Stroke最新文献

Background: Stroke causes somatic dysfunction and psychological disorders, leading to poststroke depression (PSD). This study investigates mood alterations in PSD models via cerebellar intermittent theta burst stimulation (iTBS).

Methods: PSD animal models were developed using middle cerebral artery occlusion and chronic unpredictable mild stress procedures. PSD models underwent cerebellar iTBS with different pulse numbers. Neurological recovery was evaluated using open-field test, sucrose preference test, forced swimming test, and balance beam test. Golgi and hematoxylin-eosin staining assessed neuronal repair, while quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and Western blotting evaluated effects on BDNF (brain-derived neurotrophic factor), hypothalamic-pituitary-adrenal axis factors, and the cAMP/PKA (protein kinase A)/CREB (cAMP-response element-binding protein) pathway. The study first determined the effects of different intensities of iTBS stimulation on neurological recovery in PSD rats. Second, the effects of iTBS stimulation on the cAMP/PKA/CREB pathway were verified using adenoviral blockade of PKA and CREB at iTBS-1800.

Results: PSD models showed decreased vertical movement, locomotor distance, and sucrose preference and increased immobility time and balance beam test score, which were reversed by iTBS. iTBS increased dendritic length and spine density in Purkinje cells, alleviated neuronal damage in multiple brain regions, and enhanced BDNF synthesis. It also regulated adrenocorticotropic hormone, cortisol, and GR (glucocorticoid receptor) expression, and activated the cAMP/PKA/CREB pathway.

Conclusions: Cerebellar iTBS improves PSD by activating the cAMP-PKA/CREB pathway, increasing BDNF, and reducing hypothalamic-pituitary-adrenal axis hyperactivity, suggesting potential for human PSD treatment.

Background: The purpose of this study is to examine the association between race and ethnicity and ischemic stroke severity in the United States.

Methods: We performed an analysis of adult hospital discharges in the National Inpatient Sample from 2018 to 2021 with a primary discharge diagnosis of ischemic stroke. We stratified our cohort based on self-reported race and ethnicity and evaluated stroke severity using the National Institutes of Health Stroke Scale. Age- and sex-adjusted estimates of the National Institutes of Health Stroke Scale were derived from linear regression models.

Results: We included 231 396 stroke discharges with a mean National Institutes of Health Stroke Scale of 6.5±7.2. The cohort was 68.1% White, 17.4% Black, 8.2% Hispanic, and 6.3% other. The age- and sex-adjusted National Institutes of Health Stroke Scale for White patients was 6.25 (95% CI, 6.22-6.29), for Black patients was 7.12 (95% CI, 7.05-7.19), for Hispanic patients was 6.86 (95% CI, 6.76-6.97), and for patients of other races and ethnicities was 7.29 (95% CI, 7.18-7.41). Further adjustment for the Charlson Comorbidity Index, socioeconomic factors, and poorly controlled hypertension or diabetes did not significantly alter these findings.

Conclusions: In a large, contemporary, and nationally representative sample of patients with acute ischemic stroke, we show an association between non-White race and ethnicity and higher stroke severity. These results are concerning for an underappreciated health disparity in acute ischemic stroke.

Background: Whether the long-term benefit of stroke prevention when stenting is added to medical therapy (MT) over MT alone for symptomatic severe intracranial artery stenosis offsets the perioperative risks of the stenting has not been directly evaluated in a randomized trial. We aimed to compare the long-term (>3 years) effect of stenting versus MT alone in patients with symptomatic severe intracranial artery stenosis in a randomized trial.

Methods: We extended the follow-up of 358 subjects enrolled in a multicenter, open-label, randomized trial conducted at 8 centers in China. Patients with transient ischemic attack or stroke attributed to severe intracranial stenosis (70% to 99%) were recruited between March 5, 2014, and November 10, 2016. The primary outcome was a composite of stroke or death within 30 days or stroke in the territory of the qualifying artery beyond 30 days. Other secondary outcomes included stroke in the territory of the qualifying artery, as well as disabling stroke or death after enrollment.

Results: A total of 358 patients (stenting 176 versus MT 182) were recruited from March 5, 2014, and followed up till January 22, 2024. The median duration of follow-up was 7.4 years (interquartile range, 6.0-8.0). The primary outcome was not significantly different (stenting 14.8% versus MT 14.3%; hazard ratio, 1.02 [95% CI, 0.58-1.77]; P=0.97). No significant difference was found between groups for the secondary outcomes: stroke in the territory of qualifying artery (14.8% versus 14.3%; hazard ratio, 1.02 [95% CI, 0.58-1.77]; P=0.97), disabling stroke or death (16.5% versus 14.3%; hazard ratio, 1.12 [95% CI, 0.66-1.91]; P=0.70), and death (9.1% versus 7.1%; hazard ratio, 1.22 [95% CI, 0.58-2.58]; P=0.60).

Conclusions: This study provides compelling evidence that, even over prolonged observed periods, the addition of stenting to MT does not confer additional benefits to MT alone in patients with symptomatic severe intracranial artery stenosis. These results underscore the importance of MT as the cornerstone of long-term stroke prevention in this patient population.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01763320.

Background: Past failures in translating stroke cerebroprotection provoked calls for a more rigorous methodological approach, leading to the stroke preclinical assessment network SPAN (Stroke Preclinical Assessment Network), where uric acid (UA) treatment exceeded a prespecified efficacy boundary for the primary functional outcome. Still, successful translation to humans requires confirmation of the effect of UA across key biological variables relevant to patients with stroke.

Methods: We measured the effects of intravenous UA treatment (16 mg/kg) versus intravenous saline in groups of animals enrolled in the SPAN network with diverse comorbidities, sex, and age. The masked study drug or placebo was administered during reperfusion in rodents undergoing a transient middle cerebral artery filament occlusion. The primary outcome was the modified corner test index at day 30 poststroke, and numerous secondary outcomes were collected. A modified intention-to-treat population was used in the analysis. We tested for any interactions with sex, age, and comorbidities (obesity-induced hyperglycemia and hypertension).

Results: In total, 710 animals were randomized to receive either intravenous UA or saline. After accounting for procedural dropouts and exclusions from treatment, a total of 687 animals were qualified and analyzed, including 458 assigned to UA and 229 to intravenous saline control. UA-treated animals exhibited a better primary functional outcome at day 30 (probability, 0.56 [95% CI, 0.52-0.60]; P=0.006). UA-treated animals also had a better corner test index at day 7 (probability, 0.55 [95% CI, 0.5-0.59]; P=0.035) and a higher survival rate at day 30 (hazard ratio, 1.41 [95% CI, 1.08-1.83]; P=0.011). Brain morphometry at day 2 and 30 was comparable between the treatment groups. The improved functional outcome and survival in UA-treated animals were preserved across different species, sexes, ages, and comorbidities.

Conclusions: UA provides ischemic stroke cerebroprotection across key relevant biological variables, making it a promising intervention to be further tested in human clinical trials.

Background: Providing equitable health care to rural stroke patients is challenging and associated with less intervention and poorer outcomes. We assessed how several distinct patient-related geographic classifications influenced stroke care and outcomes in Scotland, United Kingdom.

Methods: We conducted a population-level data-linkage study of ischemic stroke patients admitted to the hospital (2010-2018). Geographic classifications included 2 binary (urban versus rural; accessible versus remote) and 1 six-category classification encompassing both rurality and accessibility (large urban areas, other urban areas, accessible small towns, remote small towns, accessible rural areas, and remote rural areas). Process outcomes included achievement of a stroke care bundle and thrombolysis administration. Clinical outcomes included 30-day discharge from hospital care, 90-day home time, inpatient and 1-year all-cause mortality.

Results: We included 42 917 ischemic stroke patients (35 766 urban and 7151 rural). Binary classifications of rurality or accessibility missed important differences in stroke care and outcomes revealed using 6-category classification. Using the latter, compared with large urban areas, patients in accessible rural areas were more likely to receive a complete stroke care bundle (adjusted odds ratio, 1.21 [95% CI, 1.12-1.31]); patients in remote rural areas were less likely (adjusted odds ratio, 0.85 [95% CI, 0.78-0.93]). Compared with large urban areas, 30-day discharge from hospital care was more likely for patients residing elsewhere (eg, remote rural areas adjusted subdistribution hazards ratio, 1.11 [95% CI, 1.05-1.17]); home time within 90 days was higher for other urban areas (adjusted incidence rate ratio, 1.05 [95% CI, 1.03-1.07]) and accessible rural areas (adjusted incidence rate ratio, 1.03 [95% CI, 1.01-1.06]); and 1-year mortality was less likely in other urban areas (adjusted hazard ratio, 0.93 [95% CI, 0.88-0.98]) and remote small towns (adjusted hazard ratio, 0.89 [95% CI, 0.80-0.99]).

Conclusions: When considering geographic disparities in stroke care and outcomes across Scotland, it is important to account for both home location and accessibility of care. Despite patients residing in remote rural areas being less likely to achieve a complete stroke care bundle, this did not translate into poorer outcomes.

Brain arteriovenous malformations (AVMs), cerebral cavernous malformations (CCMs), and intracranial aneurysms are major causes of hemorrhagic stroke, yet noninvasive therapies to prevent growth or rupture are lacking. Understanding the genetic basis of these malformations is critical for uncovering underlying mechanisms, developing targeted prevention strategies, and identifying novel therapeutic targets. This review highlights the causal genes and signaling pathways in AVMs, CCMs, and intracranial aneurysms, noting both their commonalities and differences. For AVMs, somatic mutations in the Ras/MAPK (mitogen-activated protein kinase) and MAPK/ERK (extracellular signal-regulated kinase) pathway are key, particularly in sporadic cases, whereas hereditary conditions like hereditary hemorrhagic telangiectasia and capillary malformation-AVM involve the TGF-β (transforming growth factor β), Ephrin receptor, and angiopoietin-VEGF (vascular endothelial growth factor) signaling pathways. In CCMs, pathways affecting endothelial junctions and vascular stability, such as the ROCK (RhoA/Rho-associated coiled-coil containing kinases) pathway, play a central role. Although the genetic drivers of intracranial aneurysms are more diverse and less clearly linked to specific pathways, there is some overlap with genes in the TGF-β and endothelial function pathways seen in AVMs and CCMs. Emerging therapies for AVMs and CCMs include MAPK/ERK inhibitors, anti-VEGF treatments, and RhoA/ROCK inhibitors, showing potential in preclinical models. Due to the genetic overlap, these advancements may also offer future therapeutic strategies for intracranial aneurysms. As personalized medicine progresses, the development of reliable biomarkers, such as the candidate biomarker VEGF for AVMs and CCMs, will be crucial for guiding treatment decisions. In conclusion, ongoing research into genetic pathways holds promise for novel therapeutic targets that could transform the management of vascular malformations and reduce the risk of hemorrhagic stroke.

Background: It is unclear how poststroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic and hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, and cryptogenic/other determined causes), and poststroke cognitive decline.

Methods: We pooled participants from 4 US cohort studies (1971-2019). Outcomes were change in global cognition (primary) and changes in executive function and memory (secondary). Outcomes were standardized as T scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1 SD difference in cognition. The median follow-up for the primary outcome was 6.0 (interquartile range, 3.2-9.2) years. Linear mixed-effects models estimated changes in cognition after stroke.

Results: We identified 1143 dementia-free individuals with acute stroke during follow-up: 1061 (92.8%) ischemic, 82 (7.2%) hemorrhagic, 49.9% female, and 30.8% Black. The median age at stroke was 74.1 (interquartile range, 68.6-79.3) years. On average, ischemic stroke survivors showed declines in global cognition (-0.35 [95% CI, -0.43 to -0.27] points/y; P<0.001), executive function (-0.48 [95% CI, -0.59 to -0.36] points/y; P<0.001), and memory (-0.27 [95% CI, -0.36 to -0.19] points/y; P<0.001). Poststroke declines in global cognition, executive function, and memory did not differ between hemorrhagic and ischemic stroke survivors. Differences in poststroke cognitive slope between hemorrhagic and ischemic stroke survivors were global cognition (0.02 [95% CI, -0.21 to 0.26] points/y; P=0.85), executive function (-0.13 [95% CI, -0.48 to 0.23] points/y; P=0.48), and memory (0.19 [95% CI, -0.05 to 0.43] points/y; P=0.12). On average, small vessel stroke survivors showed declines in global cognition (-0.33 [95% CI, -0.49 to -0.16] points/y; P<0.001), executive function (-0.44 [95% CI, -0.68 to -0.19] points/y; P<0.001), and memory (-0.19 [95% CI, -0.35 to -0.03] points/y; P=0.02). Poststroke cognitive declines did not differ between small vessel survivors and survivors of other ischemic stroke subtypes.

Conclusions: Stroke survivors had cognitive decline in multiple domains. Declines did not differ by stroke type or ischemic stroke subtype.

Background: As the impact of stroke remains, primary healthcare will continue to be a critical platform managing the poststroke journey. We aimed to identify stroke survivors assisted by community health worker in Brazil and how they relate to the location of rehabilitation facilities locations.

Methods: We developed a cross-sectional study using deidentified data from a real-world database generated by a free data collection app used by community health workers from May 2015 to January 2021 in Brazil to identify stroke survivors and to assess demographics and clinical characteristics. We used data from a public database, Cadastro Nacional de Estabelecimentos de Saúde, for identifying rehabilitation facilities. Locations were obtained by a geocoding application programming interface (Google Maps Platform), distances were measured in kilometers, and travel time in minutes.

Results: Among 2 397 764 individuals assisted by community health workers, 21 785 were stroke survivors, representing a 0.9% prevalence. Among this subgroup, the majority were in the Northeast region (n=10 951; 50.3%) and 16 922 (77.7%) in urban areas. Most individuals (n=11 504; n=142; 52.8%) were women, the mean age was 66.5 (SD, 14.7), and 4313 reported physical disability. In total, 348 rehabilitation facilities were identified, mostly located in the Southeast region (40.8%). The mean distance from stroke survivor to facility was 79.13 km (SD, 97.73; median [1Q, 3Q], 47.64 km [12.19, 107.80 km]), and mean travel time was 81.18 minutes (SD, 85.85). The Southern region recorded the largest mean and median distance (mean 175.58 km; SD, 163.18; median [1Q, 3Q] 88.47 [59.38, 425.38]) to rehabilitation center and the longest mean travel time (144.48 minutes; SD, 112.57; median [1Q, 3Q] 92.34 [60.59, 305.12]).

Conclusions: Despite the availability of rehabilitation centers in Brazil, geographic access as represented by the distances and travel times observed access is still suboptimal. As a means of improving the clinical pathway and resource allocation, the use of large real-world databases and adequate analysis may become a key component for real needs assessments.

Background: Various measures of abnormal left atrial (LA) structure or function (LA myopathy) are associated with a higher risk of ischemic stroke and dementia, independent of atrial fibrillation. However, limited data exist on their prognostic usefulness. Therefore, we aimed to assess the ability of markers of LA myopathy to improve the prediction of ischemic stroke and dementia.

Methods: The ARIC study (Atherosclerosis Risk in Communities) is a prospective community-based cohort study. For this analysis, we included participants who attended visit 5 (2011-2013) without a history of stroke or atrial fibrillation and had a 12-lead ECG and a transthoracic echocardiogram. Markers of LA myopathy included P wave abnormalities from 12-lead ECG, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and LA volume and strain parameters from the echocardiogram. The primary composite outcome comprised ischemic stroke and dementia, which were ascertained through hospital surveillance, cohort follow-up, and death registries. To determine improvement in risk prediction of the composite outcome, each marker was individually added to a model that included CHA₂DS₂-VASc variables, and Akaike information criterion, C statistic, and its change were computed. Cox proportional hazards models were used to assess the independent association of LA myopathy markers with the outcome.

Results: Among 4712 participants (59% female; mean age, 74 years), 193 ischemic strokes and 769 dementia cases were ascertained over a median follow-up of 8.3 years. Of LA myopathy markers, only LA reservoir strain and NT-proBNP significantly improved C statistic when added to the CHA₂DS₂-VASc model (base C statistic, 0.677) for the prediction of the composite outcome. Adding the LA reservoir yielded the highest increase in C statistic (0.010 [95% CI, 0.003-0.017]), and the model including the LA reservoir showed the lowest Akaike information criterion. In multivariable regression models, LA volume index, NT-proBNP, and LA strain parameters were significantly associated with the composite outcome.

Conclusions: Of various LA myopathy markers, LA reservoir yields the greatest improvement in the prediction of ischemic stroke and dementia, supporting its use to identify people at high risk of cerebrovascular events and dementia.