ABSTRACT Background Myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) is typically considered responsive to immunotherapy with a good prognosis. However, some patients develop severe symptoms and the underlying pathologic and immunologic mechanisms remain unclear. We report a severe, progressive, and fatal case of MOGAD treated with rituximab (RTX). Case Presentation A 43‐year‐old woman was admitted to the hospital for bilateral vision loss followed by a convulsive seizure and comatose state. Her serum and cerebrospinal fluid (CSF) tested positive for MOG‐IgG using our in‐house living cell–based assay, with higher antibody titers in her CSF than in her serum. She was diagnosed with MOGAD and treated with intravenous methylprednisolone, plasma exchange therapy, and immunoglobulin therapy. However, she was refractory to these treatments, leading to progressive leukodystrophy‐like white matter lesions. A brain biopsy at this time revealed widespread demyelination as well as massive infiltration of CD4‐positive cells and macrophages. We then treated her with intravenous cyclophosphamide therapy. Still, her MRI showed progressive exacerbation, and we detected a marked increase in B‐cell lineage cells such as CD19 + CD27 − IgD − CXCR5 − (double‐negative B cells) and plasma cells in peripheral blood and CSF. As a result, we tried RTX, which resulted in MRI lesion reduction in part initially after a progressively worsened course. The comatose state persisted, and she eventually died of aspiration pneumonia 1 year later. Conclusions We report a severe refractory case of MOGAD that responded only to RTX. Early RTX treatment should be considered for patients with severe MOGAD.

ABSTRACT Objectives The clinical features of ocular myasthenia gravis (OMG) appeared to be diverse in terms of age at onset and autoantibody titers, suggesting the possibility of the existence of multiple subgroups. To characterize each subgroup, we investigated the clinical characteristics of Japanese patients with OMG. Methods We performed a retrospective cross‐sectional survey of OMG patients from eight hospitals in Japan. Clinical information was obtained, including age at onset, autoantibodies including anti‐acetylcholine receptor (AChR) titers, complications, and clinical course. Results In total, 135 patients with OMG (67 men, 68 women) were included. There appeared to be three peaks in onset age; one was below 5 years old, and others at 45–49 and 60–64 years old. Moreover, 20.7% developed OMG after 65 years old. Anti‐AChR antibodies were detected in 77.6%, among which 31.3% had rather low titers (0.2–1.9 nmol/L), while 12 patients had very high titers (50–1720 nmol/L). There were thymic abnormalities and/or autoimmune complications, as seen in patients with generalized MG. Conclusions The clinical features of OMG appeared to be heterogeneous, with several potential subgroups including childhood onset, a subset with very high antibody titers, and an elderly onset group.

ABSTRACT Accumulating evidence underscores the pivotal role of adaptive immunity in the pathogenesis of AQP4‐IgG‐positive neuromyelitis optica spectrum disorder (NMOSD). Autoreactive B cells produce pathogenic antibodies against aquaporin‐4 (AQP4), and their dysregulation is evident in both peripheral blood and cerebrospinal fluid. These abnormalities include an increased frequency of plasmablasts and the expansion of atypical B‐cell subsets enriched for autoreactivity. Their activation and survival are supported by inflammatory cytokines such as interleukin‐6 (IL‐6), a key target of current immunotherapies. T‐cell subsets, including follicular helper T (Tfh) cells and Th17 cells, play essential roles by promoting B‐cell differentiation and amplifying inflammation. The interplay between B and T cells, together with cytokine dysregulation, constitutes a central immunopathogenic axis in NMOSD. Notably, some disease‐modifying therapies for multiple sclerosis have been shown to worsen NMOSD, suggesting fundamental differences in the underlying immune dynamics between the two diseases. This contrast highlights the need for disease‐specific therapeutic approaches and a deeper understanding of adaptive immune processes unique to NMOSD. Here, we revisit the immunopathogenesis of AQP4‐IgG‐positive NMOSD with a focus on adaptive immune mechanisms. We discuss current evidence on B‐ and T‐cell abnormalities, intrathecal immune responses, and how these insights have informed the development of targeted therapies.

ABSTRACT Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system, characterized by severe relapses that can lead to blindness or paralysis. However, NMOSD presents with a broad spectrum of symptoms, including optic neuritis, transverse myelitis, and area postrema syndrome, along with distinctive findings on magnetic resonance imaging. In Japan, where the prevalence of NMOSD is relatively high, nationwide surveys and regional studies have revealed its detailed epidemiological and clinical characteristics. The discovery of aquaporin‐4 autoantibodies has not only distinguished NMOSD from multiple sclerosis but also provided critical insights into its immunopathogenesis, resulting in the development of molecular‐targeted therapies capable of inhibiting key immune pathways, including the complement system, interleukin‐6 signaling, and B‐cell‐mediated immunity. Several biological agents, such as eculizumab, ravulizumab, satralizumab, inebilizumab, and rituximab, have demonstrated high efficacy in preventing relapse in clinical trials. Although long‐term safety data remain limited for most agents, Japanese real‐world data support their effectiveness and safety. This review summarizes the clinical features, imaging characteristics, and current treatment strategies for NMOSD, with a particular focus on the therapeutic mechanisms of biological agents and the insights they provide into disease pathophysiology.