Journal of Stroke最新文献

Early neurologic deterioration (END) is common and occurs within a few hours to days after an ischemic stroke. Traditionally, END has been treated as a collective entity, including the occurrence of new deficits (recurrence) and the aggravation of pre-existing neurologic deficits (progression). END arises from distinct mechanisms that require different therapeutic approaches. We reviewed clinical and experimental studies addressing the epidemiology, mechanisms, and treatment of END, focusing on differentiating END due to recurrence from END due to progression and on interventions including antiplatelet therapy, direct thrombin inhibition, and induced hypertension. Early recurrence is closely associated with thrombus growth and new ischemic events, particularly in atherothrombotic disease. Early recurrence is also common in patients with cancer-associated stroke. Thrombin and platelet activation play central roles under both conditions. In contrast, progression is mainly driven by infarct growth, that is, the evolution from incomplete infarction to complete infarction due to impaired perfusion, especially in lesions involving the subcortical fiber tracts. Therapeutic implications differ accordingly. Recurrence may respond to potent antithrombotic strategies, including combined antiplatelet and direct thrombin inhibition, whereas progression may benefit from induced hypertension. However, recurrence and progression often occur simultaneously, making clinical differentiation challenging. END should be conceptualized as a spectrum of clinical presentations arising from distinct mechanisms. Recognizing recurrence and progression as separate processes is essential for mechanism-oriented treatments. Future trials should adopt this framework to develop individualized strategies and improve outcomes in patients with acute stroke.

Background and purpose: Accurately predicting long-term functional outcomes of basilar artery occlusion (BAO) remains challenging. We compared the predictive performance of the baseline, 24-hour, and 72-hour National Institutes of Health Stroke Scale (NIHSS) scores for 90-day BAO functional outcomes using the Acute Basilar Artery Occlusion: Endovascular Thrombectomy versus Standard Medical Treatment (ATTENTION) trial data. We identified the optimal assessment time point, determined treatment-specific NIHSS cutoff values, and explored the role of early neurological function in treatment effects.

Methods: This retrospective post hoc analysis included 324 patients with acute BAO with baseline NIHSS scores ≥10 and complete NIHSS assessments at each time point. The primary outcome was a favorable 90-day functional outcome (modified Rankin Scale score, 0-3). Receiver operating characteristic curve analysis was used to assess the predictive ability of NIHSS scores. The optimal 72-hour NIHSS predictive cutoff values were determined for the endovascular treatment (EVT) and best medical management (BMM) subgroups.

Results: The 72-hour NIHSS score showed the highest predictive accuracy for the primary outcome (area under the receiver operating characteristic curve [AUC]: 0.954), outperforming the 24-hour (AUC: 0.903) and baseline (AUC: 0.688) scores; its optimal predictive cut-off value was ≤11 in the EVT group (sensitivity: 85.6%, specificity: 92.9%, positive predictive value [PPV]: 91.8%, negative predictive value [NPV]: 87.4%) and ≤9 in the BMM group (sensitivity: 84.6%, specificity: 95.1%, PPV: 84.6%, NPV: 95.1%).

Conclusions: The 72-hour NIHSS score outperformed the baseline and 24-hour scores in predicting 90-day functional outcomes and mediating the effects of EVT. Treatment-specific 72-hour NIHSS cut-off values may guide early risk stratification and prognostic assessments.

White matter hyperintensity (WMH), a common magnetic resonance imaging (MRI) marker of cerebral small-vessel disease, is associated with chronic cerebral ischemia; however, the mechanistic heterogeneity of WMH remains poorly defined. This review integrates multimodal MRI findings into a mechanism-oriented framework spanning four axes: WMH versus normal-appearing white matter (NAWM), periventricular versus deep location, lesion core versus perilesional penumbra, and longitudinal evolution. Periventricular WMHs are associated with blood-brain barrier dysfunction, interstitial fluid accumulation, and venous remodeling, whereas deep WMHs are more closely associated with impaired glymphatic/perivascular clearance and enlarged perivascular spaces, and demyelination/macromolecular compromise varying by context. The perilesional penumbra emerges as a critical transition zone, showing distance-dependent gradients of microstructural rarefaction, extracellular fluid expansion, perfusion deficits, and reduced vascular reactivity that extend beyond fluid-attenuated inversion recovery-defined borders and relate to subsequent lesion growth. Longitudinal data further indicate that abnormalities in diffusion, perfusion, and vascular reserve within NAWM precede new WMHs, nominating imaging biomarkers of progression risk. This framework supports risk stratification beyond total lesion burden, links therapeutic opportunities to mechanism (e.g., blood-brain barrier integrity, glymphatic clearance, and cerebrovascular reactivity), and motivates biologically interpretable readouts for patient selection and treatment monitoring. Looking forward, standardized spatial classification (including fine-grained, distance-informed parcellations), harmonized penumbra definitions, and integration of multimodal MRI with pathology will be essential to validate mechanism-specific subtypes and translate them into scalable, clinically usable endpoints.

Acute ischemic stroke is the leading cause of permanent disability and second leading cause of death worldwide. Over the past 10 years, mechanical thrombectomy has become a powerful technique for improving outcomes after large-vessel occlusion in patients with a small baseline infarct. Reperfusion in patients with extensive infarction has historically been considered futile or harmful. However, a recent series of trials showed that endovascular therapy benefits patients who present with extensive baseline infarction. These new data represent a paradigm shift in the approach to stroke therapy, leading to an expansion of indications. Therefore, more patients will benefit from mechanical thrombectomy. Furthermore, these data challenge current definitions of infarct and ischemia as seen on imaging. The data suggest a new era of reperfusion therapy that focuses on optimizing patient-specific approaches and developing adjunctive neuroprotectants and neurorestorative therapies.

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.

Conclusions: 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: 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 recovery-related 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: 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.