Mutations in myelin regulatory factor (MYRF) are linked to demyelinating disorders. We report a 38‐year‐old male who developed acute symmetric leukoencephalopathy mimicking a stroke following an influenza A virus infection. While clinical symptoms markedly improved with corticosteroids, MRI revealed persistent white matter lesions, contrasting with the known phenotype of MYRF‐related mild encephalopathy with reversible myelin vacuolization (MMERV). Genetic analysis identified a novel MYRF variant (c.2204G>A, p.Gly735Asp) in its C‐terminal domain, with familial cosegregation confirming autosomal dominant inheritance. This case demonstrates that viral infections can trigger severe MYRF‐related pathology and establishes persistent leukoencephalopathy as a novel clinical phenotype within the MYRF disease spectrum.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune astrocytopathy characterized by inflammatory demyelinating lesions in the central nervous system. Area postrema syndrome (APS), marked by intractable nausea, vomiting, and hiccups, is a recognized but less common initial manifestation. Post‐infectious autoimmunity triggered by SARS‐CoV‐2 has been increasingly associated with NMOSD pathogenesis; however, the clinical significance of direct viral neuroinvasion and its relationship to divergent patient outcomes remains poorly understood. Methods: We report two female patients who developed isolated APS shortly after COVID‐19 infection. Both patients underwent comprehensive neurological evaluation, including brain and spinal magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis with metagenomic next‐generation sequencing (mNGS), and serological testing for aquaporin‐4 immunoglobulin G (AQP4‐IgG), myelin oligodendrocyte glycoprotein immunoglobulin G (MOG‐IgG), and glial fibrillary acidic protein immunoglobulin G (GFAP‐IgG) using cell‐based assays. Clinical outcomes were compared in the context of antibody serostatus and treatment strategies. A review of the relevant literature on post‐COVID NMOSD was also performed. Results: Both patients presented with intractable vomiting and hiccups following SARS‐CoV‐2 infection, and MRI demonstrated isolated T2/FLAIR hyperintense lesions in the dorsal medulla consistent with area postrema involvement. SARS‐CoV‐2 RNA sequences were detected in the CSF of both patients via mNGS, suggesting direct viral neuroinvasion or blood–brain barrier compromise. Despite similar initial presentations, their outcomes diverged dramatically. Patient 1 was AQP4‐IgG negative, responded well to immunotherapy with intravenous immunoglobulin and corticosteroids followed by mycophenolate mofetil maintenance, and remained relapse‐free at 12‐month follow‐up with significant lesion regression on MRI. Patient 2 was AQP4‐IgG positive in both serum and CSF, and despite acute treatment, experienced a fatal relapse 6 months later with longitudinally extensive transverse myelitis while on low‐dose prednisone monotherapy. Conclusions: Isolated APS may represent an important yet under‐recognized manifestation of post‐COVID‐19 autoimmune neuroinflammation. Detection of SARS‐CoV‐2 in CSF supports a role for direct viral neuroinvasion as a localized inflammatory stimulus. AQP4‐IgG serostatus serves as a critical prognostic determinant: seronegativity is associated with a benign, monophasic course, whereas seropositivity mandates prompt initiation of potent immunosuppressive therapy to prevent devastating relapses. Clinicians should maintain a high index of suspicion for NMOSD in patients with unexplained persistent vomiting following COVID‐19, and perform urgent neuroimaging and antibody testing for early risk stratification.

Progressive Multiple Sclerosis (PMS) remains a major cause of irreversible disability in Multiple Sclerosis (MS), yet current disease-modifying therapies incompletely address the compartmentalized Central Nervous System (CNS) inflammation, sustained microglial activation, chronic demyelination, and axonal degeneration that characterize progression. This topic is timely because the evidence linking Epstein–Barr Virus (EBV) to MS susceptibility, the recognition of B cell–myeloid interactions within the CNS, and the clinical development of CNS-penetrant Bruton’s Tyrosine Kinase inhibitors (BTKi) now converge on a common translational question: whether a connected EBV– B cell–microglia–BTK axis can explain part of progression independent of relapse activity and inform therapy for PMS. EBV establishes lifelong latency in memory B cells and may contribute to MS through molecular mimicry, aberrant antigen presentation, and persistent pro-inflammatory signaling. In progressive disease, B cells can interact with microglia and macrophages to sustain compartmentalized inflammation, while BTK links B-cell receptor and myeloid Fc receptor signaling. This review synthesizes EBV-associated B-cell dysregulation, B cell–microglia crosstalk, BTK biology, BTKi trial evidence, biomarkers, and safety considerations in an evidence-stratified framework. Rather than presenting a linear causal model, we distinguish established observations from emerging mechanisms and speculative hypotheses. We propose that this integrated pathophysiological framework may help clarify patient stratification, CNS target engagement, and rational therapeutic development for PMS while defining the limits that future studies must address.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune astrocytopathy characterized by inflammatory demyelinating lesions in the Optic nerve,brain and spinal cord. Presentation with area postrema syndrome (APS), marked by intractable nausea, vomiting, and hiccups, as the initial symptom is a recognized but less common initial manifestation. Post-infectious autoimmunity triggered by viral infections, including SARS-CoV-2, is thought to be associated with NMOSD pathogenesis. We report two female patients who developed isolated APS shortly after COVID-19 infection but with markedly different outcomes. One patient was aquaporin-4 immunoglobulin G (AQP4-IgG) negative and recovered fully with a monophasic course, while the other, AQP4-IgG positive, eventually progressed to recurrent NMOSD and died. Notably, SARS-CoV-2 sequences were detected in the cerebrospinal fluid of both patients, suggesting a direct inflammatory trigger. This study highlights the prognostic differences determined by serostatus through a direct side-by-side comparison and suggests that isolated APS may be a key manifestation of post-COVID autoimmune neuroinflammation. Clinicians should maintain a high index of suspicion for NMOSD in patients with unexplained persistent vomiting following COVID-19. Prompt neuroimaging and antibody testing are critical for initiating immunotherapy, avoiding misdiagnosis, and improving outcomes in this rare yet treatable complication.