Stroke最新文献

Background: The neurorestorative potential of HUK (human urinary kallidinogenase) has drawn considerable clinical attention. Our study aimed to explore the therapeutic efficacy of HUK in patients with acute ischemic stroke.

Methods: Our data were retrospectively extracted from CASTOR (Chinese Acute Ischemic Stroke Treatment Outcome Registry), a prospective, multicenter study from 2015 to 2019 in China. The data was separated into 2 categories, the mild group (0-5 points) and the moderate group (6-25 points), according to the National Institutes of Health Stroke Scale score measured at admission and analyzed by propensity score matching with HUK or non-HUK ratio of 1:1. The percentage of patients with modified Rankin Scale score ≤1 at 3 months after onset was the primary outcome.

Results: Ten thousand two patients were recruited, after the criteria were filtered, 9005 patients were investigated. Following propensity score matching, a total of 6530 patients were ultimately enrolled in the analysis, consisting of 4284 patients in the mild group and 2246 patients in the moderate group. In the mild group, the mean age was 63.5±11.7 years, and females accounted for 31.91%. In the moderate group, the mean age was 64.7±10.9 years, and females occupied a proportion of 36.78%. At the 3-month follow-up, a significantly higher proportion of HUK-treated patients achieved the primary outcome compared with controls in both mild (76.89% [1647/2142] versus 74.13% [1588/2142]; P=0.0013) and moderate (43.10% [484/1123] versus 38.02% [427/1123]; P=0.03) groups.

Conclusions: HUK therapy has potential efficacy in improving the prognosis of patients with both mild and moderate severity of acute ischemic stroke. Nevertheless, additional rigorously designed randomized controlled trials are essential to substantiate these findings.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02470624.

Background: Spinal arteriovenous metameric syndrome (SAMS) is a rare form of spinal cord arteriovenous malformations with a metameric distribution affecting the spinal cord and related structures derived from the same embryological segment. Its natural history and impact on clinical outcomes, compared with nonmetameric spinal cord arteriovenous malformations, remain unclear.

Methods: This retrospective, single-center study included 253 patients with intradural spinal cord arteriovenous malformations between 2002 and 2024, that have either not been considered for embolization or followed up during the period before embolization. This study aimed to evaluate the natural history of SAMS and identify the risk factors for clinical worsening, hemorrhagic events, and angiographic worsening during observation. A stratified log-rank test and Cox proportional hazards model were used to estimate hazard ratios (HRs) and 95% CI.

Results: In the overall population, the median age of onset was 24 years, females accounted for 130 patients (51.3%), and the median observational period was 19 months. This cohort included 71 patients with SAMS and 182 without SAMS. The 10-year cumulative rates of clinical worsening were 27.0% in the metameric and 18.0% in the nonmetameric group. The risk of clinical worsening and hemorrhagic events did not show statistically significant differences between the 2 groups (HR, 1.71 [95% CI, 0.83-3.54]; P=0.137 and HR, 1.65 [95% CI, 0.75-3.61]; P=0.199). The metameric group with hemorrhagic onset had the highest risk of experiencing hemorrhagic events compared with the nonmetameric group without hemorrhagic onset (HR, 4.87 [95% CI, 1.35-17.53]; P=0.015). The metameric group exhibited significantly higher rates of angiographic worsening compared with the nonmetameric group (HR, 11.37 [95% CI, 1.32-97.78]; P=0.005). The presence of nonspinal cord-associated metameric lesions did not significantly affect the natural history of SAMS.

Conclusions: SAMS had higher angiographic worsening than non-SAMS. Hemorrhagic onset in SAMS was an independent predictor of rebleeding during observation, without any influence of nonspinal cord-associated metameric lesions. Close radiological follow-up and early intervention, particularly for hemorrhagic-onset cases, may be necessary to improve outcomes.

This article describes the remarkable progress over the past 50 years in acute stroke therapy, stroke prevention, and, to a lesser extent, stroke recovery, and forecasts advances in stroke care for 2050. Stroke has gone from an untreatable and unpreventable disease to a disease with effective medical and interventional treatments for acute ischemic and hemorrhagic stroke, many new medical, surgical, and interventional treatments for primary and secondary stroke prevention, and the beginnings of a revolution in our understanding of the neural code that portends a great future for stroke recovery. Progress in management of stroke risk factors has been mixed, with a major increase in obesity but a decrease in the prevalence of smoking, as well as better control of hypertension and hyperlipidemia in the United States and other high-income countries. The incidence rate of stroke in the US population studies has decreased, but with recent increases in younger segments of the population. Because age remains the most important risk factor for stroke, the burden of stroke is likely to continue to increase as the population ages. In 2050, we will use artificial intelligence to pull clinical trial data from multiple trials in the context of a patient's demographics, medical history, and biometric, imaging, and laboratory data to recommend the best treatment for that patient-true precision medicine. Making these precision treatments in the hospital, clinic, and home settings available to everyone, regardless of geographic, social, and economic situation, is one of our challenges of the next century. As we make greater progress in stroke prevention, acute treatment, and stroke recovery, we will need larger trials and more efficient trial designs. Large trials will require global efforts. The last 50 years have been about advances in stroke prevention and acute treatment. The next century will be about advances in recovery and rehabilitation after stroke and addressing current global disparities in access to proven therapies. Until we can mitigate mechanisms associated with aging, stroke will remain common and a tremendous societal and financial burden. We have made a significant dent in this burden over the past 50 years; the best is yet to come.

Background: Cognitive decline and gait disturbance are often observed simultaneously in patients with small vessel disease (SVD), also known as motoric cognitive dysfunction. However, it remains unknown whether cholinergic system disruption contributes to motoric cognitive dysfunction.

Methods: In this cross-sectional, single-center study conducted in the Netherlands, we included 213 patients with SVD between 2020 and 2021, all of whom had multimodal magnetic resonance imaging scans, gait assessments using the 6-meter walk test, and cognitive test battery data available. Cholinergic cortical (through external capsule and cingulum) and thalamic projections (pedunculopontine nucleus to thalamus) were reconstructed using probabilistic tractography on diffusion images, followed by the quantification of the disruption in these tracts with diffusion metrics derived from neurite orientation dispersion and density imaging model. Conventional magnetic resonance imaging markers for SVD were assessed.Covariates, including neurite orientation dispersion and density imaging metrics in the white matter control mask and SVD markers, were adjusted in linear regression.

Results: A total of 213 patients with SVD were included, with a mean (SD) age of 74.6 (6.8) years, of whom 96 (45.1%) were women. Conventional SVD markers are differentially associated with disrupted cholinergic pathways, with white matter hyperintensities (WMH) being the main contributor (R² highest for neurite density index, 0.38). WMH within the external capsule cholinergic pathway is more strongly associated with the neurite orientation dispersion and density imaging metrics in this tract compared with total WMH volume or WMH outside cholinergic projections. In contrast, WMH within the cingulum pathway contributes less to neurite orientation dispersion and density imaging variability (R²=0.18-0.33 versus 0.22-0.38). Disruption in cholinergic cortical pathways was associated with concurrent decline in performance of cognition and gait (external capsule pathway cerebrospinal fluid isotropic volume fraction, β=-10.77; P=0.004; cingulum pathway cerebrospinal fluid isotropic volume fraction, β=-13.38; P=0.011), adjusted for the covariates.

Conclusions: Taken together, our findings suggest that disruption in cholinergic cortical pathways attributable to SVD, rather than cholinergic thalamic pathways, contributes to the motoric cognitive dysfunction in patients with SVD.

Background: Maintaining walking ability in the long term after a stroke is challenging. Furthermore, access to ongoing physiotherapy is limited. This trial determined the feasibility of a clinical trial of a high-dose walking booster program (HiWalk) and measured clinical outcomes.

Methods: A multisite, assessor-blinded pilot and feasibility randomized trial was conducted in Australia (June 2023 to July 2024). Participants had a stroke 6 months to 8 years prior and could walk unaided at 0.4 m/s to 1.0 m/s. The experimental group received HiWalk plus usual care, while the control group received usual care alone. HiWalk was group-based motor training to improve walking, 43 hours over 3 weeks. Feasibility outcomes included recruitment and retention. Clinical outcomes included walking speed (preferred and fast over 5 m, fast over 6 minutes), and self-efficacy at 1 and 6 months.

Results: Eighty-two individuals were screened, and 47 participated: age 58 (SD, 16), time poststroke 2.7 years (SD, 2.1), and baseline fast walking speed 0.9 m/s (SD, 0.4). Feasibility outcomes: the HiWalk trial was feasible in terms of recruitment (refusal rate 27%), retention at 1 month (98%), adherence (mean 91% [SD 13] attendance once commenced), safety (minor adverse events 0.4/wk), and measurement (98% of data collected at 1 month). Clinical outcomes: at month 1, there was a beneficial effect on a 30-point self-efficacy scale (mean difference, 3.0 [95% CI, 0.1-5.9]). However, despite a small positive mean effect of HiWalk on fast walking speed (mean difference, 0.05 m/s [95% CI, -0.09 to 0.19]), there were no other significant between group differences. Exploratory analysis suggests the effect on walking speed for those not undertaking rehabilitation was 0.24 m/s (95% CI, 0.06-0.43) more than for those who were.

Conclusions: The HiWalk booster program was a feasible way to deliver mobility training in the community after stroke. Benefits in clinical outcomes were found for the subgroup of participants no longer undertaking rehabilitation. Therefore, future research should target this subpopulation.

Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12623000316606.

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.