Incidence and Risk Factors for Serious Infections in Patients with Neuromyelitis Optica Spectrum Disorder: A Claims Database Study in Japan.

Introduction: Serious infection is a leading cause of mortality in patients with neuromyelitis optica spectrum disorder (NMOSD). We assessed the incidence of and risk factors for serious infections in patients with NMOSD.

Methods: This observational, retrospective cohort study included patients with a first NMOSD diagnosis (index date) between January 2016 and August 2022 in Japan.

Intracellular and Extracellular Localization of Transthyretin and Its Association With Amyloid-β in Alzheimer's Disease Brains.

Transthyretin (TTR) can bind to Aβ and prevent the formation of Aβ fibrils in vitro; it is thus a highly interesting molecule in the field of Alzheimer's disease (AD) research. However, the distribution of TTR and its affinity to Aβ in both healthy human brains and those of AD patients remain unclear. We therefore examined TTR in human brains using postmortem brain samples.

Associations between serum levels of alpha-calcitonin gene-related peptide and clinical features of neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) are characterized by severe inflammation-mediated astrocytopathy in the central nervous system. Neuropathic pain (NP) is highly prevalent among patients with NMOSD, and significantly impairs their quality of life. Alpha-calcitonin gene-related peptide (α-CGRP) is a neuropeptide related to pain and neuroinflammation in the central and peripheral nerves; however, the involvement of α-CGRP in NMOSD pathophysiology remains unexplored.

Effectiveness of satralizumab in a real-world clinical setting in Japan: Interleukin-6 receptor inhibition in neuromyelitis optica spectrum disorder: A six-month interim analysis of a multicenter medical chart review.

Background: Satralizumab is approved in Japan for relapse prevention of neuromyelitis optica spectrum disorder (NMOSD) in aquaporin-4 immunoglobulin G-seropositive (AQP4[+]) patients. However, clinical trial data for Japanese patients are limited.

Methods: SAkuraBeyond, an ongoing real-world observational study (UMIN000050027), evaluates NMOSD relapse over 2.

Plexin D1 accumulation in the spinal motor neurons of patients with amyotrophic lateral sclerosis.

Background: Plexin D1 in endothelial cells (ECs) in the spinal cord (SC) has emerged as a key protein in spinal motor neuron (MN) maturation. Here, we pathologically investigated plexin D1 expression in the SCs of patients with sporadic amyotrophic lateral sclerosis (sALS) to clarify the association between plexin D1 expression in ECs and MN degeneration.

Methods: We measured plexin D1 expression in the ECs of lumbar SC tissue samples from 11 patients with sALS and 8 age- and sex-matched patients with other non-inflammatory neurological diseases (OND) by immunohistochemistry.

FVC-DiP correlates with neurofilament light chain levels in serum and cerebrospinal fluid in patients with ALS.

Background: We previously reported a scale to assess the disease progression rate in patients with amyotrophic lateral sclerosis (ALS), the forced vital capacity decline pattern scale (FVC-DiP). In this study, we investigated the association between FVC-DiP scores and neurofilament light chain (NfL) in the serum and cerebrospinal fluid (CSF) in patients with ALS.

Methods: We performed a retrospective study to examine the association between NfL levels and the rate of disease progression (N=41).

Epitope Mapping of Anti-Neurofascin 155 Antibody in a Large Cohort of Autoimmune Nodopathy Patients.

Objective: Autoimmune nodopathy (AN), a newly recognized disease entity, is an immune-mediated polyneuropathy involving autoantibodies against cell adhesion molecules located in nodes of Ranvier and paranodal regions, such as neurofascin 186 (NF186) and neurofascin 155 (NF155). The present study aimed to identify the epitopes for autoantibodies against NF155 in a large cohort of Japanese patients with anti-NF155 antibody-positive (anti-NF155+) AN.

Methods: Human embryonic kidney 293 cells stably expressing NF155, NF186, or the third to fourth fibronectin type III domain region (Fn3-Fn4) of NF155, as well as cells transiently expressing Fn3, Fn4, or the shorter Fn3-Fn4 region of NF155, were developed.

[Sex-Based Differences and Shared Decision-Making in Myasthenia Gravis].

Myasthenia gravis is an autoimmune disease of the neuromuscular junctions. Studies have shown that its prevalence is slightly higher in females, that female patients are more refractory to treatment, and that their post-treatment quality of life is more difficult to improve. Recently, multiple novel treatment options have become available, and more opportunities for shared decision-making are being observed in the process of treatment selection.

Contribution of germline and somatic mutations to risk of neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease characterized by optic neuritis and transverse myelitis, with an unclear genetic background. A genome-wide meta-analysis of NMOSD in Japanese individuals (240 patients and 50,578 controls) identified significant associations with the major histocompatibility complex region and a common variant close to CCR6 (rs12193698; p = 1.8 × 10, odds ratio [OR] = 1.

Blood exosome connexins and small RNAs related to demyelinating disease activity.

Objectives: To assess blood exosome (Ex)-connexin (Cx)43 (encoded by GJA1) and its truncated isoforms in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), which show distinct alterations in astroglial Cx43.

Methods: Serum Exs from 48 patients with MS (34 relapsing-remitting, 14 secondary-progressive), 35 with NMOSD, 20 with other inflammatory neurologic diseases (OIND), and 17 healthy controls (HC) were subjected to quantitative Western blotting for Cx43, single-molecule array for neurofilament-L, and quantitative polymerase chain reaction for non-coding RNAs detected by RNA sequencing. Sera from control and astroglia-specific Cx43 inducible conditional knockout (Cx43-icKO) mice with experimental autoimmune encephalomyelitis (EAE) were also tested.

The flow cytometric analysis of depression focusing on modern-type depression and hikikomori: Exploring the link between subtypes of depression and immunological imbalances.

Introduction: Depression includes different phenotypes. Modern-type depression (MTD) is a gateway disorder to pathological social withdrawal, known as hikikomori. Adverse childhood experiences (ACEs) are also important aetiologies of depression.

The Efficacy of Eculizumab in the Acute Phase of Neuromyelitis Optica Spectrum Disorder: A Case Series Study.

Eculizumab, a monoclonal antibody against complement C5, has been approved to prevent neuromyelitis optica spectrum disorder (NMOSD) relapse. Although complement activation leads to neuroinflammation and tissue necrosis in NMOSD attacks, clinical reports on the efficacy of eculizumab in the acute phase of NMOSD are limited. To clarify its effectiveness against clinical symptoms in NMOSD attacks, we described five patients with NMOSD who were administered eculizumab soon after treatment for an attack.

Postnatal Allergic Inhalation Induces Glial Inflammation in the Olfactory Bulb and Leads to Autism-Like Traits in Mice.

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. To explore its pathophysiology, we investigated the association between neonatal allergic exposure and behavioral changes. Adult female C57BL/6J mice were immunized with adjuvant (aluminum hydroxide) or ovalbumin emulsified with adjuvant.

Clinical practice guidelines for multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease 2023 in Japan.

Background: The previous Japanese clinical practice guidelines for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) were published in 2017. Recently, for the first time in 6 years, the MS and NMOSD guideline development committee revised the Japanese guidelines for MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Methods: The committee utilized the Grading of Recommendations Assessment, Development, and Evaluation system based on the "Minds Handbook for Clinical Practice Guideline Development 2020 Ver.

A rapidly progressive multiple system atrophy-cerebellar variant model presenting marked glial reactions with inflammation and spreading of α-synuclein oligomers and phosphorylated α-synuclein aggregates.

Multiple system atrophy (MSA) is a severe α-synucleinopathy facilitated by glial reactions; the cerebellar variant (MSA-C) preferentially involves olivopontocerebellar fibres with conspicuous demyelination. A lack of aggressive models that preferentially involve olivopontocerebellar tracts in adulthood has hindered our understanding of the mechanisms of demyelination and neuroaxonal loss, and thus the development of effective treatments for MSA. We therefore aimed to develop a rapidly progressive mouse model that recaptures MSA-C pathology.

Distinct retinal reflectance spectra from retinal hyperspectral imaging in Parkinson's disease.

Background: Recent developments in the retinal hyperspectral imaging method have indicated its potential in addressing challenges posed by neurodegenerative disorders, such as Alzheimer's disease. This human clinical study is the first to assess reflectance spectra obtained from this imaging as a tool for diagnosing patients with Parkinson's disease (PD).

Methods: Retinal hyperspectral imaging was conducted on a total of 40 participants, including 20 patients with PD and 20 controls.

Network Meta-analysis of Ravulizumab and Alternative Interventions for the Treatment of Neuromyelitis Optica Spectrum Disorder.

Introduction: Anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) is a complement-mediated autoimmune disease in which unpredictable and relapsing attacks on the central nervous system cause irreversible and accumulating damage. Comparative efficacy of new NMOSD therapies, such as ravulizumab, with established therapies is critical in making informed treatment decisions.

Methods: Efficacy of ravulizumab relative to established AQP4-Ab+ NMOSD treatments, such as eculizumab, inebilizumab, and satralizumab, was evaluated in a Bayesian network meta-analysis (NMA).