Clinical and Experimental Neuroimmunology最新文献

{"title":"An Adult Case of Severe, Refractory, and Progressive Leukodystrophy-Like Diffuse Encephalitis With MOG-IgG Treated With Rituximab","authors":"Yuki Matsumoto,&nbsp;Hirohiko Ono,&nbsp;Tatsuro Misu,&nbsp;Yoshiki Takai,&nbsp;Shuhei Nishiyama,&nbsp;Toshiyuki Takahashi,&nbsp;Kazuhiro Kurosawa,&nbsp;Masashi Aoki","doi":"10.1111/cen3.70035","DOIUrl":"https://doi.org/10.1111/cen3.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We report a severe refractory case of MOGAD that responded only to RTX. Early RTX treatment should be considered for patients with severe MOGAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of Ocular Myasthenia Gravis: Potential Subgroups","authors":"Tomoko Narita,&nbsp;Akiko Nagaishi,&nbsp;Shunya Nakane,&nbsp;Hidenori Matsuo","doi":"10.1111/cen3.70034","DOIUrl":"https://doi.org/10.1111/cen3.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent Asystole Without Generalized Dysautonomia in Anti-NMDA Receptor Encephalitis: A Case Report","authors":"Tetsuya Oyama,&nbsp;Hirotaka Nakanishi","doi":"10.1111/cen3.70033","DOIUrl":"https://doi.org/10.1111/cen3.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Life-threatening arrhythmias in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are typically regarded as part of a generalized autonomic storm. However, severe bradyarrhythmia occurring as the primary life-threatening feature in the absence of a generalized autonomic storm is rare.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>A 27-year-old woman presented with a 2-week history of neuropsychiatric symptoms. She was diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, supported by a positive cerebrospinal fluid (CSF) antibody test and an ovarian teratoma. Her hospital course was complicated by recurrent asystolic cardiac arrests, which occurred as the most critical feature of her autonomic instability and required temporary pacing. The patient recovered fully after immunotherapy and tumor resection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This report identifies a critical diagnostic pitfall and highlights the necessity of continuous cardiac monitoring during the acute phase, even in patients who appear autonomically stable.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Japan Neuromyelitis Optica Spectrum Disorders/Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Registry: Background Analysis of the Initial 116 Cases","authors":"Yusei Miyazaki,&nbsp;Hideyuki Takeuchi,&nbsp;Takao Kiriyama,&nbsp;Hikoaki Fukaura,&nbsp;Juichi Fujimori,&nbsp;Katsuhisa Masaki,&nbsp;Sonoko Misawa,&nbsp;Katsuichi Miyamoto,&nbsp;Nobuaki Yoshikura,&nbsp;Shoko Ukita,&nbsp;Kengo Nagashima,&nbsp;Ichiro Nakashima","doi":"10.1111/cen3.70032","DOIUrl":"https://doi.org/10.1111/cen3.70032","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To describe the baseline clinical characteristics of patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) enrolled in the Japan NMOSD/MOGAD Registry (UMIN000051988) and to assess their representativeness of both conditions in the Japanese population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective multicenter observational registry study was conducted at 10 neurology referral centers in Japan. Patients with NMOSD or MOGAD were enrolled based on established diagnostic criteria. Clinical data, treatment history, and biological samples were collected annually. The present analysis includes patients registered between December 20, 2023 and July 31, 2024. Descriptive statistics were used to summarize the clinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 116 patients (NMOSD, <i>n</i> = 110; MOGAD, <i>n</i> = 6) were analyzed. Among NMOSD patients, the mean age at onset was 50.0 years, and 89.1% were female. Most were anti-aquaporin 4 antibody seropositive (93.6%). The median Expanded Disability Status Scale (EDSS) was 3.5%, and 67.3% had a relapsing course. Biologic agents were used in 63.6% of NMOSD patients. Among MOGAD patients, the mean age at onset was 27.3 years, and all were anti-myelin oligodendrocyte glycoprotein antibody seropositive. Visual symptoms predominated, and the median EDSS was 2.25.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The clinical characteristics of NMOSD patients in the registry are consistent with prior epidemiological data, supporting the representativeness of the cohort. The high rate of biologic agent use reflects current treatment practices in Japan. In contrast, the representativeness of MOGAD cases could not be evaluated due to their limited number, highlighting the need to further accumulate cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to “Seroconversion After SARS-CoV-2 Vaccination in B-Cell-Depleted Patients: The Missing Factors”","authors":"Hideyuki Takeuchi","doi":"10.1111/cen3.70031","DOIUrl":"https://doi.org/10.1111/cen3.70031","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145750695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMOSD: Adaptive Immunity Revisited","authors":"Ritsu Akatani,&nbsp;Norio Chihara","doi":"10.1111/cen3.70030","DOIUrl":"https://doi.org/10.1111/cen3.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"310-318"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seroconversion After SARS-CoV-2 Vaccination in B-Cell-Depleted Patients: The Missing Factors","authors":"Christian Messina","doi":"10.1111/cen3.70028","DOIUrl":"https://doi.org/10.1111/cen3.70028","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"376-377"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromyelitis Optica Spectrum Disorder: Clinical Features and Treatments Revisited","authors":"Mitsuru Watanabe","doi":"10.1111/cen3.70029","DOIUrl":"https://doi.org/10.1111/cen3.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"319-331"},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Symptoms of Neuromyelitis Optica Spectrum Disorder and Patient-Determined Oral Glucocorticoid–Related Adverse Events on Patients' Daily Living and Emotions: A Qualitative Analysis From Japan","authors":"Yuko Shimizu,&nbsp;Ichiro Nakashima,&nbsp;Ryotaro Ikeguchi,&nbsp;Tadashi Nagatsuka,&nbsp;Katsuhisa Yamashita,&nbsp;Yuta Fukuoka,&nbsp;Tatsunori Murata,&nbsp;Kazuo Fujihara","doi":"10.1111/cen3.70026","DOIUrl":"https://doi.org/10.1111/cen3.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Neuromyelitis optica spectrum disorder (NMOSD) is a chronic disorder with a relapsing–remitting disease course that impacts patients' quality of life. Oral glucocorticoids (OGCs) have been the standard of care for NMOSD in Japan; however, their chronic use is associated with adverse events (AEs). We investigated the causal relationship between NMOSD symptoms and patient-determined OGC-related AEs (Pd-OGC-AEs) and their impact on patients' daily living and emotions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This online interview survey was conducted between August and December 2023. Adult Japanese patients with aquaporin-4 immunoglobulin G–seropositive NMOSD and currently taking or having a history of OGC use were asked about their episodes of NMOSD symptoms and Pd-OGC-AEs experienced to date and their impact on daily living and emotions. A qualitative analysis was performed by coding and categorizing data and assessing the causality of symptoms and AEs with patients' daily living and emotions, and a conceptual framework was developed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifteen patients (14 females; median [range] age, 53 [23–66] years) were included. Neurological findings were normal in four patients, with very mild symptoms in seven patients and mild disability and relatively severe impairment in two patients each. NMOSD symptoms such as visual and sensory disturbances and patient-determined OGC-related Cushing's syndrome affected patients' daily living and emotions by increasing their dependence on others and made them feel hopeless.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NMOSD symptoms and Pd-OGC-AEs adversely impacted patients' daily living and emotions. Based on these results, a survey questionnaire is being planned to assess patient preferences for tailored NMOSD treatment options.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMOSD Revisited","authors":"Izumi Kawachi","doi":"10.1111/cen3.70025","DOIUrl":"https://doi.org/10.1111/cen3.70025","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"292-293"},"PeriodicalIF":0.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}