Stroke最新文献

Background: Up to 15% of strokes occur in young adults, with more cryptogenic cases, raising the possibility of rare causes, such as genetic diseases. Although available in everyday practice, genetic analyses are usually reserved for patients with evocative personal or family history. We aimed to assess the interest of systematic genetic analyses in young adults with cryptogenic stroke and estimate the true frequency of genetic disorders in such patients.

Methods: We conducted a retrospective observational cohort study with additional prospective genetic testing. We screened all patients under 50 admitted to Dijon University Hospital stroke unit between 2018 and 2021. Those already genetically tested during etiological work-up were included in a first cohort (cohort 1). Among the remaining patients, those with unexplained intracerebral hemorrhage or stroke (ie, cryptogenic stroke), or a stroke subtype known to have monogenic forms, were offered exome sequencing to form cohort 2. Monogenic diagnoses were defined by likely pathogenic/pathogenic variants according to American College of Medical Genetics and Genomics criteria.

Results: Among 305 patients with stroke screened, 24 had prior genetic testing (cohort 1) with exome sequencing, genome sequencing, gene panels or targeted gene analyses, leading to a molecular diagnosis in 8 (33%). Of the remaining 281 patients, 71 met eligibility criteria and 35 consented to the study (cohort 2). Exome sequencing identified pathogenic variants in 4 of them (11%). The overall diagnostic yield of genetic tests was 20.3% (12/59 patients tested across both cohorts). In total, monogenic causes explained 3.9% (12/305) of all young stroke cases. Notably, most diagnosed patients (66%) had no family history of stroke. Genetic cardiopathies and conditions conferring increased cardiovascular risk factors accounted for 50% of diagnoses.

Conclusions: Genetic analyses should be considered in all unexplained strokes or in stroke subtypes with known genetic forms (eg, moyamoya syndrome, cardiopathy, small vessel disease), even without an evocative family history.

Background: Decompressive craniectomy (DC) seemed to reduce the risk of death or profound disability (modified Rankin Scale score, 5-6) after deep intracerebral hemorrhage (ICH) by an absolute 13% (95% CI, 0%-26%) in the SWITCH trial (Swiss Trial of Decompressive Craniectomy versus Best Medical Treatment of Spontaneous Supratentorial Intracerebral Hemorrhage). Whether the effect of DC differs by ICH location is unknown.

Methods: Post hoc analysis of participants with supratentorial severe deep ICH from the intention-to-treat population of the SWITCH randomized controlled trial. We categorized ICH as involving (1) the basal ganglia (BG) alone, (2) BG and the posterior limb of the internal capsule (PLIC), or (3) BG, PLIC, and thalamus. We examined the interaction between ICH location and DC's effect on primary (modified Rankin Scale score, 5-6) and secondary outcomes (death; full modified Rankin Scale score range) at 180 days using unadjusted and adjusted logistic or survival models.

Results: Of 197 participants comprising the trial's intention-to-treat population, 184 were available for analysis (median age, 61 years; 59 women; 91 randomized to DC plus best medical treatment; and 93 to best medical treatment). ICH involved BG alone in 26 (14%), BG+PLIC in 94 (51%), and BG+PLIC+thalamus in 64 participants (35%). The marginal risk of the primary outcome after adjustment for age, ICH severity, and volume was lower with DC by 15.6% (95% CI, -49.2% to 18.1%) in participants with ICH of BG alone, by 11.4% (-29.3% to 6.6%) in those with ICH of BG+PLIC, and by 9% (-31% to 12.9%) in those with ICH of BG+PLIC+thalamus, without evidence for treatment-by-location interaction (P=0.95). Secondary outcome analyses yielded consistent results.

Conclusions: The potential benefits of DC seemed preserved regardless of the location of severe deep ICH.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02258919.

Background: Depression is common after stroke and is associated with increased mortality. However, there are few data on the prevalence, predictors, or prognosis of depression after transient ischemic attack (TIA). Although poststroke depression is often assumed to be due to the brain lesion or disability, patients with TIA may also be susceptible due to shared risk factors, lifestyle/medication changes, or worries about stroke.

Methods: The prevalence of depression 1 and 12 months after TIA was assessed in a population-based cohort (OXVASC [Oxford Vascular Study]) from 2014 to 2020. Depression was related to risk factors (including infarction on brain imaging) in a multivariable logistic regression model and outcome (disability, quality of life, institutionalization, recurrent events, and mortality) in a Cox proportional hazard regression model during 5-year follow-up after adjustment for covariates that were found to be significant (P<0.1) in the age-/sex-adjusted models.

Results: Of 519 patients (mean age, 70.5 [13.1]; female, 51.1%), 126 (24.3%) had depression after TIA, with a higher rate at 1 versus 12 months (99/20.7% versus 66/14.9%; P=0.022). Depression was independently associated with younger age (adjusted odds ratio/decade, 0.74 [95% CI, 0.60-0.90]), low baseline mood (4.06 [95% CI, 2.31-7.15]), past depression (1.81 [95% CI, 1.09-3.03]), multimorbidity (1.19 [95% CI, 1.02-1.39]), living alone (1.94 [95% CI, 1.14-3.32]), disability (3.53 [95% CI, 1.89-6.59]), and deprivation (1.28 [95% CI, 1.03-1.59]). After adjustment for confounders, depression did not predict risk of recurrent vascular events (adjusted hazard ratio [aHR], 1.42 [95% CI, 0.76-2.64]; P=0.27) but did predict increased 5-year all-cause mortality (aHR, 2.27 [95% CI, 1.21-4.27]; P=0.011), independently of acute lesions on brain imaging (aHR, 2.18 [95% CI, 1.09-4.34]; P=0.027), and particularly when persistent (present at 1- and 12-month follow-up; aHR, 4.58 [95% CI, 2.07-10.13]; P<0.001). Persistent depression was also independently associated with disability (adjusted odds ratio, 12.10 [95% CI, 6.18-23.7]; P<0.001) and institutionalization (aHR, 5.83 [95% CI, 1.84-18.50]; P=0.003) within 5 years and with reduced quality of life (coefficient, -0.245; P<0.001).

Conclusions: Depression is common early after TIA, independent of acute ischemia on brain imaging, and persistent depression is also strongly associated with adverse outcomes.

Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials. mpRCTs offer advantages such as increased sample sizes, robust statistical design, incorporation of heterogeneity, and standardized protocols, but they face challenges in finding the right balance between standardization and heterogeneity, appropriate stroke model selection, and outcome measures, as well as the implementation of complex network infrastructure. We discuss the importance of rigorous study design, including appropriate stroke models, representation of biological variables and comorbidities, functional outcome readouts, and handling of attrition and mortality. Statistical considerations such as adaptive sequential designs, covariate adjustments, and appropriate handling of missing data are also addressed. The integration of machine learning, the implementation of common data elements, and the selection of appropriate therapeutic candidates are crucial for maximizing the efficiency and utility of mpRCTs. Furthermore, the transition toward mpRCT platforms, akin to clinical trial platforms, holds promise for facilitating continuous evaluation of therapies. Finally, we discuss data-sharing practices and the collateral benefits of mpRCTs, emphasizing their potential to improve preclinical stroke research and bridge the translational gap. Altogether, we hope that this article will serve as a starting point for a lasting debate on the future of stroke mpRCTs and their evolution toward a universally accepted set of principles.

Background: Following an acute ischemic stroke, the risk of recurrent stroke is highest in the first 90 days. It is unclear whether this risk is altered by reperfusion therapy. In this meta-analysis, we aim to evaluate the risk of early recurrent stroke and other nonstroke thrombotic events postreperfusion therapy in acute ischemic stroke.

Methods: In this meta-analysis, randomized controlled trials (RCTs) were included in adults aged 18 years or older with acute ischemic stroke, comparing reperfusion treatment with best medical management (MED). We searched PUBMED, Embase, Cochrane Library, and Web of Science databases. The studies were grouped into endovascular thrombectomy (EVT) versus MED and intravenous thrombolysis versus MED. We performed a meta-analysis using a random-effects model (restricted maximum likelihood) to estimate the log risk ratio (RR) of early recurrent stroke and nonstroke thrombotic events (NSTE)-including myocardial infarction, acute coronary syndrome, deep vein thrombosis, pulmonary embolism, and peripheral embolism-after reperfusion therapy compared with MED at 90 days after symptom onset. This study is registered with PROSPERO (The International Prospective Register of Systematic Reviews).

Results: A total of 15 RCTs (n=4898) comparing EVT versus MED observed no difference in early recurrent stroke (5.5%, 143/2618 versus 4.5%, 102/2280; RR, 1.2 [95% CI, 0.9-1.6]). Nine RCTs (n=7193) comparing intravenous thrombolysis versus MED observed no difference in early recurrent stroke (2%, 73/3615 versus 1.8%, 66/3578; RR, 1.1 [95% CI, 0.8-1.5]). Fourteen RCTs (n=4033) comparing EVT versus MED reported NSTE. There was no difference in NSTE in the EVT arm (3.1%, 62/2024 versus 3.1%, 62/2009; RR, 1 [95% CI, 0.7-1.4]). Five RCTs (n=4961) comparing intravenous thrombolysis versus MED observed no difference in NSTE (2%, 51/2479 versus 2.2%, 54/2482; RR, 0.9 [95% CI, 0.6-1.4]).

Conclusions: Reperfusion therapies (EVT±intravenous thrombolysis) in acute ischemic stroke within 24 hours of symptom onset were not associated with increased recurrent stroke or NSTE within 90 days compared with best medical therapy.

Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42024542020.

Background: Equipoise persists whether patients with stroke with carotid tandem lesions undergoing endovascular treatment (EVT) should undergo acute carotid stenting, and whether intravenous thrombolysis (IVT) before EVT should influence this decision. We assessed functional and safety outcomes of acute carotid stenting in patients with carotid tandem lesions randomized to IVT plus EVT or EVT alone.

Methods: Individual participant data meta-analysis of 6 randomized clinical trials conducted in Asia, Europe, and Oceania between 2017 and 2021 investigating IVT plus EVT versus EVT alone in patients with carotid tandem lesions presenting directly to EVT-capable centers. The primary outcome was the 90-day modified Rankin Scale score, assessed with mixed-effect ordinal regression models. Safety outcomes were any intracranial hemorrhage and symptomatic intracranial hemorrhage. A secondary analysis used inverse probability of treatment weighting. Treatment effect heterogeneity between IVT plus EVT and EVT alone was assessed in a 2-step meta-analysis.

Results: Overall, 340 of 2267 (15%) patients had carotid tandem lesions with 113 of 329 (34%) undergoing acute carotid stenting. Stenting was associated with better 90-day functional outcomes (adjusted common odds ratio, 1.60 [95% CI, 1.03-2.47]), confirmed in inverse probability of treatment weighting analysis (adjusted common odds ratio, 1.66 [95% CI, 1.08-2.54]). Patients undergoing stenting had no statistically significant higher rates of any intracranial hemorrhage (44% versus 35%; adjusted odds ratio, 1.30 [95% CI, 0.79-2.15]) and symptomatic intracranial hemorrhage (6.3% versus 3.7%; adjusted odds ratio, 2.09 [95% CI, 0.78-5.59]). No heterogeneity in treatment effect was observed in patients randomized to IVT plus EVT (adjusted common odds ratio, 2.07 [95% CI, 1.06-4.07]) or EVT alone (1.21 [95% CI, 0.59-2.50]; P interaction=0.81).

Conclusions: In this international individual participant data meta-analysis of patients with carotid tandem lesions randomized to EVT alone or IVT followed by EVT, acute carotid stenting during EVT was associated with better functional outcomes, and this association was not modified by prior treatment with IVT.

Intracerebral hemorrhage (ICH) is one of the leading causes of death and disability worldwide, and the limited number of proven treatments is a critical area of medical concern. Although tremendous advances have been made in our knowledge of the patterns, risk factors, prognosis, management, and prevention, there has been limited success in defining therapeutic strategies and care remains fragmented and haphazard. The establishment of targeted, timely, and comprehensive management for patients with ICH is an urgent and critical priority. This consensus statement proposes an integrated ICH care pathway across stroke service levels, embedding ICH-specific protocols, time targets, and structured follow-up within existing stroke systems to ensure timely, evidence-based, and comprehensive management. The integrated ICH care pathway is designed to optimize ICH management across multiple dimensions, facilitate rapid decision-making and the initiation of treatments that span emergency medical services, emergency departments, and inpatient units, and extend through discharge and follow-up. The primary objective is to reduce delays and reinforce seamless collaboration between services to ensure all patients receive optimal care. By integrating evidence-based protocols for acute management, secondary prevention, rehabilitation, and follow-up, the integrated ICH care pathway aims to improve outcomes from ICH and foster a standardized multidisciplinary care framework with the goal of alleviating the clinical burden and socioeconomic impact of ICH.

Background: Inpatient rehabilitation plays a pivotal role in the stroke recovery continuum. We have previously shown how rehabilitation clinical guidelines and health care design guidelines may not fully align to support recovery needs. Building on our previous work describing the current stroke inpatient rehabilitation service, we aimed to articulate and propose recommendations for an optimal inpatient service through the integration of stakeholder feedback, clinical guidelines, and health care design principles.

Methods: We used value-focused thinking, living-lab, and codesign principles to evaluate a re-imagined stroke rehabilitation service. Participants reviewed 21 care process activity blocks derived from our previous work, with proposed changes to the admission, discharge processes, and weekday routines (morning, afternoon, and evening) of a typical Australian inpatient stroke service. Participants used an agreement scale to rate the proposed changes against predefined objectives focusing on safety, efficiency, emotional well-being, and opportunities for practice, rest, and autonomy. The reimagined stroke service was reviewed and iteratively refined through further validation sessions with selected participants.

Results: Twenty-six stakeholders participated in our evaluation, including stroke survivors, caregivers, clinicians, researchers, and health care facility designers and planners. Nineteen activity blocks were rated, generating 152 individual votes and 15 recommendations for service improvement. Overall, the agreement rate across all proposed changes was 76%. The highest agreement was observed in the evening (100%) and admission (81%) blocks, with strong endorsement for improved information delivery and environmental flexibility. Lower agreement was noted for discharge (61%), reflecting the complexity and varied perspectives on transition planning. Validation with 7 participants confirmed the relevance and feasibility of most proposed changes, especially those that support personalization, autonomy, and early engagement.

Conclusions: Stakeholder-informed redesign of stroke rehabilitation services can enhance alignment between clinical processes and environmental enablers. These findings offer a practical foundation for codesigned models of care that are both evidence-based and experientially grounded.