Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"TRUE-MOGAD Score: A Novel Scoring System to Identify MOGAD Among Positive MOG-IgG Test Results.","authors":"Andreu Vilaseca, Angeliki G Filippatou, Yana Said, Elia Sechi, Stephanie B Syc-Mazurek, Laura Cacciaguerra, Kai Guo, Nisa Vorasoot, Moritz Niederschweiberer, Smathorn Thakolwiboon, Jessica A Sagen, Sebastian A Lopez-Chiriboga, Jan-Mendelt Tillema, John J Chen, Sean J Pittock, Elias S Sotirchos, Eoin P Flanagan","doi":"10.1212/NXI.0000000000200563","DOIUrl":"10.1212/NXI.0000000000200563","url":null,"abstract":"<p><strong>Objectives: </strong>Myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-IgG) are a biomarker of MOG antibody-associated disease (MOGAD). However, false positives remain common. We aimed to develop a scoring tool to guide interpretation.</p><p><strong>Methods: </strong>Observational study of MOG-IgG-positive patients at Mayo Clinic (May 2022-December 2024). The primary outcome was fulfillment of 2023-MOGAD diagnostic criteria. Predictive variables were identified using logistic regression, and scoring systems were derived and evaluated using receiver operating characteristic analysis. Internal (n = 92) and external (Johns Hopkins, n = 117) validation was performed.</p><p><strong>Results: </strong>Of 215 MOG-IgG positive patients, 144 were true positive per 2023-MOGAD diagnostic criteria (positive predictive value, 67.0%). The <b>TRUE-</b><b>MOGAD</b> score included: <b>T</b>iters (MOG-IgG clear positive [+1 point]), <b>R</b>elapsing optic neuritis (≥3 [+1 point]), <b>U</b>nder 18 years at onset [+1 point], <b>E</b>ncephalitis phenotype (ADEM or cerebral cortical encephalitis at onset [+2 points]), <b>M</b>RI or other supportive features from 2023-MOGAD-criteria [+2 points], <b>O</b>ligoclonal bands in CSF [-2 points], <b>G</b>radually progressive or <b>A</b>brupt onset [-2 points], and <b>D</b>isappearance ≥1 T2-lesion [+1 point]. The score showed an area under the curve (AUC) of 0.983 (95%CI 0.961-1.000). The score was validated internally (AUC = 0.976) and externally (AUC = 0.977).</p><p><strong>Discussion: </strong>The TRUE-MOGAD score is a practical tool that accurately identifies MOGAD among positive MOG-IgG test results and may guide diagnostic and therapeutic decisions in clinical practice.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that a TRUE-MOGAD score of 2 or more accurately predicts MOGAD in patients with MOG-IgG titers of 1:20 or higher using the assay described.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200563"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593869","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":"Low Prevalence and Inconsistency of LRP4-IgG Detection in Suspected Myasthenia Gravis: A Multicenter CBA Comparison.","authors":"Ilaria Gligora, Pietro Businaro, Lucrezia Serra, Silvia De Pasqua, Fortuna Ricciardiello, Luana Morelli, Chiara Morandi, Stefano Masciocchi, Antonio Malvaso, Corrado Ballestracci, Vitantonio Di Stasi, Veria Vacchiano, Anna Fetta, Simone Rossi, Keivan Kaveh Moghadam, Giovanni Rizzo, Domenica Chiara Milano, Andrea Zini, Duccio Maria Cordelli, Rita Rinaldi, Vincenzo Donadio, Rocco Liguori, Matteo Gastaldi, Maria Pia Giannoccaro","doi":"10.1212/NXI.0000000000200554","DOIUrl":"10.1212/NXI.0000000000200554","url":null,"abstract":"<p><strong>Background and objectives: </strong>Myasthenia gravis (MG) is an autoimmune disorder primarily caused by antibodies targeting neuromuscular junction proteins, particularly the acetylcholine receptor and the muscle-specific tyrosine kinase. However, 10%-20% of patients with MG are double-seronegative (dsMG). Antibodies against low-density lipoprotein receptor-related protein 4 (LRP4-IgG) have been found in a variable proportion of dsMG cases, but their frequency and clinical relevance remain unclear because of differences in assay methodologies and study populations. In this study, we assessed the frequency of LRP4-IgG in patients with suspected MG using different cell-based assay (CBA) protocols.</p><p><strong>Methods: </strong>In this multicenter observational study, we enrolled consecutive patients presenting with symptoms suggestive of MG. LRP4-IgG was tested by 2 centers using 3 different CBAs: live (l-CBA), methanol-fixed (mf-CBA), and paraformaldehyde-fixed (pf-CBA). Patients were classified as having MG or other disorders (ODs). Positive samples were cross-tested between centers.</p><p><strong>Results: </strong>Among 684 patients (302 with MG, 382 with ODs), LRP4-IgG was detected by mf-CBA in 2% (6/302) of MG cases and in 0.52% (2/382) of OD cases. Among patients with MG, 3.9% (4/102) of dsMG and 1% (2/200) of seropositive patients tested positive. Only 50% of mf-CBA-positive cases were confirmed by pf-CBA, and none were detected by l-CBA. Cross-center testing showed partial reproducibility.</p><p><strong>Discussion: </strong>LRP4-IgG detection in suspected MG is rare and inconsistent across assays, suggesting that routine testing is not currently warranted and that these antibodies are at present of limited diagnostic value. These findings highlight the need for standardized, validated LRP4-IgG assays. Future studies should focus on direct comparison and harmonization of testing protocols to clarify the clinical utility of LRP4-IgG testing.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200554"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258870","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":"Shared Epitope-Positive <i>HLA</i> Alleles Protect Against Alpha-Synuclein Pathology in a Model of Parkinson Disease.","authors":"Jonathan J Carver, Bryce A Pugh, Qin Ma, Stacy J Caillier, Rachael R Denbrock, Cindy C Martines, Alexandra E Puckett, Taylor C Roberson, Marcelo A Fernandez-Viña, Jill A Hollenbach, Jorge Oksenberg, Joseph Holoshitz, Alessandro Didonna","doi":"10.1212/NXI.0000000000200580","DOIUrl":"10.1212/NXI.0000000000200580","url":null,"abstract":"<p><strong>Background and objective: </strong>There is increasing evidence that human leukocyte antigen (<i>HLA</i>) allelic variants play a role in the genetic predisposition to Parkinson disease (PD). In this regard, we have recently reported that the <i>HLA-DRB1*04:01</i> allele, typified by residues Q/R-K/R-R-A-A at positions 70-74 in the HLA-DRβ1 chain in combination with valine at position 11 (11-V), confers moderate protective effects. In this study, we tested whether <i>HLA-DRB1*04:01</i> can modulate PD pathology in vivo.</p><p><strong>Methods: </strong>We induced the alpha-synuclein preformed fibrils seeding PD model in humanized mice expressing the <i>HLA-DRB1*04:01</i> or <i>HLA-DRB1*04:02</i> allele. We then performed a comprehensive histopathologic and molecular characterization of the main disease phenotypes by combining quantitative histopathology, RNA-sequencing, flow cytometry immunophenotyping, and cytokine profiling.</p><p><strong>Results: </strong>Mice expressing <i>HLA-DRB1*04:01</i> display limited alpha-synuclein aggregation and lower dopaminergic axonal injury compared with mice expressing <i>HLA-DRB1*04:02</i>, along with reduced systemic inflammation. We also show that the microglia compartment in <i>HLA-DRB1*04:01</i> mice is in an activated steady state, possibly suggesting their mechanistic involvement in alpha-synuclein clearance.</p><p><strong>Discussion: </strong>Altogether, our findings provide the first experimental evidence of the genetic association between the HLA locus and PD susceptibility and support a neuroprotective function for the <i>HLA-DRB1*04:01</i> allele against alpha-synuclein pathology.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200580"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717680","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":"Cytomegalovirus Drives the Development of Cytotoxic CD4⁺ T Cells in Patients With Multiple Sclerosis.","authors":"Cindy Hoeks, Bram Boeckx, Paulien Baeten, Doryssa Hermans, Joanna Randall, Bart Van Wijmeersch, Veronica Popescu, Veerle Somers, Piet Stinissen, Diether Lambrechts, Bieke Broux, Niels Hellings","doi":"10.1212/NXI.0000000000200561","DOIUrl":"10.1212/NXI.0000000000200561","url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic immune activation is a hallmark of latent viral infections and autoimmune disorders, profoundly shaping immune cell phenotypes, including CD4⁺ cytotoxic T lymphocytes (CD4 CTL). The mechanisms underlying CD4 CTL development remain elusive, although antigenic triggers and the local microenvironment are thought to influence their phenotype. In this study, it was investigated if CD4 CTL induced under different circumstances exhibit phenotypic differences.</p><p><strong>Methods: </strong>Using single cell multiomics, we analyzed CD4 CTL from healthy cytomegalovirus (CMV)-seropositive donors, patients with CMV-seronegative relapsing-remitting multiple sclerosis (RR-MS) (autoimmune trigger), and patients with CMV-seropositive RR-MS (combination of viral and autoimmune trigger).</p><p><strong>Results: </strong>Our findings reveal that the heterogeneous pool of CD4 CTL encompasses distinct subsets with divergent expression of proinflammatory, cytotoxic, and migratory markers. Moreover, we identified a pathogenic CD4 CTL subset coexpressing the MS-associated transcription factor eomesodermin (EOMES) and the migratory receptor class I-restricted T-cell-associated molecule, which accumulates in MS lesions and demonstrates resistance to natalizumab treatment.</p><p><strong>Discussion: </strong>CMV was implicated as a dominant driver of development of highly cytotoxic CD4⁺ T cells, as these cells were markedly enriched in CMV-seropositive individuals. This comprehensive phenotypic atlas of CD4 CTL advances our understanding of their development and highlights potential targets for diagnosing, treating, and preventing MS progression.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200561"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504557","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":"Integrin β1 Demarks Precursors of Brain-Residing Antibody-Secreting Cells in Multiple Sclerosis.","authors":"Kirsten L Kuiper, Laurens Bogers, Jasper Rip, Yifan van Hasselt, Marie-José Melief, Annet F Wierenga-Wolf, Romy A M Klein Kranenbarg, Eric Bindels, Harmen J G van de Werken, Janet de Beukelaar, Ide Smets, Beatrijs Wokke, Joost Smolders, Marvin M van Luijn","doi":"10.1212/NXI.0000000000200553","DOIUrl":"10.1212/NXI.0000000000200553","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is characterized by CXCR3⁺ memory B cells that infiltrate the CNS to mature into antibody-secreting cells (ASCs). It remains elusive how to benefit from this disease hallmark as a prognostic tool. We aimed to uncover markers that reflect B-cell entry and maturation in the CNS and, on that basis, explore associations with response to high-efficacy MS therapies.</p><p><strong>Methods: </strong>Ex vivo single-cell technologies were applied to blood samples and postmortem CNS suspensions from MS and control donors, either treated or untreated. In addition, in vitro assays were performed on blood samples from healthy individuals to functionally asses B-cell activation, differentiation, and transmigration.</p><p><strong>Results: </strong>Single-cell RNA sequencing revealed <i>ITGB1</i> (integrin β1/CD29) as a major discriminator of CXCR3⁺ memory B cells in blood, which was validated using spectral flow cytometry. CD29⁺CXCR3⁺ memory B cells preferentially crossed a brain microvascular endothelial layer and were highly receptive to T-cell help to become ASCs in vitro. In contrast to blood, CD29 and CXCR3 coexpression was restricted to ex vivo ASCs derived from CSF, meninges, and brain tissue of people with MS, which was supported by enhanced CD29 upregulation on in vitro-differentiated ASCs. While CD29 was downregulated on CXCR3⁺ memory B cells that accumulated in the blood of natalizumab-treated patients, CD29 levels were only reduced on CXCR3⁺ memory B cells that repopulated in cladribine-treated patients without early disease activity.</p><p><strong>Discussion: </strong>These findings put forward CD29 as a putative marker on CXCR3⁺ precursors of CNS-residing ASCs for predicting treatment responses in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200553"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207332","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":"Ganglion Cell Layer Compared With Inner Plexiform Layer Atrophy After Optic Neuritis Associated With NMOSD, MOGAD, and MS.","authors":"Angeliki G Filippatou, Georgios Gakis, Anna Bacchetti, Anna Kim, Yana Said, Brenna McCormack, Ting-Yi Lin, Adam Didouchevski, Nicole Pellegrini, Kathryn C Fitzgerald, Peter A Calabresi, Shiv Saidha, Elias S Sotirchos","doi":"10.1212/NXI.0000000000200567","DOIUrl":"10.1212/NXI.0000000000200567","url":null,"abstract":"<p><strong>Background and objectives: </strong>Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS), aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Compared with MS-ON, AQP4-ON and MOGAD-ON eyes exhibit more severe thinning of the macular composite ganglion cell + inner plexiform layer (GCIPL), as measured by optical coherence tomography (OCT). The individual measurement of the ganglion cell (GCL) and inner plexiform (IPL) layers, typically assessed together as the composite GCIPL thickness, has remained largely unexplored. In this study, we aimed to examine the relative contribution of GCL and IPL thinning to overall GCIPL thinning in MS-ON, AQP4-ON, and MOGAD-ON eyes.</p><p><strong>Methods: </strong>For the cross-sectional analysis, MS, AQP4+NMOSD, and MOGAD participants with a history of ON >6 months prior and healthy controls (HC) underwent retinal imaging. For the longitudinal analysis, the evolution of GCL and IPL thinning was examined in people with baseline OCT within 30 days of a first episode of acute ON.</p><p><strong>Results: </strong>In the cross-sectional cohort, GCL and IPL volumes were lower in AQP4-ON (n = 30 eyes) and MOGAD-ON (n = 47 eyes), as compared with MS-ON (n = 66 eyes), but did not differ between AQP4-ON and MOGAD-ON eyes. The GCL/GCIPL ratio was lower in ON eyes relative to HC and was correlated with GCIPL volume, with a similar pattern across disease groups. AQP4-ON and MOGAD-ON eyes had a lower GCL/GCIPL ratio compared with MS-ON, with no significant difference between AQP4-ON and MOGAD-ON. In the longitudinal cohort, the GCL/GCIPL ratio was already reduced in the ON eyes (n = 19 eyes) compared with the fellow non-ON eyes at the baseline scan within the first month from ON (-1.01% [-1.59% to -0.44%], <i>p</i> = 0.002). A greater loss of GCIPL volume after acute ON was associated with a greater decrease of the GCL/GCIPL ratio (r = 0.50, <i>p</i> < 0.001).</p><p><strong>Discussion: </strong>More severe GCIPL thinning after ON was associated with a lower GCL/GCIPL ratio, supporting that more GCL than IPL thinning occurs after ON. The pattern was similar across neuroinflammatory conditions including MS, MOGAD, and AQP4+NMOSD. Our findings may help shed light into dynamics of inner retinal layer atrophy after ON.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200567"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513799","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":"Interleukin-9 Regulates NF-kB-Mediated Activation of Astrocytes in Multiple Sclerosis Brain.","authors":"Miriam Cinotti, Susanna Amadio, Daniele Tidei, Gloria Donninelli, Costanza Stacchiotti, Veronica De Paolis, Emanuela Colombo, Anthea De Angelis, Francesca Ruffini, Gianvito Martino, Cinthia Farina, Chiara Parisi, Cinzia Volonté, Elisabetta Volpe","doi":"10.1212/NXI.0000000000200574","DOIUrl":"10.1212/NXI.0000000000200574","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200574"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348569","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":"Comparative Effectiveness of Disease-Modifying Treatments in Double Seronegative Neuromyelitis Optica Spectrum Disorder.","authors":"Joao Vitor Mahler, Gerome B Vallejos, Takahisa Mikami, Philippe A Bilodeau, Monique Anderson, Natalia Drosu, Natasha Bobrowski-Khoury, Guilherme Diogo Silva, Marina Solti, Samira Luisa Apóstolos-Pereira, Dagoberto Callegaro, Bruna Leles Vieira de Souza, Giovanna Sophia Manzano, Anastasia Vishnevetsky, Rebecca Gillani, Olivia Pasquale, Angie Kim, Raveena Vij, Ilya Kister, Emily L Gibbons, Anu Jacob, Saif Huda, Yana Said, Jonathan D Krett, Elias S Sotirchos, Manisha Ramprasad, Hesham Abboud, Viviane Tavares Carvalho Crelier, Gutemberg Dos Santos, Ekdanai Uawithya, Sasitorn Siritho, Ahmetcan Sezen, Ayse Altintas, Feng Gai, Yanjun Guo, Shamik Bhattacharyya, Michael Levy, Marcelo Matiello","doi":"10.1212/NXI.0000000000200589","DOIUrl":"10.1212/NXI.0000000000200589","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200589"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699302","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":"Real-World Efficacy and Safety of Neuromyelitis Optica Spectrum Disorder Disease-Modifying Treatments.","authors":"Philippe A Bilodeau, Mattia Wruble Clark, Avanteeka Ganguly, Jenna Bernice Harowitz, Joao Vitor Mahler, Mulan Jiang, Sathya S Narasimhan, Danielle Kei Pua, Brian C Healy, Farrah Jasmine Mateen, Michael Levy, Shamik Bhattacharyya","doi":"10.1212/NXI.0000000000200536","DOIUrl":"10.1212/NXI.0000000000200536","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neuromyelitis optica spectrum disorder (NMOSD) is characterized by inflammatory relapses that result in severe disability, including blindness and paralysis. Relapse prevention with safe and effective treatments is key to reducing long-term disability. We aim to compare the efficacy and safety of rituximab-the most commonly used treatment-with recently approved NMOSD-specific treatments-eculizumab, inebilizumab, satralizumab-and other common off-label NMOSD treatments-mycophenolate mofetil (MMF) and azathioprine. The primary outcomes are relapse-free survival and annualized relapse rate. Secondary outcomes are serious infectious adverse event (SIAE) and treatment-limiting adverse event (TLAE)-free survival.</p><p><strong>Methods: </strong>A retrospective cohort study of NMOSD was conducted on patients at the Mass General Brigham hospital network. Patients meeting 2015 NMOSD diagnostic criteria, who were seen between 2000 and 2024 were included. Poisson regression, frequentist negative binomial analysis with inverse probability of treatment weighting, and Cox proportional hazard models were used to assess relapse rates, relapse-free survival, and SIAEs.</p><p><strong>Results: </strong>A total of 176 patients with NMOSD were followed for a median of 9 years (interquartile range: 5-14), contributing 691 relapse assessments. The median age at first attack was 42 years, and 83% were female. Compared with rituximab, relapse risk was significantly lower with C5 inhibitors (HR 0.12, 95% CI 0.07-0.24), inebilizumab (HR 0.22, 95% CI 0.12-0.65), and satralizumab (HR 0.19, 95% CI 0.11-0.42). Annualized relapse rates were the lowest for C5 inhibitors (0, 95% CI 0-0.063) and the highest for azathioprine (0.34, 95% CI 0.18-0.56). A composite outcome of relapse, SIAE, and TLAE favored C5 inhibitors (HR 0.22, 95% CI 0.05-0.67), while azathioprine (HR 2.33, 95% CI 1.08-4.86) and MMF (HR 1.75, 95% CI 1.02-2.95) showed increased risk compared with rituximab. C5 inhibitors had the lowest incidence of serious infections (incidence rate ratio 0.16, 95% CI 0.05-0.42 vs rituximab).</p><p><strong>Discussion: </strong>Clinicians should consider using NMOSD-approved treatments given their favorable efficacy and safety profiles in the real-world setting. MMF and azathioprine should be avoided. We caution against rituximab as a default first-line given the cumulative risk of relapse, SIAEs, and TLAEs over time.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that, in patients with NMOSD, FDA-approved disease-modifying therapies are associated with lower relapse rates and fewer serious adverse events compared with rituximab.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 2","pages":"e200536"},"PeriodicalIF":7.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912472","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":"Niacin Modulates Immune Responses in a Phase I Dose-Escalation Clinical Trial of Newly Diagnosed Glioblastoma.","authors":"Candice C Poon, Kathleen M Hagen, Susobhan Sarkar, Reza Mirzaei, Claudia Silva, Aito Ueno, Paula de Robles, Gloria Roldan-Urgoiti, V Wee Yong","doi":"10.1212/NXI.0000000000200530","DOIUrl":"10.1212/NXI.0000000000200530","url":null,"abstract":"<p><strong>Background and objectives: </strong>Glioblastoma, a highly aggressive and uniformly lethal brain tumor, resists current treatments and immunotherapies by creating a potently immunosuppressive microenvironment. The objective of this study was to determine whether niacin modulates systemic immunity in patients with newly diagnosed glioblastoma.</p><p><strong>Methods: </strong>In a first-in-human phase I clinical trial (NCT04677049), we investigated the immunologic effects of niacin administration alongside standard-of-care surgery and chemoradiation in patients with newly diagnosed glioblastoma.</p><p><strong>Results: </strong>Niacin treatment increases the frequencies of circulating memory T cells and natural killer cells while decreasing nonclassical monocytes. Furthermore, niacin elevated serum levels of the proinflammatory cytokine interleukin (IL)-12p70 and granulocyte colony-stimulating factor and reduced growth-regulated α protein.</p><p><strong>Discussion: </strong>These data demonstrate that niacin induces systemic immunomodulatory effects in patients with glioblastoma, shifting the immune landscape toward an antitumor profile and supporting further evaluation of niacin as a potential therapeutic adjunct.</p><p><strong>Trial registration information: </strong>This ongoing study was registered as NCT04677049 on March 1, 2021, with the first patient enrolled on March 18, 2021.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that niacin dose escalation modulates immune response in patients with glioblastoma treated with standard of care, including maximal safe resection, concurrent radiation and temozolomide, and adjuvant temozolomide administration. This is a Class IV study because it is an open-label trial with no blinding or comparison group.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 2","pages":"e200530"},"PeriodicalIF":8.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12879028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113956","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}