Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Use of Fluid Biomarkers in NMOSD and MOGAD: Clinical and Research Applications.","authors":"Sara Mariotto, Alvaro Cobo-Calvo, Michael Khalil, Thais Armangue, Orhan Aktas, Romana Höftberger, Rinze Frederik Neuteboom, Anne-Katrin Pröbstel, Markus Reindl, Patrick J Waters, Georgina Arrambide, Friedemann Paul, Jacqueline Palace, Romain Marignier, Yael Hacohen","doi":"10.1212/NXI.0000000000200627","DOIUrl":"10.1212/NXI.0000000000200627","url":null,"abstract":"<p><p>Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are inflammatory disorders of the CNS with distinct immunopathologic mechanisms and treatment responses and partially overlapping clinical phenotypes. The identification of aquaporin-4 (AQP4)-IgG and MOG-IgG has transformed disease classification and diagnosis, enabled a classification of antibody-defined subgroups, and facilitated the development of targeted therapies. However, optimal use of these biomarkers in clinical practice requires careful interpretation within the appropriate clinical and radiologic context. This review synthesizes current evidence on established and emerging fluid biomarkers in NMOSD and MOGAD, with emphasis on analytical performance, biological relevance, and clinical utility. We review antibody detection using cell-based assays, highlighting differences between live and fixed platforms and the impact of antigen conformation on sensitivity and specificity, particularly for MOG-IgG. Common causes of false-positive and false-negative results are discussed, including low-titer reactivity, testing in low pretest probability populations, treatment-related antibody titer reduction, and assay-specific limitations. The diagnostic challenges posed by indiscriminate testing in adult cohorts with multiple sclerosis, in whom disease prevalence markedly exceeds that of MOGAD, are emphasized. We also discuss the role of repeat testing during acute attacks and paired serum-CSF analysis in improving diagnostic confidence when results are equivocal or discordant. Beyond disease-defining antibodies, we examine biomarkers of tissue injury and immune activation. Serum and CSF neurofilament light chain and glial fibrillary acidic protein provide complementary measures of neuroaxonal and astrocytic damage and show associations with attack severity, disease activity, relapse risk, and long-term disability. Cytokines, chemokines, and complement components reflect inflammatory pathways, including IL-6-driven immune activation in NMOSD and MOGAD and complement-mediated astrocytopathy in NMOSD, and may support mechanistic stratification and treatment monitoring in both conditions. We further review the contribution of CSF analysis, neuropathology, genetics, and antigen discovery platforms to refine disease classification, particularly in seronegative or atypical presentations. Finally, we outline priorities for future research, including assay harmonization, standardized sampling protocols, longitudinal biomarker profiling, and integrative multiomic approaches. Collectively, advances in biomarker science have the potential to improve diagnostic precision, guide individualized therapeutic strategies, and support de-escalation decisions in NMOSD and MOGAD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200627"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713312","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":"\"Home\": How Immune Cells Enter the Central Nervous System.","authors":"Lawrence Steinman","doi":"10.1212/NXI.0000000000200625","DOIUrl":"10.1212/NXI.0000000000200625","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200625"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813562","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":"Prognostic Determinants of Presentation and Outcome in Anti-IgLON5 Disease.","authors":"Lidia Sabater, Mar Guasp, Raquel Ruiz García, Laura Naranjo Rondán, Luis Querol, Lorena Martín-Aguilar, Paula Llarch, Mircea Balasa, Albert Lladó, Celia Painous, Yaroslau Compta, Ana Beatriz Serafim, Angelica Montini, Alex Iranzo, Joan Santamaria Cano, Josep O Dalmau, Francesc Graus, Carles Gaig","doi":"10.1212/NXI.0000000000200600","DOIUrl":"10.1212/NXI.0000000000200600","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-IgLON5 disease is characterized by substantial clinical heterogeneity and variable outcomes. We investigated the associations of clinical features as well as serum neurofilament light chain (NfL), phosphorylated tau (p-tau), IgG4 levels, and the HLA-DRB110:01∼DQB105:01 haplotype with disease presentation and outcome.</p><p><strong>Methods: </strong>This is a retrospective observational study of patients with anti-IgLON5 disease diagnosed in our laboratory with adequate clinical information and follow-up. Neurologic disability was evaluated with the modified Rankin Scale (mRS) and the anti-IgLON5 composite score (ICS). Serum NfL and p-tau181 levels were measured using a commercial single-molecule array (Simoa) assay and IgG4 levels by flow cytometry. Associations between biomarkers and baseline clinical features were assessed using Spearman rank correlation and linear regression analyses. Prognostic variables were evaluated using binary logistic and Cox proportional hazards regression models.</p><p><strong>Results: </strong>We included 78 patients (median age 66 years, 55% male). Higher serum NfL levels correlated with clinical severity at diagnosis, as measured with the mRS (<i>r</i> = 0.438; <i>p</i> = 0.002) and ICS (<i>r</i> = 0.30; <i>p</i> = 0.029). Patients with the HLA-DRB1*10:01∼DQB1*05:01 haplotype more frequently presented with the bulbar or sleep phenotypes (24/41; 58%) compared with those without the haplotype (4/28; 14%; <i>p</i> = <0.001). Sixty-six patients received immunotherapy, and 14 (21%) showed clinical improvement at the last follow-up. In the multivariate Cox regression model, the neuromuscular phenotype was the only independent predictor of good outcome (mRS: 0-3; HR: 10.8; 95% CI 2.48-47.1; <i>p</i> = 0.002). Among the 30 patients who died (42%), the strongest independent predictor of mortality was the bulbar phenotype (HR: 2.59; 95% CI 1.08-6.21; <i>p</i> = 0.033), while serum NfL levels showed a significant but limited association (HR: 1.02; 95% CI 1.00-1.04; <i>p</i> = 0.02).</p><p><strong>Discussion: </strong>Serum NfL levels correlate with neurologic disability, whereas the bulbar phenotype was the main risk factor of mortality, indicating that these patients should be closely monitored and considered for early interventions (i.e., tracheostomy) that may modify an otherwise poor prognosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200600"},"PeriodicalIF":8.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163905","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":"Brain Immune Cell Composition in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy After Natalizumab: An Immunohistochemical Cohort Study.","authors":"Benita-Sophie Raabe, Lidia Stork, Adriane Kutllovci, Susan E Goelz, Imke Metz","doi":"10.1212/NXI.0000000000200610","DOIUrl":"10.1212/NXI.0000000000200610","url":null,"abstract":"<p><strong>Background and objectives: </strong>Natalizumab therapy in multiple sclerosis (MS) increases the risk of progressive multifocal leukoencephalopathy (PML) and may alter lymphocyte distribution within the CNS. Tissue-resident memory CD8⁺ T cells (T_RM CD8⁺), which rely on activation through CD4⁺ T cells, are essential for antiviral defense and may contribute to JC virus (JCV) control. We, therefore, investigated lymphoid infiltrates in patients with MS after natalizumab treatment and in patients with natalizumab-associated PML to assess antiviral immunity and clinical outcomes.</p><p><strong>Methods: </strong>Fluorescence immunohistochemistry was performed on brain biopsies and autopsies from patients with MS (n = 34) and those with PML (n = 27) with and without prior natalizumab exposure and from healthy controls (n = 11). The analysis included CD103+ (T_RM) CD8⁺, total CD8⁺, and CD4⁺ T cells; CD209⁺ dendritic cells; and JCV-infected cells. Cell densities were correlated with clinical outcomes using the modified Rankin Scale and Expanded Disability Status Scale.</p><p><strong>Results: </strong>T_RM CD8⁺ T-cell numbers remained stable in the normal-appearing white matter of patients with MS previously treated with natalizumab and matched levels in healthy controls. By contrast, CD4⁺ and CD8⁺ T cells were elevated in MS irrespective of natalizumab exposure and increased further beyond 35 days after treatment cessation, suggesting immune restoration that may reduce PML risk, particularly under extended-interval dosing. In PML lesions, T_RM CD8⁺ T cells were abundant, and natalizumab-associated PML demonstrated infiltrates comparable to inflammatory PML lesions (>500 T cells/mm²), indicating strong local immune activation. Approximately 4 months after natalizumab withdrawal, marked viral clearance was observed and higher densities of T_RM CD8⁺ and total CD8⁺ T cells were associated with better clinical outcomes.</p><p><strong>Discussion: </strong>T_RM CD8⁺ T cells appear central to CNS antiviral defense and remain largely preserved during natalizumab therapy. Although natalizumab restricts T-cell trafficking, the postwithdrawal rise in CD4⁺ and CD8⁺ T cells indicates immune reconstitution that may enhance T_RM CD8⁺ activation. In natalizumab-associated PML, the presence of strong T-cell infiltrates and declining viral loads after treatment cessation underscore the importance of restored local immunity for effective JCV control. Higher densities of T_RM CD8⁺ and total CD8⁺ T cells were linked to better clinical outcomes, highlighting their contribution to viral clearance and recovery.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200610"},"PeriodicalIF":8.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227220","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":"Prognostic Biomarker Signature of Relapse in Neuromyelitis Optica Spectrum Disorders in the CIRCLES Observational Study.","authors":"Elea Bach, Alessandra Breschi, Yuliang Wang, Megan K Carroll, Wilman Luk, Andrew Han, Sarah Short, Peter Cimermančič, Katherine A Drake, Lawrence J Cook, Thomas Snyder, Terry J Smith, Michael R Yeaman, Charles C Kim","doi":"10.1212/NXI.0000000000200611","DOIUrl":"10.1212/NXI.0000000000200611","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neuromyelitis optica spectrum disorders (NMOSDs) comprise rare autoimmune diseases of the CNS in which disabilities accrue with relapses. The ability to predict and prevent relapses could dramatically improve clinical outcomes, potentially reducing morbidity and quality-of-life declines. This proteomic study aimed to identify individual and composite candidate serum biomarkers predictive of NMOSD relapse.</p><p><strong>Methods: </strong>Patients with NMOSD previously enrolled in the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) cohort were selected based on documented relapses simultaneous with retrievable banked cryopreserved serum. Longitudinal serum proteomic profiles were characterized using high-resolution mass spectrometry. We used linear models with logistic regression, Cox proportional hazards models with fixed-time intervals, and time-dependent Cox proportional hazards models to analyze individual proteins and proteomic profiles for their association with future relapses factoring demographics, clinical phenotype/course, and treatments.</p><p><strong>Results: </strong>We characterized a total of 305 longitudinally collected serum samples (N = 126), using high-resolution mass spectrometry, and identified 265 proteins overall. There was a 10-protein signature with the highest average association coefficient consistently across at least 4 of the 6 modeling analyses, including factor XI, surfactant protein B, C1RL, filamin A, cholesteryl ester transfer protein, cathelicidin antimicrobial peptide, C4A, transferrin receptor, for consistency immunoglobulin kappa constant, and serum amyloid A2 protein. This signature could significantly stratify patients with higher vs lower risk of subsequent relapse. These proteins differed in their increasing or decreasing abundance trajectories in advance of relapse. Most belong to pathways plausibly related to the immunopathology of NMOSD.</p><p><strong>Discussion: </strong>Collectively, these findings provide a basis for novel biomarker development to predict NMOSD relapses sufficiently in advance to enable preventive treatment.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200611"},"PeriodicalIF":8.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308915","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":"Specific HLA-DRB1 Alleles Associate With Anti-Caspr1 and Anti-CNTN1 Autoantibodies in Autoimmune Nodopathies.","authors":"Cinta Lleixà, Elba Pascual-Goñi, Lorena Martín-Aguilar, Marta Caballero-Ávila, Roger Collet-Vidiella, Clara Tejada-Illa, Paula Llarch, Eduard Gallardo, Gemma Boera-Carnicero, Verónica Calahorro, Ilaria Callegari, Andrea Cortese, Emilien Delmont, Jerome Devaux, Claudia C Giannotta, Eduardo Nobile-Orazio, Romana Höftberger, Johann Sellner, Sarah Andrée Annie J Herdewyn, Carvajal Alejandra, Laura Torné, Ivonne Jericó, Simon Rinaldi, Claudia Sommer, Kathrin Doppler, Thais Armangue, Maarten J Titulaer, Bart C Jacobs, Ruth Huizinga, Julia V Wanschitz, Nicolau Ortiz Castellon, Davide Sparasci, Paolo Ripellino, Helena Pérez-Pérez, Alejandro Horga, Alicia Alonso-Jiménez, Jonathan De Winter, Amaia Jauregui, Oscar de la Calle-Martin, Laura Martinez-Martinez, Luis Querol","doi":"10.1212/NXI.0000000000200602","DOIUrl":"10.1212/NXI.0000000000200602","url":null,"abstract":"<p><strong>Background and objectives: </strong>This study describes the human leukocyte antigen (HLA) Class II allele frequencies in patients with anti-CNTN1+ and anti-Caspr1+ autoimmune nodopathy (AN).</p><p><strong>Methods: </strong>Forty-four AN patients and 50 seronegative CIDP patients from 19 different European hospitals were included in the study. Thirty AN patients had anti-contactin 1 (CNTN1) antibodies, 11 anti-contactin-associated protein 1 (Caspr1) antibodies, and 3 had antibodies against both proteins. HLA-DRB1 was genotyped at the 4-digit allele levels, and the percentage of individuals carrying each allele was compared with that of the general population, obtained from the <i>Allele frequencies</i> database.</p><p><strong>Results: </strong>HLA-DRB1*11 alleles appeared in higher proportions in anti-CNTN1+ patients than in seronegative CIDP patients and in the general population (46.7% vs 18% vs 28.4%), with an odds ratio of 3.99 (CI = 1.44 to 11.03, <i>p</i> = 0.01) and 2.2 (CI = 1.07 to 4.53, <i>p</i> = 0.04), respectively. HLA-DRB1*03:01 alleles appeared in significantly higher proportions in anti-Caspr1+ patients than in CIDP patients and in the general population (64.3% vs 22% vs 24.2%), with an odds ratio of 6.38 (CI = 1.77 to 22.99, <i>p</i> = 0.007) and 5.64 (CI = 1.876 to 16.96, <i>p</i> = 0.002), respectively. In the anti-Caspr1+ group, we included 3 patients presenting with antibodies against both CNTN1 and Caspr1 proteins in the acute phase, in which the anti-CNTN1 antibodies disappeared in the chronic phase.</p><p><strong>Discussion: </strong>HLA-DRB1*11 alleles are associated with the detection of anti-CNTN1 antibodies in AN patients, and HLA-DRB1*03:01 alleles associate with anti-Caspr1 antibodies. In addition, our study suggests that antiparanodal antibodies targeting both Caspr1 and CNTN1 are present in a small number of patients with AN. These data reinforce the idea that these patients represent specific subsets with clinical features and risk factors that differ from seronegative CIDP patients and from other AN patients. However, further studies should address the functional relevance of these associations and their pathophysiologic implications.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200602"},"PeriodicalIF":8.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308869","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":"Immunity Gone Viral: Subacute Cognitive Decline With Multifocal Brain Lesions in Neuromyelitis Optica Spectrum Disorder.","authors":"Sonali Ajwani, Brian G Weinshenker, Caterina Giannini, Thomas M Habermann, Yucai Wang, Pamela Skrabek, Abedallah Balusha, Michel Toledano, Susan E Horsman, Claudia Francesca Lucchinetti, Eoin P Flanagan","doi":"10.1212/NXI.0000000000200607","DOIUrl":"10.1212/NXI.0000000000200607","url":null,"abstract":"<p><p>Subacute cognitive decline and imbalance in aquaporin-4-antibody-seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD) treated with mycophenolate has a broad differential diagnosis, including cerebral involvement of AQP4+NMOSD, infections, or other complications of immunosuppression. In this article, we highlight the diagnostic and treatment approach in a patient with AQP4+NMOSD who developed multifocal brain lesions.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200607"},"PeriodicalIF":8.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13308546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308871","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":"Immuno-Proteomic Features Associated to Relapse Risk in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.","authors":"Gerardina Gallaccio, Anna Müller, Meng Wang, Lisa-Marie Diekmann, Carolin Otto, Alessandro Dinoto, Vanessa Chiodega, Carolin Schwake, Sven Jarius, Tatiana Usnich, Pia Sophie Sperber, Lina Anderhalten, Tatchaporn Ongphichetmetha, Angus Byars, Deni Subasic, Desiree Kunkel, Ilya Ayzenberg, Sara Mariotto, Sara Samadzadeh, Friedemann Paul, Chotima Böttcher","doi":"10.1212/NXI.0000000000200615","DOIUrl":"10.1212/NXI.0000000000200615","url":null,"abstract":"<p><strong>Background and objectives: </strong>Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory demyelinating disorder that overlaps clinically with multiple sclerosis (MS) but immunopathologically distinct. Although often considered an acute inflammatory disease, recurrent attacks in MOGAD can lead to demyelination, axonal injury, and secondary neurodegeneration. Reliable biomarkers associated with relapse risk and disease subphenotypes, including optic neuritis, remain limited. Here, we aimed to define molecular and cellular signatures that distinguish MOGAD from MS as a prototypical neuroinflammatory disease and from Alzheimer disease (AD) as a proxy of neurodegeneration and to identify candidate immune-proteomic features associated with relapse frequency and clinical phenotype in MOGAD.</p><p><strong>Methods: </strong>CSF, serum, and whole-blood samples from patients with MOGAD (n = 67), MS (n = 49), and AD (n = 36) were profiled using NULISAseq™ CSF proteomics, Olink Explore 3072 CSF and serum proteomics, and high-dimensional mass cytometry for immune cell characterization. In MOGAD, longitudinal clinical data, including total attack counts from the earliest documented attack through follow-up, were integrated with immune and proteomic profiles to assess associations with disease course and clinical phenotype.</p><p><strong>Results: </strong>CSF and blood proteomic profiling revealed distinct inflammatory and cardiometabolic proteomic profiles in MOGAD, differentiating it from both MS and AD. Compared with MS, MOGAD showed relative reductions in lymphocyte populations with regulatory phenotypes. Within MOGAD, relapsing disease was associated with reduced frequencies of CD8⁺CCR7⁺CD31⁺CTLA4⁺ T cells and concurrent expansion of double-negative γδ T-cell subsets. IL-13 correlated positively with relapse frequency and inversely with circulating regulatory T cells, whereas IL-32 and CASP4 showed opposite associations, correlating negatively with relapse count and positively with Treg frequency. IL-13 was also inversely associated with CD31-expressing CD8⁺ T cells. Phenotype-stratified analyses suggested that these immune-proteomic relationships differed according to clinical presentation, including optic neuritis vs nonoptic neuritis phenotypes.</p><p><strong>Discussion: </strong>This integrative immune-proteomic analysis identifies cellular and molecular features associated with relapsing vs monophasic MOGAD, suggesting a model of impaired peripheral immune regulation in relapsing disease. While exploratory, these findings generate a concrete hypothesis for future longitudinal and functional studies aimed at refining biomarker-based monitoring and informing individualized therapeutic strategies in MOGAD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200615"},"PeriodicalIF":8.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308851","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 Case of Persistent Ataxia and Atypical Brain Lesions: From the National Multiple Sclerosis Society Case Conference Proceedings.","authors":"Rachel E Rodin, Giovanna Sophia Manzano, Eric C Klawiter, Bart K Chwalisz, Scott S Zamvil, Myla D Goldman, Claire Riley, Tanuja Chitnis","doi":"10.1212/NXI.0000000000200603","DOIUrl":"10.1212/NXI.0000000000200603","url":null,"abstract":"<p><p>We describe a case of fluctuating ataxia in a 37-year-old man. Workup demonstrated multiple brainstem and cerebellar lesions, cerebellar atrophy, and CSF lymphocytic pleocytosis with oligoclonal bands. Ten months after symptom onset, the patient developed a mesial temporal lobe abnormality and had a first-time seizure, prompting additional workup that revealed a diagnosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200603"},"PeriodicalIF":8.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258615","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":"Inside the Heterogeneity of Primary CNS Vasculitis: A Single-Center 40-Year Experience.","authors":"Carlo Salvarani, Gene G Hunder, Teresa Christianson, John Huston, Caterina Giannini, Robert D Brown","doi":"10.1212/NXI.0000000000200573","DOIUrl":"10.1212/NXI.0000000000200573","url":null,"abstract":"<p><strong>Background and objectives: </strong>Primary CNS vasculitis (PCNSV) is a heterogeneous condition. This study examines a large cohort with long-term follow-up to identify potential disease subsets.</p><p><strong>Methods: </strong>We retrospectively analyzed 216 patients with PCNSV (Mayo Clinic, 1983-2023), using standardized diagnostic criteria, classifying by vessel size, histopathology, and outcomes. Subsets and predictors of functional and therapeutic outcomes were evaluated.</p><p><strong>Results: </strong>Diagnosis was based on cerebral angiography in 142 patients and histologically confirmed in 74. Isolated small vessel involvement was positively associated with mass-lesion presentation (odds ratio [OR] 19.38, <i>p</i> = 0.02), meningeal-enhancing lesions (OR 39.10, <i>p</i> < 0.0001), elevated CSF protein (OR 4.04, <i>p</i> = 0.03), and β-amyloid vascular deposits (OR 23.43, <i>p</i> = 0.0001), but negatively with focal manifestations (OR 0.32, <i>p</i> = 0.04) and cerebral infarcts (OR 0.22, <i>p</i> = 0.003). Lymphocytic vasculitis was linked to younger age at diagnosis (<i>p</i> = 0.006), longer symptom-to-diagnosis interval (<i>p</i> = 0.05), more seizures (<i>p</i> = 0.04), and lower disability (<i>p</i> = 0.003) and mortality (<i>p</i> = 0.008). Necrotizing vasculitis was associated with intracranial hemorrhage (<i>p</i> = 0.008). Two or more relapses occurred in 12.7%, associated with histologic diagnosis (OR 3.15, <i>p</i> = 0.009) and inversely with gadolinium-enhanced lesions (OR 0.33, <i>p</i> = 0.01). Therapy response occurred in 82.9%, long-term remission in 23.6%. Cerebral infarcts, especially multiple, were associated with poor therapy response (OR 0.11, <i>p</i> = 0.03). Histologic diagnosis was inversely associated with long-term remission (OR 0.44, <i>p</i> = 0.03), whereas aspirin use was positively associated (OR 2.8, <i>p</i> = 0.002). A rapidly progressive course occurred in 13.4% of patients and was linked to increasing age (OR 1.34/10 years, <i>p</i> = 0.04), cognitive dysfunction (OR 5.59, <i>p</i> = 0.02), cerebral infarctions (OR 5.02, <i>p</i> = 0.004), and large vessel involvement (OR 3.51, <i>p</i> = 0.02). Gadolinium-enhanced lesions (OR 0.36, <i>p</i> = 0.04) and aspirin (OR 0.42, <i>p</i> = 0.08) were protective. Mortality (21.3%) was associated with older age (HR 1.42, <i>p</i> = 0.002), cognitive dysfunction (HR 3.93, <i>p</i> = 0.006), and cerebral infarctions (HR 1.94, <i>p</i> = 0.03).</p><p><strong>Discussion: </strong>PCNSV heterogeneity, driven by vessel size and histology, affects presentation and outcomes; our findings offer insights to improve diagnosis and treatment.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200573"},"PeriodicalIF":8.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147932194","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}