Stroke最新文献

Background: Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is recommended for secondary prevention in patients with a minor stroke or transient ischemic attack. However, the effectiveness of DAPT can be significantly influenced by genetic variations. This study aimed to estimate the impact of multiple single-nucleotide polymorphisms across various genes on DAPT efficacy using polygenic risk score (PRS).

Methods: In this post hoc analysis, we included 2905 patients from the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), which enrolled a total of 5170 patients in China between October 2009 and July 2012. The primary outcome was new stroke within 90 days. Sixteen single-nucleotide polymorphisms across 7 genes involved in clopidogrel metabolism were selected for PRS development. PRS were calculated by summing single-nucleotide polymorphisms from each individual. The Cox proportional-hazards regression model was utilized to estimate the hazard ratio (HR) and 95% CIs of PRS. The predictive value of PRS was estimated by C statistic and compared with a previously validated model.

Results: The elevated PRSs were associated with an increased risk of new stroke within 90 days (P_trend=0.01). The efficacy of DAPT versus aspirin alone in preventing 1-year composite vascular events was significantly different between patients with low (adjusted HR, 0.47 [95% CI, 0.31-0.71]) and high PRSs (adjusted HR, 0.84 [95% CI, 0.60-1.18]; P_interaction=0.03). In patients receiving DAPT, higher PRSs were associated with increased risk of new stroke and composite vascular events at 90 days (adjusted HR per SD increase was 1.51 [95% CI, 1.15-1.99]) and at 1 year (adjusted HR per SD increase was 1.34 [95% CI, 1.08-1.67]). The C statistic for predicting 90-day new stroke using the PRS developed in this study was 0.57 (95% CI, 0.52-0.62), compared with 0.52 (95% CI, 0.48-0.55) for the ABCD-GENE score.

Conclusions: Using PRS integrating multiple genes may enhance the precision of secondary prevention strategies for patients with minor stroke or transient ischemic attack in the short and long term.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00979589.

Background: More than half of patients with ischemic stroke experience futile reperfusion, increasing the risk of death and disabilities despite a successful recanalization. The reason behind this is debated, and we aim to investigate cerebrovascular changes toward a broader understanding of these conditions. We hypothesize that ischemic stroke reperfusion modifies the expression profile in the microvasculature in a spatial manner toward peri-infarct brain edema and circulatory failure.

Methods: We investigated the early (24-hour) changes in spatial gene expression in the brain parenchymal endothelial cells and mural cells following ischemia stroke reperfusion in 13- to 14-week-old C57BL/6JRj male mice (n=5). Ischemia was induced by occlusion of the middle cerebral artery for 60 minutes, and Nissl staining was used to validate infarct size. Spatial transcriptomics complemented by bulk proteomics was conducted in the peri-infarct cortex region and validated with immunohistochemical semiquantification of proteins of interest. To avoid individual biological variations, changes in the peri-infarct cortex region were expressed relatively to the matching contralateral hemisphere region.

Results: Ischemic stroke reperfusion impaired the blood-brain barrier integrity through junctional Cldn5 (claudin-5) downregulation, changes of the actin cytoskeleton adhesion, and high expression of the proinflammatory Il-6 (interleukin-6). Molecules important for extracellular Ca²⁺ influx and intracellular Ca²⁺ release, Cacna1e (R-type Ca²⁺ channels), Orai2, Ryr3, Itpr1, and Itpka (inositol-trisphosphate 3-kinase A), were markedly reduced. Furthermore, reduced Grm5 (glutamate receptor 5) associated with upregulated Nfatc3 and Stat3 implicates suppression of the contractile phenotype, suggesting reduced poststroke vascular resistance due to loss of mural cell tone. The complete spatial transcriptomics map over the ipsilateral and contralateral hemispheres is available online as a Web tool.

Conclusions: Emphasizing the spatial molecular pattern behind blood-brain barrier disruption and loss of the vascular tone in the acute phase following ischemic stroke reperfusion suggests the gene expression contribution for a therapeutic target in ischemia-reperfusion abnormalities.

Background: Prior studies on the clinical impact of intracerebral hemorrhage (ICH) location have used visual localization of hematomas to neuroanatomical structures. However, hematomas often cross neuroanatomical structure boundaries with inter-reviewer variability in visual localization. To address these limitations, we applied voxel-wise analysis to identify brain regions where ICH presence is independently predictive of worse outcomes.

Methods: We included consecutive patients with acute spontaneous ICH from a comprehensive stroke center in a derivation cohort and validated the results in patients from the control arm of a multicenter clinical trial. Using general linear models, we created and publicly shared a voxel-wise map of brain regions where ICH presence was associated with higher 3-month modified Rankin Scale scores, independent of hematoma volume and clinical risk factors. We also determined the optimal overlap threshold between baseline hematoma and voxel-wise map to categorize ICH location into high versus low risk.

Results: Excluding those with missing variables, head computed tomography processing pipeline failure and poor scan quality, 559 of 780 patients were included in derivation (mean age, 69.3±14.5 years; 311 [55.6%] males) and 345 of 500 (mean age, 62.5±12.9 years; 206 [59.7%] males) in validation cohorts. In a voxel-wise analysis, ICH presence in deep white matter, thalami, caudate, midbrain, and pons was associated with worse outcomes. At the patient level, >22% overlap of baseline hematoma with voxel-wise map optimally binarized ICH location to high- versus low-risk categories. In both the derivation and validation cohorts, a high-risk ICH location was independently associated with worse outcomes (higher 3-month modified Rankin Scale score), after adjusting for patients' age, symptom severity at admission, baseline hematoma volume, and the presence of intraventricular hemorrhage, with adjusted odds ratios of 2 ([95% CI, 1.3-3.0] P=0.001) and 1.7 ([95% CI, 1.1-2.9] P=0.027), respectively.

Conclusions: We created and publicly shared a voxel-wise map of brain regions where hematoma presence predicts worse outcomes, independent of volume and clinical risk factors.

Background: The benefits and safety of mechanical thrombectomy (MT) in patients with prestroke disability, classified as modified Rankin Scale (mRS) score of 3 to 4, and anterior circulation stroke remain uncertain. This study aims to evaluate these factors using data from the Italian Registry of Endovascular Treatment in Acute Stroke.

Methods: We analyzed data collected between 2015 and 2021, comparing functional outcomes (mRS), symptomatic intracerebral hemorrhage, and recanalization rates (Thrombolysis in Cerebral Infarction) at 90 days post-MT in patients with prestroke mRS score of 3 to 4 versus 0 to 2. A good outcome was defined as no change in the mRS score from baseline. Subgroup analysis was stratified by age.

Results: A total of 11.411 (96%) patients with prestroke mRS score of 0 to 2 and 477 (4%) patients with prestroke mRS score of 3 to 4 were included. Compared with patients with a baseline mRS score 0 to 2, those with mRS score 3 to 4 were older (82 versus 75 years; P<0.001) and predominantly female (71.7% versus 53%; P<0.001). The maintenance of the same mRS score after MT was observed in 100 (23.3%) patients with prestroke mRS score 3 to 4, compared with 2332 (22.1%) patients with mRS score 0 to 2 (P=0.556). Mortality was significantly higher in the mRS score 3 to 4 group (n=159 [37.1%] versus n=1939 [18.4%]; P<0.001). Successful recanalization (Thrombolysis in Cerebral Infarction score ≥2b) was lower in the mRS score 3 to 4 group (n=333 [71.6%] versus n=8706 [77.7%]; P=0.002), while no significant differences in symptomatic intracerebral hemorrhage were found. The benefit of MT was maintained in patients aged 80 to 85 and over 85 years with prestroke mRS score 3 to 4, although mortality remained higher.

Conclusions: Our data suggest that prestroke disability does not imply less chance of returning to prestroke conditions after MT, even in octogenarians, despite higher mortality and lower recanalization rate. More data are warranted to better understand the benefit of MT in this subgroup of patients.

Subarachnoid hemorrhage is a critical neurological condition accounting for about 5% of all strokes, and survivors experience long-term cognitive deterioration and increased risk of dementia. The major processes involved in such decline include early brain injury, delayed cerebral ischemia, neuroinflammation, superficial siderosis, and hydrocephalus. These have emerging treatments that offer promise for the mitigation of effects such as inflammation, iron chelation, and microvascular dysfunction. Genetic predispositions have been associated with post-subarachnoid hemorrhage cognitive outcomes and emphasize a role for personalized care strategies. Management techniques reviewed include long-term cognitive health, such as endovascular coiling and surgical clipping. Other rehabilitation strategies that enhance cognitive reserve and pharmacological interventions are discussed about improving the quality of life in survivors. The review highlights the need for further research into targeted therapies, genetic markers, and innovative approaches to prevent cognitive decline, ultimately aiming to optimize long-term outcomes for individuals affected by subarachnoid hemorrhage.

Background: Subarachnoid hemorrhage (SAH) is a critical condition that has far-reaching implications for public health systems globally due to its severe consequences and long-term disabilities. This study aims to provide a comprehensive analysis of SAH trends from 1990 to 2021 and project future trends up to 2041, aiding in better understanding and management of its global burden.

Methods: We utilized data from the GBD (Global Burden of Disease) 2021 database, using joinpoint regression, frontier, and decomposition analyses to assess changes in SAH burden. Bayesian Age-Period-Cohort modeling was implemented to predict future trends. Our study included populations from 204 countries and territories.

Results: From 1990 to 2021, SAH incidence decreased by -1.03% for men and -1.16% for women, while mortality rates declined by -2.56% for men and -2.69% for women. Middle sociodemographic index locations and East Asia experienced substantial declines, particularly among women. However, countries like the Philippines and Turkmenistan showed increasing trends. Population aging and growth significantly contributed to these trends, while epidemiological changes led to reductions in SAH burden. The prediction model forecasts continued decreases in SAH mortality and disability-adjusted life years over the next 20 years, although incidence rates may slightly increase.

Conclusions: The global burden of SAH has significantly diminished from 1990 to 2021, with considerable variations across regions, sexes, and countries. Ongoing and future research should prioritize high-risk populations and develop innovative interventions to further decrease SAH incidence and enhance outcomes.

Background: We performed a prespecified subgroup analysis of the CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to compare the effect of early versus delayed antihypertensive treatment on death and disability in patients with and without medical history of hypertension.

Methods: CATIS-2 is a multicenter randomized clinical trial conducted in 106 hospitals in China. The trial randomized 4810 patients with acute ischemic stroke within 24 to 48 hours of symptom onset and elevated systolic blood pressure between 140 and <220 mm Hg to receive antihypertensive treatment immediately after randomization or to discontinue antihypertensive medications for 7 days and then receive treatment on day 8. The primary outcome was a combination of death or functional dependency (modified Rankin Scale score ≥3) at 90 days.

Results: At the 90-day follow-up, the primary outcome of death or functional dependency was not different between early- and delayed-treatment groups according to the history of hypertension; the odds ratios (95% CIs) associated with the early-treatment group were 1.11 (0.91-1.36) and 1.38 (0.92-2.08) for participants with and without a history of hypertension. However, the ordinal logistic regression showed that early antihypertensive treatment was associated with the odds of a higher modified Rankin Scale score in patients without hypertension (odds ratio, 1.35 [95% CI, 1.01-1.82]), but not in those with hypertension (odds ratio, 0.95 [95% CI, 0.82-1.10]; P=0.04 for interaction).

Conclusions: Early antihypertensive treatment did not reduce the odds of dependency or death at 90 days by hypertension history among patients with ischemic stroke but worsened functional outcomes for patients without hypertension in the ordinal analysis.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03479554.