Posterior fossa ring-enhancing lesions in the adult immunocompetent host: illustrative cases, systematic review, and proposed diagnostic algorithm.

Purpose: Posterior fossa ring-enhancing lesions (PFREL) in the adult immunocompetent hosts pose a diagnostic challenge. We aimed to evaluate the spectrum of PFREL etiologies and propose a diagnostic algorithm.

Methods: This study involved a retrospective analysis of PFREL cases from our institution (January 2023 to April 2024) and a systematic literature review conducted using Embase and PubMed databases following the PRISMA 2020 guidelines.

Safety and Efficacy of Fingolimod and Ocrelizumab in Pediatric Patients With Multiple Sclerosis.

Background: Fingolimod and ocrelizumab are approved treatments for adults with multiple sclerosis (MS); however, only fingolimod is approved by the Food and Drug Administration for the treatment of pediatric MS. Currently, there are limited data for the safety and efficacy of ocrelizumab use in children.

Methods: This retrospective cohort study included patients with relapsing-remitting MS who started either ocrelizumab or fingolimod before age 18 years.

Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.

Age-related dopamine (DA) neuron loss is a primary feature of Parkinson's disease. However, whether similar biological processes occur during healthy aging, but to a lesser degree, remains unclear. We therefore determined whether midbrain DA neurons degenerate during aging in mice and humans.

Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease.

Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, most of the disease heritability has yet to be uncovered, suggesting that there is substantial genetic risk conferred by other forms of genetic variation. There are over one million short tandem repeats (STRs) in the genome, and their link to AD risk has not been assessed.

Sub-cellular population imaging tools reveal stable apical dendrites in hippocampal area CA3.

Apical and basal dendrites of pyramidal neurons receive anatomically and functionally distinct inputs, implying compartment-level functional diversity during behavior. To test this, we imaged in vivo calcium signals from soma, apical dendrites, and basal dendrites in mouse hippocampal CA3 pyramidal neurons during head-fixed navigation. To capture compartment-specific population dynamics, we developed computational tools to automatically segment dendrites and extract accurate fluorescence traces from densely labeled neurons.

Net Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: The net clinical effect of early vs later direct oral anticoagulant (DOAC) initiation after atrial fibrillation-associated ischemic stroke is unclear.

Objective: To investigate whether early DOAC treatment is associated with a net clinical benefit (NCB).

Design, Setting, And Participants: This was a post hoc analysis of the Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation (ELAN) open-label randomized clinical trial conducted across 103 sites in 15 countries in Europe, the Middle East, and Asia between November 6, 2017, and September 12, 2022, with a 90-day follow-up.

Reshaping computational neuropsychiatry beyond synaptopathy.

Computational neuropsychiatry is a leading discipline to explain psychopathology in terms of neuronal message passing, distributed processing, and belief propagation in neuronal networks. Active Inference (AI) has been one of the ways of representing this dysfunctional signal processing. It involves that all neuronal processing and action selection can be explained by maximizing Bayesian model evidence, or minimizing variational free energy.

Characteristics of TSPO expression in marmoset EAE.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and is a leading non-traumatic cause of disability in young adults. The 18 kDa Translocator Protein (TSPO) is a mitochondrial protein and positron emission tomography (PET)-imaging target that is highly expressed in MS brain lesions. It is used as an inflammatory biomarker and has been proposed as a therapeutic target.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

14-3-3 promotes sarcolemmal expression of cardiac Ca1.2 and nucleates isoproterenol-triggered channel superclustering.

The L-type Ca channel (Ca1.2) is essential for cardiac excitation-contraction coupling. To contribute to the inward Ca flux that drives Ca-induced-Ca-release, Ca1.

Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Randomized Clinical Trial.

Importance: In the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial, anticoagulation did not prevent recurrent stroke among patients with a recent cryptogenic stroke and atrial cardiopathy. It is unknown whether anticoagulation prevents covert infarcts in this population.

Objective: To test the use of apixaban vs aspirin for prevention of nonlacunar covert infarcts after cryptogenic stroke in patients with atrial cardiopathy.

Linking higher amyloid beta 1-38 (Aβ(1-38)) levels to reduced Alzheimer's disease progression risk.

Introduction: The beneficial effects of amyloid beta 1-38, or Aβ(1-38), on Alzheimer's disease (AD) progression in humans in vivo remain controversial. We investigated AD patients' cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.

Methods: Cognitive function and diagnostic change were assessed annually for 3 years in 177 Aβ-positive participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia from the German Center for Neurodegenerative Diseases (DZNE) longitudinal cognitive impairment and dementia study (DELCODE) cohort using the Mini-Mental State Examination (MMSE), Preclinical Alzheimer's Cognitive Composite (PACC), Clinical Dementia Rating (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

Association of a multiplex immune marker panel with incident cognitive impairment and dementia: The Northern Manhattan Study.

Objective: To determine whether a panel of immune markers adds significant information to known correlates of risk of dementia and cognitive impairment.

Background: The impact of immune mechanisms on dementia risk is incompletely characterized.

Design/methods: A subsample of the Northern Manhattan Study, a prospective cohort study in the racially/ethnically diverse population of New York City, underwent comprehensive neuropsychological testing up to three times, at approximately 5-year intervals.

Heterozygous variants in AP4S1 are not associated with a neurological phenotype.

Biallelic loss-of-function variants in AP4S1 cause childhood-onset hereditary spastic paraplegia. A recent report suggested that heterozygous AP4S1 variants lead to a syndrome of lower limb spasticity and dysregulation of sphincter function. We critically evaluate this claim against clinical observations in 28 heterozygous carriers of the same AP4S1 variant (NM_007077.

Amyotrophic lateral sclerosis caused by FUS mutations: advances with broad implications.

Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.

Background: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.

Methods: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally.

Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study.

Background: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study.

Gene Therapy for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a devastating, aggressive primary brain tumor with poor patient outcomes and a five-year survival of less than 10%. Significant limitations to effective GBM treatment include poor drug delivery across the blood-brain barrier, drug resistance, and complex genetic tumor alterations. Gene therapy uses a mechanism different from other GBM therapies to reduce tumor growth and enhance antitumor immunity.

MicroRNA Expression Profile in Acute Ischemic Stroke.

Acute ischemic stroke with large vessel occlusion (LVO) continues to present a considerable challenge to global health, marked by substantial morbidity and mortality rates. Although definitive diagnostic markers exist in the form of neuroimaging, their expense, limited availability, and potential for diagnostic delay can often result in missed opportunities for life-saving interventions. Despite several past attempts, research efforts to date have been fraught with challenges likely due to multiple factors, such as the inclusion of diverse stroke types, variable onset intervals, differing pathobiologies, and a range of infarct sizes, all contributing to inconsistent circulating biomarker levels.

Elevated uric acid levels, mortality and cognitive impairment in children with severe malaria.

We investigated the role of uric acid in the pathogenesis of severe malaria (SM) in two independent cohorts of children with SM. Hyperuricemia (blood uric acid ≥ 7 mg dl) was present in 25% of children with SM and was associated with increased in-hospital mortality and postdischarge mortality in both cohorts. Increased blood uric acid levels were also associated with worse scores in overall cognition in children with SM < 5 years old in both cohorts.

Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice.

The gut microbiome modulates the anti-seizure effects of the ketogenic diet, but how specific dietary formulations differentially modify the gut microbiome in ways that impact seizure outcome is poorly understood. We find that medical ketogenic infant formulas vary in macronutrient ratio, fat source, and fiber content and differentially promote resistance to 6-Hz seizures in mice. Dietary fiber, rather than fat ratio or source, drives substantial metagenomic shifts in a model human infant microbial community.

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.

3-HKA Promotes Vascular Remodeling After Stroke by Modulating the Activation of A1/A2 Reactive Astrocytes.

Ischemic stroke is the most common cerebrovascular disease and the leading cause of permanent disability worldwide. Recent studies have shown that stroke development and prognosis are closely related to abnormal tryptophan metabolism. Here, significant downregulation of 3-hydroxy-kynurenamine (3-HKA) in stroke patients and animal models is identified.