International Journal of Stroke最新文献

Background: Management of large cerebellar infarctions with potential malignant evolution is highly heterogeneous across physicians, and recommendations rely on low-evidence studies.

Aim: We aimed to perform a systematic review and meta-analysis on patients with large cerebellar infarction undergoing neurosurgery, to study mortality and functional outcome, according to neurosurgical technique.

Summary of review: We searched on PubMed and Embase according to pre-defined selection criteria and we assessed their quality according to a predefined risk of bias scale. Our primary outcomes were mortality and functional outcome rates. Favorable outcome was defined as a modified Rankin scale of 0-2, a Glasgow Outcome Scale of 4-5, or a Barthel Index > 90%. Pooled rates were obtained using random effect model and heterogeneity was quantified using I² statistics. Among 27 included studies (including 1173 patients), we studied the 662 patients undergoing neurosurgery. All studies were retrospective and observational; there was no randomized clinical trial (RCT). The median selection bias score was 5 (IQR, 4-6). Mortality rate was estimated at 18% [95% CI, 13-24%], I² 58%. Among survivors, 64% achieved a favorable functional outcome [95% CI, 51-77%], I² 82%. Study design and heterogeneity in patients' characteristics limited a meaningful comparison of mortality and functional outcome according to neurosurgical techniques.

Conclusion: High-quality evidence on neurosurgical treatment for large cerebellar infarctions remains limited. Our systematic review and meta-analysis, despite moderate risk of bias, suggest that neurosurgery may reduce mortality and improve functional outcomes. These findings support its potential benefit, but RCTs are needed to confirm effectiveness and evaluate best surgical technique.

Background: The clinical utility of implantable cardiac monitors (ICMs) for atrial fibrillation (AF) detection following cryptogenic stroke or embolic stroke of undetermined source (ESUS) is well established. However, the optimal timing for ICM implantation to maximize diagnostic yield remains uncertain.

Aims: To systematically review the literature and conduct a meta-analysis to determine whether earlier ICM implantation after cryptogenic stroke or ESUS ischemic stroke improves detection rates and reduces the time to AF diagnosis.

Summary of review: A comprehensive search of PubMed, Embase, and Cochrane CENTRAL was conducted from inception to June 2025, without language restrictions. References of retrieved articles and relevant reviews were manually searched. We included observational studies or randomized trials reporting ICM use in patients with ESUS or cryptogenic stroke/transient ischemic attack (TIA), providing data on AF detection rates and/or timing metrics (stroke-to-ICM interval, ICM-to-AF interval). Two reviewers independently screened studies and extracted data. Disagreements were resolved by consensus or third-party adjudication. Data were extracted following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Study-level AF detection rates were modeled using logit-transformed proportions and pooled using random-effects models (REML). Mixed-effects meta-regressions assessed the effect of timing (stroke-to-ICM interval) on AF detection and diagnostic delay, adjusting for ICM monitoring duration. The primary outcomes were pooled AF detection rate and mean time from ICM implantation to AF diagnosis. Timing of implantation was assessed as a continuous and categorical (early, intermediate, delayed) variable. Forty-seven studies (N = 6918 patients) were included. The pooled AF detection rate was 27.3% (95% CI: 24.6-30.2), with substantial heterogeneity (I² = 80.8%). Early ICM implantation (<31.5 days from index event) was associated with a higher AF detection rate compared with delayed implantation (30.0% vs 23.7%; p = 0.0017), independent of monitoring duration. Stratified meta-regression confirmed that delayed implantation was associated with lower AF detection even after adjusting for ICM duration. For each additional day of delay in ICM implantation, the time from AF diagnosis increased by an additional 0.32 days on average, even after accounting for monitoring duration (p = 0.0007).

Conclusion: These findings suggest that earlier ICM implantation enhances AF detection after ESUS or cryptogenic stroke and shortens diagnostic delay. Optimizing timing of post-stroke monitoring may improve patient selection for anticoagulation and reduce recurrent stroke risk.CRD 420251064227.

Background: Decreased cardiorespiratory fitness (CRF) is prevalent in stroke patients, and aerobic training can improve CRF in this population. Protein supplementation has been proposed as a strategy to enhance exercise adaptations by promoting muscle protein synthesis, reducing muscle loss, and improving physical function. However, the potential of protein supplementation to further improve CRF during aerobic training among stroke patients remains unclear. This study aims to evaluate the effect of protein supplementation on CRF and physical performance in patients with chronic stroke undergoing aerobic training.

Methods: This multicenter, participant- and assessor-blinded, randomized clinical trial enrolled 114 ambulatory adults with chronic stroke at four teaching hospitals. Participants were randomized to receive protein supplementation (n = 58) or an isocaloric carbohydrate placebo (n = 56) during 30 supervised aerobic training sessions over 10 weeks. The primary outcome was the change in peak oxygen consumption (V̇O₂peak, mL/kg/min) at 11 weeks. Secondary outcomes included CRF-related measures, body composition (total lean and fat mass), and physical performance (Short Physical Performance Battery (SPPB), Physical Performance Test, Berg Balance Scale, and Timed Up-and-Go test).

Results: Participants had a mean age of 57.2 years, 30% were women, and 87% completed the primary outcome assessment. At the 11-week follow-up, V̇O₂peak increased by 1.7 mL/kg/min (95% CI: 1.0-2.4) in the protein group and 1.6 mL/kg/min (95% CI: 0.9-2.3) in the placebo group, with no between-group difference (mean difference, 0.1 mL/kg/min; 95% CI: -0.8 to 1.1; p = 0.43). Both groups showed improvements in most CRF-related and physical performance measures. At 20 weeks, the protein group demonstrated greater SPPB improvement (mean difference, 0.7 points; 95% CI: 0.1-1.3; p = 0.03) and lower fat mass at 11 weeks (mean difference, -0.6 kg; 95% CI: -1.2 to -0.06; p = 0.04).

Conclusions: Protein supplementation during aerobic training did not significantly enhance CRF compared with an isocaloric placebo. These findings warrant further investigation in populations with a broader range of baseline protein intake.

Background: The optimal timing for initiating antihypertensive therapy after acute ischemic stroke (AIS), particularly regarding cognitive outcomes, remains uncertain. This study investigated the association between treatment timing and 3-month cognitive function.

Methods: This prespecified analysis of the China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) included patients completing 3-month Montreal Cognitive Assessment (MoCA). Participants were randomized to early (immediate) or delayed (day 8) antihypertensive treatment, with MoCA score as primary outcome.

Results: A total of 1682 patients completed the cognitive assessment; 823 received early antihypertensive treatment and 859 received delayed treatment. Baseline characteristics were comparable between the two groups. The median MoCA score was 23 in both groups (β, -0.06; 95% CI, -0.16 to 0.03; P = .19). In addition, the proportion of individuals with MoCA scores < 25 was similar between the two groups (62% vs 59%; OR, 1.15; 95% CI, 0.95 to 1.40; P = 0.16). Exploratory subgroup analyses suggested a potential interaction by prior antihypertensive use, whereby early antihypertensive treatment was associated with worse cognitive outcomes in patients with prior antihypertensive use (OR, 1.34; 95% CI, 1.01-1.77; p = 0.03; P for interaction = 0.04).

Conclusions: Early antihypertensive initiation did not improve 3-month cognitive outcomes in AIS patients, highlighting the importance of individualized therapy, especially for high-risk PSCI subgroups.

Background: The value of intravenous thrombolysis (IVT) prior to endovascular therapy (EVT) with emergent stenting for intracranial atherosclerotic disease (ICAD)-large vessel occlusion (LVO) is unknown. We aimed to investigate the safety and efficacy of IVT among patients with adjuvant intracranial stenting after EVT.

Methods: RESISTANT is a study of consecutive acute ischemic stroke patients who underwent EVT and intracranial stenting from 36 comprehensive stroke centers in 7 countries across 3 continents. The primary outcome of interest was ordinal shift of the modified Rankin Scale (mRS) score at 90 days after the intervention. Secondary outcomes were excellent outcome (mRS 0-1) and functional independence (mRS 0-2) at 90 days. Safety outcomes were rates of symptomatic intracranial hemorrhage (sICH) at 24-hour and 90-day mortality. Adjusted multivariate ordinal and logistic regressions were performed for all outcomes.

Results: Of 828 patients (median age 67 years, interquartile range (IQR) 59-77; 65% male), 23% have received IVT. In the adjusted analysis, receiving IVT was not associated with mRS ordinal shift (aOR 0.8, 95% CI 0.6 -1.1), nor with functional independence (aOR 1.1, 95% 0.7-1.7). However, there was a positive association with excellent outcome (aOR 1.6, 95% CI 1.0-2.7). There were no differences in sICH rates at 24-h (aOR 1.5, 95% CI 0.8-2.9), nor 90-day mortality (aOR 0.8, 95% 0.5-1.3).

Conclusion: In this multi-center study of patients who underwent EVT with emergent intracranial stenting, IVT was associated with excellent clinical outcome, possibly due to indication bias, and there were no safety concerns. Receiving IVT should not be a criterion for deferring acute stenting among patients with ICAD-associated LVO and IVT should not be routinely withheld in suspected ICAD cases.

Background: Socioeconomic status (SES), often measured by education, income, occupation, or area-level deprivation, impacts stroke incidence and outcomes, yet the underlying mechanisms remain unclear. This review synthesizes causal analyses quantifying drivers of these inequalities.

Methods: We conducted a systematic review (PROSPERO CRD42024554285) and reported following the PRISMA-2020 guidelines. Observational studies applying causal mediation analysis between SES and stroke risk, disability, or mortality were included from PubMed, Embase, Scopus, and Google Scholar. SES indicators, outcomes, mediators, and decompositions into natural direct effect (NDE) and natural indirect effect (NIE) were extracted. Risk of bias and certainty of evidence were assessed using ROBINS-E and GRADE. A narrative synthesis was undertaken, and findings were illustrated in causal diagrams.

Results: Of 12,034 records, 19 studies (15 in high-income countries) were included. Lower SES increased stroke incidence through hypertension (NIE 14-21% of the total effect, moderate certainty), although one study restricted to women reported smaller effects (2-4%). Smoking (6-19.9%, very low certainty). At 3 months post-stroke, the combined outcome of death or disability was higher due to severe strokes (38.5% for ischemic, 57-94% for hemorrhagic, moderate certainty). One study found that hypertension, atrial fibrillation, and smoking together mediated 28.5% of the SES effect on stroke severity (low certainty). Reduced access to thrombolysis and stroke units mediated 2.7% of 3-month disability/mortality (very low certainty), while greater distance to specialized centers explained 48% of inequalities in thrombectomy access (low certainty). Long-term mortality (⩾6 months) was mediated by comorbidities (18%) and healthcare coverage (24-55%), both with low certainty.

Conclusions: Hypertension, smoking, and differential stroke severity at presentation are the main pathways through which low SES increases stroke risk and causes worse outcomes. Targeting these may reduce inequalities, though evidence from low-income settings and emerging mediators (e.g. early-life SES, environmental exposures, care quality) is lacking.

Background: Timely identification of stroke etiology is crucial in managing large vessel occlusion (LVO) strokes. However, a substantial proportion remains cryptogenic despite comprehensive workup, raising concern about underdiagnosed cardioembolic sources. This study assessed the diagnostic contribution of early combined brain-cardiac CT imaging in patients with LVO stroke and explored imaging markers associated with each etiological subtype.

Methods: A total of 252 consecutive patients admitted for LVO stroke who underwent standardized acute-phase brain and cardiac CT imaging were included. Patients were classified as atheromatous, cardioembolic, or cryptogenic LVO stroke before and after consideration of cardiac CT results. Clinical and imaging characteristics of patients were compared according to final causes of stroke.

Results: Cardiac CT led to etiological reclassification in 8 patients (3.2%), including 7 cryptogenic cases upgraded to cardioembolic due to detection of intracardiac thrombi in the absence of atrial fibrillation. Patients with cardioembolic LVO stroke (n = 137, 54%) were older, more frequently women, and had higher left atrial surface areas and volumes compared to atheromatous (n = 40, 16%) and cryptogenic cases (n = 75, 30%). Epicardial adipose tissue volume was highest in atheromatous strokes, while cryptogenic cases lacked markers of atrial cardiomyopathy. At follow-up, mortality was highest in the cardioembolic group.

Conclusion: Early brain-cardiac CT imaging enhances etiological classification in LVO strokes by identifying intracardiac thrombi and other cardioembolic markers missed by standard workup. A substantial subset of cryptogenic LVO strokes may represent a distinct pathophysiological entity. Broader adoption of cardiac CT could inform targeted stroke prevention strategies.

Background: Atrial fibrillation (AF) detected after stroke or transient ischemic attack (AFDAS) is a critical but often underdiagnosed condition with implications for secondary stroke prevention. This distinctive type of AF is increasingly studied to provide a more comprehensive understanding of its complex pathophysiology, which may involve both cardiogenic mechanisms and stroke-induced autonomic dysfunction, a concept known as the neurogenic hypothesis. This study aims to identify the prevalence and predictors of AFDAS to help refine monitoring strategies and improve patient outcomes.

Methods: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We included English-language retrospective and prospective cohort studies published from January 1999 to January 2025, analyzing data from 91 studies for prevalence and 54 studies for predictors. We categorized AF detection by different monitoring methods, including electrocardiogram (ECG), Holter monitoring, external loop recorders, and implantable cardiac monitors (ICM). Predictors were grouped into demographic, cardiogenic, neurogenic, and laboratory factors.

Results: The overall prevalence of AFDAS varied significantly based on monitoring technique. The pooled prevalence was 7% (95% CI 4.6-10.5) by emergency room ECG, 12.7% (95% CI 9-17.8) by inpatient ECG, 11.9% (95% CI 7.8-17.9) by continuous ECG monitoring, 11.5% (95% CI 8-16.1) by external loop recording, 5.1% (95% CI 2.6-9.7) by Holter monitor, 21.3% (95% CI 18.3-24.7) by ICM, and 17.2% (95% CI 10-28.1) by multiple monitoring methods. Key predictors of AFDAS included older age, female sex, hypertension, chronic kidney disease, left atrial enlargement, advanced interatrial block, and higher NIHSS scores. Insular involvement and major strokes were strongly associated with AF detection, supporting the neurogenic hypothesis. Elevated N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and B-type Natriuretic Peptide (BNP) levels were also linked to a higher AF risk.

Conclusion: AFDAS is a frequent but variably detected condition, with its prevalence strongly dependent on monitoring duration and modality. Identifying high-risk patients using a combination of clinical, cardiogenic, neurogenic, and laboratory markers can optimize screening strategies and early anticoagulation initiation, potentially reducing stroke recurrence. Future research should focus on refining risk scores integrating neurogenic and cardiogenic markers to guide personalized monitoring approaches and to define the distinct characteristics of AFDAS from known atrial fibrillation (KAF).

Background: Rinvecalinase alfa (DM199), a recombinant form of human tissue kallikrein-1 (KLK1), aims to promote local vasodilation to ischemic brain and enhance collateral blood flow. The ReMEDy1 trial tested the safety and tolerability of rinvecalinase alfa in ischemic stroke.

Methods: ReMEDy1 was a phase II, randomized, double-blind, placebo-controlled, study conducted at 13 Australian sites. Ninety-two patients with NIH Stroke Scale (NIHSS) 6-25 were enrolled within 24 h of ischemic stroke onset. Patients were randomized 1:1 to receive rinvecalinase alfa (1 µg/kg intravenous infusion followed by 3 µg/kg subcutaneously every 3 days for 22 days) or placebo. The primary outcome was safety, assessed by adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes included changes in NIHSS, modified Rankin Scale (mRS), and Barthel Index (BI) at Days 22 and 90. Post hoc analyses excluded patients who underwent endovascular therapy (EVT).

Results: The median age was 72, NIHSS 10, and onset-to-randomization was 19.5 h. SAEs were reported in 20/47 (43.5%) rinvecalinase alfa patients and 14/45 (31.1%) placebo patients. Most patients experienced at least one AE; the most common in the rinvecalinase alfa group were constipation (60.9%), oral candidiasis (23.9%), and nausea (17.4%). Stroke-in-evolution by Day 90 occurred in 0 (0%) rinvecalinase alfa patients versus 6 (13.3%) placebo patients; 4/6 (66.7%) placebo patients with stroke-in-evolution died. No significant differences were observed in secondary efficacy outcomes at Day 90. Post hoc analyses in patients not treated with EVT suggested a tendency toward improved excellent global outcomes with rinvecalinase alfa.

Conclusions: Rinvecalinase alfa appeared to be safe and generally well-tolerated in ischemic stroke patients, with potential efficacy in reducing stroke progression. Further studies are needed to confirm efficacy and long-term benefits in patients without EVT.

Registrations: https://www.

Clinicaltrials: gov/study/NCT03290560.

Background: This study aims to evaluate the efficacy and safety of dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT) for patients with a first-ever embolic stroke of undetermined source (ESUS).

Methods: We assembled a multicenter cohort and a propensity score-matched (PSM) subset to compare DAPT with SAPT. The primary outcome was a composite of recurrent ischemic stroke, myocardial infarction, or all-cause death, and the safety outcome was major bleeding. Follow-up extended to 3 years (median, 2.6 years). We used Cox proportional hazards models to complement time-stratified (piecewise) analyses and restricted mean survival time (RMST).

Results: In the total cohort (n = 1675), DAPT was associated with a lower hazard of the composite outcome (adjusted hazard ratio (HR) = 0.56, 95% confidence interval (CI) = 0.44-0.70). Stroke recurrence and mortality were likewise reduced, while myocardial infarction events were infrequent. There was no significant difference in major bleeding between groups (e.g. incidence-rate ratio ≈1.0; p > 0.05). The annual incidence rate for the composite was 5.5%/year with DAPT versus 10.1%/year with SAPT. Time-stratified analyses revealed that the ischemic benefit was most pronounced between 6 and 12 months and appeared to persist thereafter. Bleeding, however, showed only a numerical increase beyond 1 year without statistical significance. RMST differences favored DAPT from 1 year onward and increased over 1000 days.

Conclusion: In this ESUS cohort, DAPT was associated with fewer ischemic events and no increased major bleeding. The benefit was most evident at 6-12 months and was sustained over a longer follow-up period.