Clinical neurology:

Recently, 6 randomized controlled trials of endovascular treatment (EVT) versus medical management in anterior circulation large vessel occlusion with large-core documented significant benefit of EVT on functional outcome. Moreover, one trial reported the benefit of EVT in the large-core category (Alberta Stroke Program Early Computed Tomography Score, 0-2). These results are considered paradoxical by some as they contradict the prevailing view that the presence of a large core precludes the possibility of good outcomes following reperfusion. They, in turn, led some investigators to question the applicability of the core/penumbra model in the case of large-core stroke and even its overall validity, specifically regarding the notion that the core reliably predicts tissue infarction. Here, we discuss the trial results and propose alternative explanations for the large-core paradox. First, although EVT does improve outcomes as compared with medical management, overall outcomes remain poor in ≈80% of the treated population. Second, the assessment of core extent on imaging, particularly with computed tomography, is potentially inaccurate, especially in the early time window. Third, consistent with observational studies, some randomized controlled trial substudies suggest that the benefit of EVT in this population derives at least in part from the salvage of penumbra, which appears to have been present in a large percentage of enrolled patients. Fourth, the markedly reduced perfusion that prevails within large cores facilitates the early development of vasogenic edema. This heterogeneity of tissue injury may, in turn, lead to an overestimation of true core/neuronal death as estimated with computed tomography and magnetic resonance imaging. Assessing patients with apparent large core should consider these notions when discussing eligibility for EVT. Early reperfusion of large-core patients is expected to both target any residual penumbra and prevent the development of vasogenic edema within the severely hypoperfused areas. These considerations underscore the need for more reliable methods to identify irreversible neuronal injury inside the imaging-based estimated core.

CONCLUSIONS: RAR is significantly associated with the prevalence and prognosis of depression. Nevertheless, more investigation is required to elucidate the underlying processes.

BACKGROUND AND OBJECTIVES: Phosphorylated tau at threonine 217 (p-tau217) is a highly sensitive blood-based biomarker for Alzheimer disease (AD) pathology, showing high diagnostic accuracy. However, its prognostic value across different clinical stages of AD remains unclear. The aim of this study was to assess the prognostic utility of plasma p-tau217, measured using a commercially available immunoassay, regarding clinical and functional decline across the clinical stages of AD in a cohort with up to 10 years of follow-up.

BACKGROUND: Depression is a major global mental health issue. Previous studies have suggested an association between the intake of polyunsaturated fatty acids (PUFAs) and depression, but the conclusions remain controversial. Additionally, there is limited research on the relationship between the intake of specific fatty acid subtypes, such as linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and Docosapentaenoic acid (DPA), and depression.

Secondary stroke prevention encompasses many approaches, including antithrombotic therapy, risk factor management, and a healthy lifestyle. Recommendations are typically based on the results of randomized clinical trials that provide evidence of benefit. However, in some situations, clinicians extrapolate the results of clinical trials into everyday practice, or trials have not provided sufficient information to make treatment decisions. This review will discuss 4 scenarios: dual-antiplatelet therapy, the perils of combining antiplatelet and anticoagulation, indications for statin therapy, and therapeutic considerations for patients with paroxysmal atrial fibrillation.

OBJECTIVES: We analyzed the genotypic and phenotypic features of patients with psychosis of epilepsy (POE).

OBJECTIVE: The goal was to examine the effect of sociodemographic variables, Alzheimer's disease (AD) clinical stages and pathology on brain metabolism in Down syndrome (DS).

CONCLUSIONS: There is a stable negative correlation between dietary fiber intake and stroke risk. High fiber intake is associated with reduced all-cause mortality among stroke survivors. Additionally, genetic prediction further demonstrates a causal relationship between dietary fiber and reduced risk of small vessel stroke.

BACKGROUND: Weight loss behaviors are increasingly common worldwide. While healthy weight loss methods, such as calorie control and exercise, can improve both physical and mental health, harmful practices-such as extreme dieting and the misuse of diet pills-may contribute to depressive symptoms. Understanding the psychological impact of different weight loss strategies is essential for promoting overall well-being.

CONCLUSIONS: CMI is associated with an increased risk of suicidal ideation, with depression and CVD acting as partial mediators in this relationship. Reducing CMI with the goal of improving obesity and glucose and lipid disorders may be a key strategy to reduce suicidal ideation.

CONCLUSIONS: The AISI level exhibited a U-shaped association with depression, indicating that maintaining AISI within a reasonable range may help reduce the prevalence of depression.

CONCLUSIONS: ASyS timing and type significantly affect epilepsy and mortality risk after stroke, improving epilepsy prediction and guiding patient counseling.

CONCLUSIONS: These findings suggested that dysfunction in mitochondria-related genes may underlie the molecular mechanisms of ADHD and SCZ, providing novel biomarkers for diagnosis and therapeutic interventions.

Abstract: Among the intrathecal inflammatory niches where compartmentalized inflammation persists and plays a pivotal role in progressive multiple sclerosis (MS), choroid plexus (CP) has recently received renewed attention. To better characterize the neuropathological/molecular correlates of CP in progressive MS and its potential link with other brain inflammatory compartments, such as perivascular spaces and leptomeninges, the levels, composition and phenotype of CP immune infiltration in lateral ventricles of the hippocampus were examined in 40 post-mortem pathologically confirmed MS and 10 healthy donors, using immunochemistry/immunofluorescence and in-situ sequencing. Significant inflammation was detected in the CP of 21 out of the 40 MS cases (52%). The degree of CP inflammation was found correlated with: number of CP macrophages (R: 0.878, p = 1.012 x 10) and high frequency of innate immune cells expressing the markers MHC-class II, CD163, CD209, CD11c, TREM2 and TSPO; perivascular inflammation (R: 0.509, p = 7.921 x 10), and less with meningeal inflammation (R: 0.365, p = 0.021); number of active lesions (R: 0.51, p: 3.524 x 10). However, it did not significantly correlate with any clinical/demographic characteristics of the examined population. In-situ sequencing analysis of gene expression in the CP of 3 representative MS cases and 3 controls revealed regulation of inflammatory pathways mainly related to 'type 2 immune response', 'defense to infections', 'antigen processing/presentation'. Analysis of 78 inflammatory molecules in paired post-mortem CSF, the levels of fibrinogen (R: 0.640, p = 8.752 x 10), PDGF-bb (R: 0.470, p = 0.002), CXCL13 (R: 0.428, p = 0.006) and IL15 (R: 0.327, p = 0.040) were correlated with extent of CP inflammation. Elevated fibrinogen and complement deposition were found in CP and in underlying subependymal periventricular areas, according to "surface-in" gradient associated with concomitant prominent microglia activation. CP inflammation, predominantly characterized by innate immunity, represents another key determinant of intrathecal, compartmentalised inflammation persisting in progressive MS, which may be possibly activated by fibrinogen and influence periventricular pathology, even without substantial association with clinical features.

CONCLUSIONS: The study provides evidence for the association between urticaria subtypes and psychiatric disorders, complementing existing observational studies. In addition, our study implies the involvement of gut microbiota in idiopathic and allergic urticaria. However, the specific mechanisms of bacterial action remain to be clarified.

BACKGROUND: The RECOVER trial randomized 493 patients with markedly treatment-resistant major depressive disorder to treatment-as-usual with or without active vagus nerve stimulation (VNS Therapy). While the primary outcome measure did not statistically separate the treatment conditions, the field may lack optimal metrics for quantifying symptom improvement in markedly treatment-resistant patients.

OBJECTIVE: The objective was to investigate the efficacy and safety of clopidogrel-aspirin versus aspirin alone in patients after ischemic stroke by glycemic status using data from the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial.

OBJECTIVES: The aim of this study was to report the clinical features, disease-modifying treatment (DMT) response, and outcomes of children with MOG-IgG who fulfill the 2017 McDonald criteria for multiple sclerosis (MS).

OBJECTIVE: We aimed to assess the bidirectional relationship between mental disorders and menstrual irregularities using a two-sample Mendelian randomization (MR) approach.

IMPORTANCE: Guidelines recommend 150 min per week (min/wk) or more of moderate to vigorous physical activity (MVPA) for mental health benefits. However, the relative effects of concentrated against more evenly distributed activity patterns remain unclear.