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Background: The real-world data evidences how establishment of neuromyelitis optica (NMO) disease concept and development disease modifying therapy affect the patients with multiple sclerosis (MS) and NMO are lacking. The aim of this study is to clarify the diachronic trend of the severity and admissions of patients with MS and NMO., Methods: We retrospectively investigated the trends in admissions, treatments, and disabilities in the patients with MS and NMO using the Japanese administrative data between 2012 and 2017., Results: We analyzed acute stage 9545 and 2035 admissions in each 6100 MS and 1555 NMO patients. The annual number of admission in MS significantly decreased in 6 years; however, those in NMO consistently increased. The patient proportion with lower disability was significantly increased in MS and NMO. These trends were especially observed in patients admitted to centralized hospitals with more active treatments, such as second-line disease modifying therapy for MS and plasmapheresis for NMO. Patients with NMO using DMT for MS diminished in 6 years., Conclusion: A gradual improvement of disability in patients with MS and NMO was observed, probably due to advanced treatments, increased NMO awareness, and decreased misdiagnosis, which seems to be the key for better prognosis in MS and NMO., Competing Interests: Declaration of Competing Interest Y. Matsumoto and K. Tarasawa report no disclosure. T. Misu received speaker honoraria from Tanabe Mitsubishi Pharma, Novartis Pharma., Alexion Pharma., Teijin Pharma., Viela Bio, and Biogen Idec Japan, and received research support from Cosmic Corporation, and Medical and Biological Laboratories Co.; and received Grant-in-Aid for scientific research from Ministry of Education, Culture, Sports, Science, and Technology. C. Namatame and Y. Takai and H. Kuroda report no disclosure. K. Fujihara serves on the advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Alexion Pharmaceuticals, and Medimmune; has received travel funding and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai Inc, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co., Daiichi Sankyo, and Nihon Pharmaceutical; is on the editorial board for Clinical and Experimental Neuroimmunology; is an advisory board member for Sri Lanka Journal of Neurology; and received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Genzyme Japan, Ministry of Education, Science and Technology of Japan, and Ministry of Health, Welfare and Labor of Japan. K. Fushimi and K. Fujimori report no disclosures. M. Aoki received research support from the Japanese Ministry of Health Labor and Welfare, and the Japanese Ministry of Education, Culture, Sports, Science, and Technology., (Copyright © 2023. Published by Elsevier B.V.)

The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99-100%] and 99% (95% CI 97-100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While microbiome plays key roles in the etiology of multiple sclerosis (MS), its mechanism remains elusive. Here, we conducted a comprehensive metagenome-wide association study (MWAS) of the relapsing-remitting MS gut microbiome ( n case = 26, n control = 77) in the Japanese population, by using whole-genome shotgun sequencing. Our MWAS consisted of three major bioinformatic analytic pipelines (phylogenetic analysis, functional gene analysis, and pathway analysis). Phylogenetic case-control association tests showed discrepancies of eight clades, most of which were related to the immune system (false discovery rate [FDR] < 0.10; e.g., Erysipelatoclostridium&#95;sp . and Gemella morbillorum ). Gene association tests found an increased abundance of one putative dehydrogenase gene (Clo1100&#95;2356) and one ABC transporter related gene (Mahau&#95;1952) in the MS metagenome compared with controls (FDR < 0.1). Molecular pathway analysis of the microbiome gene case-control comparisons identified enrichment of multiple Gene Ontology terms, with the most significant enrichment on cell outer membrane ( P = 1.5 × 10 -7 ). Interaction between the metagenome and host genome was identified by comparing biological pathway enrichment between the MS MWAS and the MS genome-wide association study (GWAS) results (i.e., MWAS-GWAS interaction). No apparent discrepancies in alpha or beta diversities of metagenome were found between MS cases and controls. Our shotgun sequencing-based MWAS highlights novel characteristics of the MS gut microbiome and its interaction with host genome, which contributes to our understanding of the microbiome's role in MS pathophysiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kishikawa, Ogawa, Motooka, Hosokawa, Kinoshita, Suzuki, Yamamoto, Masuda, Matsumoto, Nii, Maeda, Nakamura, Inohara, Mochizuki, Okuno and Okada.)

In recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD‐specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders. [ABSTRACT FROM AUTHOR]

The spectrum of MOG-IgG-associated disease (MOGAD) includes optic neuritis (ON), myelitis (MY), acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, cerebral cortical encephalitis (CE) and AQP4-IgG-negative neuromyelitis optica spectrum disorder (NMOSD). In MOGAD, MOG-IgG are usually detected in sera (MOG-IgGSERUM), but there have been some seronegative MOGAD cases with MOG-IgG in CSF (MOG-IgGCSF), and its diagnostic implications remains unclear. In this cross-sectional study, we identified patients with paired serum and CSF sent from all over Japan for testing MOG-IgG. Two investigators blinded to MOG-IgG status classified them into suspected MOGAD (ADEM, CE, NMOSD, ON, MY and Others) or not based on the current recommendations. The MOG-IgGSERUM and MOG-IgGCSF titres were assessed with serial 2-fold dilutions to determine end point titres [≥1:128 in serum and ≥1:1 (no dilution) in CSF were considered positive]. We analysed the relationship between MOG-IgGSERUM, MOG-IgGCSF and the phenotypes with multivariable regression. A total of 671 patients were tested [405 with suspected MOGAD, 99 with multiple sclerosis, 48 with AQP4-IgG-positive NMOSD and 119 with other neurological diseases (OND)] before treatment. In suspected MOGAD, 133 patients (33%) tested MOG-IgG-positive in serum and/or CSF; 94 (23%) double-positive (ADEM 36, CE 15, MY 8, NMOSD 9, ON 15 and Others 11); 17 (4.2%) serum-restricted-positive (ADEM 2, CE 0, MY 3, NMOSD 3, ON 5 and Others 4); and 22 (5.4%) CSF-restricted-positive (ADEM 3, CE 4, MY 6, NMOSD 2, ON 0 and Others 7). None of AQP4-IgG-positive NMOSD, multiple sclerosis or OND cases tested positive for MOG-IgGSERUM, but two with multiple sclerosis cases were MOG-IgGCSF-positive; the specificities of MOG-IgGSERUM and MOG-IgGCSF in suspected MOGAD were 100% [95% confidence interval (CI) 99–100%] and 99% (95% CI 97–100%), respectively. Unlike AQP4-IgG-positive NMOSD, the correlation between MOG-IgGSERUM and MOG-IgGCSF titres in MOGAD was weak. Multivariable regression analyses revealed MOG-IgGSERUM was associated with ON and ADEM, whereas MOG-IgGCSF was associated with ADEM and CE. The number needed to test for MOG-IgGCSF to diagnose one additional MOGAD case was 13.3 (14.3 for ADEM, 2 for CE, 19.5 for NMOSD, infinite for ON, 18.5 for MY and 6.1 for Others). In terms of MOG-IgGSERUM/CSF status, most cases were double-positive while including either serum-restricted (13%) or CSF-restricted (17%) cases. These statuses were independently associated with clinical phenotypes, especially in those with ON in serum and CE in CSF, suggesting pathophysiologic implications and the utility of preferential diagnostic testing. Further studies are warranted to deduce the clinical and pathological significance of compartmentalized MOG-IgG. [ABSTRACT FROM AUTHOR]

Purpose: We developed a novel method which is applicable to visualize contrast according to myelin components in the human brain using relaxation time derived from quantitative parameter mapping magnetic resonance imaging (QPM-MRI).Materials and Methods: Using healthy volunteer data (n = 10), we verified that our method demonstrated that the myelin-weighted contrast increased proportionally by products R1 and R2*, i.e., QPM-myelin-weighted image, in which modified T1-weighted/T2-weighted (T1w/T2w) ratio mapping method was applied. We compared measurement values in white matter (WM) and gray matter (GM) regions of the T1w/T2w ratio and R1·R2* product maps of healthy volunteers. Linear regression analysis between each value. Mann Whitney U test between WM and GM signals in each myelin map. In addition, Additionally, QPM-myelin-weighted image was applied to a 32-year-old female MS patient.Results: Linear regression analysis showed a highly significant correlation between conventional T1w/T2w ratios and R1·R2* products derived from QPM (R = 0.73, P < 0.0001). Moreover, there is a significant difference between WM and GM structures in each myelin images (both, P < 0.0001). Additionally, in a clinical case, MS lesions enabled observation of not only MS plaques but also heterogeneous myelin signal loss associated with demyelination more clearly than T2w image and conventional T1w/T2w ratio image.Conclusion: Our myelin-weighted imaging technique using QPM may be useful for myelin visualization and is expected to become independent of measurement conditions due to having quantitative characteristics of QPM itself. [ABSTRACT FROM AUTHOR]