Clinical and Experimental Neuroimmunology最新文献

{"title":"Not All Patients Start From the Same Line: Rethinking Outcome Interpretation in Myasthenia Gravis","authors":"Christian Messina","doi":"10.1111/cen3.70027","DOIUrl":"https://doi.org/10.1111/cen3.70027","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751135","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":"Genetic Insights Into Neuromyelitis Optica Spectrum Disorder","authors":"Hisashi Murata,&nbsp;Makoto Kinoshita","doi":"10.1111/cen3.70024","DOIUrl":"https://doi.org/10.1111/cen3.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system characterized by recurrent inflammation, primarily targeting the optic nerves and spinal cord. The presence of anti-aquaporin 4 antibodies has revealed core aspects of its immunopathology, but growing evidence suggests that genetic factors also contribute to individual susceptibility, clinical heterogeneity, and treatment response. Recent advances in genome-wide association studies (GWAS), whole exome sequencing (WES), and Mendelian randomization (MR) have identified genetic variants associated with NMOSD. These findings span human leukocyte antigen (HLA) class II alleles, non-HLA immune-related genes, and somatic mutations acquired by clonal hematopoiesis. Importantly, genetic associations vary by ethnicity and may underlie the disparities seen in disease prevalence and phenotype. In addition, MR studies are revealing potential causal pathways involving immune mediators, cytokines, and metabolites, providing a new perspective on the disease mechanism. These genomic findings are accelerating our understanding of NMOSD and are expected to lead to risk stratification, refinement of diagnostic classification, and development of targeted therapies. This review provides an integrated overview of current genetic research in NMOSD and identifies implications for future precision medicine.</p>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"294-300"},"PeriodicalIF":0.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436163","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":"Acute Denervation Revealed by Electromyography, in Conjunction With Normal Appearing Lumbar Spinal Cord in NMOSD: Case Report","authors":"Stefania Kalampokini,&nbsp;Effrosyni Koutsouraki,&nbsp;Paschalis Devranis,&nbsp;Martha Spilioti,&nbsp;Maria Moschou,&nbsp;Konstantinos Notas,&nbsp;Vasilios K. Kimiskidis","doi":"10.1111/cen3.70021","DOIUrl":"https://doi.org/10.1111/cen3.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). Segmental denervation has been rarely reported in NMOSD resulting from severe myelitis leading to anterior horn cell loss or inflammatory myeloradiculitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>A 21-year-old woman presented due to lower limb dysesthesias evolving to paraparesis and sphincter disorders over a month. Electromyographic examination revealed acute denervation in L5/S1-innervated muscles with normal peripheral nerve conduction, pointing to anterior horn affection. Magnetic resonance imaging (MRI) showed a lesion at the level of T8-T9 in the thoracic spine and hypothalami. Serum aquaporin-4 antibody and cerebrospinal fluid (CSF) oligoclonal IgG bands were positive. The patient improved with intravenous methylprednisolone within 2 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overlapping inflammation of the central and peripheral nervous system can occur in NMOSD. Electromyography could be a helpful diagnostic tool in selected cases of NMOSD in the early diagnostic process, especially in patients with normal MRI findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751042","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","authors":"Hideyuki Takeuchi,&nbsp;Yusei Miyazaki,&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/cen3.70023","DOIUrl":"https://doi.org/10.1111/cen3.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>In Japan, five biologics (eculizumab, ravulizumab, satralizumab, inebilizumab, and rituximab) are currently available for treating neuromyelitis optica spectrum disorder (NMOSD). These biologics have dramatically suppressed the disease relapse rate; however, a big problem remains: there are no useful biomarkers or sufficient evidence in drug selection and drug switch for each patient. Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been recently identified, and its therapeutic strategy is still under investigation. To solve these problems, the Japan NMOSD/MOGAD Registry was launched in December 2023. In this paper, we summarize the current clinical problems of NMOSD and MOGAD in Japan and review the Japan NMOSD/MOGAD Registry project.</p>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751389","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":"Steroid-Responsive Morvan Syndrome in a Post-Thymectomy Generalized Myasthenia Gravis Patient: A Case Report","authors":"Mario B. Prado Jr,&nbsp;James Matthew Lansang,&nbsp;Gerald T. Pagaling,&nbsp;Karen Joy Adiao","doi":"10.1111/cen3.70020","DOIUrl":"https://doi.org/10.1111/cen3.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Morvan syndrome (MoS) occurring after or concomitant with myasthenia gravis (MG) in patients with unresected thymoma has already been reported in the literature. Accordingly, the presence of thymoma may result in decreased immune tolerance, diminished regulatory T cells, and escape of immature autoreactive T lymphocytes, increasing the risk of both conditions. Here we report a young MG male patient in remission who, despite having undergone thymectomy several years ago, still developed the classic signs and symptoms of MoS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>Our patient is a male 39-year-old AChR antibody-positive generalized thymomatous MG patient who underwent thymectomy 2 years prior to the current admission. Over the last 6 months, the patient developed severe burning sensation in the hands and feet, insomnia with occasional hallucinations, intermittent high-grade fever, myokymia, and cramps. Nerve muscle ultrasound showed high frequency to-and-fro movement of the muscle fascicles, and electromyogram confirmed it to be myokymia. The involvement of the central, peripheral, and autonomic nervous systems led us to treat the case as MoS, despite not having recurrence of thymoma on the chest CT scan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Despite the post-thymectomy status, there is still a risk of developing MoS among MG patients. Nevertheless, we hypothesize that the symptoms of MoS in these cases can easily be controlled by steroid pulse therapy and medications that suppress hyperexcitability.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751373","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: Innate Immunology Revisited","authors":"Fumihiro Yanagimura,&nbsp;Akihiro Nakajima,&nbsp;Etsuji Saji,&nbsp;Izumi Kawachi","doi":"10.1111/cen3.70019","DOIUrl":"https://doi.org/10.1111/cen3.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing autoimmune/inflammatory disease of the central nervous system (CNS) that causes severe neurological deficits, including optic neuritis and longitudinally extensive myelitis. The autoantigen of NMOSD is the water channel “aquaporin-4 (AQP4),” which is highly expressed in the endfeet of astrocytes, the ependymal cell lining of the ventricles, and Müller cells in the retina throughout the CNS. AQP4-IgG autoantibodies produced by peripheral plasmablasts/plasma cells can cross the blood–brain barrier and primarily damage astrocytes, leading to secondary demyelination and axonal injury. The mechanism of AQP4 antibody-guided CNS injury ‘AQP4-opathy’ in NMOSD is mainly complement-dependent cytotoxicity, but it can also be attributed to antibody-dependent cellular cytotoxicity or AQP4 internalization. Moreover, recent research has demonstrated that stage-dependent immune dynamics orchestrate AQP4 antibody-guided lesions as follows: adaptive immune elements, including AQP4 autoantibodies with activated T_H17 cells, could form AQP4-opathy specific to NMOSD, synchronizing with the activation of innate immune dynamics, including complements, granulocytes, and microglia/macrophages in active phases. In particular, activated neutrophils with extracellular traps and tissue-resident memory T cells expressing granzyme B infiltrate during the initial and early active phases of NMOSD. These immune cells may be involved in lesion expansion and trigger relapses in cooperation with active AQP4 antibody-guided NMOSD pathology. These newly identified insights will lead to a better understanding of innate immunology and novel therapeutic strategies for NMOSD.</p>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"301-309"},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436232","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 Prior Intravenous Immunoglobulin and Plasmapheresis on Eculizumab or Ravulizumab Treatment for Generalized Myasthenia Gravis: An Analysis of the MG SPOTLIGHT Registry","authors":"Akiyuki Uzawa,&nbsp;Ema Rodrigues,&nbsp;Hiroyuki Murai","doi":"10.1111/cen3.70017","DOIUrl":"https://doi.org/10.1111/cen3.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The complement component 5 inhibitor therapies (C5ITs) eculizumab and ravulizumab are approved for the treatment of generalized myasthenia gravis (gMG). We evaluated the real-world effectiveness and safety of eculizumab and ravulizumab in patients with gMG with or without prior intravenous immunoglobulin (IVIg) or plasma exchange (PLEX) treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from enrollment up to January 1, 2024, were collected from the real-world, multinational, observational MG SPOTLIGHT Registry (NCT04202341). Patients were grouped by the presence/absence of IVIg/PLEX use within 12 months prior to C5IT initiation. Myasthenia Gravis Activities of Daily Living (MG-ADL) total scores and Myasthenia Gravis Foundation of America (MGFA) classification were assessed before and after C5IT initiation. Safety was assessed by the number of serious adverse events (SAEs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data from 219 patients were included in this analysis: 106 had received IVIg/PLEX during the 12 months prior to eculizumab or ravulizumab initiation, and 113 had not. Demographics and disease characteristics at Registry enrollment were similar between the groups. For patients with and without prior IVIg/PLEX, mean (±SD) MG-ADL total scores were 8.2 (±4.0) and 7.3 (±3.5), respectively, before eculizumab or ravulizumab treatment and 3.7 (±4.0; <i>p</i> &lt; 0.0001) and 3.9 (±3.7; <i>p</i> &lt; 0.0001) at last assessment. After initiation, both groups also showed increases in the proportion of patients with MGFA classification of 0–II. Safety profiles were similar in both groups, although fewer SAEs were observed in patients without prior IVIg/PLEX.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This MG SPOTLIGHT Registry analysis demonstrates the clinical benefit of eculizumab and ravulizumab in patients with gMG regardless of prior IVIg or PLEX therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751107","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":"Differences in COVID-19 Vaccine Efficacy Among Types of B-Cell Depletion Therapy","authors":"Hideyuki Takeuchi","doi":"10.1111/cen3.70018","DOIUrl":"https://doi.org/10.1111/cen3.70018","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 4","pages":"374-375"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145436218","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":"Aging and Neuroimmunological Disorders","authors":"Takuya Matsushita","doi":"10.1111/cen3.70016","DOIUrl":"https://doi.org/10.1111/cen3.70016","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 3","pages":"192-193"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782821","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":"Aging and Multiple Sclerosis","authors":"Takuya Matsushita","doi":"10.1111/cen3.70015","DOIUrl":"https://doi.org/10.1111/cen3.70015","url":null,"abstract":"<p>Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. While typically diagnosed in young adults, late-onset MS (LOMS, onset &gt; 50 years) is becoming increasingly recognized, presenting with distinct features such as higher rates of progressive onset and motor symptoms. With prolonged life expectancy and widespread use of disease-modifying therapies (DMTs), the population of aging individuals with MS is growing. Managing DMTs in this population is challenging, requiring the balancing of decreased relapse frequency against increased comorbidity and treatment risks. Discontinuation decisions are complex, as disease activity, including progression-independent of relapse activity (PIRA), can persist. Research, including ongoing trials, is evaluating the role of DMTs in preventing progression in older patients. Furthermore, aging involves biological processes such as immunosenescence, inflammaging (driven by cells with a senescence-associated secretory phenotype), and structural central nervous system changes such as enlarged perivascular spaces. These age-related alterations in immune and neurodegenerative pathways show significant overlap with MS pathophysiology. Understanding this intersection is crucial for optimizing clinical management in older MS patients and may identify novel targets for disease modification.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 3","pages":"208-213"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782328","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}