Meyer L, Gellißen S, Thomalla G
… +54 more, Bendszus M, Broocks G, Bechstein M, Thaler C, Subtil F, Bonekamp S, Aamodt AH, Fuentes B, Gizewski ER, Hill MD, Krajina A, Pierot L, Simonsen CZ, Zeleňák K, Blauenfeldt RA, Cheng B, Denis A, Deutschmann H, Dorn F, Flottmann F, Gerber JC, Goyal M, Haring J, Herweh C, Hopf-Jensen S, Hua VT, Jensen M, Kastrup A, Keil CF, Klepanec A, Kurča E, Mikkelsen R, Möhlenbruch M, Müller-Hülsbeck S, Münnich N, Pagano P, Papanagiotou P, Petzold GC, Pham M, Puetz V, Raupach J, Reimann G, Ringleb PA, Schell M, Schlemm E, Schönenberger S, Tennøe B, Ulfert C, Vališ K, Vítková E, Vollherbst DF, Wick W, Fiehler J, Kniep H
Int J Stroke
· 2026 Jun · PMID 41058068
·
Full text
BACKGROUND: While thrombectomy benefits patients with large infarcts, it is unclear whether this benefit persists across different levels of reperfusion. AIMS: This study investigates how the degree of reperfusion influe...BACKGROUND: While thrombectomy benefits patients with large infarcts, it is unclear whether this benefit persists across different levels of reperfusion. AIMS: This study investigates how the degree of reperfusion influences the effectiveness of endovascular thrombectomy (EVT) combined with best medical treatment (BMT), compared to BMT alone, in patients with large infarcts. METHODS: This post hoc analysis of the TENSION trial, a randomized controlled study, assessed EVT versus BMT in patients with extensive infarction (Alberta Stroke Program Early CT Score (ASPECTS) 3-5). Primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included infarct volume at 24 h, mortality, and symptomatic hemorrhage. Outcomes were stratified by final reperfusion level, measured with the modified thrombolysis in cerebral infarction (mTICI) scale. Confounder-adjusted common odds ratios (cORs) and average treatment effects (ATEs) were estimated using inverse probability weighting with regression adjustment. RESULTS: A total of 246 patients (median age, 74 years (interquartile range (IQR), 65-80); median baseline ASPECTS, 4 (IQR, 3-5)) were included. Compared to BMT alone, unsuccessful EVT (mTICI ⩽ 2a) was not associated with worse functional outcomes (cOR:1.2, 95% CI, 0.95 to 1.52; p = 0.131), higher mortality (ATE: -11.6%; 95% CI, -28.82 to 5.61; p = 0.187), or larger infarct volumes on follow-up (ATE:0.99 mL; 95% CI, -45.30 to 45.32; p = 0.965). First-pass complete reperfusion (mTICI 3) showed the greatest treatment benefit, significantly improving all endpoints, with a cOR of 4.85 (95% CI, 3.74-6.31; p < 0.001) for improved mRS scores and a 29% absolute reduction in mortality. CONCLUSION: In this post hoc analysis of the TENSION trial, unsuccessful EVT did not worsen outcomes compared to BMT alone. The highest benefit of EVT occurred with first-pass complete reperfusion, emphasizing the importance of achieving optimal reperfusion in this vulnerable stroke subgroup. These findings do not justify general treatment recommendations.
Zheng L, Liu Y, Nie X
… +13 more, Yan H, Gu W, Liu X, Duan W, Zhang Z, Liu J, Wei Y, Wen M, Yang Z, Pan Y, Leng X, Miao Z, Liu L
Int J Stroke
· 2026 Jun · PMID 41024332
·
Publisher ↗
BACKGROUND: The role of intravenous (IV) tirofiban administered following endovascular therapy (EVT) for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) remains uncertain. AIMS: To investigate the associa...BACKGROUND: The role of intravenous (IV) tirofiban administered following endovascular therapy (EVT) for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) remains uncertain. AIMS: To investigate the associations of IV tirofiban following EVT with clinical outcomes in patients with acute LVO stroke and to determine whether the associations differ between anterior-circulation stroke (ACS) and posterior-circulation stroke (PCS). METHODS: In this prospective, national, multicenter registry, patients with AIS due to intracranial LVO who underwent EVT within 24 h of onset were enrolled and categorized into IV tirofiban and no-IV tirofiban groups. The primary outcome was functional independence at 90 days, defined as a modified Rankin Scale of 0-2. Secondary outcomes included the distribution of 90-day mRS, independent ambulation, symptomatic intracranial hemorrhage (sICH), early neurological deterioration (END), and 90-day mortality. Analyses included univariate and multivariable logistic regression and propensity score matching (PSM, 1:1 ratio). RESULTS: Among 1836 eligible patients (1342 ACS; 494 PCS), 362 (19.7%) received IV tirofiban following EVT. After PSM, 720, 498, and 196 patients were included in the entire, ACS, and PCS cohorts, respectively. In the ACS cohort, IV tirofiban was associated with higher odds of functional independence (57.0% vs. 43.8%; adjusted odds ratio (aOR) 1.55, 95% confidence interval (CI) = 1.08-2.22; P = 0.02) and a favorable shift in 90-day mRS. In the entire cohort, the association was attenuated after adjustment (aOR = 1.33, 95% CI = 0.99-1.79; P = 0.06). In the PCS cohorts, IV tirofiban was associated with numerically higher functional independence (31.6% vs. 18.4%), but without statistical significance (aOR = 1.54, 95% CI = 0.74-3.17; P = 0.25). No significant differences were found in sICH, END, or 90-day mortality between groups across all cohorts. CONCLUSION: IV tirofiban administration following EVT was associated with improved favorable functional outcomes in AIS patients with anterior-circulation LVO, without increasing the risk of sICH or END, but no significant association was observed in PCS patients. Further randomized controlled trials are warranted to verify these findings.
Liegeois C, Altersberger V, Gerschenfeld G
… +24 more, Olindo S, Salerno A, Heldner MR, Martinez-Majander N, Gensicke H, Forlivesi S, De Marchis GM, Chausson N, Cimflova P, Pico F, Seners P, Baik J, Hobeanu C, Dittrich TD, Marnat G, Smadja D, Curtze S, Zini A, Maury A, Strambo D, Alamowitch S, Engelter ST, Turc G, TETRIS and EVATRISP collaborators
Int J Stroke
· 2026 Jun · PMID 41024325
·
Publisher ↗
BACKGROUND: Intravenous thrombolysis with tenecteplase within 4.5 h after ischemic stroke is noninferior to alteplase. However, it is uncertain whether this is also true in patients last known to be well more than 4.5 h...BACKGROUND: Intravenous thrombolysis with tenecteplase within 4.5 h after ischemic stroke is noninferior to alteplase. However, it is uncertain whether this is also true in patients last known to be well more than 4.5 h before treatment initiation (last known to be well more than 4.5 h before treatment initiation (LKW > 4.5 h)). We aimed to compare tenecteplase and alteplase in this population using data from two large multicenter registries. METHODS: Pooled retrospective analysis of acute stroke patients LKW > 4.5 h treated with tenecteplase 0.25 mg/kg (Tenecteplase Treatment in Ischemic Stroke Registry (TETRIS) registry) or alteplase 0.9 mg/kg (EVATRISP registry plus 4 French centers participating in TETRIS) based on the results of magnetic resonance imaging (MRI) or perfusion computed tomography (CT). Excellent functional outcome at 3 months (modified Rankin Scale (mRS) 0-1) was the primary outcome. Secondary outcomes were mRS 0-2, shift analysis of the mRS, any intracranial hemorrhage (ICH), symptomatic ICH, and death. Propensity-score overlap weighting (PSOW) was used to account for imbalance in baseline characteristics. RESULTS: A total of 897 patients (tenecteplase: n = 419; alteplase: n = 478) were included between 2015 and 2024 (mean age: 74 (IQR 64-84); median National Institutes of Health Stroke Scale 11 (6-17) unknown stroke onset in 777 (86.6%) patients). At 3 months, mRS 0-1 was achieved in 138 (32.9%) and 178 (37.2%) patients treated with tenecteplase and alteplase, respectively (crude OR 0.83 (95% confidence interval (CI) 0.63-1.09); PSOW-OR 0.92 (95% CI 0.66-1.30)). Compared with alteplase, tenecteplase was not significantly associated with mRS 0-2 (PSOW-OR 0.78 (95% CI 0.56-1.08)) or better functional outcome over the whole range of the mRS (PSOW-common OR 0.83 (95% CI 0.62-1.11)). Tenecteplase was associated with significantly higher odds of any ICH (PSOW-OR: 1.79 (95% CI 1.25-2.57)), but not symptomatic intracranial hemorrhage (PSOW-OR 1.12 (95% CI 0.61-2.05)). CONCLUSIONS: The functional outcomes of patients LKW > 4.5 h treated with tenecteplase or alteplase did not significantly differ in this pooled analysis of two observational registries. However, the direction of the associations did not favor tenecteplase over alteplase, and therefore, more comparative studies-ideally randomized-are needed before routinely switching to tenecteplase in this population.
Tscherner M, Elbischger J, Hatab I
… +12 more, Berger N, Haidegger M, Fandler-Höfler S, Pichler A, Heine M, Jagiello J, Koller H, Lilek S, Veeranki SPK, Enzinger C, Gattringer T, Kneihsl M
INTRODUCTION: Early initiation of neurorehabilitation (NR) at the stroke unit is recommended and has been associated with improved outcomes. However, ensuring a direct, uninterrupted transition to subsequent inpatient NR...INTRODUCTION: Early initiation of neurorehabilitation (NR) at the stroke unit is recommended and has been associated with improved outcomes. However, ensuring a direct, uninterrupted transition to subsequent inpatient NR remains challenging in clinical practice. This study investigates whether direct transfer to inpatient NR is associated with functional recovery at 3-month post-stroke. METHODS: This study is based on prospectively collected registry data of all stroke patients discharged with functional dependence (modified Rankin Scale (mRS) 3-5) from five stroke units in Styria, Austria, between 2012 and 2023. All patients received standardized inpatient NR, either immediately after acute stroke care or-due to limited NR bed availability-following interim care on a general neurological ward without specialized rehabilitation. The primary outcome was a ⩾ 1-point mRS improvement from discharge to the 3-month follow-up. Outcome predictors were analyzed using univariable and multivariable methods. RESULTS: Of 2497 included patients (median age: 74 years; 44.7% female), 740 (29.6%) were directly transferred to NR after stroke unit care, while 1757 patients (70.4%) were not, with a median delay to NR of 8 days. Improvement in mRS during follow-up was observed in 1665 patients (66.7%). In multivariable analysis, direct transfer to NR was independently associated with mRS improvement (adjusted odds ratio 1.57, 95% CI 1.25-1.94) as were younger age, male sex, absence of prior stroke, and lower NIHSS score at discharge. CONCLUSIONS: Direct transition from the stroke unit to inpatient NR is associated with a greater likelihood of functional improvement at 3 months post-stroke. These findings support the value of implementing continuous post-stroke rehabilitation pathways.
BACKGROUND: Stroke remains a leading cause of mortality in the United States, with evolving epidemiologic patterns over five decades. This study analyzes stroke mortality trends from 1968 to 2023, focusing on disparities...BACKGROUND: Stroke remains a leading cause of mortality in the United States, with evolving epidemiologic patterns over five decades. This study analyzes stroke mortality trends from 1968 to 2023, focusing on disparities across age, sex, race, and geographic regions. METHODS: This population-based descriptive study used national mortality data from CDC WONDER. Stroke deaths among individuals aged ⩾ 25 years were identified using International Classification of Diseases (ICD) codes from 1968 to 2023. Age-adjusted mortality rates (AAMRs) per 100,000 individuals were calculated using US Census data. Temporal trends were analyzed using the Joinpoint regression. RESULTS: From 1968 to 2023, 8,933,826 stroke deaths occurred. AAMRs declined from 250.6 (95% CI = 249.5 to 251.8) in 1968 to 60.0 (95% CI = 59.7 to 60.3) in 2023, with rapid declines from 1973 to 1981, slower reductions until 2000, and modest rise post-2011. Males consistently had higher AAMRs than females. Among males, AAMR fell from 268.4 (95% CI = 266.5 to 270.3) to 60.5 (95% CI = 60.1 to 61.0), while in females, it declined from 236.8 (95% CI = 235.4 to 238.2) to 58.7 (95% CI = 58.3 to 59.1). Racial disparities persisted, with Black individuals having higher AAMRs than White individuals in 2023 (83.2 vs 58.6). The Southern United States had the highest AAMRs, with recent increases post-2011. In 2022-2023, stroke mortality ranged from 37.3 (95% CI = 36.6 to 37.9) in New York to 92.9 (95% CI = 88.4 to 97.4) in Delaware. Ischemic stroke AAMR declined from 59.9 (95% CI = 59.3 to 60.4) to 12.4 (95% CI = 12.3 to 12.5), with increases observed post-2014. Hemorrhagic stroke AAMR fell from 79.4 (95% CI = 78.7 to 80.0) to 10.0 (95% CI = 9.9 to 10.1), with continued decline from 1997 onward. CONCLUSION: Despite long-term declines, stroke mortality has recently increased, particularly among younger adults, racial minorities, and the Southern United States. These findings underscore the need for targeted public health interventions to address disparities.
Liu Y, Zou Y, Zhou H
… +11 more, Ding M, Liu N, Guo H, Zhang Y, Dai Y, Li X, Hu Y, Liu C, Gao S, Xu Y, Xu W
Int J Stroke
· 2026 Jun · PMID 40973985
·
Publisher ↗
BACKGROUND: Asymptomatic intracranial atherosclerotic stenosis (ICAS) is frequently identified in stroke screening programs, particularly in Asian populations. However, the prognosis and management strategies for inciden...BACKGROUND: Asymptomatic intracranial atherosclerotic stenosis (ICAS) is frequently identified in stroke screening programs, particularly in Asian populations. However, the prognosis and management strategies for incidentally detected asymptomatic ICAS in hospital-based, stroke-free populations remain unclear. AIMS: This study aimed to investigate the incidence of symptomatic transition and associated long-term prognostic evolution in this population, providing evidence to inform primary stroke prevention. METHODS: We conducted a prospective cohort study that included 1004 patients with asymptomatic ICAS (⩾50%) screened by transcranial Doppler ultrasound (TCD) between January 2016 and May 2022, with follow-up through August 2023. Using the Fine and Gray competing risk model, we analyzed the incidence of symptomatic transition, defined as a first-ever ischemic stroke or transient ischemic attack occurring within the ICAS territory. Post-transition outcomes, including recurrent stroke, major adverse cardiovascular events (MACE), disability (modified Rankin Scale score > 2), and patient-reported cognitive decline (Everyday Cognition-12 score ⩾ 2), were evaluated by comparative analysis. RESULTS: Over a median follow-up of 3.7 years (IQR 2.4-5.2), 43 (4.3%) patients with asymptomatic ICAS experienced a symptomatic transition under routine clinical surveillance, yielding a 5-year cumulative transition rate of 5.6%. After adjusting for potential confounders, hypertension (hazard ratio (HR) 3.33, 95% CI 1.25-8.87) and hyperlipidemia (HR 2.71, 95% CI 1.28-5.74) were independent predictors of the transition. Through extended follow-up, post-transition risks significantly increased for ischemic stroke (HR 3.37, 95% CI 1.17-9.68), MACE (HR 4.48, 1.83-10.99), disability (odds ratio (OR) 4.80, 2.17-10.64), and patient-reported cognitive decline (OR 3.43, 1.19-9.94). CONCLUSIONS: Asymptomatic ICAS detected by TCD incidentally in hospital-based, stroke-free populations carries a substantial risk of symptomatic transition and subsequent adverse outcomes. These findings underscore the prognostic importance of identifying asymptomatic ICAS clinically and highlight the necessity for intensive vascular risk factor management in this under-recognized group to guide primary stroke prevention strategies.
BACKGROUND: An in-hospital double-dose influenza vaccination strategy's effect on preventing major adverse cardiovascular events (MACE) in patients with previous stroke is still uncertain. This study is a prespecified an...BACKGROUND: An in-hospital double-dose influenza vaccination strategy's effect on preventing major adverse cardiovascular events (MACE) in patients with previous stroke is still uncertain. This study is a prespecified analysis of the vaccine against influenza to avoid cardiovascular events after the Acute Coronary Syndrome (VIP-ACS) trial. METHODS: The VIP-ACS trial was a randomized, pragmatic, multicenter, open-label trial with blinded-adjudication endpoints. Adult patients with acute coronary syndrome (ACS) ⩽ seven days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine or a standard-dose vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of all-cause death, myocardial infarction (MI), stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analyzed by the win ratio (WR) method. The secondary endpoint was a hierarchical composite consisting of CV death, MI and stroke (MACE). Patients were followed for 12 months each influenza season. RESULTS: The trial enrolled 1801 patients (31% female). A total of 67 patients had a history of stroke. There were no significant differences between groups on the primary hierarchical endpoint: 11.4% wins (862 patients) in the double-dose vaccine group versus 12.1% wins (872 patients) in the standard-dose vaccination group (WR: 0.94; 95% CI: 0.72-1.24; p = 0.69) without a history of stroke. However, in-hospital double-dose vaccination favored individuals (34 patients) with previous stroke (WR: 2.62; 95% CI: 1.10-6.25; p = 0.03; 43.9% wins vs 16.8% wins). Results were consistent for hierarchical MACE (WR: 3.01; 95% CI: 1.15-7.88; p = 0.02; 41.3% wins vs 13.7% wins) in favor of in-hospital double-dose vaccination (34 patients). CONCLUSIONS: After an ACS, in-hospital double-dose influenza vaccination prevents hospitalizations and death compared with standard-dose vaccination at 12 months in individuals with previous strokes. CLINICALTRIALS: gov number:NCT04001504.
Lakhani DA, Salim HA, Yedavalli V
… +63 more, Musmar B, Milhem F, Adeeb N, Faizy TD, Daraghma M, El Naamani K, Henninger N, Sundararajan SH, Kühn AL, Khalife J, Ghozy S, Scarcia L, Yeo LL, Tan BY, Regenhardt RW, Heit JJ, Cancelliere NM, Rouchaud A, Fiehler J, Sheth S, Puri AS, Dyzmann C, Colasurdo M, Renieri L, Filipe JP, Harker P, Radu RA, Abdalkader M, Klein P, Marotta TR, Spears J, Ota T, Mowla A, Jabbour P, Biswas A, Clarençon F, Siegler JE, Nguyen TN, Varela R, Baker A, Essibayi MA, Altschul D, Gonzalez NR, Möhlenbruch MA, Costalat V, Gory B, Stracke CP, Hecker C, Marnat G, Shaikh H, Griessenauer CJ, Liebeskind DS, Pedicelli A, Alexandre AM, Tancredi I, Kalsoum E, Lubicz B, Patel AB, Pereira VM, Wintermark M, Guenego A, Dmytriw AA, MAD MT Investigators
Int J Stroke
· 2026 Mar · PMID 40954523
·
Publisher ↗
BACKGROUND: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to...BACKGROUND: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to early neurological deterioration (END) in this patient population are understudied, but END is known to result in poor functional outcomes. Therefore, we aimed to investigate the factors contributing to END in minor AIS-DMVO cases. METHODS: We included patients with AIS-DMVO and minor strokes from 37 sites across North America, Asia, and Europe. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score of ⩽5. The primary outcome measure, END, was defined as a shift of ⩾4 points in the NIHSS score at day one after treatment compared to baseline. Univariable and multivariable logistic regression analyses were performed to identify factors associated with END. RESULTS: Among 559 consecutive patients with DMVO and minor strokes, END was reported in 68 patients. In multivariable analysis, mechanical thrombectomy (MT) was independently associated with higher odds of END (adjusted odds ratio [aOR] 2.37, 95% CI 1.12-5.02, = 0.02), while intravenous thrombolysis (IVT) was associated with lower odds of END (aOR 0.46, 95% CI 0.26-0.81, = 0.008). However, the association between MT and END was no longer statistically significant in the IPTW-adjusted analysis (OR 1.65, 95% CI 0.69-3.98, = 0.26). Hypertension and antiplatelet use at baseline were also independently associated with END. Among MT-treated patients, successful and excellent recanalization and first-pass effect were protective against END. CONCLUSION: MT was associated with END in patients with minor AIS-DMVO, although this association was not significant after IPTW adjustment. IVT was independently associated with reduced risk of END. These findings support careful patient selection and further study in randomized trials.
BACKGROUND: Ischemic stroke remains a leading cause of morbidity and mortality worldwide. Cardioembolic sources account for a significant proportion of these events, necessitating accurate identification of underlying st...BACKGROUND: Ischemic stroke remains a leading cause of morbidity and mortality worldwide. Cardioembolic sources account for a significant proportion of these events, necessitating accurate identification of underlying structural heart abnormalities. Traditionally, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have been utilized for this purpose, although both have limitations. Cardiac computed tomography (CCTA) has emerged as a potential alternative, offering non-invasive imaging with high sensitivity and specificity for detecting intracardiac thrombi. OBJECTIVE: This study aimed to evaluate the diagnostic yield of CCTA compared to TTE and TEE in detecting high-risk cardioaortic sources of embolism, including left ventricular (LV) thrombus, left atrial (LA) thrombus, valvular thrombus, and ulcerated aortic plaques, in patients with ischemic stroke. METHODS: We conducted a retrospective, single-center cohort study at Mayo Clinic, Rochester, MN, including 426 ischemic stroke patients who underwent CCTA within 30 days of stroke onset between March 2019 and June 2023. We compared the diagnostic yields of CCTA, TTE, and TEE in detecting structural cardiac sources of embolism. RESULTS: The overall diagnostic yield of CCTA for detecting high-risk cardioaortic sources was 15.5%. Specifically, CCTA identified LV thrombus in 2.3% of patients, LA thrombus in 4.0%, valvular thrombus in 2.8%, and ulcerated aortic plaques in 7.0%. In comparative analysis, CCTA demonstrated a higher yield than TTE (16.0% vs 3.5%, p < 0.001) and a comparable yield to TEE (25.3% vs 20.7%, p = 0.47) in detecting these sources. CONCLUSIONS: CCTA proved to be a viable option for identifying high-risk structural sources of cardioembolism in ischemic stroke patients. Its non-invasive nature, coupled with the ability to perform imaging soon after stroke onset, underscores its clinical utility. However, further prospective and blinded studies are required to validate these findings and fully establish the efficacy of CCTA in this context.
BACKGROUND: Evidence on the role of herpes-zoster (shingles) vaccination in reducing stroke risk is inconsistent and limited, particularly concerning intracerebral hemorrhage (ICH). We aimed to examine the association be...BACKGROUND: Evidence on the role of herpes-zoster (shingles) vaccination in reducing stroke risk is inconsistent and limited, particularly concerning intracerebral hemorrhage (ICH). We aimed to examine the association between zoster live vaccine (ZVL) and overall stroke, as well as its main subtypes. METHODS: We conducted a population-based nested case-control study using the database of Israel's largest healthcare provider. The underlying cohort consisted of individuals aged 50 years or older, regardless of prior stroke status, from 2015 to 2022, with follow-up through June 2023. Stroke cases diagnosed during follow-up were matched with controls based on age, sex, population sector, and index date. ZVL exposure was defined as the prior filling of a prescription of the vaccine. RESULTS: Among 37,027 matched case-control pairs, ZVL was associated with significantly reduced odds of stroke, with an adjusted odds ratio (OR) of 0.65 (95% confidence interval (CI), 0.58-0.72) for overall stroke, 0.65 (95% CI, 0.58-0.73) for ischemic stroke, and 0.64 (95% CI, 0.47-0.89) for ICH. The protective association with overall stroke decreased as time since vaccination increased; adjusted OR of 0.56 (0.48-0.65) within the first 2.5 years, 0.71 (95% CI, 0.58-0.87) after 2.5 to 5 years, and 0.81 (95% CI, 0.65-1.01) after 5 years. The association between ZVL and stroke was modified by age and sex, with a stronger association in individuals younger than 65 years ( for interaction = 0.004) and males ( for interaction = 0.031). CONCLUSIONS: ZVL is associated with a reduced risk of both ischemic stroke and ICH. The protective association appears to decrease over time and to be stronger in males and younger individuals.
BACKGROUND: Endothelial inflammation is involved in cerebral small vessel disease (CSVD) pathogenesis. Vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) are biomarkers of endotheli...BACKGROUND: Endothelial inflammation is involved in cerebral small vessel disease (CSVD) pathogenesis. Vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) are biomarkers of endothelial inflammation. AIMS: This study investigated the association of VCAM-1 and ICAM-1 with the presence of CSVD and CSVD burden. METHODS: This cross-sectional study included community residents from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study. Fasting venous blood was drawn to assay VCAM-1 and ICAM-1. Cognition was assessed by the Montreal Cognitive Assessment (MoCA). Cognitive impairment was defined as MoCA scores < 26. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated in a 3.0T MRI scanner. CSVD burden was rated according to the criteria of Wardlaw's (score 0-4) and Rothwell's (score 0-6), and classified into four grades. Presence of CSVD was defined as CSVD burden score ⩾ 1. RESULTS: This study included 2596 participants with a mean age of 61.2 ± 6.7 years and 50.9% of males. Elevated VCAM-1 was associated with increased odds of presence of CSVD (Rothwell: odds ratio (OR) = 1.16, 95% confidence interval (CI): 1.06-1.26, = 0.001), higher CSVD burden (Wardlaw: common OR (cOR) = 1.11, 95% CI: 1.02-1.21, = 0.02; Rothwell: cOR = 1.16, 95% CI: 1.07-1.25, < 0.001), and presence of cognition-impaired CSVD (Rothwell: OR = 1.15, 95% CI: 1.05-1.25, = 0.003). VCAM-1 improved net reclassification index and integrated discrimination improvement for the presence of CSVD (Rothwell) and cognition-impaired CSVD (Rothwell). However, ICAM-1 was not associated with CSVD and did not improve prediction of CSVD. CONCLUSION: Endothelial inflammation, especially VCAM-1, was associated with the presence of CSVD and higher CSVD burden.
Vyas MV, de Oliveira C, Saposnik G
… +9 more, Austin PC, Yu AY, Haldenby O, Fang J, Fischer CE, Lipson D, Quraishi F, Kapral MK, Bhat V
Int J Stroke
· 2026 Apr · PMID 40913243
·
Full text
BACKGROUND AND OBJECTIVES: We examined the timing of suicide after stroke, the sociodemographic factors associated with the risk of suicide, and whether major depression modified the stroke-suicide association. METHODS:...BACKGROUND AND OBJECTIVES: We examined the timing of suicide after stroke, the sociodemographic factors associated with the risk of suicide, and whether major depression modified the stroke-suicide association. METHODS: We conducted a population-based retrospective cohort study of all adults in Ontario hospitalized for stroke between January 1, 2008, and December 31, 2017, who were matched 1:1 to controls from the general Ontario population on age, sex, neighborhood-level income, rurality, and comorbidities. Suicide, a composite of deliberate self-harm or death by suicide, was ascertained based on hospitalizations and emergency department visits. Cause-specific hazard models were used to evaluate the association between stroke and suicide, and major depression was treated as a time-varying covariate. Cause-specific hazard models evaluated the association between sociodemographic factors and suicide in stroke survivors. The modifying effect of major depression was assessed by adding an interaction term between stroke and major depression. RESULTS: We included 64,719 matched pairs of patients with stroke and general population controls (45.4% female, mean age 71.4 years). In the 627,774 person-years follow-up, 436 cases and controls had an episode of self-harm or died by suicide, with 203 (67.4%) events in stroke survivors occurring after the first year. Compared to matched controls, stroke survivors had a higher rate of suicide (11.1 vs 3.2 per 10,000 person-years, hazard ratio (HR) 2.87; 2.35-3.51). The association between stroke and suicide did not vary by the presence of major depression (P = 0.51). Suicide rates were elevated in younger stroke survivors (HR 4.34; 2.48-7.61), those living in low-income neighborhoods (HR 1.88; 1.30-2.70), and those with major depression (HR 12.3; 7.63-19.7). DISCUSSION: The elevated rate of suicide after stroke persists beyond one year, highlighting the need for long-term screening for suicidality, especially in younger stroke survivors and those residing in low-income neighborhoods and with major depression after stroke.
BACKGROUND: Using mobile low-field magnetic resonance imaging (MRI) in the emergency department to detect cerebral infarction(s) in patients with minor ischemic stroke (MIS) and transient ischemic attack (TIA) has not ye...BACKGROUND: Using mobile low-field magnetic resonance imaging (MRI) in the emergency department to detect cerebral infarction(s) in patients with minor ischemic stroke (MIS) and transient ischemic attack (TIA) has not yet been thoroughly reported. AIM: We aimed to evaluate the performance of mobile low-field (0.23T) MRI in detecting acute ischemic infarction in MIS or TIA patients within 72 h of symptom onset and compare it to computed tomography (CT) in those scanned within 24 h. We also aimed to analyze predictors of DWI-positive lesions on mobile MRI. METHODS: This prospective observational cohort consecutively included patients with MIS (National Institutes of Health Stroke Scale (NIHSS) ⩽ 5) or TIA who underwent mobile low-field MRI within 72 h of symptom onset in the emergency department of a tertiary general hospital. The MRI protocol included localizer, axial T1-weighted fluid-attenuated inversion recovery (FLAIR), axial T2-weighted FLAIR, axial T2-weighted fast spin-echo, hematoma-enhanced inversion recovery (HEIR), and diffusion-weighted imaging (DWI) with apparent diffusion coefficient sequences. The total acquisition time is 10 min 28 s. Two raters, blinded to clinical information and CT findings, interpreted the MRI images for acute infarction. Multivariable logistic regression identified predictors of DWI positivity. The primary outcome was restricted diffusion (acute infarction) on the brain low-field MRI scan. We analyzed patients who underwent head CT scan within 24 h of low-field MRI to compare the detection rates of acute infarction between low-field MRI and head CT. RESULTS: A total of 974 patients (564 men and 410 women; mean (standard deviation, SD) age, 61.3 (14.9) were enrolled. New ischemic lesions were detected by low-field MRI on the DWI sequence in 37.4% (338 in 974) of patients. Among them, 304 underwent head CT within 24 h of the low-field MRI scan; CT identified new ischemic lesions in only 122 (40.1%) of these. Higher NIHSS score (hazard ratio, 1.36 (95% confidence interval (CI), 1.21-1.54); < 0.01), longer onset to imaging time (hazard ratio, 1.33 (95% CI, 1.10-1.63); < 0.01), aphasia (hazard ratio, 2.24 (95% CI, 1.36-3.71); < 0.01), and hemiplegia (hazard ratio, 2.50 (95% CI, 1.76-3.55); < 0.01) were independently associated with DWI positivity on mobile low-field MRI. Female sex (hazard ratio, 0.57 (95% CI, 0.42-0.79); < 0.01) and non-focal symptoms were negatively associated with DWI positivity. CONCLUSION: Mobile low-field MRI provides a safe, efficient, and accessible imaging solution for MIS and TIA evaluation in emergency settings and detects more acute infarctions than non-contrast head CT. Higher NIHSS score, longer onset to imaging time and focal clinical features were independently associated with DWI positivity.
Gonzalez F, López JI, Tamagnini F
… +61 more, Bonardo P, Cotti N, Zavattieri A, Carobolante L, A Arias C, Acosta MV, Balian N, L Armaretti M, A Mena I, Gonzalez L, Lepera S, Claverie S, D Monclá T, C Ureña B, Apaza PI, Farcy N, Kerz C, Luraschi A, Ludvik E, Padilla IS, F Rea S, Bizantino G, Da Prat G, Antelo C, Domeniconi G, Ávila A, Ferreyra C, Espinosa ML, Cristani L, Lazzaneo S, Chaves M, Bergagna I, Galliussi P, Diego A, Pigretti S, Guyon J, Orzuza G, Torres E, Palavecino A, Bruera G, Lammertyn P, Jairala J, Cea C, Firpo C, Lazarte Y, Mosconi S, Tapia D, Cossio J, Fernández J, Fernández MS, Persi G, De Paul G, H Apaza M, S de Paz P, Caballero M, Cirio J, Rosales J, Lopez M, Chasco M, Barber-Otero J, Alet MJ
Int J Stroke
· 2026 Jan · PMID 40905624
·
Publisher ↗
BACKGROUND: Young adults account for up to 15% of all ischemic strokes, yet data from Latin America remain scarce. Understanding their clinical profile and outcomes is essential to inform targeted interventions and publi...BACKGROUND: Young adults account for up to 15% of all ischemic strokes, yet data from Latin America remain scarce. Understanding their clinical profile and outcomes is essential to inform targeted interventions and public health strategies. We aimed to characterize demographics, vascular risk factors, stroke etiology, access to acute reperfusion therapies, and 90-day outcomes in Argentine patients aged 18-50 years with ischemic stroke. METHODS: We conducted a retrospective multicenter cohort study including consecutive patients aged 18-50 years with ischemic stroke, enrolled between January 2015 and December 2023 across 26 centers in Argentina. Primary outcomes were functional dependence (modified Rankin scale (mRS) 3-5), stroke recurrence, and all-cause mortality at 90 days. RESULTS: Among 18,934 ischemic stroke patients, 1422 (7.5%) were young adults. Median age was 43 years (interquartile range (IQR) 36-47), and 53.7% (n = 763) were male. The most prevalent risk factors were hypertension (31.0% (n = 441)), smoking (29.3% (n = 417)), and obesity (18.8% (n = 267)). Median National Institute of Health Stroke Scale (NIHSS) on admission was 3 (IQR 1-8). Acute reperfusion therapy was administered in 18.9% (n = 269). Stroke etiology remained undetermined in 50.4% (n = 717) of cases; within this group, 26.1% (n = 312) fulfilled criteria for embolic stroke of undetermined source (ESUS), and 17.8% (n = 198) were cryptogenic strokes associated with patent foramen ovale. Arterial dissection accounted for 56.6% (n = 193) of other determined causes. At 90 days, functional dependence was observed in 12.1% (n = 110), stroke recurrence in 3.9% (n = 37), and mortality in 4.8% (n = 44). CONCLUSION: In Argentina, nearly 1 in 13 ischemic strokes occurs in young adults. Despite generally mild presentations, functional dependence and mortality remain substantial. The high rate of undetermined etiology underscores the need for standardized diagnostic protocols in this population, whose strokes carry a disproportionate individual and societal burden due to their early onset.
BACKGROUND: Leadership development is essential to advancing stroke care globally. The World Stroke Organization (WSO) Future Stroke Leaders Program (FSLP) was established to identify and support global early-career prof...BACKGROUND: Leadership development is essential to advancing stroke care globally. The World Stroke Organization (WSO) Future Stroke Leaders Program (FSLP) was established to identify and support global early-career professionals in stroke care worldwide. The program offers structured leadership training, mentorship, and seed funding for implementation projects. Selection criteria prioritize diversity, leadership potential, and institutional support. The article describes the design and implementation of the WSO FSLP and evaluates its contribution to stroke care advancement, professional development, and global collaboration. METHODS: This is a descriptive narrative of the WSO FSLP, based on program documentation, participant surveys, and public databases. Programmatic key performance indicators (KPIs) aligned with WSO's strategic goals were used to track impact. RESULTS: Among 56 participants in the first two cohorts, selected from over 35 countries, engagement with the WSO FSLP contributed to improved access to and delivery of care by developing stroke services in underserved areas, enhancing publication output, and supporting active involvement in international policy and advocacy efforts. Participants reported career advancement, increased research engagement, and expanded collaborative networks as a direct result of their participation in the program. CONCLUSIONS: The WSO FSLP is a model for developing global stroke leadership. Its impact spans clinical innovation, academic research, and policy influence, guiding implementation. Continued program adaptation to the changing international landscape, alumni engagement, and long-term impact evaluation will help sustain and scale worldwide contributions to stroke care equity.
Shin A, Kang S, Jung J
… +6 more, Cho IY, Han K, Kim S, Kim SY, Shin DW, Kim H
Int J Stroke
· 2026 Mar · PMID 40884091
·
Publisher ↗
BACKGROUND: Rheumatoid arthritis (RA) has been associated with an increased stroke risk, but associations by serostatus (seropositive RA (SPRA) vs seronegative RA (SNRA)) and with subtypes of stroke (ischemic stroke (IS)...BACKGROUND: Rheumatoid arthritis (RA) has been associated with an increased stroke risk, but associations by serostatus (seropositive RA (SPRA) vs seronegative RA (SNRA)) and with subtypes of stroke (ischemic stroke (IS) or hemorrhagic stroke (HS)) are not well established. In addition, it is not well-known whether the use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) are associated with altered stroke risk. METHODS: This nationwide cohort study used the Korean National Health Insurance Service database and included participants who were first diagnosed with RA in the period 2010-2017 with no previous history of stroke, and who had a health checkup within 2 years before the index date (45,175 RA patients). They were compared (1:3 ratio) with non-RA controls matched by age and sex (135,525 non-RA controls). RESULTS: Patients with RA had a significantly higher risk of both IS (adjusted hazard ratio (aHR) = 1.47, 95% confidence interval (CI) = 1.36-1.58) and HS (aHR = 1.31, 95% CI = 1.15-1.50) compared to controls. SPRA patients showed higher risk for both IS (aHR = 1.56, 95% CI = 1.43-1.69 SPRA vs aHR = 1.23, 1.08-1.41 SNRA) and HS (aHR = 1.40, 95% CI = 1.21-1.62 SPRA vs aHR = 1.09, 95% CI = 0.86-1.38 SNRA). No difference in stroke risk was observed between bDMARDs users and non-users (aHR = 1.66 for users, aHR = 1.41 for non-users). However, potential differences were noted with tsDMARDs use (aHR = 0.81 for users vs aHR = 1.43 for non-users), although not statistically significant. CONCLUSION: Patients with RA are at significantly greater risk for both IS and HS compared to those without RA, and SPRA patients showed higher risk than SNRA patients. Further studies are required to determine the potential of tsDMARDs in the prevention of stroke in RA.
Inoue M, Kamogawa N, Koga M
… +8 more, Yoshimura S, Fukuda-Doi M, Miwa K, Sasaki M, Aoki J, Kimura K, Ihara M, Toyoda K
Int J Stroke
· 2026 Mar · PMID 40884089
·
Publisher ↗
BACKGROUND AND AIMS: FLAIR vessel hyperintensities (FVH)-Alberta Stroke Program Early CT Score (ASPECTS) is an imaging marker but its clinical implications remain unclear. We estimated the correlation between FVH-ASPECTS...BACKGROUND AND AIMS: FLAIR vessel hyperintensities (FVH)-Alberta Stroke Program Early CT Score (ASPECTS) is an imaging marker but its clinical implications remain unclear. We estimated the correlation between FVH-ASPECTS and clinical outcomes in patients with wake-up stroke or unknown time of stroke onset. METHODS: The THrombolysis for Acute Wake-up and Unclear-onset Strokes with Alteplase at 0.6 mg/kg (THAWS) trial was a multicenter, randomized controlled trial conducted at 40 sites in Japan between 2014 and 2018. Patients with unknown stroke onset and diffusion-weighted imaging (DWI)-FLAIR mismatch were randomly assigned to receive either intravenous alteplase (0.6 mg/kg) or standard medical treatment. FVH-ASPECTS, a semiquantitative scoring system assessing FVH prominence in the seven cortical ASPECTS regions, was evaluated for its association with favorable outcomes (modified Rankin Scale 0-2 at 90 days). The optimal FVH-ASPECTS threshold was determined using receiver operating characteristic (ROC) analysis and its correlation with favorable outcomes was assessed. RESULTS: Among 131 patients (mean age, 76 ± 13 years; 42% women), 71 received alteplase and 60 did not. Median NIHSS score was 7 (interquartile range [IQR] 4-13), and median FVH-ASPECTS was 4 (IQR 2-4). ROC analysis identified FVH-ASPECTS 3 or more as predictive of favorable outcomes (sensitivity 80%, specificity 51%, area under the ROC curve [AUC] 0.717). A significant correlation was observed between FVH-ASPECTS 3 or more and favorable outcomes (adjusted odds ratio [OR] 4.50, 95% confidence interval [CI] 1.89-10.75; p < 0.001). CONCLUSION: FVH-ASPECTS could offer an indicator for achieving favorable clinical outcomes among stroke patients with unknown time of onset, with a threshold of 3 or more.
INTRODUCTION: Cerebrovascular diseases (CeVD) and neurodegenerative diseases (NDs) are two major neurological disorders, which are associated with increasing global morbidity and mortality. Population-based studies have...INTRODUCTION: Cerebrovascular diseases (CeVD) and neurodegenerative diseases (NDs) are two major neurological disorders, which are associated with increasing global morbidity and mortality. Population-based studies have indicated a complex link between CeVD and ND. However, the shared genetic etiology between these disease conditions remains less explored. METHODS: We conducted genome-wide genetic correlation analysis and investigated the shared genetic architecture through pleiotropy analysis between ND and CeVD, like stroke and its subtypes, to understand shared genetic factors and biological mechanisms. Publicly available large-scale genome-wide association studies (GWAS) summary statistics data of cross-ancestry, European, and South Asian (SAS) ancestry were analyzed using methods implemented in the tools linkage disequilibrium score regression (LDSC), PLeiotropic Analysis under COmposite null hypothesis (PLACO), and Bayesian-based method of colocalization (COLOC). RESULTS: We detected 116 shared genetic loci consisting of 770 lead pleiotropic single nucleotide polymorphisms (SNPs) (ND-CeVD P-range: 4.81×10 to 4.57×10) and 40 shared causal genetic regions (ND-CeVD PP.H4-range: 0.70-0.9, posterior probability of H4 (PP.H4) ⩾ 0.7) between multiple CeVD and ND pairs. The genetic regions near genes were identified as highly pleiotropic across multiple CeVD-ND pairs. We report (5q35.1) for the first time as a shared causal genetic locus between Amyotrophic Lateral Sclerosis and small vessel stroke. The genetic risk score of stroke derived from the SAS population of the GIGASTROKE study was associated with ND (P-range = 2.23×10 to 0.02), despite a small sample size compared to other ethnic groups, indicating high penetrance. CONCLUSION: The shared genetic loci and pathway analysis in this study provide new genes and pathways shared between ND and CeVD, which may help in a better understanding of disease mechanisms in these neurological diseases.