age group, and the highest death counts in the 85- to 89-year age group. Men accounted for more incident and prevalent cases in absolute terms, whereas women accounted for more deaths and DALYs; age-standardized rates indicated higher male incidence, prevalence, and DALYs, but essentially equivalent mortality between sexes. High-SDI settings carried the largest absolute burden and the highest rates across all major metrics. Overall, the findings indicate a marked expansion in the global AF/AFL burden, with important heterogeneity by age, sex, and socio-demographic development. CONCLUSION: AF/AFL remains a major and growing global public health challenge. The burden is increasingly concentrated in older populations, shows persistent sex differences, and remains greater in high-SDI settings. These findings reinforce the relevance of AF/AFL to stroke prevention, health-system planning, and long-term cardiovascular care worldwide.
Stroke in South-Asian Populations: Unique Susceptibility, Risk Factors, and Treatment Considerations.
Giff AE, Totwani MT, Cure HW … +1 more , Singhal AB
Int J Stroke · 2026 Jun · PMID 42332402 · Publisher ↗
South-Asians comprise one-quarter of the world's population, yet account for 40% of global stroke deaths. They experience earlier stroke onset than whites, a 1.5-fold higher stroke mortality than Europeans, and a higher...
South-Asians comprise one-quarter of the world's population, yet account for 40% of global stroke deaths. They experience earlier stroke onset than whites, a 1.5-fold higher stroke mortality than Europeans, and a higher risk relative to other Asian populations. However, most studies aggregate South-Asians with other Asian populations or compare native South-Asians with other immigrant groups. This review synthesizes current evidence on the burden of stroke, epidemiology, risk factors, clinical presentation, subtypes, mechanisms, and treatment in South-Asians, with an emphasis on disparities compared to other ethnic groups. We discuss risk factors including distinct cardiometabolic profiles, genetic polymorphisms that affect homocysteine levels and drug metabolism, dietary patterns, and lifestyle factors. We review stroke subtypes in South-Asians and explore treatment and prevention strategies. Finally, we offer recommendations to target the multifactorial origins of elevated stroke burden in South-Asians, including improvements in screening, pharmacogenomic testing, and thresholds for intracranial vessel imaging. To address this disparity and reduce the high burden of stroke in these communities, it is important to develop tailored management strategies, increase clinical trial representation, and establish South-Asian stroke registries.
Stroke in Pregnancy.
Arias V, Yilmaz Soylu I, Miller EC
Int J Stroke · 2026 Jun · PMID 42319009 · Publisher ↗
Maternal stroke, while rare, leads to significant maternal morbidity and mortality. Physiologic changes in pregnancy and the postpartum period disrupt cerebrovascular homeostasis, predisposing to pregnancy specific syndr...
Maternal stroke, while rare, leads to significant maternal morbidity and mortality. Physiologic changes in pregnancy and the postpartum period disrupt cerebrovascular homeostasis, predisposing to pregnancy specific syndromes and tripling stroke risk. Mechanisms of pregnancy related stroke are diverse and include cardioembolism, vasculopathies (cervical artery dissections, reversible cerebral vasoconstriction syndrome), intracranial hemorrhage related to vascular lesions or preeclampsia, and cerebral venous thrombosis. Heterogeneity of presentation and limited experience treating pregnant women can contribute to challenges in diagnosis and management. This article reviews physiologic changes of pregnancy, as well as pregnancy associated syndromes that predispose to stroke, including preeclampsia and other hypertensive disorders of pregnancy, peripartum cardiomyopathy, and amniotic fluid embolism. We propose that hypertensive disorders of pregnancy and certain types of pregnancy related stroke may share underlying mechanisms and represent a continuum of pregnancy-associated vasculopathy characterized by endothelial dysfunction and sympathetic hyperactivity. We also offer practical considerations for stroke clinicians, including safety of imaging modalities, therapeutic options both for prevention and treatment of pregnancy-related stroke, and prognosis after pregnancy associated stroke.
Early versus Late starting of Direct Oral Anticoagulants after breakthrough ischemic stroke: A Target Trial Analysis from the ASPERA-R Study.
D'Anna L, Foschi M, Gabriele F … +95 more , Ornello R, Zini A, Paolucci M, Forlivesi S, Gentile M, Urbinati G, Cascio Rizzo A, Sessa M, Schwarz G, Tortorella R, Prandin G, Banerjee S, Desai G, Pantoni L, Mele F, Scopelliti G, Cova I, Valente M, Maisano D, Antonelli L, Bagnato MR, Di Mauro G, Bernocchi F, Di Donna MG, Casolla B, Mazloum MP, Kacani K, Noufel-Anis D, Gonzalez-Martín L, Rigual R, Fuentes B, Hervás C, Candelaresi P, Andreone V, De Mase A, Spina E, Aguiar de Sousa D, Almudi Souza M, Fior A, Serôdio M, Caliandro P, Zauli A, Reale G, Abdelalim A, Ahmed SM, Ismail SA, Zhang L, Latimer T, Elboghdany M, Elbassiouny A, Roushdy T, Shokri HM, Ferrari F, Loizzo N, Mazzacane F, Guarino M, Barone V, Forti P, Rinaldi G, Rossi M, Laterza V, Frisullo G, Rizzo PA, Broccolini A, Mannino M, Terruso V, Caggiula M, Scalise S, Fonseca ACG, Antunes B, Budinčević H, Crnac P, Viticchi G, Silvestrini M, Barba L, Otto M, Musienko V, Lochner P, Landau B, Buddha S, Khalil R, Piscaglia MG, Miserocchi LM, Zedde M, Nasreldein A, Vinciguerra L, Costa LR, Elsayed A, AlBanna M, Tudisco L, Mosconi MG, Merlino G, Polymeris AA, De Santis F, Sacco S
Int J Stroke · 2026 Jun · PMID 42318991 · Publisher ↗
BACKGROUND AND PURPOSE: Randomized trials support early initiation of direct oral anticoagulants (DOACs) after atrial fibrillation (AF)-related ischemic stroke, but patients with breakthrough ischemic stroke occurring de...
BACKGROUND AND PURPOSE: 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. METHODS: 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, multicentre 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. RESULTS: 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. CONCLUSIONS: 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.
HERMES-24 score for outcome prediction in large vessel occlusion stroke: Real-world data from the Austrian stroke network.
Gattringer T, Pichler A, Mikšová D … +18 more , Fandler-Höfler S, Deutschmann H, Kneihsl M, Grams AE, Gizewski ER, Dejakum B, Kiechl S, Weber J, De Paoli L, Werner P, Cejna M, Sommer P, Schernthaner R, Sykora M, Ferrari J, Neumann C, Enzinger C, Knoflach M
Int J Stroke · 2026 Jun · PMID 42290034 · Publisher ↗
BACKGROUND: The HERMES-24 score has recently been proposed to estimate the 90-day outcome in patients with anterior circulation large vessel occlusion (LVO) stroke. AIM: We aimed to further validate the HERMES-24 score i...
BACKGROUND: The HERMES-24 score has recently been proposed to estimate the 90-day outcome in patients with anterior circulation large vessel occlusion (LVO) stroke. AIM: We aimed to further validate the HERMES-24 score in a real-world setting of LVO patients who had received endovascular stroke treatment (EVT). METHODS: We used data of consecutive LVO patients treated with EVT in six Austrian stroke centers. The performance of the HERMES-24 score for outcome prediction at 90 days (modified Rankin Scale (mRS)) was investigated in predefined subgroups of anterior and vertebrobasilar LVO and within or beyond 6 h/unknown time windows. RESULTS: We analyzed 1571 patients with available 90-day follow-up. The HERMES-24 score was predictive of 90-day mRS ⩽ 2 for the total cohort, those with anterior LVO <6 h, anterior LVO ⩾6 h/unknown, vertebrobasilar LVO < 6 h, and vertebrobasilar LVO ⩾ 6 h/unknown with c-statistics (95% confidence interval (CI)) 0.90 (0.88-0.92), 0.90 (0.88-0.92), 0.89 (0.86-0.92), 0.88 (0.79-0.98) and 0.98 (0.96-1.0), respectively. The HERMES-24 score also yielded excellent outcome prediction for 90-day mRS ⩽ 3, an ordinal mRS, and mortality in all subgroups (c-statistics: 0.83-0.99). CONCLUSION: The HERMES-24 score is highly predictive for 90-day outcome in real-world patients with LVO stroke treated with EVT regardless of LVO localization or symptom onset to treatment time.
Adjunctive Intra-Arterial Alteplase After Near-Complete or Complete Reperfusion in Acute Ischemic Stroke: A Post Hoc Analysis of the PEARL Trial.
Bao M, Chen C, Sun H … +9 more , Deng Z, Chen Y, Xue R, He B, Yang X, Li Y, Xiao S, Tang Y, Xu Y
Int J Stroke · 2026 Jun · PMID 42265863 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. AIMS: The study aimed to explore whether intra-arterial alteplase was associated with improved outcomes in patients with eTICI 2c/3 after thrombectomy compared to standard treatment. METHODS: 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 hours, and mortality at 90 days. RESULTS: 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% 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 hours (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. CONCLUSIONS: 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. REGISTRATION: Clinicaltrials.gov identifier: NCT05856851.
Small vessel disease burden and response to induced hypertension therapy in small vessel occlusion stroke with early neurological deterioration.
Yang W, Kim KY, Lee JK … +6 more , Oh H, Song JY, Kim BJ, Kang DW, Kwon SU, Chang JY
Int J Stroke · 2026 Jun · PMID 42265861 · Publisher ↗
BACKGROUND: Induced hypertension therapy (iHT) is used to rescue early neurological deterioration (END) in small vessel occlusion (SVO) stroke. However, underlying perforator dysfunction reflected by small vessel disease...
BACKGROUND: Induced hypertension therapy (iHT) is used to rescue early neurological deterioration (END) in small vessel occlusion (SVO) stroke. However, underlying perforator dysfunction reflected by small vessel disease (SVD) burden may attenuate its therapeutic effect. AIM: To investigate whether white matter hyperintensity (WMH) volume and total SVD score are associated with neurological response to iHT. METHODS: Consecutive patients with acute SVO stroke who developed END and received iHT were identified from a prospective registry (January 2017-July 2025). Regional WMH volumes were quantified on magnetic resonance imaging fluid-attenuated inversion recovery images. Outcomes included early neurological improvement (ENI) following iHT and 3-month modified Rankin Scale (mRS). Associations were evaluated using binary and ordinal logistic regression. RESULTS: Among 178 patients (median age, 68 years; 55.6% men), 93 (52.2%) achieved ENI. Higher WMH volumes were independently associated with a lower likelihood of ENI (odds ratio [OR] per twofold increase [95% confidence interval]: total, 0.57 [0.43-0.76]; periventricular, 0.57 [0.43-0.76]; deep, 0.68 [0.54-0.86]). Periventricular WMH volume was also associated with an unfavorable shift in 3-month mRS (common OR, 0.80 [0.65-0.99]). Increasing total SVD score was associated with worse 3-month mRS shift (common OR, 0.61 [0.43-0.85]) and a non-significant trend against ENI (OR, 0.70 [0.48-1.01]; P = 0.056). CONCLUSIONS: Greater SVD burden was associated with a poorer neurological response to iHT in SVO stroke with END. Imaging markers of SVD may help identify patients less likely to achieve neurological improvement following iHT, suggesting a need for alternative individualized rescue strategies.
The role of inflammation in cerebral small vessel disease and vascular cognitive impairment, and therapeutic implications.
Brown R, Allan SM, Markus HS
Int J Stroke · 2026 Jun · PMID 42257423 · Publisher ↗
Increasing evidence suggests that inflammation occurs in cerebral small vessel disease (SVD). Inflammation has been hypothesised to play a role in disease pathogenesis, and also in progression to vascular cognitive impai...
Increasing evidence suggests that inflammation occurs in cerebral small vessel disease (SVD). Inflammation has been hypothesised to play a role in disease pathogenesis, and also in progression to vascular cognitive impairment and dementia (VCID), suggesting that targeting inflammation may offer a novel treatment option. In this review, we summarise the evidence that both systemic and central nervous system (CNS) inflammation occur in SVD and VCID, critically examine whether associations are causal, and review the evidence that anti-inflammatory interventions might represent possible treatments. We include coverage of sporadic SVD, cerebral amyloid angiopathy, and genetic small vessel diseases.CNS inflammation has been demonstrated in SVD both in post-mortem brains, and in vivo using positron emission tomography with radioligands targeted against the translocator surface proteins in microglia, but robust evidence showing such changes are causally related to disease progression is lacking. Peripheral inflammation can be measured in the blood using targeted assays, and more recently large scale proteomic panels. Proteins involved in coagulation, endothelial cell activation and immune cell adhesion have been associated with SVD, as well as specific cytokines, although not all findings have been replicated, and there is limited data examining whether individual proteins predict future disease progression. Genetic data can be used to inform whether such associations are likely to be casual and prioritise treatment targets. However to date, few treatment trials have investigated whether drugs that target specific inflammatory pathways can reduce SVD progression and onset of VCID, and those that have been performed have used non-specific inhibitors such as minocycline and colchicine.In summary, considerable data supports the presence of both systemic and CNS inflammation in SVD and VCID. However, whether these associations are causal remains unclear, and more longitudinal and interventional studies are required. Better understanding of the molecular basis of inflammation and immune dysfunction in SVD, also allow more precise therapeutic targeting.
Two distinct patterns of progression of sporadic cerebral small vessel disease.
Chen Y, Hong H, Tozer D … +6 more , Sun Z, Cai L, Li H, Tuladhar AM, De Leeuw FE, Markus HS
Int J Stroke · 2026 Jun · PMID 42237534 · Publisher ↗
BACKGROUND: Sporadic cerebral small vessel disease (cSVD) is the most common cause of vascular dementia. cSVD features a wide range of neuroimaging markers, including white matter hyperintensity (WMH), lacunes, perivascu...
BACKGROUND: Sporadic cerebral small vessel disease (cSVD) is the most common cause of vascular dementia. cSVD features a wide range of neuroimaging markers, including white matter hyperintensity (WMH), lacunes, perivascular spaces, microbleeds, and diffusion magnetic resonance imaging (MRI)-based markers of white matter (WM) injury, and is accompanied by progressive cognitive decline. However, few studies have systematically investigated how and when various imaging and cognitive markers change along the complete cSVD progression trajectory. AIMS: To establish changes in imaging and cognitive markers along the cSVD progression trajectory. METHODS: In this cohort study, we selected 496 participants from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUNDMC) cohort as the discovery data set. The subtype and stage inference model was used to identify cSVD subtypes and their progression patterns. Five neuroimaging markers (WMH volume, median mean diffusivity (MD) in WM, WM volume, gray matter (GM) volume, and ventricle volume) were used in trajectory construction. The validation cohort was Cambridge cSVD (CamcSVD; n = 330). RESULTS: We identified two subtypes in RUNDMC and replicated this finding in CamcSVD. One subtype displayed early WMH increase, followed by increased WM MD and tissue volume loss. The other subtype, which we termed "atrophy predominant," showed early loss of GM and WM and ventricle enlargement, followed by WMH increase and increased WM MD. This subtype displayed an increase in markers of idiopathic normal pressure hydrocephalus (iNPH). CONCLUSION: We have delineated two distinct progression patterns in sporadic cSVD. Further studies are needed to investigate the relationship between the atrophy-predominant cSVD subtype and iNPH.Data access statement:Datasets may be shared upon request to the corresponding author.
Large Artery occlusion Treated in Extended Time with Mechanical Thrombectomy (LATE-MT): Protocol for a multicenter randomized clinical trial.
Shen H, Yang P, Song L … +9 more , Zhang Y, Zhang X, Zhao Y, Wang L, Xing P, Zhang L, Anderson CS, Liu J, for LATE-MT Investigators
Int J Stroke · 2026 May · PMID 42216854 · Publisher ↗
BACKGROUND: High-quality randomized controlled trials (RCTs) have extended the endovascular therapy (EVT) time window to 24 h post-stroke onset in selected patients with acute ischemic stroke (AIS). Recent retrospective...
BACKGROUND: High-quality randomized controlled trials (RCTs) have extended the endovascular therapy (EVT) time window to 24 h post-stroke onset in selected patients with acute ischemic stroke (AIS). Recent retrospective studies indicate that EVT performed beyond 24 h may still improve clinical outcomes. However, the specific benefit-risk profile in this ultra-late window remains unclear. AIM: The trial is designed to address this evidence gap and determine the benefit-risk balance of EVT in the ultra-late window. METHODS AND DESIGN: The Large Artery occlusion Treated in Extended Time with Mechanical Thrombectomy (LATE-MT) is an investigator-initiated, multicenter, prospective, randomized, open, blinded-endpoint assessment (PROBE) clinical trial. The trial adopted an adaptive group-sequential design, recruiting 336 AIS patients with large-vessel occlusion within 24-72 h of the last known well across 35 stroke centers in China. Eligible subjects who meet both clinical and imaging selection criteria are randomized 1:1 to EVT or medical management. OUTCOMES: The primary outcome is an ordinal shift analysis of scores on the modified Rankin scale (mRS) at 90 days. Key secondary outcomes include neurological function at 24 h and 7 days, death/major disability, and utility-weighted mRS (UW-mRS) at 90 days. Safety outcomes include any intracranial hemorrhage (ICH), symptomatic ICH, serious adverse event, and all procedural complications.
Safety and efficacy of early antiplatelet therapy after intravenous thrombolysis for acute ischemic stroke: A comprehensive meta-analysis with trial sequential analysis.
Makhlouf HA, Harb A, Abouelmagd ME … +6 more , Mansour A, Osman ASA, Mosad N, Abdelaal AH, Kassar O, Saver JL
Int J Stroke · 2026 May · PMID 42187174 · Publisher ↗
BACKGROUND: Early antiplatelet therapy after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients may prevent re-occlusion and early neurological deterioration, but it could increase hemorrhagic transfo...
BACKGROUND: Early antiplatelet therapy after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients may prevent re-occlusion and early neurological deterioration, but it could increase hemorrhagic transformation. Evidence remains conflicting, particularly with emerging contemporary trials. METHODS: We conducted a Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-guided systematic review of randomized controlled trials (RCTs) comparing early antiplatelet therapy (eAPT) initiated within 24 h after IVT (with or without thrombectomy) versus standard timing (>24 h), placebo, or no antiplatelet therapy (CRD420251276445). Random-effects models were used to estimate odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). Trial sequential analysis, subgroup analyses, meta-regression, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) certainty ratings were performed. RESULTS: Twelve RCTs with 4595 patients were included. Early antiplatelet therapy led to higher non-significant odds of symptomatic intracranial hemorrhage (sICH; OR = 1.68, 95% CI = 0.94-3.01; = 10.4%; GRADE moderate), and mortality (OR = 1.15, 95% CI = 0.83-1.58; = 14.8%; GRADE moderate) but not intracranial hemorrhage (OR = 1.01, 95% CI = 0.64-1.60; = 52.6%; GRADE low). Functional outcomes were not improved: Modified Rankin Scale (mRS) 0-1 (OR = 1.10, 95% CI = 0.83-1.46; = 60.5%; GRADE low) and mRS 0-2 (OR = 1.27, 95% CI = 0.89-1.80; = 73.4%; GRADE very low). Trial sequential analysis indicated evidence remains inconclusive. Agent-specific subgroup analyses suggested higher sICH with early aspirin (OR = 2.13, 95% CI = 1.02-4.45) and possible benefit for mRS 0-2 with tirofiban (OR = 2.07, 95% CI = 1.25-3.43). CONCLUSION: Routine early antiplatelet therapy within 24 h after IVT does not provide conclusive functional benefit, and our analysis cannot exclude clinically meaningful hemorrhagic harm. Further adequately powered RCTs are needed to define whether any selected regimen-especially tirofiban-has a favorable risk-benefit profile.
Risk of growth of tiny (⩽3 mm) unruptured intracranial aneurysms: A retrospective cohort study of 228 tiny aneurysms.
van de Putte JD, Vergouwen MD, Kamphuis MJ … +3 more , van der Kamp LT, van der Schaaf IC, Ruigrok YM
Int J Stroke · 2026 May · PMID 42179330 · Publisher ↗
BACKGROUND: Tiny unruptured intracranial aneurysms, defined as ⩽ 3 mm, are increasingly detected due to advancements in imaging. However, the optimal management approach remains uncertain. Studies have questioned the nec...
BACKGROUND: Tiny unruptured intracranial aneurysms, defined as ⩽ 3 mm, are increasingly detected due to advancements in imaging. However, the optimal management approach remains uncertain. Studies have questioned the necessity of long-term radiological monitoring because of presumed low risks of growth, yet robust data are limited. AIMS: This retrospective cohort study aimed to estimate the 5-year growth risk of conservatively managed tiny unruptured intracranial aneurysms and assess potential differences in growth between men and women. METHODS: We conducted a single-center retrospective cohort study including adult patients diagnosed with one or more tiny saccular unruptured intracranial aneurysms at a tertiary academic hospital between 2008 and 2020. Patients were included if at least two imaging studies (baseline and ⩾1 follow-up) were available. Growth was defined as a ⩾1 mm increase in size or a morphological change. Growth risk was calculated, and cumulative incidence was estimated using the Kaplan-Meier analysis. Sex differences were analyzed using the log-rank tests. RESULTS: A total of 182 patients (142 women; median age = 54 years) with 228 tiny unruptured intracranial aneurysms were followed for a median of 5.5 years. Growth was observed in 29 unruptured intracranial aneurysms (12.7%). The Kaplan-Meier analysis showed cumulative growth of 9.7% (95% confidence interval = 5.1-14.2%) at 5 years. Growth rates were comparable between men and women (p = 0.63). CONCLUSIONS: Approximately one in eight tiny unruptured intracranial aneurysms demonstrated growth over long-term follow-up, indicating a clinically relevant growth risk despite small initial size. No sex-related differences in growth were observed. These findings support the importance of long-term radiological monitoring. Future studies should investigate whether tiny unruptured intracranial aneurysms may be safely followed with longer surveillance intervals than larger unruptured intracranial aneurysms.Data access statement:The data underlying this study are not publicly available due to institutional and ethical restrictions but may be accessed upon reasonable request and subject to approval by the appropriate review committees.
Early hematoma absorption after intracerebral hemorrhage: Clinical characteristics, neurological evolution, and outcomes.
Hu X, Wang Z, Liu M … +6 more , Zhu L, Dong Q, Chen C, Li J, Liu X, Li Q
Int J Stroke · 2026 May · PMID 42179303 · Publisher ↗
BACKGROUND: Early hematoma absorption (HA) has been insufficiently investigated in patients with intracerebral hemorrhage (ICH). This study aimed to determine the prevalence of HA and to evaluate its association with neu...
BACKGROUND: Early hematoma absorption (HA) has been insufficiently investigated in patients with intracerebral hemorrhage (ICH). This study aimed to determine the prevalence of HA and to evaluate its association with neurological and functional outcomes. METHODS: We analyzed prospectively collected data from patients with primary ICH. Eligible patients underwent baseline computed tomography (CT) within 6 h of symptom onset and follow-up CT within 36 h. HA was defined as an absolute reduction in hematoma volume > 2 mL or a relative decrease > 10%. Pronounced HA was defined as an absolute reduction > 3 mL or a relative decrease > 20%. Early neurological deterioration (END) and early neurological improvement (ENI) were defined as an increase of ⩾ 4 points and a decrease of ⩾ 2 points in the National Institutes of Health Stroke Scale (NIHSS), respectively. Functional outcomes at 3 months were assessed using the modified Rankin Scale (mRS), with poor outcome defined as mRS 4-6. RESULTS: Among 515 patients (median age, 60 years; 31.7% female), 109 (21.2%) exhibited early HA. END occurred in 65 patients (12.6%), and ENI in 93 patients (18.1%). In multivariable analyses, HA was independently associated with the absence of hypertension and with the presence of intraventricular hemorrhage (odds ratio (OR), 2.00; 95% confidence interval (CI), 1.19 to 3.36; p = 0.009). HA was also significantly associated with greater neurological improvement, reflected by a larger reduction in NIHSS score (β = -2.093; 95% CI, -3.369 to -0.816; p = 0.001) in adjusted linear regression models. While HA was not associated with 3-month functional outcome overall, pronounced HA was independently associated with a reduced risk of poor outcome (OR, 0.325; 95% CI, 0.133 to 0.795; p = 0.014). CONCLUSION: Early hematoma absorption occurs in approximately one-fifth of patients with acute ICH and is associated with favorable early neurological evolution. These findings suggest that HA may reflect endogenous hematoma resolution processes and represent a potential therapeutic target in ICH.
Methodological advances in the design and analysis of stroke trials.
Lin X, Anderson C
Int J Stroke · 2026 May · PMID 42178669 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. SUMMARY OF REVIEW: 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. CONCLUSION: 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.
Patent foramen ovale closure, improving fitness after stroke, optimizing hyperacute stroke treatment, and the Global Stroke Action Coalition.
Markus HS
Int J Stroke · 2026 Jun · PMID 42175744 · Publisher ↗
Abstract loading — click title to view on PubMed.
Endovascular thrombectomy in addition to intravenous thrombolysis versus intravenous thrombolysis alone in medium distal vessel occlusions: Results from the SITS International Stroke Treatment Register.
Keselman B, Mazya MV, Strbian D … +9 more , Nunes AP, Naldi A, Toni D, Petruzzellis M, Frisullo G, Jatuzis D, Strumia S, Ahmed N, Moreira T
Int J Stroke · 2026 May · PMID 42175680 · Publisher ↗
BACKGROUND: 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 wi...
BACKGROUND: 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? METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
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