Stroke最新文献

Stroke remains a leading cause of death and disability worldwide, with both ischemic and hemorrhagic subtypes triggering complex inflammatory cascades that exacerbate neuronal damage and impede recovery. Despite significant advances in understanding stroke pathophysiology, therapeutic interventions targeting neuroinflammation have shown limited clinical efficacy. Low-intensity focused ultrasound stimulation has emerged as a noninvasive neuromodulatory approach with promising potential for modulating poststroke immune responses and promoting neuroprotection. Low-intensity focused ultrasound stimulation can enhance stroke recovery by modulating immune cell activity and alleviating neuroinflammation. This review explores the multifaceted interplay between low-intensity focused ultrasound stimulation and the immune response in stroke, examining how ultrasound parameters can be optimized to achieve anti-inflammatory effects. We discuss preclinical evidence that highlights the therapeutic benefits of low-intensity focused ultrasound stimulation in stroke models, elucidate underlying mechanisms of action, and consider translational prospects and challenges for clinical application in patients with stroke.

Background: Genetic predisposition is increasingly recognized as an important contributor to cerebral venous thrombosis (CVT), yet findings from individual studies remain inconsistent. We conducted an updated meta-analysis to quantify associations between specific genetic variants and adult CVT.

Methods: We systematically searched PubMed, EMBASE, and Web of Science up to January 2025 for case-control studies comparing the prevalence of genetic variants in adults with CVT versus healthy controls. Pooled odds ratios (ORs) with 95% CIs were calculated using random-effects models in this meta-analysis.

Results: Sixty-one studies comprising 4106 patients with CVT and 12 323 controls were analyzed. Significant associations were identified for germline variants, including factor V Leiden (238/2753 [8.6%] versus 387/8747 [4.4%]; OR, 2.59 [95% CI, 2.06-3.26]; P<0.00001), prothrombin G20210A (290/2483 [11.7%] versus 235/8197 [2.9%]; OR, 6.05 [95% CI, 4.59-7.98]; P<0.00001), and inherited deficiencies of protein C (24/624 [3.8%] versus 7/2027 [0.3%]; OR, 10.30 [95% CI, 4.19-25.30]; P<0.00001), protein S (9/567 [1.6%] versus 1/1125 [0.1%]; OR, 6.86 [95% CI, 2.12-22.24]; P=0.001), and antithrombin (11/440 [2.5%] versus 3/989 [0.3%]; OR, 5.73 [95% CI, 1.98-16.55]; P=0.001). The somatic JAK-2 (Janus kinase-2) V617F mutation was likewise associated with increased risk (27/569 [4.7%] versus 13/1777 [0.7%]; OR, 9.17 [95% CI, 3.61-23.27]; P<0.00001). By contrast, MTHFR (methylenetetrahydrofolate reductase) C677T and PAI-1 (plasminogen activator inhibitor-1) 4G/5G polymorphisms showed no significant associations. Overall effect sizes were comparable to those reported in pediatric CVT but exceeded those in adult arterial ischemic stroke.

Conclusions: These findings support a genetic basis for adult CVT. Risk associations are broadly similar to pediatric CVT yet stronger than those reported for adult arterial ischemic stroke, highlighting distinct patterns of genetic susceptibility in venous stroke and the potential value of selective genetic testing for risk stratification and management.

Background: Endovascular therapy (EVT) has demonstrated efficacy in patients with large core infarctions, yet favorable outcomes remain limited. Although mismatch profiles have long informed EVT decision-making in small-core strokes, their prognostic significance in large-core infarcts remains uncertain and may be affected by time from symptom onset. This study aims to evaluate the relationship between mismatch profiles, time distribution, and EVT efficacy in patients with large ischemic cores.

Methods: This was a secondary posthoc analysis of the ANGEL-ASPECT trial (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core) in patients with large ischemic cores randomized to EVT or medical management. The primary outcome was the modified Rankin Scale score of 0 to 3 at 90 days. Analyses were stratified by mismatch profile (mismatch ratio ≥1.8 and volume ≥15 mL) and onset-to-imaging time (≤6 hours versus >6 hours).

Results: For the primary end point (modified Rankin Scale score, 0-3 at 90 days), no significant treatment-by-time interaction was observed (P for interaction=0.412); within time strata, treatment-by-mismatch interaction tests were also nonsignificant (≤6 hours, P for interaction=0.166; >6 hours, P for interaction=0.301). In the early window (≤6 hours), EVT was associated with higher odds of favorable functional outcome (modified Rankin Scale score, 0-3 at 90 days) in patients with mismatch (48.9% versus 28.4%; odds ratio, 2.41 [95% CI, 1.28-4.55]; P=0.006), but not in those without mismatch (23.8% versus 27.3%; odds ratio, 0.83 [95% CI, 0.21-3.29]; P=0.795). In the late window (>6 hours), EVT was not associated with a significant improvement in modified Rankin Scale score 0 to 3 in either subgroup.

Conclusions: Among patients with large infarct cores, the absence of mismatch was more common in the early time window and was associated with diminished benefit from EVT. These results suggest that mismatch evaluation-even in early presenting patients-may help inform treatment selection for patients with large ischemic cores. All interaction tests were nonsignificant; these findings are hypothesis‑generating and require prospective, prespecified confirmation.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04551664.

Background: OPTIMISTmain (Main Optimal Post rtPA-IV Monitoring in Ischemic Stroke Trial) has shown that low-intensity monitoring is feasible and safe compared with standard monitoring in stable patients who receive thrombolysis treatment for acute ischemic stroke of mild-to-moderate neurological impairment. We aimed to estimate the economic benefits of low-intensity care compared with standard care.

Methods: A cost-minimization analysis based on OPTIMISTmain was conducted for Australia, China, Malaysia, the United Kingdom, the United States, and Vietnam. A decision tree model comprising 2 arms was developed from the trial design. State transition probabilities for each country were extracted from the trial, and cost data were sourced from the existing literature. Mean costs over the 90-day duration of follow-up were compared, and univariate and probabilistic sensitivity and scenario analyses were performed.

Results: Low-intensity monitoring had the highest probability of cost saving in China (100.00%) and the United Kingdom (100.00%), followed by Australia (99.94%), the United States (95.91%), and Vietnam (86.66%), as patients in this group incurred US dollars savings of 239, 133, 647, 943, and 3 in direct costs compared with patients in the standard group, respectively. In Malaysia, however, the intervention costs slightly exceeded those for standard care (US dollars 5643 versus 5378). Countries with higher proportions of patients having intensive care unit monitoring had greater cost savings. Cost-saving thresholds of monitoring costs were 1.24, 1.30, 1.26, 1.24, 1.01, and 0.91 times the base case value in Australia, China, the United Kingdom, the United States, Vietnam, and Malaysia, respectively.

Conclusions: The low-intensity monitoring protocol was cost saving in countries with high proportions of intensive care resources for postthrombolysis treatment monitoring, such as in the United States.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03734640. URL: https://www.anzctr.org.au/; Unique identifier: ACTRN 12619001556134p.

Acute stroke due to medium vessel occlusion (MeVO) accounts for 25% to 40% of all acute ischemic stroke cases and is associated with substantial morbidity despite current best medical management. This motivated several recently published and ongoing trials that investigate(d) the benefit of endovascular thrombectomy (EVT) for MeVO stroke. Two of these trials have been published, an interim analysis of a third has been presented, and a fourth will be presented soon. The available trial results suggest no difference in outcomes between EVT and best medical management, and a possibility of harm with EVT. Preliminary post hoc analyses have however identified promising patient subgroups that may derive benefit from EVT. Improving EVT tools and techniques, together with adjunctive treatments, may further increase the technical efficacy of MeVO EVT. This review summarizes clinical and imaging features of MeVO stroke, reviews current evidence for medical and endovascular treatment, discusses recent MeVO EVT trial results, and outlines possible pathways forward for future MeVO trials.

Background: Recent research has shown that neuroinflammation progresses rapidly within a few hours after stroke; however, the relationship between its progression and clinical outcomes remains unclear. Therefore, this study aimed to investigate the effect of neuroinflammation, measured by serum GFAP (glial fibrillary acidic protein), on patient outcomes, as well as the influence of baseline peripheral inflammation on the progression of neuroinflammation.

Methods: This prospective cohort study enrolled patients with acute ischemic stroke who received intravenous thrombolysis (IVT) between September 2016 and April 2023 across 16 centers in China. Serum GFAP levels were measured before (baseline, within 4.5 hours of onset) and at 24 hours after IVT. GFAP changes were determined by subtracting baseline levels from those measured 24 hours post-IVT. Outcome measures included final infarct volume during hospitalization, National Institutes of Health Stroke Scale scores at 24 hours and 7 days post-IVT, early neurological deterioration within 24 hours, delayed neurological deterioration within 7 days, and 3-month modified Rankin Scale scores. A modified Rankin Scale score of ≥2 was classified as an unfavorable outcome. Peripheral inflammation indicators were measured at baseline. Binary logistic and linear regressions were used as the main statistical methods.

Results: Overall, 743 patients were included. A significant increase in GFAP levels was observed, indicating progression of neuroinflammation. Regression analyses revealed that increased GFAP after IVT was independently associated with larger infarct volume (β, 30.965 [95% CI, 19.185-42.745]; P<0.001), higher 24-hour and 7-day National Institutes of Health Stroke Scale scores (24-hour: β, 2.632 [95% CI, 1.644-3.620]; P<0.001; 7-day: β, 3.298 [95% CI, 2.179-4.417]; P<0.001), and unfavorable outcomes (odds ratio, 3.631, [95% CI, 2.159-6.106]; P<0.001). Furthermore, baseline peripheral inflammation, assessed using peripheral inflammation indicators, was significantly associated with elevated GFAP levels.

Conclusions: The increase in GFAP levels over the first 24 hours after IVT is independently associated with clinical outcomes, with higher baseline peripheral inflammation correlating with greater GFAP elevation during that period.

Background: This study aimed to investigate whether net water uptake (NWU) is associated with 3-month catastrophic functional outcome (modified Rankin Scale score, 5-6) and to develop predictive models with preprocedural factors, including NWU, in patients with large infarcts who underwent endovascular thrombectomy.

Methods: This multicenter observational cohort study conducted in Korea included patients with anterior circulation stroke and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of ≤5 receiving endovascular thrombectomy between 2015 and 2023. NWU, a quantitative imaging biomarker reflecting the degree of hypoattenuation on noncontrast computed tomography, was measured across the entire ASPECTS region (ASPECTS10-NWU), and its association with catastrophic functional outcome was assessed using a mixed-effects logistic regression model, adjusting for age, sex, prestroke modified Rankin Scale score, baseline National Institutes of Health Stroke Scale score, baseline ASPECTS, onset-to-baseline noncontrast computed tomography time, and intravenous tissue-type plasminogen activator, with hospital included as a random effect. Moreover, a predictive model has been developed with preprocedural factors that were significant covariates from the mixed-effects logistic regression analysis.

Results: A total of 255 patients were included (mean age, 71.0±12.6 years; 54.9% male). The median ASPECTS10-NWU was 3.0% (interquartile range, 1.9%-4.1%). Higher ASPECTS10-NWU was independently associated with catastrophic functional outcome (adjusted odds ratio, 1.70 [95% CI, 1.33-2.17]; P<0.001). The model integrating ASPECTS10-NWU with preprocedural variables suggested predicted catastrophic functional outcome probabilities; as ASPECTS10-NWU and baseline National Institutes of Health Stroke Scale score increased, the marginal probability of catastrophic functional outcome increased in all age (<80 and ≥80 years) and prestroke modified Rankin Scale score (0-1 and 2-4) groups, with the patients aged ≥80 years and with prestroke modified Rankin Scale score of 2 to 4 having higher outcome probability.

Conclusions: Elevated ASPECTS10-NWU is strongly associated with catastrophic functional outcome in patients with large infarcts treated with endovascular thrombectomy. Integrating the ASPECTS10-NWU with clinical variables may provide patient-specific prognostication that may assist clinicians in decision-making for endovascular thrombectomy in large infarcts.

Background: Dual antiplatelet therapy (DAPT) is recommended within 24 hours for patients with minor ischemic stroke or high-risk transient ischemic attack. However, the optimal timing for initiating DAPT remains unclear.

Methods: From a prospective multicenter cohort involving 20 stroke centers between January 2011 and April 2023, patients with minor noncardioembolic ischemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk transient ischemic attack who presented within 7 days of symptom onset were included. We evaluated outcomes based on in-hospital initiation of DAPT versus monotherapy (aspirin or clopidogrel alone). The primary outcome was a composite of recurrent stroke, myocardial infarction, and death within 90 days. Patients were grouped by time from symptom onset to hospital arrival: 0 to 24 hours, 24 to 72 hours, and >72 hours. Time-to-treatment effects were analyzed using Cox proportional hazards models, with inverse probability of treatment weighting based on propensity scores. The adjusted models incorporated demographic factors, baseline clinical characteristics, vascular risk factors, stroke subtype, relevant arterial status, and prior antiplatelet use.

Results: Among the 41 530 patients (mean age, 66.3 years; 25 771 [62%] male), 25 112 (60.5%) received DAPT. The 90-day primary outcome occurred in 2663 (10.7%) of the DAPT group versus 1900 (11.6%) in the monotherapy group (hazard ratio, 0.82 [95% CI, 0.77-0.87]). The benefit of DAPT was most pronounced when initiated within 24 hours (hazard ratio, 0.74 [95% CI, 0.69-0.79]). No significant benefit was observed when DAPT was initiated between 24 and 72 hours (hazard ratio, 1.00 [95% CI, 0.88-1.15]), and a higher risk was suggested for initiation beyond 72 hours (hazard ratio, 1.25 [95% CI, 1.01-1.55]). Time-dependent analysis showed a benefit crossing the null at ≈42 hours.

Conclusions: Early initiation of DAPT was associated with the greatest clinical benefit, consistent with current guideline recommendations. The therapeutic effect appeared to decline progressively beyond this period, with an estimated threshold around 42 hours.