International Journal of Stroke最新文献

Background: The global prevalence of ischemic stroke in young adults is increasing, leading to a significant social impact. Fabry disease is a recognized cause of ischemic stroke in young patients, and although disease-modifying treatments are available, further evidence is needed to confirm their effectiveness in reducing the incidence of ischemic strokes.

Aims: This study aimed to identify undiagnosed Fabry disease in young adult patients with ischemic stroke in a Taiwanese cohort.

Methods: This multicenter, prospective cohort study enrolled patients aged 20-55 years who had experienced an ischemic stroke or transient ischemic attack (TIA) within 10 days, from 1 January 2016 to 31 December 2020. Screening for Fabry disease was performed using a dry blood test to measure α-galactosidase activity in male patients and blood globotriaosylsphingosine (lyso-Gb3) levels in female patients. For patients with positive screen results, genetic diagnosis of Fabry disease was pursued through Sanger sequencing of the GLA gene, covering all exons and a segment of intron 4.

Results: A total of 977 patients (659 male, 68%) were enrolled from seven hospitals across Taiwan. Four patients (0.4%, all male) had positive screening results, and two patients (0.2%) were genetically diagnosed with Fabry disease. Case 1 had the GLA c.658C>T mutation and experienced ischemic stroke in the bilateral occipital regions. Case 2 had the GLA c.640-801G>A mutation and experienced an ischemic stroke in the left superficial watershed area.

Conclusion: The prevalence of undiagnosed Fabry disease in this cohort of Taiwanese young adults with ischemic stroke or TIA was 0.3% among the young male population. Understanding the prevalence of undiagnosed Fabry disease in young adults with ischemic stroke could help shape future Fabry disease screening policies.

Data access statement: The collected data will be available upon reasonable request from the corresponding author.

Background and aims: Physical activity is a key component of secondary stroke prevention. Mobile health (mHealth) interventions show promise for enhancing post-stroke physical activity, but most studies have combined mHealth with onsite services. This study evaluated the feasibility and acceptability of a fully digitalized mHealth intervention for physical activity among individuals post-stroke or transient ischemic attack (TIA) in Sweden.

Methods: In this two-arm feasibility randomized controlled trial, adults with stroke or TIA were randomized to one of the following 6-month interventions: (1) the experiment group, receiving mHealth-delivered supervised exercise (two sessions weekly during months 1 to 3, one session weekly during months 4 to 6) and behavioral change techniques for physical activity (including two individual counseling and six follow-up sessions) or (2) the control group, receiving two mHealth-delivered individual counseling and three follow-up sessions. Feasibility (reach, retention, adherence, fidelity, safety) and acceptability were assessed according to pre-specified progression criteria.

Results: Of 114 participants, 105 (92%) completed the 6-month intervention and 102 (89%) completed the 12-month follow-up assessment. The intervention reached individuals from 20 of 21 Swedish regions. Sixty-eight percent of participants had a stroke (of which 96% were mild), 64% were female, and the average age was 71 years (standard deviation = 9). Ninety-five percent were born in Sweden, had a high level of education (61%), and an average daily step count of 6451 steps. Completion of outcome measures included digital questionnaires (98%), sensor-derived physical activity (92%), and blood pressure monitoring (97%). A total of 1781 supervised exercise sessions were delivered to the experiment group, with an adherence rate of 76%, and adherence to individual counseling and follow-up sessions was 96%. Ninety-five adverse events were recorded, of which 16 were related to the intervention (predominantly pain or muscle soreness) but non-serious. Overall satisfaction with the mobile app was 71%, and 76% of the experiment group believed the app could partly replicate in-person visits.

Conclusion: The mHealth intervention was overall feasible and acceptable; however, there is a need to develop recruitment procedures to increase diversity of included participants regarding socioeconomic status and physical activity level, prior to a phase 3 trial.

Trial registration: ClinicalTrials.gov (NCT05111951).

Background: Secondary stroke prevention in patients with atrial fibrillation (AF) is one of the fastest growing areas in the field of cerebrovascular diseases. This scientific statement from the World Stroke Organization Brain & Heart Task Force provides a critical analysis of the strength of current evidence on this topic, highlights areas of current controversy, identifies knowledge gaps, and proposes priorities for future research.

Methods: We select topics with the highest clinical relevance and perform a systematic search to answer specific practical questions. Based on the strength of available evidence and knowledge gaps, we identify topics that need to be prioritized in future research. For this purpose, we adopt a novel classification of evidence strength based on the availability of publications in which the primary population is patients with recent (<6 months) cerebrovascular events, the primary study endpoint is a recurrent ischemic stroke, and the quality of the studies (e.g. observational versus randomized controlled trial).

Summary: Priority areas include AF screening, molecular biomarkers, AF subtype classification, anticoagulation in device-detected AF, timing of anticoagulation initiation, effective management of breakthrough strokes on existing anticoagulant therapy, the role of left atrial appendage closure, novel approaches, and antithrombotic therapy post-intracranial hemorrhage. Strength of currently available evidence varies across the selected topics, with early anticoagulation being the one showing more consistent data.

Conclusion: Several knowledge gaps persist in most areas related to secondary stroke prevention in AF. Prioritizing research in this field is crucial to advance current knowledge and improve clinical care.

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

Methods: We conducted a multinational, multicenter, propensity score-weighted analysis within the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry. Patients with AIS due to DMVO, treated with MT, were included. We compared outcomes between patients on pre-stroke low-dose aspirin (75-100 mg) and those not on antiplatelet therapy. The primary outcome was functional independence at 90 days (mRS 0-2). Secondary outcomes included excellent functional outcome at 90 days (mRS 0-1), mortality, and day-one post-MT NIHSS score. Safety outcomes focused on hemorrhagic complications, including symptomatic intracerebral hemorrhage (sICH).

Results: Among 1,354 patients, 150 were on pre-stroke low-dose aspirin. After applying Inverse Probability of Treatment Weighting (IPTW), Aspirin use was associated with significantly better functional outcomes (mRS 0-2: OR =1.89 , 95% CI, 1.14 to 3.12 ) and lower 90-day mortality (OR = 0.56, 95% CI, 0.32 to 1.00). The aspirin group had lower NIHSS scores on day one (β = -1.5, 95% CI, -2.8 to - 0.27). The sICH rate was not significantly different between the groups (OR = 0.92, 95% CI, 0.60 to 1.43).

Conclusions: Pre-stroke low-dose aspirin was associated with improved functional outcomes and reduced mortality in patients with DMVO undergoing MT, without a significant increase in sICH. These findings suggest that low-dose aspirin may be safe and associated with more frequent excellent outcomes for this patient population. Further prospective studies are needed to validate these results and assess long-term outcomes.

Background: Falls are common after stroke and can have serious consequences such as hip fracture. Prior research shows around half of individuals will fall within the 12 months post stroke, and these falls are more likely to cause serious injury compared to people without stroke. However, there is limited research on risk factors collected in the immediate post-stroke period that may relate to falls risk. Furthermore, the circumstances and consequences surrounding falls resulting in serious adverse events (serious falls) is underexplored.

Aims: Using longitudinal cohort data from A Very Early Rehabilitation Trial (AVERT), we aimed to describe the occurrence, consequences, and circumstances of serious falls over 12 months post stroke and examine potential risk factors associated with these serious falls.

Methods: Data from participants included in the AVERT trial (n = 2104; recruited from 56 stroke units across five countries) were analyzed. Serious falls were defined as those resulting in death, were life threatening, or required/prolonged hospitalization. Baseline variables included: demographics, pre-morbid function, stroke severity, hemi-neglect, functional independence, and mobility. Statistical analysis included Wilcoxon-Mann-Whitney tests, Fisher's tests, and Firth's logistic regressions (adjusting for age, stroke severity, and AVERT intervention group).

Results: Of the 2104 participants, 85 (4%) experienced at least one serious fall (mean age 78.1 years, 45 male), with 91 individual falls. Fifty-five (60%) serious falls resulted in fracture, with 23 (42%) being hip fractures. Two (2%) falls resulted in death. Serious falls were most common during the day (26 of 38 reported), at home (30 of 63 reported) and while ambulating (22 of 42 reported). More serious falls were experienced by participants who were older, had worse pre-morbid mobility, were unable to walk 10 m independently in the first 24 hours post stroke, or required longer than 14 days to walk 50 m unassisted.

Conclusion: This large international prospective study found 1 in 25 stroke survivors experienced serious falls in the first year after stroke. Fractures were a common outcome of these falls, but the true post-stroke fracture rate is likely to be underestimated due to our study methods, such as the exclusion of individuals with poor pre-morbid mobility and the absence of data on fractures not relating to falls or leading to an inpatient hospital admission. Clear associations between older age, impaired pre- and early post-stroke mobility and heightened risk of serious falls were found. Integrating these factors into post-stroke screening tools could improve identification of individuals at greater risk of serious falls and lead to more focused rehabilitation and injury prevention.

Background: It is acknowledged that penumbra can exist beyond 24 hours after stroke onset.

Aims: The aim of this study was to explore the association between penumbral persistence at 24-72 hours and clinical outcomes in patients who did not achieve major reperfusion.

Methods: Eligible patients participating in the International Stroke Perfusion Imaging Registry with repeated 24-72 hours perfusion imaging were retrospectively included in this study. Persistent penumbra was evaluated as the volume of hypoperfusion lesion on repeated perfusion imaging divided by infarct volume on the follow-up imaging at 24-72 hours post arrival. Short-term clinical outcomes were defined as neurological deterioration at 24-72 hours and modified Rankin Scale (mRS) 0-2 at discharge. Long-term outcome was defined as mRS 0-2 at 3 months. The association between persistent penumbra and clinical outcomes was explored using multivariable-adjusted logistic regression models.

Results: A total number of 203 patients were included in this study. Persistent penumbra was associated with decreased odds of neurological deterioration at 24-72 hours (multivariable-adjusted OR=0.3, 95% CI 0.1-0.8, P=0.01) and increased odds of mRS 0-2 at 3 months (multivariable-adjusted OR=2.7, 95% CI 1.1-6.8, P=0.03). Persistent penumbra was not associated with mRS 0-2 at discharge (multivariable-adjusted OR=2.5, 95% CI 0.4-14.7, P=0.30).

Conclusions: Persistent penumbra in acute stroke patients without major reperfusion was generally associated with a better clinical outcome. This evidence suggested that there were patients with persistent hemodynamic support, for whom major reperfusion might not be pivotal to achieve a good clinical outcome. How to identify these patients and what treatment strategy can be made to stabilize the hemodynamics need future investigation.

Data access statement: Anonymized data not published within this article will be made available at the request of qualified investigators whose proposal of data use has been approved by an independent review committee.

Background: Stroke is a significant cause of morbidity and mortality worldwide, contributing substantially to the global burden of disease. In low- and middle-income countries, stroke tends to occur at younger ages, with infection being one of the notable contributing factors. Previous studies have explored the impact of nontyphoidal Salmonella (NTS) on vascular and blood-related diseases, with animal experiments confirming related mechanisms. This study aims to investigate the association between NTS and cerebrovascular diseases (CVDs), with a focus on identifying specific patient populations more susceptible to stroke due to infection.

Methods: This retrospective cohort study utilized the TriNetX database, including 4708 patients infected with NTS compared with a healthy population, with disease risk tracked over 6 months, 1 year, and lifelong periods. The primary outcome was CVDs (ICD-10-CM: I60-I69), while secondary outcomes examined hemorrhagic stroke (ICD-10-CM: I60-I62) and ischemic stroke (ICD-10-CM: I63). Subgroup analyses were conducted based on gender and age at index, with sensitivity analysis performed by comparing hospitalized patients, utilizing different databases, and evaluating the specificity of the NTS-CVD association by examining patients with a higher risk of acute myocardial infarction (AMI).

Results: The lifelong hazard ratios (HRs) for cerebrovascular diseases (CVD), hemorrhagic stroke, and ischemic stroke following NTS infection were 1.606 (95% confidence interval (CI), 1.410-1.830), 1.866 (95% CI, 1.304-2.669), and 1.717 (95% CI, 1.385-2.130), respectively. A significant increase in the risk of hemorrhagic stroke was observed in the short term and mid-term, with HRs of 3.345 (95% CI, 1.091-10.259) and 2.816 (95% CI, 1.184-6.699), respectively. Subgroup analyses indicated statistically significant associations with the primary outcomes across all age groups. Males demonstrated a higher risk of hemorrhagic stroke, with an HR of 1.891 (95% CI, 1.142-3.310), whereas females exhibited a stronger association with ischemic stroke, with an HR of 1.592 (95% CI, 1.189-2.132). These associations remained significant among hospitalized patients, while no significant relationship was observed between NTS infection and AMI. The findings of this study were reproducible in a US-based database.

Conclusion: There is a significant association between NTS and CVD, with a particularly important impact on the occurrence of stroke in younger populations, especially regarding the elevated risk of hemorrhagic stroke.

Background: The usual antithrombotic treatment for symptomatic intracranial atherosclerotic stenosis (ICAS) consists of dual treatment with clopidogrel and aspirin for 90 days followed by aspirin alone but the risk of recurrent stroke remains high up to 12 months. The Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial was designed to determine whether other combinations of dual antithrombotic therapy are superior to clopidogrel and aspirin.

Methods: CAPTIVA is an ongoing, prospective, double-blinded, three-arm clinical trial at over 100 sites in the United States and Canada that will randomize 1683 high-risk subjects with a symptomatic infarct attributed to 70-99% stenosis of a major intracranial artery to 12 months of treatment with (1) ticagrelor (180 mg loading dose, then 90 mg twice daily), (2) low-dose rivaroxaban (2.5 mg twice daily), or (3) clopidogrel (600 mg loading dose, then 75 mg daily). All subjects receive aspirin (81 mg daily), intensive risk factor management, and will undergo blinded CYP2C19 genotype analysis. The primary goal of the trial is to determine whether rivaroxaban or ticagrelor or both are superior to clopidogrel for lowering the primary endpoint (ischemic stroke, intracerebral hemorrhage (ICH), or vascular death) within 12 months. A prespecified interim safety analysis will be conducted when the first 450 randomized subjects have been followed for 12 months to evaluate the risk of major hemorrhage in the rivaroxaban and ticagrelor arms.

Results: Enrollment began in August 2022 and, as of 26 June 2024, the 450th subject was randomized into the study.

Conclusion: CAPTIVA is evaluating two alternative dual antithrombotic therapies to clopidogrel and aspirin to maximize the chance of establishing more effective antithrombotic therapy for symptomatic ICAS, one of the most common and high-risk cerebrovascular diseases worldwide.

Rationale: The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.

Aims: This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.

Sample size: To detect an estimated 15% difference in the primary outcome between the two groups, a total of 376 patients will be enrolled. This sample size allows for 80% power and a 5% significance level, with an interim analysis planned after half of the sample (188 patients) has completed a 90-day follow-up.

Methods and design: The Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP) trial is a multicenter, prospective, randomized clinical trial using an open-label treatment design with blinded endpoint assessment (PROBE) conducted in China. Patients with acute basilar artery occlusion will be randomly assigned in a 1:1 ratio to receive either intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) or standard care following successful thrombectomy (defined as expanded thrombolysis in cerebral infarction [eTICI] ⩾ 2b50).

Study outcomes: The primary outcome is the modified Rankin Scale (mRS) score of 0-2 at 90 days. Key secondary outcomes include changes in eTICI scores after intra-arterial thrombolysis (in the experimental group), mRS 0-3 at 90 days, ordinal shift analysis of mRS at 90 days, early neurological improvement at 48 h, and improvement in National Institutes of Health Stroke Scale (NIHSS) scores at 48 h and 7 days or discharge. Safety outcomes include symptomatic intracranial hemorrhage (sICH) rates at 48 h, 90-day mortality, non-intracranial hemorrhagic complications, and non-hemorrhagic serious adverse events.

Discussion: The IAT-TOP trial will provide crucial evidence regarding the potential benefits of adjunctive intra-arterial alteplase in patients with AIS-LVO in the posterior circulation following successful thrombectomy.

Trial registration: ClinicalTrials.gov NCT05897554.

Background: Covert brain infarction (CBI) is common and poses a potential and non-negligible burden of disease worldwide. The prevalence and risk factors for CBI have been reported inconsistently in previous studies.

Aims: This study aims to ascertain the prevalence and risk factors of CBI and its imaging phenotypes in community-dwelling adults.

Methods: The study population was derived from the baseline survey of a population-based cohort from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events study, involving adults aged 50-75 years from Lishui City, Southeast China. The 3.0T magnetic resonance imaging (MRI) was performed to access CBI and detect intracranial and extracranial vascular lesions. The prevalence rates of CBI and three imaging phenotypes were stratified separately by age, sex, atherosclerotic burden, and artery stenosis. The intracranial and extracranial atherosclerotic burden was graded by summing atherosclerosis scores. Multivariable logistic regression with a stepwise selection method was used to identify independent CBI risk factors.

Results: A total of 2947 participants (mean age of 61.1 ± 6.6 years, 53.8% women) were included. CBI prevalence among study subjects was 9.6%, and the most common subtype was other chronic infarction (5.6%), followed by cavitatory lesions (4.6%) and acute cerebral infarction (0.5%). In multivariable analysis, older age (odds ratio (OR): 1.59, 95% confidence interval (CI): 1.40-1.83), hypertension (OR: 1.45, 95% CI: 1.08-1.94), higher levels of low-density lipoprotein cholesterol (LDL-C) (OR: 1.17, 95% CI: 1.04-1.32), homocysteine (OR: 1.12, 95% CI: 1.01-1.23) and diastolic blood pressure (DBP) (OR: 1.22, 95% CI: 1.06-1.41), intracranial artery plaque (OR: 1.56, 95% CI: 1.16-2.10), and severe extracranial atherosclerotic burden (OR: 6.57, 95% CI: 1.67-25.79) were associated with a higher CBI odds. There is a linear relationship between age, DBP, LDL-C, and CBI odds, while homocysteine shows a nonlinear relevancy. Age, DBP, homocysteine, and LDL-C elevation increase CBI risk.

Conclusion: CBI prevalence in this Chinese community-based population was not low. Age, hypertension, intracranial artery plaque, extracranial atherosclerotic burden, homocysteine, LDL-C, and DBP were found to be the risk factors of CBI.