ObjectiveTo characterize the burden and MRI subtypes of cerebral small vessel disease (cSVD) in antiphospholipid syndrome (APS) and to identify clinical factors associated with cSVD.MethodsWe retrospectively analyzed 132 patients with APS and age- and sex-matched healthy controls. MRI markers for cSVD, including lacunes, enlarged perivascular spaces (EPVS), microbleeds, and white matter hyperintensities (WMH), were rated using validated scales. Total cSVD scores (0-4) were calculated. Logistic regression analyses adjusted for age, sex, and disease duration were used to identify risk factors.ResultsMore than half of patients with APS (51.5%) exhibited cSVD, whereas only 24.2% had a history of stroke. Lacunes were the predominant subtype (46.2%), followed by WMH (16.7%), EPVS (14.4%), and microbleeds (12.1%). Subclinical cSVD was present in 34.8% of patients with APS without neurological symptoms. Hypertension (OR 3.69, 95%CI 1.17-11.65, p = 0.026), prior thrombosis (OR 22.15, 95%CI 2.11-232.27, p = 0.010), and prior stroke (OR 10.71, 95%CI 2.47-46.36, p = 0.002) were independently associated with cSVD, while individual aPL profiles were not.ConclusioncSVD is a common feature in patients with APS and often occurs in the absence of neurological manifestations. The predominance of lacunes suggests a pattern of recurrent microvascular injury. Hypertension and thrombotic history are major contributors, underscoring the need for comprehensive vascular risk assessment. These findings highlight the potential value of MRI screening in selected patients with APS and call for longitudinal studies to clarify its prognostic significance.

Acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) are both cerebrovascular accidents where clinical management remains predominantly symptomatic, with few immunologically-targeted approaches. This cross-sectional study compared AIS (n = 73), ICH (n = 28), and controls (n = 31) in terms of demographic, clinical, laboratory, and immunological parameters, including regulatory T cells (Tregs), effector regulatory T cells (eTregs), CD4[+] T cells, and cytokines. ICH patients showed lower total cholesterol (TCHO), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) than both controls and AIS patients, whereas AIS patients had reduced high-density lipoprotein cholesterol (HDL-C) versus controls. Both stroke groups exhibited higher proportions of Tregs and eTregs versus controls. Correlation analyses revealed divergent immune networks: in AIS, the percentages of Tregs and eTregs positively correlated with interleukin-10 (IL-10), interleukin-1β (IL-1β), and interleukin-2 receptor (IL-2R), whereas in ICH, these percentages negatively correlated with tumor necrosis factor-α (TNF-α). We conclude that AIS features 'compensatory immune regulation', while ICH is characterized by 'uncontrolled innate immune inflammation', indicating two distinct immunological diseases with implications for subtype-specific therapy.

Vascular Cognitive Impairment and Dementia (VCID) comprises a heterogeneous group of cognitive disorders linked to cerebrovascular pathology and represents a major contributor to age-related cognitive decline worldwide. A hallmark pathological feature across VCID subtypes, including post-stroke dementia, subcortical ischemic vascular dementia, and mixed dementia, is chronic cerebral hypoperfusion, which is associated with progressive white matter (WM) degeneration. In preclinical research, sustained hypoperfusion is most commonly modeled using bilateral carotid artery stenosis (BCAS) in mice to investigate VCID mechanisms and therapeutic strategies. BCAS studies reveal that variables, including the severity of stenosis and the duration of hypoperfusion, critically influence the magnitude and temporal trajectory of WM pathology and cognitive dysfunction. Following BCAS, disease progression proceeds as a spatiotemporally ordered cascade of injury, characterized by early neuroinflammatory activation, blood-brain barrier dysfunction, progressive oligodendrocyte loss and demyelination, and subsequent cognitive decline. These pathological processes are modifiable through pharmacological, genetic, lifestyle, and neuromodulatory interventions that preserve WM integrity and cognitive function. The BCAS model is a critical platform for defining WM pathology, clarifying the temporal evolution of VCID, and advancing the development of therapeutic strategies targeting vascular contributions to cognitive aging.

Multi-infarct dementia (MID) is a major subtype of vascular cognitive impairment, second only to Alzheimer's disease as a leading cause of dementia worldwide. Unlike neurodegenerative dementias, MID results from recurrent vascular insults, producing stepwise cognitive decline. Animal models have become indispensable for understanding MID mechanisms and testing therapies, yet no single model fully captures human disease complexity. This review synthesizes current knowledge of embolic, chronic cerebral hypoperfusion, hypertensive, and large animal models of MID. We compare methodological strategies, neuropathological features (including white matter injury, neuroinflammation, and blood-brain barrier disruption), and behavioral outcomes. Key limitations include poor replication of infarct heterogeneity, absence of comorbidities, and translational failures. Emerging directions such as multi-hit paradigms and mixed dementia models are discussed. We conclude that integrative, multifactorial models are essential for improving translational relevance and developing effective therapies.

Calmodulinopathies are caused by mutations in calmodulin (CaM) and result in debilitating cardiac arrythmias such as long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). In addition, many patients exhibit neurological comorbidities, including developmental delay and autism spectrum disorder. Prior studies have identified the impairment of Ca2+/CaM-dependent inactivation (CDI) of CaV1.2 channels as a major pathogenic mechanism leading to the LQTS phenotype in these patients. However, the impact of these mutations on other voltage-gated calcium channels (VGCCs) has yet to be fully explored. Here, we examine the potential for pathological CaM variants to impair the Ca2+/CaM-dependent regulation of CaV1.3 and CaV2.1, both essential for neuronal function. We find that pathogenic mutations in CaM can impair the CDI of CaV1.3, with overlapping yet distinct disruption of the Ca2+-dependent facilitation (CDF) of CaV2.1 channels. Moreover, while the majority of CaM variants demonstrated the ability to bind the IQ region of each channel, differences were noted between CaV1.3 and CaV2.1, demonstrating unique CaM interactions across the two channel subtypes. Further, C-lobe CaM variants display a reduced ability to sense Ca2+ when in complex with the CaV IQ domains, explaining the Ca2+/CaM regulation deficits. Overall, these results support the possibility that disrupted Ca2+/CaM regulation of multiple VGCCs may contribute to the pathogenesis of calmodulinopathies.

BACKGROUND: Lesion location is a major source of post-stroke neurophysiological heterogeneity, yet most electroencephalography (EEG) studies analyze patients as a single group, limiting lesion-specific biomarkers and translation. We proposed a lesion-centric, multi-scale EEG framework integrating local oscillations, inter-regional connectivity, and hemispheric asymmetry with machine learning to characterize and decode basal ganglia (P1), fronto-temporal/centrum semiovale (P2), and brainstem (P3) lesions. METHODS: Five-minute eyes-open, 128-channel resting EEG ([Formula: see text]) was recorded in 57 subacute stroke patients (P1 = 22, P2 = 18, P3 = 17) and 22 matched controls. From artifact-minimized [Formula: see text] segments, ROI-averaged power spectral density (PSD) (θ: 4–[Formula: see text]; α: 7–[Formula: see text]; [Formula: see text]: 12–[Formula: see text]; peak α frequency), current source density (CSD)-based magnitude-squared coherence, and directional BSI (dirBSI) were computed. Between-group and subgroup differences were assessed using t-tests/Wilcoxon and ANOVA/Kruskal–Wallis with Benjamini–Hochberg FDR ([Formula: see text]). EEG–behavior associations were examined with Spearman correlations. For machine learning, common spatial patterns (CSP) features were classified using linear discriminant analysis (LDA) with leave-one-subject-out cross-validation. To align with clinical workflow, we report HC vs P as “stroke detection/screening” and patient-only P1/P2/P3 classification as “lesion subtype decoding for stratification” (along with pairwise P1 vs P2, P1 vs P3, and P2 vs P3 models). An EEGNet baseline was evaluated for comparison. RESULTS: Increased α power and a leftward peak α shift were observed in patients (HC: [Formula: see text]; P: [Formula: see text]; [Formula: see text]). Pre-FDR, θ-band frontal–motor connectivity was strengthened, while posterior P–O connectivity in α/[Formula: see text] was weakened. Ipsilesional dominance in θ was indicated by dirBSI (HC: [Formula: see text]; P: [Formula: see text]; [Formula: see text]). Across lesions, [Formula: see text] power differences in central/parietal/occipital ROIs were detected pre-FDR, with higher parietal [Formula: see text] in P3; α-band asymmetry was stronger in P1/P2 and more symmetric in P3 ([Formula: see text]). EEG–behavior correlations did not survive FDR. Using CSP+LDA, accuracies of 92.41% (HC vs P), 94.87% (P1 vs P3), 85.71% (P2 vs P3), and 82.50% (P1 vs P2) were achieved; all binary AUCs exceeded 0.85; three-class accuracy reached 85.96%. CONCLUSION: This multi-scale EEG framework identifies lesion-associated neurophysiological signatures and demonstrates feasible lesion subtype decoding, supporting the potential of EEG biomarkers for objective stratification and precision neurorehabilitation.