Journal of Stroke最新文献

Background and purpose: Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD).

Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert's syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al.

Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41-2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43-2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45-2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson-Neyman analyses showed cut-off concentrations of 22.3-22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not.

Conclusions: Mildly elevated TBIL may modify the association between hypertension and CSVD.

Background and purpose: Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions.

Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states.

Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis.

Conclusions: Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Background and purpose: Cardioembolic sources account for 20%-30% of acute ischemic strokes (AIS), often with high morbidity. Conventional imaging confirms etiology retrospectively but lacks insight into the dynamic behavior of embolic transport. We aimed to predict stroke laterality by integrating patient-specific computational fluid dynamics (CFD) simulations with robust Bayesian logistic regression modeling.

Methods: Eight patients (median age 77.5 years; 2 females) with anterior circulation AIS of confirmed cardiac origin underwent high-resolution computed tomography angiography. Vascular geometries were segmented to generate CFD models simulating physiologic pulsatile flow. In each cardiac cycle, 1,000 massless particles were released at the aortic inlet. Two features were derived: x1 (long-term embolic bias over 10 seconds) and x2 (short-term embolic bias during the first cardiac cycle). These were used as predictors in a robust Bayesian logistic regression model.

Results: The right internal carotid artery (ICA) received more embolic particles (mean 34/s) than the left ICA (mean 28/s). Patients with right-sided strokes had higher x1 (median 0.27 vs. -0.44) and lower x2 (median -0.82 vs. 0.56) than those with left-sided strokes. The model yielded posterior mean coefficients of 1.51 (95% credible interval [CrI]: -0.46 to 4.11) for x1 and -1.96 (95% CrI: -4.88 to 0.20) for x2, achieving complete separation of stroke patients by laterality in this pilot cohort.

Conclusion: The combination of CFD-based embolic modeling and Bayesian analysis accurately predicted stroke laterality in cardioembolic AIS, exposing distinct patient-specific embolic transport dynamics.

Background and purpose: Neuroimaging is essential before intravenous thrombolysis (IVT) and endovascular treatment (EVT) for acute ischemic stroke (AIS). In May 2018, our center transitioned from computed tomography (CT) to magnetic resonance imaging (MRI) as the first-line imaging for suspected AIS. We aimed to assess the consequences of an MRI-based paradigm on patients' selection, rates of acute treatment, time metrics, safety of both IVT and EVT, and clinical outcomes.

Methods: Using data from the Acute STroke Registry and Analysis of Lausanne (ASTRAL), we analyzed an equal number of patients from the CT-period (December 2012 to May 2018) and the subsequent MRI-period (May 2018 to August 2022). We performed univariable and multivariable analysis.

Results: We included 2,972 consecutive AIS patients, 1,131 undergoing IVT and 662 EVT. Compared to the CT-period, the MRI-period showed similar rates of early and late IVT and EVT. The potentially missed-IVT opportunities decreased (3.1% vs. 0.8%; Padj<0.01). Median door-to-needle time was longer in the MRI-period (43 min vs. 31 min, β-coefficientadj=15, 95% confidence interval [CI]=11-27, Padj<0.01), while door-to-puncture time was unchanged (β-coefficientadj=9.95, 95% CI=-2.24-22.14, Padj=0.11). Rates of symptomatic intracranial hemorrhage (SICH) were similar after IVT (5.6% vs. 3.2%, Padj= 0.99) and EVT (±IVT) (6.5% vs. 4.2%, Padj=0.52). Disability at 3 months was unaffected for both IVT and EVT patients (Padj=0.36 and Padj=0.52 respectively).

Conclusion: The transition from CT to MRI as the first-line imaging reduced the rates of potentially missed IVT opportunities. While door-to-needle time increased, door-to-puncture time remained stable. Safety as measured by SICH rates and 3-month disability were unaffected by the imaging paradigm shift.

Background and purpose: Plaque rupture is the underlying cause of most cardiovascular events, such as stroke and myocardial infarction. The co-stimulatory molecule LIGHT (tumor necrosis factor superfamily member 14, TNFSF14) has been detected in foam cell-rich regions of atherosclerotic plaques, but whether it has a role in plaque stability is not known. This study investigates the association between intraplaque LIGHT levels and plaque vulnerability.

Methods: LIGHT levels were measured in homogenates of carotid endarterectomy samples by proximity extension assay (n=202) and through bulk RNA sequencing and spatial transcriptomics (Visium) of plaques from patients included in the Carotid Plaque Imaging Project. Homogenates were further examined by multiplex analyses and enzyme-linked immunosorbent assay, and plaque sections by immunohistochemistry.

Results: Plaque levels of LIGHT were associated with occurrence of preoperative cerebrovascular symptoms, including stroke. LIGHT levels correlated with a histological plaque vulnerability index, necrotic core size, and inflammatory cytokine levels. Additionally, expression of extracellular matrix turnover machinery components, including the collagen cross-linking proteoglycan fibromodulin and matrix metalloproteinases 1, 2, 9, and 10, was associated with plaque LIGHT levels.

Conclusion: Expression of LIGHT in atherosclerotic plaques not only correlates with markers of plaque destabilization, but is also significantly elevated in plaques from symptomatic compared to those from asymptomatic patients. These results associate LIGHT content with a rupture-prone plaque phenotype, potentially upregulated as part of a reparative response, warranting further studies.