Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Late-Onset Neutropenia After Rituximab in Multiple Sclerosis: Incidence, Predictors, and Outcomes in a Retrospective Multicenter Cohort.","authors":"Susanna Hallberg, Sandra Kallin, Björn Evertsson, Malin Boremalm, Pierre de Flon, Jonatan Salzer, Jan Lycke, Katharina Fink, Anders Svenningsson","doi":"10.1212/NXI.0000000000200642","DOIUrl":"10.1212/NXI.0000000000200642","url":null,"abstract":"<p><strong>Background and objectives: </strong>Late-onset neutropenia (LON) is a rare, transient reduction in absolute neutrophil count (ANC) associated with anti-CD20 therapies. In multiple sclerosis (MS), data regarding severity, infectious outcomes, and predictors remain limited. We aimed to determine the incidence, characteristics, and predictors of LON in rituximab-treated people with MS (pwMS).</p><p><strong>Methods: </strong>We conducted a registry-based retrospective multicenter cohort study of pwMS in Sweden exposed to rituximab between 2008 and 2024. Any LON was defined as ANC <1,500 cells/μL occurring at least 30 days after rituximab initiation. Grades 3-4 LON was defined as ANC <1,000 cells/μL, recording infectious complications for these events. Incidence rates (IRs) were calculated per 1,000 person-years, and event times were summarized as medians (interquartile range [IQR]). Predictors of LON events were evaluated using Cox regression with time-varying covariates and binary logistic regression.</p><p><strong>Results: </strong>Among 2,686 rituximab-exposed pwMS, 6.2% (n = 165) experienced ≥1 LON event during a median follow-up of 7.8 years (IQR 5.7-9.8). The IR for any LON (grades 2-4) was 10.1/1,000 person-years (95% CI 8.6-11.8); the median time-to-first event was 360 days (IQR 112-1,017). Most events were mild, 5.3% (grade 2, n = 142). Grades 3-4 LON occurred for 1% (23 individuals; 36 events) and IR 2.1/1,000 person-years (95% CI 1.4-2.9). Ten infections occurred among LON grades 3-4 events, classifying 8 as severe. All individuals with infectious LON grades 3-4 events (48%) recovered after hospitalization, antibiotics/antivirals, and/or granulocyte colony-stimulating factor. Rituximab was rechallenged in 89% (32/36) of grades 3-4 events: 14 recurred and 2 complicated by infections. In time-dependent Cox models, higher accumulated rituximab exposure (HR 0.87, 95% CI 0.81-0.93) and prior injectable therapy (HR 0.66, 95% CI 0.45-0.96) were associated with a lower hazard of any LON. Exploratory binary analyses of LON grades 3-4 showed associations with prior natalizumab (odds ratio [OR] 2.8) and higher body mass index (OR 0.87), not confirmed in time-to-event models.</p><p><strong>Discussion: </strong>In this large real-world cohort, high-grade LON (grades 3-4) events were rare and frequently complicated by infections. Mild (grade 2) LON events were often fluctuating and generally clinically uneventful. Rechallenge with rituximab was rarely complicated by serious adverse events. Prediction of LON remains challenging, highlighting the relevance of infection vigilance during anti-CD20 therapy.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200642"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Brain Changes Are Linked to Clinical and Cognitive Outcomes in Anti-LGI1 Encephalitis.","authors":"Wei Zhao, Katharina Wurdack, Frederik Bartels, Guido Cammà, Annalisa E Bozem, Amy Romanello, Maron Matthias Mantwill, Harald Prüss, Friedemann Paul, Christoph J Ploner, Christopher R Madan, Stephan Krohn, Carsten Finke","doi":"10.1212/NXI.0000000000200649","DOIUrl":"10.1212/NXI.0000000000200649","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1E) is traditionally considered as limbic encephalitis, but emerging evidence characterizes LGI1E as a whole-brain disorder. Furthermore, most neuroimaging studies have relied on cross-sectional designs and purely volumetric measures. Here, we integrate volume and fractal dimensionality (FD), a novel measure of structural complexity, to investigate cross-sectional and longitudinal brain changes in LGI1E and their associations with clinical and cognitive outcomes.</p><p><strong>Methods: </strong>This observational study included 3T MRI, clinical evaluations, and comprehensive cognitive assessments at Charité - Universitätsmedizin Berlin. Patients with LGI1E underwent up to 3 study visits at median disease durations of 10, 46, and 58 months. Disease severity was rated using the modified Rankin Scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). T1-weighted MRI was processed using FreeSurfer to extract volumetric data, alongside fractal analysis to estimate FD. Dominance analysis determined the relative importance of FD and volume. Longitudinal changes were examined using linear mixed-effects models in relation to age at onset, disease duration, and relapses.</p><p><strong>Results: </strong>We studied 34 patients with LGI1E (median age: 67 years; 29% female; 52 study visits) and 34 age-matched and sex-matched healthy controls. Patients showed clinical improvement in both mRS and CASE scores from peak illness to first study visit. Morphological analyses revealed reduced FD in fronto-temporo-parietal cortices and reduced FD and volume in subcortical areas, with FD more frequently emerging as the more important measure in affected areas. Furthermore, reduced FD in the pallidum at the first study visit was associated with less mRS improvement since peak illness, while reduced accumbens volume was linked to less CASE improvement. Reductions in both FD and volume in frontotemporal cortices and subcortical areas were associated with impaired overall cognition, with FD more frequently emerging as the dominant measure in brain-cognition associations. Finally, longer disease duration and relapses were associated with longitudinal reductions in FD and volume in subcortical areas.</p><p><strong>Discussion: </strong>LGI1E is characterized by widespread morphological brain alterations beyond the limbic system, with meaningful associations to clinical outcomes, cognitive function, and longitudinal disease course. FD emerged as the more comprehensive imaging marker, capturing unique morphological brain characteristics undetected by volumetry analyses.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200649"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Multiomic Signatures of Environmental Exposure Drive Immune Dysregulation and Disease Activity in Early Multiple Sclerosis.","authors":"Simon Falk, Andreas Schulte-Mecklenbeck, Patrick Ostkamp, Timo Wirth, Tilman Schneider-Hohendorf, Marie Deffner, Julia Krämer, Catharina Korsukewitz, Luisa Klotz, Catharina C Gross, Heinz Wiendl, Nicholas Schwab","doi":"10.1212/NXI.0000000000200636","DOIUrl":"10.1212/NXI.0000000000200636","url":null,"abstract":"<p><strong>Background and objectives: </strong>Environmental factors are pivotal in determining multiple sclerosis (MS) susceptibility, yet their specific influence on the immune system at the time of diagnosis remains incompletely understood. The aim of this study was to map the systemic effects of modifiable risk factors, specifically smoking, body mass index (BMI), serum vitamin D, UV exposure, and latent viral immunity, on immune function in patients with treatment-naive MS.</p><p><strong>Methods: </strong>A multiomics analysis was performed on a monocentric cohort of 96 treatment-naive patients. The study used a combination of bulk transcriptomics across 6 immune cell lineages, serum proteomics, cell-cell communication modeling, and high-dimensional flow cytometry to identify unique immunologic patterns linking environmental exposures to disease pathology.</p><p><strong>Results: </strong>Smoking was found to induce an upregulation of the tissue-homing receptor GPR15 across lineages, particularly in NK cells, which correlated with higher disability levels. Smoking also amplified a proinflammatory milieu (increased CXCL17 and LAMP3). Higher potential UV exposure seemed to counteract these effects by lowering IFI30 and LYZ expression; notably, elevated IFI30 correlated with the presence of gadolinium-enhancing lesions. Regarding metabolic factors, high BMI exerted a linear effect on monocyte metabolism, driving cholesterol biosynthesis (MVD and SQLE) and increasing proinflammatory markers (FABP4 and LEP) associated with blood-brain barrier compromise.</p><p><strong>Discussion: </strong>These findings elucidate the molecular mechanisms by which modifiable risk factors contribute to MS pathology. The data imply distinct clinical approaches for risk management: while smoking cessation must likely be absolute to reverse pathogenic trafficking signals (such as GPR15 upregulation), the linear effect of BMI suggests that incremental weight loss confers proportional immunologic benefits. These insights strongly support the integration of lifestyle interventions as a core component of early MS management.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200636"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Autoantibodies Against MOG Isoforms: α3 Antibodies Suggest Relapsing Disease Course in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.","authors":"Young Nam Kwon, Miguel Leal Rato, Jun-Soon Kim, Kyung Seok Park, Hyung-Soo Lee, Seol-Hee Baek, Byung-Jo Kim, Yeon Hak Chung, Ju-Hong Min, Sooyoung Kim, Eunhee Sohn, Seong-Il Oh, Sang Beom Kim, Seung Woo Kim, Ha Young Shin, Ki Hoon Kim, Ho Jin Kim, Boram Kim, Jung-Joon Sung, Silvia Messina, Mark R Woodhall, Halwan Bayuangga, Maria Isabel Leite, Ruth Geraldes, Jacqueline Palace, Patrick J Waters, Sung-Min Kim","doi":"10.1212/NXI.0000000000200660","DOIUrl":"10.1212/NXI.0000000000200660","url":null,"abstract":"<p><strong>Background and objectives: </strong>A proportion of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) experience relapses, but biomarkers predicting which patients are likely to relapse are not yet widely available. The MOGα1 isoform is the most commonly used in diagnostic MOG antibody assays, while the clinical relevance of antibodies against other MOG isoforms remains unclear.</p><p><strong>Methods: </strong>This study used a stepwise approach using international multicenter serum samples collected prospectively. First, diagnostic accuracy of the MOGα1 and β1 isoforms was compared using 748 consecutive sera from Korean patients suspected of having demyelinating disease of the CNS. Next, the predictive values of antibodies against each of 7 MOG isoforms for relapses were assessed on sera from Korean patients with MOGAD (derivation cohort). Finally, the association between MOG isoform antibody with relapses was validated in 2 independent cohorts: a Korean validation cohort (n = 49) and a UK validation cohort (n = 56).</p><p><strong>Results: </strong>Both MOGα1 antibody and MOGβ1 antibody assays had comparable diagnostic accuracy. Among patients with MOGAD, the presence of MOGα3 antibody was associated with a higher risk of relapse, with a hazard ratio of 4.3 in the derivation cohort (log-rank <i>p</i> < 0.001). This finding was also confirmed in an independent smaller Korean validation cohort (log-rank <i>p</i> = 0.009) and in a subgroup of UK validation cohort (log-rank <i>p</i> = 0.048).</p><p><strong>Discussion: </strong>The presence of MOGα3-IgG in patients with MOGAD may be associated with an increased risk of relapse, indicating that early preventive treatment strategies may be appropriate in these individuals. MOGβ1-IgG demonstrated diagnostic accuracy similar to MOGα1-IgG.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that MOGα1 antibody and MOGβ1 antibody assays have comparable diagnostic accuracy for MOGAD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200660"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13609827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal B-Cell Exosome Proapoptotic and Antiapoptotic Cargo in Multiple Sclerosis: Potential Implication in Progressive Disease Biology.","authors":"Gautier Breville, Ayman Rezk, Samuel Weissman, Diego A Espinoza, Simon Thebault, Luana D Yamashita, Yeseul Kim, Mihir Kakara, Liljana Nedelkoska, Nicole Doyon-Reale, Celine Delucinge-Vivier, Leah Zuroff, Hanane Touil, Paul Stemmer, Joyce A Benjamins, Robert P Lisak, Amit Bar-Or","doi":"10.1212/NXI.0000000000200657","DOIUrl":"10.1212/NXI.0000000000200657","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200657"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Prognostic Factors Associated With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Multicenter Cohort Study.","authors":"Matthew Human, Christopher G S Gilmartin, Athanasios Papathanasiou, Christopher R Tench, Pakeeran Siriratnam, Chiara Rocchi, Bruno Gran, Milan Hargovan, Ei Zune The, James A Varley, Saif Huda, Radu Tanasescu","doi":"10.1212/NXI.0000000000200651","DOIUrl":"10.1212/NXI.0000000000200651","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;It is currently difficult to accurately predict who, after the index event of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), will develop relapsing disease (R-MOGAD). Several clinical features have been reported as possibly predictive, but none have been validated in clinical practice. We used a prospectively designed analysis to assess a combined model of reported clinical prognosticators for developing R-MOGAD in 101 patients with MOGAD (86% with onset in adulthood) from 3 UK specialist centers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A multivariable binary logistic regression model using variables identified from a scoping literature review was fitted in a retrospective clinical data set of patients with MOGAD (Nottingham MS & Neuroinflammation Centre [NUH]), with validation analysis in 2 independent data sets (Walton NMOSD Specialist Centre [WSC]; Imperial College London [ICL]). Secondary analysis investigated time to first relapse using Cox proportional hazards on the combined cohort. Results from the significant variables from the initial analysis were further examined in a meta-analysis of relevant literature studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In the Neuroinflammation - Nottingham University Hospitals NHS Trust data set (n = 33), treatment with steroids ≥10 mg for ≥ 3 months after the index event was significantly associated with a lower likelihood of developing R-MOGAD (&lt;i&gt;p&lt;/i&gt; = 0.006) with sensitivity 83% (95% CI 59-96) and specificity 73% (95% CI 45-92). A persistently positive MOG-IgG status, age at onset, optic neuritis at onset, and sex were not significant predictors of developing R-MOGAD. To assess generalizability, this predictor was tested in 2 independent data sets. In Walton Centre Liverpool (n = 39), not receiving prednisolone ≥10 mg ≥ 3 months was associated with R-MOGAD (OR = 9.7; 95% CI 2.1-45.4; sensitivity 63%; 95% CI 38-84; specificity 85%; 95% CI 62-97). In ICL (n = 29), the association was directionally consistent but inconclusive, with wide confidence intervals crossing unity (OR = 2.7; 95% CI 0.5-13.4; sensitivity 73%; 95% CI 39-94; specificity 50%; 95% CI 26-74). For the combined cohort (n = 101), not receiving prednisolone ≥ 10 mg for ≥3 months was associated with increased odds of developing R-MOGAD (OR = 6.2; 95% CI 2.6-14.8; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001). Conversely, prednisolone ≥10 mg ≥ 3 months was associated with a lower hazard of relapse (HR = 0.47; 95% CI 0.24-0.91; &lt;i&gt;p&lt;/i&gt; = 0.024). Median follow-up for monophasic patients was 42 months (IQR: 17.5-64.5).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Prednisolone ≥10 mg for ≥ 3 months after the index event was associated with a lower likelihood of relapsing MOGAD. This association was supported in first external cohort and directionally consistent but inconclusive in a second, smaller cohort. Further prospective multicenter studies are required to assess the reproducibility and clinical utility of this as","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200651"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time Matters in Cerebral Amyloid Angiopathy-Related Inflammation, but How Much?","authors":"Antonio Arauz, Fabiola Eunice Serrano Arias","doi":"10.1212/NXI.0000000000200656","DOIUrl":"10.1212/NXI.0000000000200656","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200656"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early vs Delayed Steroid Treatment in Cerebral Amyloid Angiopathy-Related Inflammation: A Retrospective Cohort Study.","authors":"Giulia Negro, Michele Rossi, Elisa Cavarsaschi, Giorgia Orsani, Benedetta Storti, Mattia Losa, Nicolò Dell'Orto, Elena Moscatelli, Alessandro Francia, Giulia Marinoni, Andrea Donniaquio, Massimo Del Sette, Matteo Pardini, Anna Bersano, Jacopo C DiFrancesco","doi":"10.1212/NXI.0000000000200639","DOIUrl":"10.1212/NXI.0000000000200639","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a potentially reversible inflammatory syndrome for which corticosteroid administration constitutes the cornerstone of management. However, evidence that early steroid treatment improves clinical and radiologic outcomes remains limited. This study aimed to determine whether early steroid initiation is associated with improved clinical and radiologic outcomes compared with delayed treatment in CAA-ri and to further investigate 12-month all-cause mortality and CAA-ri recurrence.</p><p><strong>Methods: </strong>This retrospective cohort study included patients admitted up to May 31, 2025, from 3 Italian academic referral centers, with a maximum follow-up of 12 months. Eligible patients had probable CAA-ri per diagnostic criteria, comparable baseline, and follow-up MRI studies and underwent modified Rankin Scale (mRS) evaluations within 12 months. Early steroid therapy was defined as initiation within 6 weeks of CAA-ri symptom onset. Patients were compared with those who initiated steroids beyond 6 weeks. The primary outcomes were functional status and vasogenic edema severity at follow-up, assessed with the mRS and the 3-point Amyloid-related Imaging Abnormalities-Edema scale, respectively; secondary outcomes were 12-month all-cause mortality and CAA-ri recurrence. Inverse-probability weighting from a propensity-score model was used. Primary outcomes were analyzed with weighted ordinal logistic regression, and secondary outcomes with weighted Cox proportional hazards models with robust variance.</p><p><strong>Results: </strong>Of 70 screened patients, 48 were eligible. Of them, 30 received early steroids (mean age, 71.3 ± 7.8 years; 50% women) and 18 were treated late (mean age, 68.6 ± 9 years; 38.9% women). Early steroid treatment was associated with greater functional status at follow-up (odds ratio [OR], 0.14; 95% CI 0.03-0.58; <i>p</i> = 0.007) and reduced vasogenic edema (OR, 0.13; 95% CI 0.04-0.45; <i>p</i> = 0.001). No differences were found for 12-month recurrence (hazard ratio [HR], 1.25; 95% CI 0.31-5.07). Regarding mortality, a higher risk was suggested in the ES group (HR, 4.10; 95% CI 1.10-15.32), although not supported by complementary survival analyses.</p><p><strong>Discussion: </strong>Early steroid therapy was associated with more favorable functional and radiologic outcomes. Findings on mortality and recurrence were inconclusive, reflecting limited statistical power. These results suggest an association between early steroid initiation and short-term outcomes, while longer-term trajectories warrant further investigation.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200639"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Insights in Pediatric Multiple Sclerosis: DNA Methylation Highlights an Involvement of Epstein-Barr Virus Infection and Host Immune Networks.","authors":"Andrea Corona, Martina Tosi, Alen Zollo, Nadia Barizzone, Nicola Pomella, Marta Simone, Alessandra Protti, Angela Lucia Berardinelli, Antonio Gallo, Carlotta Canavese, Domizia Vecchio, Eleonora Cocco, Lucia Moiola, Marta Zaffira Conti, Simona Malucchi, Amanda Papa, Alessandra Mingione, Corinne Monzani, Pietro Annovazzi, Luigi M E Grimaldi, Roberta Lanzillo, Sarah Rasia, Stefania Maria Bova, Paolo Ravanini, Fjorilda Caushi, Valentina Liliana Adriana Maria Torri Clerici, Stefano Sotgiu, Alberto Priori, Maria Trojano, Maria Pia Amato, Roberto Bergamaschi, Silvy Pilotto, Carlo Pozzilli, Salvatore Cottone, Giuseppe Santangelo, Giovanna De Luca, Maura Pugliatti, Angelo Ghezzi, Sandra D'Alfonso, Filippo Martinelli Boneschi","doi":"10.1212/NXI.0000000000200659","DOIUrl":"10.1212/NXI.0000000000200659","url":null,"abstract":"<p><strong>Background and objectives: </strong>Pediatric-onset multiple sclerosis (PedMS) provides a unique opportunity to investigate MS pathogenesis because of the short interval between environmental exposures and disease onset. This study aimed to identify differentially methylated regions (DMRs) that mediate the interplay between environmental triggers and genomic factors in the early stages of the disease.</p><p><strong>Methods: </strong>In this multicenter study, we analyzed peripheral blood DNA from 175 Italian subjects (122 PedMS patients, 53 healthy controls) using the Infinium Methylation EPIC Array v2. All patients were enrolled within 4 years of onset. The bioinformatic pipeline included batch effect correction, normalization, and differential methylation analysis adjusted for sex and inferred cell-type proportions. DMRs were detected using DMRcate. Network analysis was performed by projecting DMR-overlapping genes onto the STRING interactome using the NDEx tool, followed by pathway enrichment analysis with gProfiler. To ensure robustness, we performed an internal 1/3-2/3 validation and sensitivity analyses on treatment-naïve and low-efficacy treatment (LETA) subgroups.</p><p><strong>Results: </strong>Our analysis revealed 55 DMRs, with 28 affecting promoter regions. Top signals involved genes such as <i>CHI3L2</i>, <i>LPCAT1</i>, <i>CD19</i>, <i>PARP1</i>, <i>CPT1B-CHKB</i>, and <i>IGF2R</i>, including several MS-associated loci. Signals mapping to <i>CHI3L2/DENND2D</i> and <i>LPCAT1</i> were highly resilient, persisting across all validation and sensitivity subsets. Network analysis identified a subnetwork of 165 nodes where the Epstein-Barr virus (EBV) infection emerged as the top-ranked enriched pathway (<i>p</i> = 3.23 *10^-40). High-centrality regulatory hubs included <i>PARP1</i> and <i>IGF2R</i>, the latter overlapping with established imprinting control regions.</p><p><strong>Discussion: </strong>Our findings identify a distinct epigenetic signature in early-stage PedMS, suggesting that DNA methylation changes are not stochastic but converge on high-centrality regulatory hubs. The stable association with EBV-related pathways and imprinting loci reinforces the hypothesis that epigenetic remodeling serves as a critical interface between early-life environmental exposures and genetic susceptibility in MS onset.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200659"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149063148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of MOG-IgG and MOG-IgA in Maternal Breast Milk and Infant Blood in MOGAD: A Case Report.","authors":"Masoud Majed, Fatemeh Khani-Habibabadi, Anjali J Panicker, Sarah Reasbeck, Christopher Orlando, Jeffrey Gluckstein, Scott S Zamvil, Lilyana Amezcua, Kevin C O'Connor","doi":"10.1212/NXI.0000000000200652","DOIUrl":"10.1212/NXI.0000000000200652","url":null,"abstract":"<p><strong>Background and objectives: </strong>Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder of the CNS characterized by pathogenic MOG autoantibodies. Data regarding maternal-infant transfer of MOG autoantibodies, particularly in breast milk, are limited. We aimed to characterize maternal MOG autoantibodies longitudinally and assess their presence in maternal plasma, breast milk, and infant blood, as well as their clinical relevance in the infant.</p><p><strong>Methods: </strong>MOG-specific IgG, IgA, and IgM, including selected subclass analyses, were assessed by cell-based assays in longitudinal maternal plasma and breast milk samples, as well as infant plasma at birth. Additional assays assessed epitope specificity and isoform recognition.</p><p><strong>Results: </strong>Maternal plasma MOG-IgG titers were persistently elevated, with transient reduction during early pregnancy. MOG-IgG and MOG-IgA were detected in maternal plasma and breast milk. Binding patterns to MOG isoforms and epitopes were near-identical between compartments and restricted to the IgG1 and IgA1 subclasses. The infant tested positive for MOG-IgG at birth. The infant remained clinically asymptomatic through 18 months, despite autoantibody detection and ongoing breastfeeding.</p><p><strong>Discussion: </strong>Maternal MOG autoantibodies in blood and breast milk were not associated with clinical disease in the infant, suggesting no increased risk of MOGAD from maternal transmission.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200652"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}