Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Pregnancy Exposure to Anti-CD20 Monoclonal Antibodies in Patients With Multiple Sclerosis: Results From an Italian Multicenter Registry Study.","authors":"Irene Gattuso, Angela Genchi, Girolama Alessandra Marfia, Doriana Landi, Assunta Bianco, Massimiliano Mirabella, Giovanna Borriello, Antonio Gallo, Laura Brambilla, Valentina Gasparini, Lorena Lorefice, Maria Pia Amato, Francesca Rinaldi, Roberta Lanzillo, Elisabetta Signoriello, Maria Cellerino, Clara Grazia Chisari, Paola Cavalla, Carla Tortorella, Giovanna De Luca, Albulena Bajrami, Roberta Fantozzi, Damiano Paolicelli, Cristina Montomoli, Massimo Filippi, Lucia Moiola","doi":"10.1212/NXI.0000000000200650","DOIUrl":"10.1212/NXI.0000000000200650","url":null,"abstract":"<p><strong>Background and objectives: </strong>Although anti-CD20 monoclonal antibodies (anti-CD20s) theoretically represent an ideal treatment option for women with multiple sclerosis (wwMS) planning a pregnancy, the paucity of real-world data still limits their use in this context. Through our Italian registry \"CD20-PREGNANCY,\" we aim to report pregnancy, infant, and maternal outcomes in wwMS treated with anti-CD20s.</p><p><strong>Methods: </strong>In this observational study, wwMS having received rituximab (RTX), ocrelizumab (OCR), or ofatumumab (OFA) before and/or during pregnancy (≤12 months for RTX/OCR, ≤6 months for OFA) were included. Considering drug pharmacokinetics and timings of immunoglobulin placental transfer, pregnancies were classified as \"exposed\" (last administration pre-pregnancy ≤2.3 months for RTX, ≤3 for OCR, ≤1.8 for OFA) and \"not-exposed\" (last administration beyond these intervals) for comparative analysis.</p><p><strong>Results: </strong>A total of 153 pregnancies (85 \"not-exposed,\" 68 \"exposed\") across 27 Italian MS centers were collected. The median age at conception was 33.9 years (interquartile range 30.0-37.6) with 39.9% of women older than 35 years. Most pregnancies occurred in patients treated with OCR (77.1%). 80.4% of pregnancies ended in livebirth and 13.1% in spontaneous abortions (SA), without stillbirths/neonatal deaths. There was a significantly higher percentage of SA in \"exposed\" pregnancies than \"not-exposed\" (20.6% vs 7.1%, <i>p</i> = 0.014), but with values similar to those reported in general population. One serious perinatal infection (\"exposed\" group) and 2 major congenital anomalies (MCA) (one per group) were reported. Compared with the 12 months pre-pregnancy, annualized relapse rate remained stable during pregnancy but slightly increased postpregnancy (0.00 vs +0.09) in \"not-exposed.\" Conversely, it decreased in both periods (-0.02 vs -0.13) among \"exposed\". Compared with pre-pregnancy, postpregnancy combined unique active lesions decreased in both groups (-0.15 in \"not-exposed\", -0.38 in \"exposed\"), while 2 confirmed disability worsening were observed (\"not-exposed\").</p><p><strong>Discussion: </strong>In conclusion, a good control of disease activity was observed without an increased risk of MCA or perinatal infections. Percentages of SA were overall in line with those of general population, although with a higher proportion in the \"exposed\" group. These findings support the use of anti-CD20 therapies in wwMS planning pregnancy, although further data are needed to better define their safety profile in this setting.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200650"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851046","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":"EBNA1_381-452 and Cross-Reactive Antibody Responses Reveal Immune Signatures in Multiple Sclerosis.","authors":"Dries De Wit, Jarne Beliën, Margaux David, Stijn Swinnen, Nina Dedoncker, Lidia Yshii, Bénédicte Dubois","doi":"10.1212/NXI.0000000000200654","DOIUrl":"10.1212/NXI.0000000000200654","url":null,"abstract":"<p><strong>Background and objectives: </strong>Infection with the Epstein-Barr virus is a prerequisite for the development of multiple sclerosis (MS). Recent evidence has identified an antibody response against a peptide region of the Epstein-Barr virus nuclear antigen-1 (EBNA1_AE; alternative epitope, amino acid residues 381-452) that harbors cross-reactive potential against multiple autoantigens. It is currently unclear whether this antibody response is a driver of MS pathology. The presence of EBNA1-cross-reactive IgG responses in the CSF and their correlation with disease activity may provide insight into this matter. The aim of this study was to characterize the EBNA1_AE response in peripheral blood and CSF of a clinically well-defined cohort of patients with MS and identify whether cross-reactive antibody responses are linked to disease characteristics.</p><p><strong>Methods: </strong>In this cross-sectional study, we quantified IgG reactivity against 4 20-mer peptides in the EBNA1_AE region and their corresponding autoantigens using indirect ELISA in plasma of patients with untreated relapse-onset MS (n = 211) and healthy spouse controls (n = 63). We extended this analysis to paired serum-CSF samples from 61 patients with MS to determine intrathecal IgG responses.</p><p><strong>Results: </strong>We observed an increased antibody response to EBNA1_AE and corresponding autoantigens, supporting Epstein-Barr virus molecular mimicry in MS peripheral blood. Dimensionality reduction and clustering of 9 epitope-specific IgG responses identified 3 distinct peripheral immune signatures: EBNA1_AE-high cross-reactive, EBNA1_AE-high selective, and EBNA1_AE-low, indicating that high EBNA1_AE responses are not necessarily associated with high IgG responses against autoantigens. The cross-reactive signature, characterized by elevated reactivity to all EBNA1_AE epitopes and their corresponding autoantigens, was enriched in MS. Increased IgG responses to a number of EBNA1_AE epitopes were observed in patients who recently experienced a clinical relapse. The immune signatures were confirmed in the serum of the paired serum-CSF cohort. The Reiber antibody index for IgGs related to the EBNA1_AE-high cross-reactive immune signature suggested intrathecal synthesis.</p><p><strong>Discussion: </strong>Our findings contribute to the accumulating evidence of a role for EBNA1_AE molecular mimicry in MS pathology and demonstrate heterogeneity in EBNA1_AE-directed immune responses among patients with MS, differing in cross-reactivity and intrathecal enrichment.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200654"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977400","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":"Daratumumab Treatment in Severe Anti-NMDAR Encephalitis: Two Case Reports and Literature Review.","authors":"Nady Ammar, Marjolaine Uginet, Pia De Stefano, Hervé Quintard, Kaveh Samii, Jörg D Seebach, Josep Dalmau, Patrice H Lalive","doi":"10.1212/NXI.0000000000200648","DOIUrl":"10.1212/NXI.0000000000200648","url":null,"abstract":"<p><strong>Objectives: </strong>To describe clinical outcomes following daratumumab therapy in severe anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, including a literature review.</p><p><strong>Methods: </strong>We report 2 patients with severe anti-NMDAR encephalitis treated with anti-CD38 daratumumab after failure of multiple immunotherapies. Clinical data, treatments, and outcomes were analyzed retrospectively. A PubMed literature review identified 4 additional cases.</p><p><strong>Results: </strong>Both patients (21 and 19 years) presented with severe anti-NMDAR encephalitis characterized by neuropsychiatric symptoms, seizures, abnormal movements, and dysautonomia. Modified Rankin Scale (mRS) reached rapidly 5 in both cases and required ICU transfer within the first 2 weeks of hospitalization. Despite high-dose methylprednisolone, IV immunoglobulin, plasma exchange, rituximab, and cyclophosphamide, neither patient showed improvement. Daratumumab (1800 mg s/c) was initiated 40 and 14 weeks after onset, respectively. Clinical improvement occurred within weeks after treatment initiation, with gradual recovery of cognitive and functional abilities and ultimately regained functional independence (mRS 0). Literature review identified 4 additional cases of anti-NMDAR encephalitis treated with daratumumab; most patients showed substantial neurologic improvement.</p><p><strong>Discussion: </strong>These observations suggest that specific plasma cell-targeted therapy may be beneficial in severe anti-NMDAR encephalitis, potentially through reduction of pathogenic autoantibody production. However, current evidence is limited to uncontrolled reports, and further studies are needed to clarify optimal timing, efficacy, and safety.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200648"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13560940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920281","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":"A 35-Year-Old Woman With Multiple Sclerosis and a New Atypical Thalamic Lesion: A Case Report From the National Multiple Sclerosis Society Case Conference Proceedings.","authors":"Nara Miriam Michaelson, Isabel C Arrillaga-Romany, Justin T Jordan, Maria Martinez-Lage, Claire Riley, Scott S Zamvil, Myla D Goldman, Eric C Klawiter","doi":"10.1212/NXI.0000000000200667","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200667","url":null,"abstract":"<p><p>In multiple sclerosis (MS), new or enlarging brain lesions often suggest disease activity, but infections or tumors may mimic relapse. We report a 35-year-old woman with MS whose enlarging thalamic lesion was ultimately diagnosed as diffuse midline glioma, underscoring the need for prompt evaluation of atypical MRI findings.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200667"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytic and Axonal Injury Biomarkers in AQP4 Antibody-Positive NMOSD: Insights From PREVENT and CHAMPION-NMOSD.","authors":"Dean M Wingerchuk, Jeffrey L Bennett, Achim Berthele, Stacey L Clardy, Ho Jin Kim, Jin Nakahara, Jérôme de Sèze, Makoto Kinoshita, Breni Sharma, Cassandra L Uchida, Ruba Deeb Bou-Chahine, Becky Parks, Kerstin Allen, Jeannette N Stankowski, Sean J Pittock","doi":"10.1212/NXI.0000000000200661","DOIUrl":"10.1212/NXI.0000000000200661","url":null,"abstract":"<p><strong>Background and objectives: </strong>Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of astrocytic and axonal injury, respectively, in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-Ab+ NMOSD). We evaluated serum GFAP and NfL levels during treatment with complement component 5 inhibitors eculizumab or ravulizumab and examined associations between pretreatment biomarker levels, clinical characteristics, and on-trial relapse risk using samples from the PREVENT (eculizumab) and CHAMPION-NMOSD (ravulizumab) phase 3 trials.</p><p><strong>Methods: </strong>Serum GFAP and NfL levels were analyzed retrospectively in PREVENT and prospectively in CHAMPION-NMOSD and compared with levels in demographically matched external healthy donors. Associations between baseline clinical characteristics and high biomarker levels (≥2 SDs above the healthy donor mean) were evaluated using logistic regression with a test-and-validate strategy. Changes throughout treatment were assessed relative to pretreatment baseline. Biomarker changes associated with adjudicated on-trial relapses were examined. Associations between baseline biomarker levels and time to first adjudicated on-trial relapse were assessed using Kaplan-Meier analyses.</p><p><strong>Results: </strong>Samples were available from 41 PREVENT and 55 CHAMPION-NMOSD patients. Pretreatment baseline GFAP and NfL levels were elevated in patients compared with healthy donors. High baseline GFAP levels were associated with older age at initial presentation, less time since last relapse, and higher baseline Hauser Ambulation Index (HAI) score. High baseline NfL levels were associated with older age and higher baseline HAI score. High baseline GFAP and NfL levels using age-adjusted Z-scores were evaluated and would not have materially changed the conclusions. The median GFAP levels declined rapidly (within 4-6 weeks) and were sustained with both eculizumab and ravulizumab. The median NfL levels declined significantly with ravulizumab but not eculizumab. In PREVENT, adjudicated on-trial relapses were associated with increased GFAP levels in placebo-treated patients, while GFAP increases were attenuated in eculizumab-treated patients.</p><p><strong>Discussion: </strong>Serum GFAP and NfL levels are elevated in patients with NMOSD and are associated with clinical features of disability. Complement component 5 blockade biologically suppresses astrocytic injury in NMOSD, validating GFAP as a pharmacodynamic biomarker and mechanistic readout of target engagement in randomized phase 3 trials. This aligns with earlier findings across different compounds in separate phase 3 trials.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200661"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137905","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":"Autologous Hematopoietic Transplantation Reduces Brain Inflammatory and Axoglial Damage Biomarkers in Multiple Sclerosis.","authors":"Laura A Cooney, Noha Lim, Kristina M Harris, Dawn E Smilek, Pradeepthi Bathala, Martin Stengelin, George Sigal, Jacob N Wohlstadter, Maria Teresa Cencioni, José Ignacio Fernández Velasco, Yang Mao-Draayer, David A Fox, Linda M Griffith, Richard Nash, Luisa María Villar, Paolo A Muraro","doi":"10.1212/NXI.0000000000200653","DOIUrl":"10.1212/NXI.0000000000200653","url":null,"abstract":"<p><strong>Background and objectives: </strong>Autologous hematopoietic stem cell transplantation (AHSCT) can induce long-lasting immune tolerance and disease quiescence in patients with severe multiple sclerosis (MS), but the underlying mechanisms are not well understood. We hypothesized that AHSCT would induce persistent decreases in inflammatory cytokines, chemokines, and axoglial damage biomarkers in serum and CSF.</p><p><strong>Methods: </strong>Longitudinal serum and CSF samples were obtained from 24 participants with severe MS undergoing AHSCT in the HALT-MS trial (NCT00288626), with serum collected at 9 time points from pretreatment through month 60 and CSF collected at 3 time points, including pretreatment, month 24, and month 48. Approximately 50 soluble biomarkers were analyzed to determine treatment-induced changes and associations with disease activity, including clinical and MRI parameters.</p><p><strong>Results: </strong>AHSCT resulted in decreased expression of many proinflammatory cytokines, chemokines, and neuroinflammatory markers for several years in both serum and CSF, including neurofilament light chain (NfL). CSF levels of glial fibrillary acid protein and IL-7, on the contrary, increased after treatment. Expansion of cytomegalovirus and/or Epstein-Barr virus early after AHSCT resulted in transient increases in inflammatory cytokines in serum, but these changes did not persist. Changes in serum were largely distinct from changes in CSF, and concentrations of cytokines and chemokines in serum rarely correlated with concentrations in CSF, except for NfL.</p><p><strong>Discussion: </strong>These results confirm the hypothesis that AHSCT results in long-lasting reductions in inflammatory cytokines, chemokines, and axoglial damage markers, consistent with persistent disease quiescence. The lack of relationships between biomarkers in serum and CSF suggests that these samples largely reflect distinct immunologic processes and compartments, and that analysis of CSF may be warranted for deeper understanding of disease processes in the CNS despite the challenges associated with performing lumbar punctures. Expression of IL-7 in CSF may be an underappreciated biomarker of the inflammatory state in the CNS and warrants further study.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200653"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081596","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":"Evaluating the Clinical Utility of TSPO-PET in MS and the Influence of Methodological Heterogeneity: A Systematic Review and Meta-Analysis.","authors":"Arian Madani Neishaboori, Mansi Agarwal, Ally Kalinsky, Justin P Lofaso, Gayatri Rampilla, Elizabeth A Kras, Sydney C Nagy, John G Cooper, Shenjian Ai, Claire K Zhang, Karl Friedrichsen, Matthew Brier, Aisling M Chaney","doi":"10.1212/NXI.0000000000200658","DOIUrl":"10.1212/NXI.0000000000200658","url":null,"abstract":"<p><strong>Background and objectives: </strong>PET imaging targeting the 18-kDa translocator protein (TSPO) is a widely used method to detect neuroinflammation <i>in</i> vivo and shows promise for detecting innate inflammatory activity in multiple sclerosis (MS). However, TSPO-PET findings in MS vary substantially across studies. We performed a systematic review and meta-analysis to quantify TSPO-PET signal differences between people with MS (PwMS) and healthy controls (HCs) and to evaluate the impact of methodological factors on study outcomes.</p><p><strong>Methods: </strong>A systematic search of Scopus, MEDLINE, Web of Science, and Embase databases was conducted through September 10, 2025. Original TSPO-PET studies in PwMS were included. Standardized mean differences (SMDs) in TSPO-PET signal between PwMS and HC were pooled using random-effects models with cluster robust variances. Heterogeneity was assessed using <i>I</i>² statistics. Meta-regression and subgroup analyses investigated methodological sources of heterogeneity. Patient-level data were analyzed for associations with clinical and demographic variables. Risk of bias and certainty of evidence were assessed using quality assessment of diagnostic accuracy studies 2 tool and GRADE framework, respectively.</p><p><strong>Results: </strong>Forty-nine studies met inclusion criteria. Overall meta-analysis revealed significantly increased TSPO-PET signal in PwMS vs HC (SMD = 0.44, 95% CI: 0.27-0.61, <i>p</i> = 0.0002, <i>I</i>²: 97.00%). TSPO-PET signal was also significantly higher in progressive MS than in relapsing-remitting MS, indicating discrimination across MS clinical subtypes. Meta-regression attributed study heterogeneity to tracer (11.47%), PET quantification method (15.37%), and region of interest (19.71%) differences. Significant PwMS vs HC differences were most consistently observed with select tracers ([¹¹C]PBR28, [¹⁸F]DPA-714, [¹¹C]ER176, and [¹¹C]PK11195) and with distribution volume ratio (DVR), nondisplaceable binding potential (BP_ND), and standardized uptake value ratio metrics. Significant effects were found in perilesional, thalamic, cortical, hippocampal, normal-appearing white matter, and T₂-weighted white matter lesion regions. Patient-level analyses, while limited in power, showed significant associations between TSPO-PET signal (DVR) and disability measures (expanded disability status scale).</p><p><strong>Discussion: </strong>TSPO-PET effectively distinguishes PwMS from HC and differentiates MS subtypes. However, radiotracer, quantification method, image analysis method, reference tissue, and region of interest significantly impact TSPO-PET outcomes and must be considered when designing and interpreting studies. Methodological standardization and improved reporting will be essential to enhance cross-study comparability and clinical interpretability.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200658"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081533","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":"Disease Activity During Pregnancy and Postpartum in Women With Multiple Sclerosis Treated With Ocrelizumab or Rituximab Before Pregnancy.","authors":"Nadine Bast, Karen Dost-Kovalsky, Sabrina Haben, Laura Witt, Ralf Gold, Sandra Thiel, Kerstin Hellwig","doi":"10.1212/NXI.0000000000200670","DOIUrl":"10.1212/NXI.0000000000200670","url":null,"abstract":"<p><strong>Background and objectives: </strong>Preliminary data suggest sustained disease control with ocrelizumab (OCR) or rituximab (RTX) in women with multiple sclerosis (MS) after pregnancy suspension; however, the influence of washout duration and cumulative dosing remains unknown. This study investigates disease activity during and after pregnancy in women with relapsing-remitting MS treated with OCR/RTX before pregnancy.</p><p><strong>Methods: </strong>In this cohort study, pregnancies of women treated with OCR/RTX documented in the German MS and Pregnancy Registry were stratified by timing of last infusion (≥ or <4 months to last menstrual period [LMP]) and number of cycles (≥ or <2 cycles). Relapses treated with high-dose glucocorticosteroids were analyzed, as was persistent disability (following a relapse) at 1-year postpartum, defined as a ≥2.0-point increase in Expanded Disability Status Scale (EDSS) or new/worsening ambulatory impairment (Severe Relapse Disability Composite Score [SRDCS]).</p><p><strong>Results: </strong>Of 294 pregnancies among 275 women, only 28.6% (n = 84) suspended OCR/RTX ≥4 months before LMP and most (79.3% [n = 233]) received ≥2 cycles. Relapses during pregnancy (2.0%) and within 12 months postpartum (8.5%) were rare. Four women (1.6%) reached the SRDCS postpartum. Neither the time of last infusion nor the number of cycles was associated with a higher relapse risk during pregnancy (time between OCR/RTX and LMP: <4 months adjusted OR: 0.60, CI: 0.09-5.02, <i>p</i> value: 0.60; number of cycles: <2 cycles adjusted OR: 2.23, CI: 0.34-15.5, <i>p</i> value: 0.39) or postpartum (time between OCR/RTX and LMP: <4 months adjusted OR: 0.62, CI: 0.23-1.77, <i>p</i> value: 0.36; number of cycles: <2 cycles adjusted OR: 0.64, CI: 0.16-2.03, <i>p</i> value: 0.48, time of anti-CD20 antibody restart postpartum: >6 weeks adjusted OR: 1.15, CI: 0.37-4.11, <i>p</i> value: 0.82) or with reaching the SRDCS or EDSS worsening postpartum. In women receiving ≥2 cycles and interrupting treatment <4 months before LMP, numerically fewer relapses during pregnancy could be observed (1/163: 0.6% vs 5/131: 3.8%, <i>p</i> value: 0.09).</p><p><strong>Discussion: </strong>Relapses and disability during and after pregnancy after OCR/RTX interruption are rare and independent of timing and number of cycles. However, potential differences may not be detectable due to the low number of events and should be evaluated in larger studies. In addition, the applicability to ofatumumab, given its different dosing interval, remains unclear.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200670"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149472","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":"The Gut Microbiome in Multiple Sclerosis.","authors":"Alicia Sánchez-Sanz, Sergio E Baranzini","doi":"10.1212/NXI.0000000000200638","DOIUrl":"10.1212/NXI.0000000000200638","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS whose risk and course are shaped by both genetic and environmental factors, among which the intestinal microbiota has emerged as a key, potentially modifiable contributor. People with MS frequently display altered gut microbiota, characterized by depletion of fiber-fermenting, short-chain fatty acid (SCFA)-producing commensals, and expansion of taxa associated with mucus degradation and proinflammatory metabolism. These compositional shifts are paralleled by broad changes in blood and CSF metabolites, including reduced SCFAs, tryptophan-derived aryl hydrocarbon receptor ligands, and secondary bile acids. In addition, several reports highlight the accumulation of aromatic amino acid-derived phenolic and indolic compounds and specific lipid mediators linked to neuroinflammation and neurodegeneration. In this up-to-date review, we synthesize evidence from experimental models and human studies showing how microbial metabolites can influence MS pathogenesis through converging mechanisms: modulation of gut and blood-brain barrier integrity; shaping of T-cell and B-cell responses; direct effects on microglia, astrocytes, and oligodendrocyte lineage cells after crossing into the CNS; and modulation of neural circuits, particularly those involving the vagus nerve. Finally, we highlight current gaps, including the need for longitudinal, harmonized multiomic cohorts, and mechanistic studies integrating microbiome, metabolome, and host readouts across gut, blood, and CNS. Overall, available data support a model in which coordinated disruption of the gut microbiota-metabolite axis, rather than any single pathogen, contributes to MS, opening avenues for microbiota-based and metabolite-based biomarkers and therapies aimed at restoring immune and neuroglial homeostasis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200638"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831143","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":"MRI-Negative Sarcoid Myelitis Revealed by Spinal ¹⁸F-FDG-PET Hypermetabolism.","authors":"Siddhartha Pandit, Inès Castarède, Kevin Battistini, Felix T Kurz, Valentina Garibotto, Patrice H Lalive","doi":"10.1212/NXI.0000000000200675","DOIUrl":"10.1212/NXI.0000000000200675","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 6","pages":"e200675"},"PeriodicalIF":8.0,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136794","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}