Stroke最新文献

Background: The Take Charge intervention-a conversation-based, community intervention to improve motivation, improved independence, and physical health 12 months after stroke in 2 randomized controlled trials with 572 participants. This article reports long-term outcomes for the 400 participants in the TaCAS study (Taking Charge After Stroke).

Methods: Follow-up study of a New Zealand multicenter, randomized, controlled, parallel-group trial. Outcomes were collected by postal questionnaire or telephone call. The TaCAS study recruited 400 participants discharged after stroke, randomized within 16 weeks to one of 3 groups: 1 session of the Take Charge intervention, 2 sessions 6 weeks apart, or no sessions (control). This study is of participants still alive and willing to answer a questionnaire 5 to 6 years after their index stroke, undertaken in 2022. The primary outcome was the Physical Component Summary of the Short Form 36, comparing the Take Charge intervention and control. Secondary outcomes were: Frenchay Activities Index; modified Rankin Scale (mRS); survival; and stroke recurrence. These outcomes were compared with those 12 months after stroke. Analysis was by ANOVA or logistic regression.

Results: Mortality data were available for all 400 participants, and functional data for 204/297 (69%) of survivors. The mean difference (95% CI) in Physical Component Summary between Take Charge and control groups was 2.8 (-0.8 to 6.5) units, P=0.12, and for independence (modified Rankin Scale score, 0-2) the odds ratio (95% CI) was 0.56 (0.28-1.16), P=0.11, both favoring Take Charge with similar point estimates to those after 12 months. Differences between Take Charge and control participants for Frenchay Activities Index scores, survival, and stroke recurrence were small and nonsignificant.

Conclusions: The clinically significant improvements in physical health and independence for Take Charge participants, observed at 12 months, were sustained 5 to 6 years after stroke, but no longer statistically significant.

Registration: URL: https://anzctr.org.au; Unique identifier: ACTRN12622000311752.

The global transition to digital health offers a critical opportunity to transform health care delivery, particularly in low- and middle-income countries. Stroke care exemplifies the need for timely, coordinated, and longitudinal management across health systems. Although substantial progress has been achieved, low- and middle-income countries continue to encounter persistent challenges, including infrastructural deficiencies, digital inequity, fragmented governance structures, and limitations within the health care workforce. Nonetheless, scalable digital health interventions, such as telestroke networks, mobile health platforms, artificial intelligence-supported diagnostics, and telerehabilitation programs, have demonstrated efficacy and impact across diverse contexts. The central challenge has, thus, shifted from technological development to the systemic integration of these solutions within existing health infrastructures. Crucially, low- and middle-income countries must not be perceived solely as passive recipients of technology but as active agents of innovation, developing efficient, adaptive, and culturally attuned models prioritizing community engagement and a holistic conception of health. To realize the transformative potential of digital health, it is imperative to invest not only in technological infrastructure but also in promoting digital literacy, establishing robust ethical and regulatory frameworks, fostering cross-sectoral partnerships, and creating inclusive innovation ecosystems. Only through such a comprehensive, human-centered approach can digital health effectively serve as a catalyst for more equitable, resilient, and sustainable health systems, particularly for populations residing in resource-constrained settings.

Background: Acute ischemic stroke models often rely on anesthesia, which alters neurovascular coupling and limits real-time functional assessment. We tested the hypothesis that an awake mouse model of thromboembolic stroke, combined with multimodal imaging, would reveal very early cerebrovascular dynamics and connectivity changes predictive of final lesion outcomes.

Methods: Male Swiss mice (6-8 weeks old; 30-40 g; n=60) were implanted with a cranial headplate and habituated to restraint and imaging. One microliter pneumatic injection of murine thrombin (1 IU) into the distal middle cerebral artery induced in situ clot formation. Twenty minutes postocclusion, mice received intravenous rtPA (recombinant tissue-type plasminogen activator; Alteplase, 10 mg/kg; 10% bolus/90% infusion over 40 minutes, n=31) or saline (n=29). Primary outcomes included lesion volume (T2-weighted magnetic resonance imaging at 24 hours), brain perfusion (ASL magnetic resonance imaging), cerebral blood volume variations (ultrafast Doppler US imaging), resting-state connectivity, and neurovascular coupling to whisker stimulation (functional ultrasound imaging). Sample size (n=12 per group for imaging) was based on prior variability. Statistical analyses included unpaired t tests, repeated-measures ANOVA with Dunnett or Tukey post hoc, and simple linear regression; significance set at P<0.05.

Results: At 24 hours, rtPA reduced lesion volumes by 36.7% (10.97±4.7 versus 17.33±5.92 mm³ in controls; t₅₈=4.624; P<0.0001). ASL magnetic resonance imaging revealed a 66.5±9.9% CBF drop at 1 hour (F=48.63; P<0.0001) and a 51.2±45.1% hyperperfusion at 24 hours compared with baseline (F=11.67; P=0.0024). CBV declined by 59.2±12.9% at 10 minutes and partially recovered with rtPA at 1 hour (+87.3±30.6%; P=0.0165). Early hypoperfused area (10 minutes) predicted final lesion observed at 24 hours (R²=0.6465; P=0.0016). Resting-state connectivity shift of 12.0° at 10 minutes was mitigated by rtPA by 1 hour (14.8° versus 3.6°; P<0.01). Whisker-evoked CBV responses were abolished ipsilaterally at 10 minutes (-100.5±3.3%; P=0.0038) and showed partial recovery by 24 hours with rtPA (+37.2% relative to 10 minutes). At this time point, responses no longer differed significantly from baseline (P=0.093), indicating a modest but functionally meaningful recovery despite marked interindividual variability.

Conclusions: Awake thromboembolic stroke model with early functional ultrasound imaging completed with magnetic resonance imaging uncovers rapid blood flow perturbations and connectivity disruptions that are sensitive to rtPA and predictive of final lesion outcome. This platform enhances translational relevance by enabling hypothesis-testing of novel thrombolytics under physiologically intact conditions.

Background: White matter hyperintensities (WMHs), the neuroimaging markers of cerebral small vessel disease, have been associated with adverse neurological recovery after stroke. However, their role in poststroke aphasia, an acquired language disorder affecting approximately one-third of stroke survivors, remains unclear. This review synthesizes evidence on the relationship between WMHs and poststroke aphasia, focusing on severity and recovery across stroke phases, associations with cognitive outcomes, and the influence of hemispheric lateralization.

Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Literature search was performed across PubMed, Scopus, and Web of Science. Thirteen studies met eligibility criteria, examining the impact of WMH severity on language and cognitive deficits in patients with poststroke aphasia. Correlation and regression analyses were the predominant statistical approaches to evaluate associations and control for confounders.

Results: Greater WMH burden was significantly associated with more severe language impairments in the chronic (6 studies, n=443), subacute (3 studies, n=117), and mixed subacute-chronic phases (1 study, n=42), particularly in object naming, word fluency, and spoken comprehension. Preliminary evidence suggests periventricular WMHs may be more linked to aphasia severity than deep WMHs, whereas treatment-related findings remain inconclusive. In the acute phase, 2 studies (n=288) found no association between WMH burden and either aphasia severity or treatment response. In chronic aphasia (4 studies, n=392), WMHs were also linked to poorer cognitive performance, especially in nonverbal reasoning and executive functions. Hemispheric assessment varied, with some studies focusing on the contralesional side to reduce lesion-related confounding, while others used bilateral measures, limiting comparability.

Conclusions: WMHs may represent neuroimaging biomarkers of language and cognitive dysfunction in chronic and subacute poststroke aphasia. Future studies with standardized imaging protocols and larger samples are needed to clarify their prognostic value and personalize rehabilitation strategies.

Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42024582826.

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.