International Journal of Stroke最新文献

Background: Stroke is associated with substantial mortality among children and adolescents, yet evidence on the death burden of stroke in this group in China is scarce.

Aims: To assess the trends of mortality and years of life lost (YLL) due to stroke in children and adolescents in China.

Methods: We estimated the number and age-standardized rate of death and YLL caused by stroke and its subtypes among children and adolescents aged 0-19 years in China and its provinces from 2005 to 2020, utilizing data from National Mortality Surveillance System.

Results: In China, the age-standardized mortality rate due to stroke among children and adolescents aged 0-19 years decreased from 1.40/100,000 to 0.51/100,000 during 2005-2020, and the YLL rate decreased from 116.28/100,000 to 38.79/100,000. During 2005-2020, intracerebral hemorrhage (ICH) consistently showed significantly higher age-standardized mortality rate than ischemic stroke (IS) and subarachnoid hemorrhage (SAH). In 2020, the mortality rate of ICH was 11.35-fold and 4.96-fold greater than that of IS and SAH, respectively (ICH 0.40/100,000, IS 0.04/100,000, SAH 0.08/100,000). Overall, males among children and adolescents exhibited higher age-standardized mortality and YLL rate due to stroke compared to females. Notably, the stroke mortality rate in 15-19 years age group increased by 16.10% during 2005-2020, primarily attributed to the significant increases in mortality rate of ICH and SAH among males in this age group (ICH males 25.51%, SAH males 107.83%). In 2020, Yunnan (1.56/100,000), Tibet (1.54/100,000), and Henan (1.47/100,000) had the highest age-standardized mortality rate of stroke among children and adolescents, while Shanghai, Fujian and Jiangsu had the lowest rates. In addition, a negative association was observed between the age-standardized YLL rates of stroke among individuals aged 0-19 years and the socio-demographic index across 31 provinces in China from 2005 to 2020.

Conclusion: In China, the death burden of ICH among children and adolescents was considerably heavier than that of SAH and IS. The rising mortality rate of ICH and SAH among males aged 15-19 years requires greater emphasis. Targeted interventions for stroke in children and adolescents should be expedited to reduce the disease burden in this particular population.

Background: Recurrent ischemic stroke (IS) disproportionately affects individuals in their most productive years, contributing to significant morbidity and mortality. Despite its growing importance, data on this critical population remain limited.

Aim: The aim of the study is to characterize rates and factors associated with recurrent IS in young adults.

Methods: We performed a retrospective multicentre cohort study of consecutive acute IS patients aged 18-50 years from three tertiary hospitals in Singapore and Christchurch, New Zealand. We characterized rates and prognostic factors associated with recurrent IS over 1-year follow-up using univariate and multivariable Cox Proportional Hazards models. We then performed a systematic review and meta-analysis of PubMed, Embase, Scopus and Cochrane databases for all studies from January 2000 to July 2024 evaluating recurrent stroke or transient ischemic attack (TIA) following an index IS or TIA. We meta-analyzed rates and factors associated with recurrent cerebrovascular events based on aggregate count, aggregate survival, and individual patient-level survival data reconstructed from Kaplan-Meier curves.

Results: The cohort study of 845 patients showed a 3.41% (95% confidence interval (CI) = 2.16-4.64) recurrence rate over 1-year follow-up. Patients with diabetes mellitus and prior stroke/TIA had significantly higher rates of recurrent IS. The systematic review and meta-analysis of 18,955 patients across 31 studies yielded a recurrence rate of 4.5-7.3% at 1 year, 10.5-12.8% at 5 years, and 14.0-20.3% at >10 years. Large artery atherosclerosis (LAA) etiology, hypertension, diabetes mellitus, and prior stroke/TIA were significantly associated with recurrent stroke or TIA.

Conclusions: Young adults with IS face a long-term risk of recurrent cerebrovascular events. More prospective studies are warranted to better characterize long-term prognosis for these patients.

Background and aims: Vasodilating drugs targeting the endothelium could reduce long-term harms due to cerebral small vessel disease (cSVD) but there are no commonly accepted methods to measure short-term disease activity or drug response. In the OxHARP clinical trial, we determined the most sensitive physiological markers of treatment response to sildenafil versus placebo on either transcranial ultrasound (TCD) or magnetic resonance imaging (MRI), and their validity compared to disease severity and other measures of other physiological mechanisms.

Methods: In the OxHARP double-blind, randomized, placebo-controlled crossover trial we measured aortic blood pressure, mean flow velocity (MFV), cerebral pulsatility, cerebrovascular conductance index (CVCi = MFV/aortic mean BP), cerebral perfusion (pcASL-MRI) and cerebrovascular reactivity to inhaled CO2 on TCD (CVR-TCD) and MRI in white (CVR-WM), gray (CVR-GM) and white matter hyperintensities (CVR-WMH). Effects of 3 weeks of sildenafil were compared to placebo. Validity of markers were determined by between-visit repeatability (intraclass correlation coefficient (ICC)); associations with CVR-TCD, CVR-WMH and CVR-GM; associations with other markers; the magnitude of response, and sensitivity, to sildenafil.

Results: In 69 participants, repeatability was greatest for MFV, pulsatility, CVCi and CVR-WMH (ICC > 0.8), very good for CVR-TCD and GM-perfusion (ICC > 0.7), and good for CVR-GM (ICC > 0.6). CVR-TCD was associated with CVR on MRI (CVR-WMH: r² = 0.12, p = 0.02; CVR-GM: r² = 0.22, p = 0.001), while blood flow measures on TCD (MFV, CVCi) were associated with CVR-TCD and perfusion-MRI (all p < 0.05). All markers were associated with WMH volume and improved by sildenafil, but CVCi was most sensitive, requiring only 20 patients for a crossover trial at 80% power, compared to 26 for GM-perfusion or 84 for CVR-GM.

Conclusions: Multiple markers were associated with cSVD, but no single marker reflected all physiological drug effects. CVCi and gray matter perfusion on MRI were the most sensitive markers of disease activity and drug response, although CVR indices may be more specific for endothelial dysfunction.

Background: The incidence of stroke is increasing in young to middle-aged adults. Assessing risk factors is important in this large population whose comorbidities may differ from older adults.

Methods: In this retrospective cohort analysis of adults aged between 20 and 50 presenting to the Stanford Healthcare system from 1 January 2000 through 31 December 2021, with no prior history of stroke or transient ischemic attack, we studied the effects of 30 risk factors on the primary endpoint of incident ischemic stroke, defined by the presence of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for stroke and confirmed by brain imaging. The secondary endpoint was incident cerebrovascular events defined by the presence of ICD-10 codes for stroke or transient ischemic attacks (TIAs). Associations were measured with time-varying multivariable survival regression.

Results: From an overall population of 1.3 million, we identified 540,999 individuals aged 20-50 years. Over the study period, 802 experienced the primary endpoint and 5734 the secondary endpoint. On multivariable analysis, non-cardiovascular risk factors were independently associated with the primary endpoint, adjusting for established cardiovascular risk factors, including sleep apnea [1.44, (1.19, 1.74)], bipolar disorder [1.88, (1.23, 2.86)], cancer [2.07 (1.71, 2.51)], and chronic kidney disease (CKD) [2.2, (1.73, 2.81)]. Other non-cardiovascular associations included ethno-racial subgroups of Black [2.05, (1.60, 2.64)], Pacific Islander [2.56, (1.70, 3.84)], and Hispanic [1.71, (1.37, 2.15)] versus white non-Hispanics. Combining non-cardiovascular risk factors significant on multivariable analysis with established cardiovascular factors significantly improved the C-index for de novo stroke to 0.814 over that obtained in either group alone (P < 0.05).

Conclusions: In this large population of young adults, several non-cardiovascular factors conferred risk for incident stroke independent of known cardiovascular risk factors and, in combination, significantly improved the prediction of incident stroke over those based on either group of factors alone. These findings may have implications for assessing risk in younger patients with distinct comorbidities.

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: Cerebral venous thrombosis (CVT) is a less common type of stroke that predominantly affects young adults, particularly women. Although CVT is generally associated with more favorable functional outcomes than other stroke subtypes, its cognitive consequences remain poorly understood.

Aims: We aimed to perform a systematic review and meta-analysis evaluating the prevalence and characteristics of cognitive impairment in patients after CVT.

Summary of review: A systematic review was conducted in accordance with PRISMA guidelines. We searched PubMed, Embase, and Cochrane databases up to May 2025 for studies assessing cognitive impairment in patients with cerebral venous thrombosis (CVT), with a minimum follow-up of 6 months. Data extraction was performed independently by two reviewers. Pooled prevalence estimates were calculated using random-effects generalized linear mixed models with logit transformation as the primary approach, with Freeman-Tukey (double arcsine) transformation applied only in analyses with zero events or extreme proportions. Heterogeneity was evaluated using the I² statistic. All statistical analyses were conducted in R (version 4.5.2). Eleven observational studies and one randomized clinical trial involving 801 post-CVT patients were included. The pooled prevalence of cognitive impairment after CVT ranged from 19.25% (95% CI: 7.15-42.47%) among studies at low risk of bias to 29.20% (95% CI: 14.91-49.27%) in the overall analysis. Memory loss and affected executive function and visuospatial domains occurred in 39.21% (95% CI: 18.70-64.40%) and 35.94% (95% CI: 21.86-52.94%) of patients, respectively. Among functionally independent patients, cognitive impairment was observed in 28.6% (95% CI: 21.0-37.6%) of those with mRS 0, 36.3% (95% CI: 26.5-47.5%) with mRS 1, and 32.7% (95% CI: 15.5-56.3%) with mRS 2.

Conclusions: Cognitive impairment affects roughly one-fifth to one-third of CVT survivors (19-29%), including those with minimal or no functional disability. These findings highlight the need to move beyond the mRS when assessing recovery and planning follow-up care.

Background: Randomized controlled trials (RCTs) have traditionally been designed with an explanatory approach, in contrast to incorporating real-world, pragmatic considerations.

Aims: This methodological review assesses the uptake of pragmatic designs in Phase III acute stroke RCTs.

Methods: We conducted a comprehensive literature search of the MEDLINE, Embase, and Cochrane Library databases from inception to 1 July 2024. Eligible articles included English-language published Phase III RCTs of acute ischemic stroke and intracerebral hemorrhage interventions. Using the Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2) tool, each trial was rated on nine key domains, and relevant study characteristics were extracted. Trials with an average rating of 3 or higher, or a total score (sum of ratings) of 27 or higher (given that all domains were assessed), were considered to adopt an overall pragmatic approach to their design. Risk of bias was evaluated using the Cochrane risk of bias tool.

Results: Of the 5663 unique articles obtained after deduplication, 136 trials were included, and 71 (52%) trials were classified as pragmatic using the PRECIS-2 tool. A majority had a low risk of bias (63.2%). Pragmatic trials were more likely to be large sample, multicenter, multinational trials with broad inclusion criteria that cover multiple types of strokes.

Conclusion: There has been an increased uptake of pragmatic designs in acute stroke over the last decade, reflecting improvements in acute stroke care and a greater consideration of real-world applicability by trialists.

Introduction: More intensive antiplatelet agents may reduce recurrent stroke risk in minor stroke and TIA, particularly those with non-cardioembolic stroke. The SOCRATES trial showed that ticagrelor was not superior to aspirin in decreasing the risk of stroke, heart attack, or death at 90 days in patients with minor ischemic stroke or TIA. Cilostazol has been shown to have similar effects on platelet reactivity and aggregation to those produced by ticlopidine and aspirin, but may be associated with fewer hemorrhagic side effects. It is also cheaper than ticagrelor; for example, it is approximately half that of ticagrelor, making it a potentially cost-effective antiplatelet agent, especially in low and middle-income countries.

Aim: To evaluate the benefits or hazards of adding cilostazol or ticagrelor to aspirin in patients with minor ischemic stroke or TIA.

Methods: We randomized 900 first-ever, large-vessel occlusion minor ischemic stroke or TIA patients in a one-to-one ratio to receive either a 200 mg loading dose of cilostazol within 24 h after acute stroke symptoms, then 100 mg twice daily until day 90 post-stroke, or a 180 mg loading dose of ticagrelor during the first 24 h, followed by 90 mg twice daily from day 2 to day 90. Both groups received an open-label 300 mg loading dose of aspirin during the first 24 h, then 75 mg once daily. We followed up with our patients for 3 months.

Results: 857 patients completed the 3-month follow-up study 34 (7.6%) patients in the cilostazol group and 29 (6.4%) patients in the ticagrelor group experienced a new stroke (either hemorrhagic or ischemic) (HR 1.37; 95% CI, 0.84-2.26; p-value = 0.21), and 44 (9.8%) patients in the cilostazol group and 40 (8.9%) patients in the ticagrelor group experienced a composite of a new stroke, myocardial infarction (MI), or death due to vascular insults (HR 1.11; 95% CI, 0.64-1.93; p-value = 0.30). Fifteen (3.3%) patients in the cilostazol arm and 30 (6.7%) patients in the ticagrelor arm experienced drug-related hemorrhagic complications (HR 0.32; 95% CI, 0.19-0.68; p-value = 0.01).

Conclusion: Combining cilostazol with aspirin in large-vessel occlusion minor ischemic stroke or TIA was as effective as ticagrelor and aspirin in preventing recurrent stroke, MI, and death due to vascular events, but resulted in significantly lower rates of hemorrhagic complications.