Stroke最新文献

Background: Cerebral infarction is a frequent and serious complication of tuberculous meningitis (TBM), contributing substantially to morbidity and mortality. Moreover, studies on infarct patterns and associated factors/predictors remain limited in TBM. ACT-TBM trial (Aspirin or Clopidogrel Therapy in the Treatment of Tuberculous Meningitis) evaluated the efficacy and safety of adjunctive antiplatelet therapy (aspirin or clopidogrel) to standard antitubercular therapy in TBM for the occurrence of stroke or cerebral infarction. Here, we conducted a secondary analysis of the ACT-TBM trial to characterize the patterns, associated factors, and predictors of cerebral infarction in TBM.

Methods: We utilized data of 237 patients from the ACT-TBM randomized controlled trial conducted at 2 tertiary centers in India (2019-2023). Serial magnetic resonance imaging and magnetic resonance angiography were performed at baseline, 1 month, and 3 months in the primary trial. Cerebral infarctions were categorized by size, vascular territory, and number. Multivariable logistic regression models were performed using variables with P<0.1 on univariable analysis and clinical relevance. Model estimates are reported as adjusted odds ratios (aORs) with 95% CIs.

Results: Of the 237 patients enrolled, 226 were included after excluding 11 with missing imaging or incomplete follow-up data. Among these, 84 (37%) had cerebral infarction. Median age of the entire cohort was 26 years (interquartile range, 20-36), and 134 (59.29%) were females. Multiple infarcts were observed in 66 (78.6%) patients. Most frequent location of infarction was in the basal ganglia (n=61, 72.6%), subcortical white matter (n=44, 52.4%), and cortex (n=32, 38.1%). Arterial occlusion occurred in 49 (61.25%) patients with cerebral infarction versus 35 (25.55%) without (P<0.001). In multivariable adjusted models, Grade 3 TBM (aOR, 3.94 [95% CI, 1.19-13.08]; P=0.025), and arterial occlusion (aOR, 4.43 [95% CI, 2.19-8.96]; P<0.001) were associated with infarction. Among those with infarction, 27 (32.14%) patients (13.17% of the available cohort) developed new infarctions on follow-up. Modified antitubercular therapy (antitubercular therapy; aOR, 3.10 [95% CI, 1.18-8.09]; P=0.021) and arterial occlusion (aOR, 4.23 [95% CI, 1.40-12.75]; P=0.01) significantly predicted new infarctions. Presence of exudates was associated with arterial occlusion (aOR, 2.86 [95% CI, 1.08-7.56]; P=0.034).

Conclusions: Cerebral infarction is common in TBM and associated with disease severity and arterial occlusion. Modified antitubercular therapy predicted new infarcts, while basal exudates were associated with vascular occlusion, highlighting the need for vigilant monitoring and optimized therapeutic strategies.

Background: Atherosclerosis remains a leading cause of cardiovascular diseases. Despite current lipid-lowering therapies, residual risk persists due to inflammation and elevated Lp(a) (lipoprotein[a]) levels. Mesenchymal stem cell-derived extracellular vesicles show promise as a novel therapeutic modality. This hypothesis-testing (new) study investigated the antiatherosclerotic effect and systemic lipid-modulating potential of the clinical-grade mesenchymal stem cell-derived extracellular vesicle product SNE-101, which is currently approved for acute ischemic stroke trials.

Methods: ApoE-/- (apolipoprotein E-deficient) mice (male, 6-8 weeks old; n=6 per group) were placed on a high-fat diet, and SNE-101 (6×10⁸ particles) was administered intravenously via the tail vein once weekly for 4 weeks. The primary exposure variable was SNE-101 treatment, and the primary outcome variable was aortic plaque burden, quantified as the percentage of Oil Red O-stained area. In vitro foam cell assays were performed to assess cholesterol efflux.

Results: In vitro, SNE-101 significantly reduced lipid accumulation and enhanced cholesterol efflux via upregulation of the PPARγ (peroxisome proliferator-activated receptor gamma)/LXRα (liver X receptor alpha)/ABCA1 (ATP-binding cassette transporter A1)/ABCgG1 (ATP-binding cassette transporter G1) axis (P<0.050). In ApoE-/- mice, SNE-101 attenuated aortic plaque burden, inflammation, and hepatic steatosis. Extracellular vesicle treatment significantly improved systemic lipid profiles by reducing LDL-C (low-density lipoprotein-cholesterol), triglyceride, PCSK9 (proprotein convertase subtilisin/kexin type 9), and Lp(a) levels (P<0.050) while restoring hepatic LDL-R (low-density lipoprotein-cholesterol) expression.

Conclusions: Mesenchymal stem cell-derived extracellular vesicles (SNE-101) represent a promising therapeutic strategy for atherosclerosis. By enhancing cholesterol efflux, suppressing PCSK9 and Lp(a), and reducing systemic inflammation, SNE-101 addresses critical cardiovascular risks. This provides strong mechanistic guidance for its application in ongoing clinical trials for acute ischemic stroke.

Stroke remains a rare but life-threatening complication of pregnancy, with significant implications for both maternal and fetal health. Current stroke prevention and treatment guidelines offer limited guidance for managing stroke in pregnant and postpartum patients. Despite advances in obstetric and neurological care, the diagnosis and management of pregnancy-associated stroke continue to be challenged by delayed recognition, a lack of tailored clinical guidelines, and persistent disparities in outcomes. This scientific statement represents a multidisciplinary effort to synthesize current knowledge of the risk factors and diverse causes of stroke in pregnancy and to offer consensus-driven suggestions for prevention, acute management, and postpartum recovery. Nearly half of all US pregnancy-associated stroke hospitalizations occur in the setting of hypertensive disorders. Primary stroke prevention strategies include risk factor modification, aggressive hypertension management and prompt treatment of severe hypertension in pregnancy and postpartum, and antithrombotic therapy in some high-risk groups. Secondary stroke prevention strategies in pregnancy depend on the mechanism of the prior stroke. Pregnancy should not delay evidence-based treatments for acute stroke. The use of telemedicine can facilitate early consultation with a vascular neurologist and a maternal-fetal medicine specialist in cases of acute pregnancy-related stroke, helping to guide initial decision-making. Computed tomography, computed tomography angiography, and magnetic resonance imaging without contrast are all safe neuroimaging modalities for rapid evaluation of pregnant patients with acute stroke symptoms. Acute stroke alone is not an indication for immediate delivery, and stabilization of the mother should come first. Vaginal delivery after stroke is preferred when feasible because it avoids the surgical risks and hemodynamic stress associated with cesarean delivery. Survivors of pregnancy-associated stroke face unique challenges such as caring for an infant and breastfeeding and require support from a multidisciplinary rehabilitation team. Continued research, including inclusive clinical trials, is urgently needed to refine stroke risk assessment, to expand treatment options, and to improve maternal outcomes.

Background: Despite antiplatelet therapy, plaque-induced strokes recur frequently. This recurrence may reflect thrombus heterogeneity driven by peri-stenotic stagnation and red blood cell (RBC) entrapment. The clinical implications of such variations for stroke outcomes remain unclear. We investigated whether plaque-derived RBC-rich thrombi, indicated by the clot sign, were associated with recurrence, lesion volume, and stenosis-related hemodynamics.

Methods: Because asymptomatic plaque rupture limits direct evaluation of hemodynamics and thrombus compositions, we performed a hybrid human-animal study. In humans, we conducted a retrospective case-control study across 2 tertiary stroke centers in the Republic of Korea between April 2017 and March 2024, evaluating stroke recurrence and lesion volume by clot sign, using inverse probability of treatment weighting. We included artery-to-artery embolization confirmed by diffusion weighted imaging, excluding other etiologies. In animals, thrombus compositions were histologically analyzed in an FeCl₃-induced stenosis model across 3 segments (ascent, peak, and descent). Peri-stenotic hemodynamics, including wall shear stress and relative residence time, were assessed using ultrafast ultrasound imaging to evaluate whether RBC entrapment correlated with elevated relative residence time.

Results: In humans, clot sign-positive patients exhibited higher recurrence risk (hazard ratio, 2.76 [95% CI, 1.32-5.74]; P=0.007), and larger lesion (mean difference, 16.14 [95% CI, 5.03-27.25]; P=0.005). In animals, RBCs proportion was increased in the descent (ascent, 23.89±15.91%; peak, 12.33±11.19%; descent, 59.58±35.09%; P=0.019), correlating with a 3-fold higher relative residence time in the descent than the other regions (ascent, 1.25±0.75 au; peak, 1.55±0.55 au; descent, 4.50±2.74 au; P=0.001).

Conclusions: Peri-stenotic stagnation was associated with RBC-rich thrombi formation under both clinical and experimental conditions, providing mechanistic insight into stroke recurrence and larger lesion volumes. Identifying peri-stenotic stagnation using ultrafast ultrasound imaging may help stratify high-risk patients; however, its therapeutic implications require validation in prospective randomized studies.

About 10% to 15% of patients with ischemic stroke have a history of cancer, half of whom have active malignancy at the time of stroke. With improved cancer treatments extending patient survival, the coprevalence of these diseases has increased steadily since 2000. This has sparked considerable growth in research and knowledge on this topic. Approximately half of ischemic strokes in patients with active cancer are due to conventional mechanisms, although cancer-related factors may contribute. The remaining half of ischemic strokes in this population are typically classified as cryptogenic or attributed to cancer-specific mechanisms. These cryptogenic strokes often have characteristic risk markers and clinical features and are extremely high risk for recurrent stroke and other adverse events, distinguishing them from other stroke subgroups. Recent epidemiological, translational, and histopathological data indicate that many of these events are likely caused by the cancer itself through multifactorial prothrombotic processes. In this scientific statement incorporating multidisciplinary expertise, we critically appraise and synthesize recent evidence and provide clinical suggestions on the epidemiology, presentation, evaluation, pathophysiology, and treatments for ischemic stroke in patients with active cancer. In addition, we propose a novel classification for ischemic stroke attributed to cancer itself, which we define as cancer-related stroke to enable consistent nomenclature and to harmonize stroke classification across clinical practice and research. This system is based on routinely available clinical data and includes different categories for certainty of causality, relating to the patient's distinctive clinical features and estimated risk for recurrent thromboembolism. We hope this framework spurs dedicated controlled trials to address areas of clinical uncertainty.

Background: Maternal stroke is an uncommon but serious complication of pregnancy. This study assessed the incidence, temporal trends, and outcomes of maternal stroke in the United States using the Cosmos Epic database.

Methods: We conducted a retrospective analysis of pregnancies resulting in births between January 1, 2016, and January 1, 2024, using the Cosmos Epic database, which includes deidentified electronic health records from >1800 US hospitals and 41 500 clinics. Maternal stroke was defined as any inpatient admission with a stroke diagnosis during pregnancy or within 6 weeks postpartum. The primary outcome was maternal stroke incidence; secondary outcomes included maternal mortality, delivery complications, and neonatal outcomes. Propensity score matching (1:1) was applied to adjust for confounding.

Results: Among 5 404 933 pregnancies, 2637 were complicated by stroke, yielding an incidence of 48.8 per 100 000 pregnancies. Ischemic stroke was most common (52.6%), followed by hemorrhagic stroke (40.7%). The overall rate remained stable though ischemic stroke showed an upward trend. Women with stroke were older and more likely to be Black, and had higher rates of hypertension, dyslipidemia, congenital heart disease, and eclampsia. In the matched cohort (n=1200 pairs), the stroke group had higher mortality (1.7% versus 0%), more delivery complications, lower birth weight, and longer neonatal hospital stays. Among 409 subsequent pregnancies, recurrent stroke occurred in 14.7% but with no maternal mortality and favorable neonatal outcomes.

Conclusions: Maternal stroke, though rare, carries substantial risks. The increasing ischemic stroke trend warrants targeted prevention and multidisciplinary perinatal management.

Background: Cerebral hemodynamic impairment in patients with asymptomatic high-grade (>70%) internal carotid artery (ICA) stenosis is associated with risk of stroke and cognitive decline, but correlations between the degree of stenosis and hemodynamic impairment are derived from small case series. Using baseline data from 242 participants in the CREST-H study (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis-Hemodynamics), we hypothesized that the degree of stenosis in the ICA would correlate with time-to-peak (TTP) delay in ipsilateral cerebral blood flow using MR/CT perfusion scans, adjusting for demographic and cardiovascular risk variables.

Methods: From all participants, ICAs were insonated using a 7 to 10 MHz probe for peak systolic velocity (PSV) and end diastolic velocity. Dynamic contrast perfusion imaging was standardized across 61 CREST-H sites, using standard sequential T2*-weighted perfusion imaging. CT perfusion used standard clinical protocols. TTP delay was calculated in the ipsilateral versus contralateral hemispheres. In cross-sectional analysis, linear regression was used to model TTP delay as the outcome variable and PSV, end diastolic velocity, and PSV ICA/common carotid artery ratio on the index and nonindex side as primary predictor variables in 6 separate models, adjusting for covariates, followed by automated backward elimination model reduction.

Results: Among 392 CREST-H participants, the 242 with complete data for all variables were included in the regression analysis (age, 70±7.6; 62% M). End diastolic velocity on the index side correlated with TTP delay (β=0.003, P=0.005). PSV had a similar correlation but did not reach significance (β=0.001, P=0.099), nor did ICA/common carotid artery ratio (β=0.003, P=0.126). Nonindex side PSV, end diastolic velocity, and ICA/common carotid artery ratio showed no correlation with TTP delay (P=0.268, P=0.495, P=0.380, respectively). Circle of Willis completeness did not correlate with TTP.

Conclusions: In this large cohort of patients with high-grade asymptomatic carotid stenosis, higher end-diastolic flow velocities correlated with greater TTP delays, supporting a definition of hemodynamically significant stenosis. Our findings have implications for the management of asymptomatic carotid stenosis, which will be tested in the CREST-H study.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03121209.