多発性硬化症／視神経脊髄炎

Multiple sclerosis (MS), an immune-mediated inflammatory demyelinating disorder of the central nervous system (CNS), is driven by microglia as key orchestrators of neuroinflammation. This study assessed the preventive potential of temporin-GHaR6R (GHaR6R), an antimicrobial peptide derived from Hylarana guentheri skin, using the experimental autoimmune encephalomyelitis (EAE) murine model of MS. Preventive administration of GHaR6R significantly reduced EAE incidence and alleviated clinical severity, while histopathological analyses (HE and LFB staining) revealed attenuated inflammatory cell infiltration and demyelination in the spinal cord. Mechanistically, GHaR6R suppressed M1 microglial polarization, thereby limiting excessive neuroinflammatory activation. In vitro, GHaR6R inhibited TNF-α and IL-6 secretion, reduced mitochondrial ROS production, preserved mitochondrial membrane potential in LPS-activated BV2 microglia, and promoted the shift from M1 to M2 microglial polarization. Consistent with these findings, GHaR6R downregulated mitochondrial fission protein Drp-1 while upregulating the fusion mediators MFN1 and MFN2 in both EAE-affected spinal cords and LPS-stimulated BV2 cells. Immunofluorescence analysis showed increased colocalization of Iba-1 with MFN1/2, indicating enhanced mitochondrial fusion in microglia. Taken together, these results demonstrate that GHaR6R ameliorates EAE progression by modulating microglial mitochondrial dynamics, mitigating neuroinflammation, and inhibiting M1 polarization, highlighting its potential as an early prophylactic intervention for MS.

BACKGROUND: Growing evidence supports choroid plexus (CP) involvement in MS pathophysiology, but phase-specific associations according to recent inflammatory activity and longitudinal dynamics remain unclear. OBJECTIVE: To characterize CP alterations in MS using volumetric and quantitative magnetic resonance imaging (MRI) and explore associations with neuroinflammation and neurodegeneration. METHODS: We analyzed cross-sectional and 2-year longitudinal data from 101 patients with active relapsing MS (RMS), 83 with inactive progressive MS (PMS), and 100 controls, with MS groups stratified by inflammatory activity within the prior year. CP volume, quantitative T1, and magnetization transfer saturation (MTsat) were assessed alongside imaging, serum, and clinical measures, with validation in a second cohort (62 active/357 inactive MS). RESULTS: CP volume was increased in both active RMS and inactive PMS and was associated with lower total and cortical brain volumes. Associations with brain microstructural damage were more pronounced in periventricular regions, compatible with a surface-in pattern. Similar associations were observed in controls, suggesting CP volume may reflect processes beyond MS-specific pathology, including physiological factors. Longitudinally, CP volume increased exclusively in active RMS, with faster expansion associated with thalamic atrophy. CP MTsat was associated with cortical and paramagnetic rim lesions in inactive PMS. CONCLUSION: CP enlargement is consistent across MS phases. Longitudinal expansion occurs in active inflammatory disease and is associated with neurodegenerative changes.

BACKGROUND: Diet intake has been implicated in multiple sclerosis (MS) risk; however, the mechanisms are unclear. OBJECTIVE: Investigated whether DNA methylation (DNAm) mediated the associations of diet and MS onset-risk. METHODS: We utilised data from the Ausimmune case-control study, comparing 201 MS cases and 342 matched controls. Diet scores were estimated from food frequency questionnaires. Genotypes and DNAm were measured using the Illumina Global Screening Array and MethylationEPIC BeadChip, respectively. The 2432 top-ranked MS-associated cytosine-guanine pairs (CpGs) were dimension-reduced using Weighted-Gene Correlation Network Analysis (WGCNA) to five (A1-A5) DNAm module scores. Diet-MS associations were evaluated using multivariable logistic regression, and mediation through DNAm modules by counterfactual mediation analysis. We conducted stratified analyses by human leukocyte antigen (HLA) genotypes. RESULTS: The alternate Mediterranean diet score (aMED) including unprocessed red meat (aMED-Red) (adjusted odds ratio (aOR) = 0.88; 95% confidence interval (CI) = 0.79-0.98) and Healthy diet scores (aOR = 0.86; 95% CI = 0.75-0.98) were associated with lower MS onset-risk. A5 DNAm module significantly mediated the associations of aMED (30.3%; p = 0.027) and aMED-Red (22.1%; p = 0.037) scores with MS onset-risk. Stratified by HLA genotypes, no differences in diet-MS associations or A5 DNAm-module mediation were seen. CONCLUSION: Up to one-third of the associations of Mediterranean diet scores with MS onset-risk were explained by DNAm in genes involved in immune function. These findings provide a better understanding of the underlying MS pathogenesis and inform future research.

INTRODUCTION: Anti-CD20 monoclonal antibodies are widely used as high-efficacy treatment agents (HETAs) in multiple sclerosis (MS). In patients treated with ocrelizumab (OCR), reduced serum IgG levels are a common laboratory abnormality. Infections are among the most frequently observed adverse events during OCR therapy. MATERIAL AND METHODS: We analyzed the humoral immune response during OCR therapy in 52 people with multiple sclerosis (PwMS) and assessed the safety of this treatment, including treatment-related adverse events and infection rates over a period of up to six years. RESULTS: After three years of treatment, immunoglobulin G (IgG) and IgG1 levels decreased, particularly in the relapsing-remitting MS (RMS) group. Higher body mass index (BMI) was associated with lower Ig levels and greater CD19+ cell depletion. Infections were more frequent in patients with relapses within 3 months prior to OCR initiation. Clinical implications/future directions. Ocrelizumab treatment for up to six years showed a manageable safety profile. Given the higher infection risk in patients with greater disease activity, earlier HETA initiation may be beneficial. The association between higher BMI and CD19+ cell depletion warrants further study to support personalized OCR dosing strategies.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a rare autoimmune demyelinating disorder of the central nervous system that can present with varied neurological symptoms. While commonly mistaken for multiple sclerosis or neuromyelitis optica spectrum disorders, MOGAD can also mimic cerebrovascular events, posing a diagnostic challenge. We report a case of a 30-year-old male who initially presented with acute-onset left-sided hemiplegia and right facial palsy, raising suspicion of an ischemic stroke. Despite thrombolysis, his recurrent neurological symptoms, including dysarthria and cerebellar ataxia, prompted further evaluation. Neuroimaging revealed hyperintense lesions in the right hemi-pons and bilateral middle cerebellar peduncles, raising the possibility of a demyelinating disorder. MOG-IgG seropositivity confirmed the diagnosis of MOG encephalitis. The patient responded well to pulse corticosteroid therapy, followed by maintenance immunosuppression with mycophenolate mofetil, and remained asymptomatic on follow-up. This case underscores the importance of considering autoimmune demyelinating disorders in young patients with recurrent neurological deficits and clinico-radiological dissociation. Early recognition and appropriate immunotherapy can prevent unnecessary thrombolysis and improve patient outcomes. Clinicians should maintain a high index of suspicion for MOGAD as a potential stroke mimic in atypical presentations.