Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Isolated Peripheral Nervous System Presentation in Ma/Ma2-Associated Autoimmunity.","authors":"Andreu Vilaseca, Macarena Villagrán-García, Antonio Farina, Jordi Bruna, Josep O Dalmau, Divyanshu Dubey, Jerome Honnorat, Francesc Graus","doi":"10.1212/NXI.0000000000200623","DOIUrl":"10.1212/NXI.0000000000200623","url":null,"abstract":"<p><strong>Objectives: </strong>Ma/Ma2-associated neurologic autoimmunity is characterized by CNS involvement. However, isolated peripheral nervous system (PNS) presentations have been rarely reported. We aimed to describe the frequency and syndromes of patients with Ma/Ma2 antibodies and isolated PNS involvement.</p><p><strong>Methods: </strong>We performed a nested case series within multicenter cohorts of patients with Ma/Ma2-associated neurologic syndromes, confirmed by tissue-based assay and line-blot. Patients with isolated PNS presentations were included.</p><p><strong>Results: </strong>Among 212 patients with Ma/Ma2 antibody-associated neurologic syndromes, 7 (3%) presented with isolated PNS involvement (median age, 68 years; 4/7 female). PNS syndromes included sensory neuronopathy (3 patients), myeloradiculopathy (1), radiculoplexopathy (1), motor neuronopathy (1), and multiple mononeuropathy. All patients were anti-Ma2-positive, whereas Ma antibodies (reactive against Ma1 and Ma2 proteins) were detected in 2 (33%)/6 tested patients. An associated cancer was identified in 6 (86%)/7 patients: pleural mesothelioma; oral squamous cell; testicular, lung, and breast cancer; and B-cell lymphoma. Five patients received immunotherapy, cancer treatment, or both. After a median follow-up of 23 months, symptoms improved or stabilized in 3 patients and progressed in 4.</p><p><strong>Discussion: </strong>Isolated PNS involvement is a rare manifestation of Ma/Ma2 associated autoimmunity. Ma/Ma2 antibody testing should be considered in neuronopathies and unexplained non-length-dependent neuropathies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200623"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308923","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":"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.0000000000200617","DOIUrl":"10.1212/NXI.0000000000200617","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200617"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437328","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 Art of Sequencing Disease-Modifying Therapies in Multiple Sclerosis.","authors":"Rick S Dersch, Steffen Pfeuffer, Gabriel Bsteh, Heinz Wiendl","doi":"10.1212/NXI.0000000000200621","DOIUrl":"10.1212/NXI.0000000000200621","url":null,"abstract":"<p><p>Over the past decade, therapeutic paradigms in multiple sclerosis have shifted toward a \"hit-hard-and-early\" approach to suppress inflammatory activity and delay progression. However, adverse events, safety concerns, aging, comorbidities, and life circumstances frequently necessitate treatment transitions during the patient journey. Sequencing decisions generally arise from 3 scenarios: insufficient efficacy, tolerability or safety issues, and conceptual considerations such as family planning or exit strategies for discontinuation. Discontinuation or de-escalation of therapy is associated with a significant risk of disease reactivation, particularly after lymphocyte-trafficking inhibitors, underscoring the importance of proactive transition planning to maintain disease control. Evidence suggests that treatment-specific immunologic effects strongly influence optimal sequencing. This narrative review synthesizes mechanistic insights and real-world clinical evidence to guide sequencing strategies for disease-modifying therapies (DMTs) in multiple sclerosis (MS), an increasingly relevant challenge in the era of early high-efficacy treatment. Following natalizumab, anti-CD20 monoclonal antibodies demonstrate superior control of relapse and MRI activity compared with sphingosine-1-phosphate receptor modulators (S1PRMs). Short transition intervals (<30 days) may minimize risk of rebound activity. After S1PRMs, rapid initiation of anti-CD20 therapies or cladribine seems effective, whereas prolonged washout periods increase relapse risk. Anti-CD20 therapies provide sustained suppression of inflammatory activity but are associated with long-term risks, including hypogammaglobulinemia and infections; cladribine may represent a viable exit strategy by enabling durable immune reconstitution. Platform therapies permit straightforward escalation without major rebound concerns, although lymphopenia must be considered when switching from dimethyl fumarate. Emerging Bruton tyrosine kinase inhibitors may further reshape sequencing paradigms, potentially functioning as maintenance therapies targeting compartmentalized inflammation after initial immune-depleting treatment. Future strategies will likely rely on close clinical and biomarker-based monitoring to individualize transitions and identify therapeutic windows. Overall, pragmatic sequencing that anticipates future switches and balances rebound risk against cumulative immunosuppression is essential for optimizing long-term outcomes in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200621"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471754","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":"<i>FCGR3A</i> Polymorphism Controls B-Cell Repopulation Kinetics in People With Multiple Sclerosis Treated With Ocrelizumab.","authors":"Gianmarco Abbadessa, Ugo Chianese, Claudia Russo, Giuseppina Miele, Elisabetta Maida, Gianmarco Esposito, Giuseppe Romano, Floriana Bile, Elisabetta Signoriello, Giacomo Lus, Luigi Lavorgna, Richard S Nicholas, Lucia Altucci, Claudio Procaccini, Giuseppe Matarese, Rosaria Benedetti, Simona Bonavita","doi":"10.1212/NXI.0000000000200634","DOIUrl":"10.1212/NXI.0000000000200634","url":null,"abstract":"<p><strong>Background and objectives: </strong>Fc gamma receptor 3A (<i>FCGR3A</i>) V158F polymorphism has been shown to modify the response to anti-CD20 therapy across several autoimmune diseases. Ocrelizumab (OCR), an anti-CD20 agent, suppresses inflammatory activity in multiple sclerosis (MS), yet whether <i>FCGR3A</i> V158F polymorphism affects its efficacy in MS remains unclear. Here, we tested whether this genetic variant influences B-cell repopulation and disease activity in MS participants treated with OCR and assessed genotype-dependent differences in OCR binding to FcγRIIIa-expressing natural killer (NK) cells.</p><p><strong>Methods: </strong>In this observational cohort study, we enrolled people with MS treated with OCR consecutively between May 2022 and August 2025. <i>FCGR3A</i> V158F genotyping was performed by pyrosequencing. The primary outcome was preinfusion CD19⁺ B-cell repopulation, defined as CD19⁺ B cells ≥1%. Secondary outcomes included clinical and MRI inflammatory activity and composite disease activity/disability-worsening measures. In a parallel mechanistic ex vivo substudy, OCR or rituximab (RTX) binding to NK cells was evaluated in genotype-selected donors by flow cytometry. Cycle-based repeated measures were analyzed using mixed-effects logistic regression.</p><p><strong>Results: </strong>In 101 participants, 500 interinfusion intervals were analyzed. The odds of B-cell repopulation decreased with higher cycle number (odds ratio [OR] per cycle 0.77; 95% CI 0.65-0.91; <i>p</i> = 0.002) and increased with longer infusion intervals (OR per +30 days, 2.02; 95% CI 1.27-3.21; <i>p</i> = 0.0029). <i>FCGR3A</i> F-carrier status significantly modified the effect of interval length (interaction OR, 2.47; 95% CI 1.04-5.89; <i>p</i> = 0.042). Specifically, the odds of B-cell repopulation increased with longer intervals in MS participants carrying the <i>FCGR3A</i>-F allele (OR, 3.67; 95% CI 1.84-7.34; <i>p</i> = 0.00023) but not in <i>FCGR3A</i>-VV individuals (OR, 1.49; 95% CI 0.87-2.54; <i>p</i> = 0.146). FCGR3A genotype was not associated with clinical or MRI activity outcomes. In ex vivo assays, NK cells from <i>FCGR3A</i>-FF donors exhibited significantly lower binding of OCR (<i>p</i> = 4.34 × 10^-4) and RTX (<i>p</i> = 0.00172) as compared with VV donors.</p><p><strong>Discussion: </strong>Longer OCR infusion intervals were associated with higher odds of B-cell repopulation. The <i>FCGR3A</i> V158F polymorphism modified this interval-dependent repopulation, possibly by affecting OCR binding to NK cells. Prospective studies are needed to determine whether <i>FCGR3A</i> V158F polymorphism and B-cell repletion kinetics can inform optimized interval-based OCR dosing in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200634"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713279","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":"Muscle Regeneration Failure May Lead to Clinical Features of Myopathy in Anti-IgLON5 Disease.","authors":"Yvette S Crijnen, Verena Endmayr, Suzanne C Franken, Nadine A M E Van Der Beek, Maartje Louter, Thomas Ströbel, Ellen Gelpi, Inga Koneczny, Ryuichi Shigemoto, Jan Lewerenz, Birgit Högl, Julia V Wanschitz, Ulrich He Hofstadt-Van Oy, Robin W Van Steenhoven, Mariska M P Nagtzaam, Jeroen Kerstens, Juliette Brenner, Anna E M Bastiaansen, Robert M Verdijk, Thierry P P Van Den Bosch, Marco Schreurs, Sharon Veenbergen, Marcel M Verbeek, Dave L Roelen, Mar Guasp, Peter A E Sillevis Smitt, Lidia Sabater, Juna M de Vries, Romana Höftberger, Maarten J Titulaer","doi":"10.1212/NXI.0000000000200525","DOIUrl":"10.1212/NXI.0000000000200525","url":null,"abstract":"<p><strong>Background and objectives: </strong>Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a novel and potentially treatable entity. Therefore, it is important to recognize all clinical symptoms and diagnostic clues. We specifically investigated neuromuscular signs and symptoms and muscle biopsy pathology, providing a link between IgLON5 and clinical features of myopathy.</p><p><strong>Methods: </strong>All patients diagnosed with anti-IgLON5 disease in the Netherlands between 2016 and 2023 were included. Serum and CSF samples were tested with immunohistochemistry on rat brain and in-house cell-based assay using live cells. Biopsies of the vastus lateralis muscle were performed in patients with neuromuscular signs and symptoms and analyzed in Vienna together with 3 biopsies of non-Dutch patients sent to Vienna for second opinion.</p><p><strong>Results: </strong>Twenty patients with anti-IgLON5 disease were included (10 male, 50%). The median age at onset was 61.5 years (range 45-85), and the median time from onset to diagnosis was 30 months (range 3-280). Neuromuscular symptoms were present in over half of the patients (11/20), including proximal limb weakness (n = 11), axial weakness (n = 1), muscle atrophy (n = 6), and fasciculations (n = 5). All 12 muscle biopsies (9 from the Dutch cohort, 3 external) showed mild myopathic alterations, 2 additionally presented target fibers and fiber type grouping (compatible with neurogenic myopathy), and 3 patients showed immune cell infiltration. We found a strong upregulation of IgLON5 expression in muscle fibers in all patients and also in different muscle disease controls, while immunoreactivity in healthy control muscle was faint/absent.</p><p><strong>Discussion: </strong>Our data support that IgLON5 might play a role in muscle regeneration, which might result in proximal myopathy as a prominent clinical feature in anti-IgLON5 disease. This finding broadens the clinical phenotype of anti-IgLON5 disease and can be an important clue for earlier diagnosis and start of immunotherapy.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200525"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437380","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":"Bilateral Orbital Fat Hyperintensity in Early Glial Fibrillary Acidic Protein Astrocytopathy: A Case Report.","authors":"Yusuke Ito, Ken Ohyama, Akio Kimura, Kei Yamashita, Mikiya Nakayabu, Yuki Fukami, Takayoshi Shimohata, Masahisa Katsuno","doi":"10.1212/NXI.0000000000200640","DOIUrl":"10.1212/NXI.0000000000200640","url":null,"abstract":"<p><strong>Objectives: </strong>Glial fibrillary acidic protein (GFAP) astrocytopathy is an inflammatory autoimmune disease of the CNS that targets astrocytes. Although optic disc edema is a frequently reported ocular manifestation in GFAP astrocytopathy, it has not been well-characterized as orbital fat hyperintensity. Here, we report a rare case in which GFAP astrocytopathy initially presented with orbital fat hyperintensity.</p><p><strong>Methods: </strong>A 26-year-old woman presenting with headache, fever, and bilateral ocular pain was evaluated using neurologic examination, CSF examination, autoantibody testing, and multimodal MRI including orbital conditions.</p><p><strong>Results: </strong>Orbital MRI revealed hyperintensity in the bilateral orbital fat tissue on short tau inversion recovery sequences without optic nerve involvement, whereas intracranial MRI was initially unremarkable. CSF examination showed increase in lymphocytes and was positive for anti-GFAP antibodies. Subsequent MRI revealed characteristic lesions in the thalamic and perivascular area. High-dose corticosteroid therapy led to rapid clinical improvement and resolution of orbital and intracranial MRI lesions.</p><p><strong>Discussion: </strong>This case demonstrates that orbital fat hyperintensity may be an early manifestation of GFAP astrocytopathy, preceding intracranial lesions. Recognition of this orbital MRI finding facilitates earlier diagnosis and treatment, potentially leading to improved prognosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200640"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813483","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":"Double-Negative Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Meta-Analysis.","authors":"Antonio Malvaso, Francesca Bovis, Giacomo Greco, Chiara Morandi, Pietro Businaro, Stefano Masciocchi, Enrico Marchioni, Diego Franciotta, Maria Pia Sormani, Matteo Gastaldi","doi":"10.1212/NXI.0000000000200613","DOIUrl":"10.1212/NXI.0000000000200613","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neuromyelitis optica spectrum disorder (NMOSD) is a severe condition usually associated with aquaporin-4 (AQP4) antibodies. A clinical presentation suggestive of NMOSD can also be associated with myelin oligodendrocyte glycoprotein (MOG) antibodies (MOGAD). NMOSD can be diagnosed in the absence of autoantibodies (double-negative NMOSD [DN-NMOSD]), but this subgroup has been poorly investigated. We conducted a systematic review and meta-analysis to define the clinical spectrum, prognosis, and treatment response in DN-NMOSD vs AQP4-NMOSD/MOGAD.</p><p><strong>Methods: </strong>We searched on PubMed, Scopus, Embase, Google Scholar, Cochrane Library, and ClinicalTrials.gov databases of studies on patients fulfilling inclusion criteria. Patient characteristics, outcome measures, and treatment regimens were extracted.</p><p><strong>Results: </strong>We included 41 of 1,027 articles screened and analyzed 671 patients with DN-NMOSD (median age 38.6 years [range IQR: 32.5-42.85]; female-to-male ratio 1.5:1; median follow-up 44.4 months [range 1-600]), 73.6% of which relapsed. In the meta-analysis, mean annualized relapse rate (ARR) was higher, albeit not significantly, in DN-NMOSD (1.08; 95% CI 0.73-1.43) vs AQP4-NMOSD (0.84; 95% CI 0.45-1.23) and MOGAD (0.61; 95% CI 0.39-0.83, <i>p</i> = 0.08). Administration of maintenance immunosuppression in DN-NMOSD led to a significant ARR reduction (pooled rate ratio 0.19, 95% CI 0.07-0.49; <i>p</i> = 0.001), with high heterogeneity (<i>I</i>² = 90%, <i>p</i> < 0.0001). In meta-regression, no covariates were associated with ARR reduction, including the administration of specific drugs (rituximab, <i>p</i> = 0.288; azathioprine, <i>p</i> = 0.291; mycophenolate, <i>p</i> = 0.918). The pooled mean difference in pre‑ and post‑maintenance treatment Expanded Disability Status Scale values indicated a significant change in disability in MOGAD (-0.93, 95% CI -1.67 to -0.19, <i>p</i> = 0.02) but not in AQP4-NMOSD (-0.62, 95% CI -1.85 to 0.61, <i>p</i> = 0.27) or DN-NMOSD (-0.52 (95% CI -1.30 to 0.25, <i>p</i> = 0.16).</p><p><strong>Discussion: </strong>DN-NMOSD is a heterogenous, severe and highly relapsing disease, where attacks lead to irreversible dysfunction. The administration of maintenance immunotherapy reduces the relapse risk and should be considered early to prevent further disability.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200613"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471756","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":"Multiplex Panel Detects Glial and Inflammatory Biomarker Signatures in Sporadic and C9orf72-ALS.","authors":"Karthik Baskar, Christina Steffke, Sarah Bernsen, Zeynep Elmas, Jasper Hesebeck-Brinckmann, Joachim Schuster, Thomas Meyer, Patrick Weydt, Jochen Weishaupt, David Brenner, Alberto Catanese","doi":"10.1212/NXI.0000000000200618","DOIUrl":"10.1212/NXI.0000000000200618","url":null,"abstract":"<p><strong>Background and objectives: </strong>CSF proteomics has emerged as a valuable strategy for identifying diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). However, the limited availability and volumes of CSF samples restrict the broader clinical application of CSF-based biomarker panels. To address this challenge, we investigated whether the novel nucleic acid-linked immuno-sandwich assay (NULISA) multiplex platform-capable of quantifying multiple neural, glial, and inflammatory markers from minimal biofluid volumes-could validate previously proposed biomarkers and identify additional candidates relevant to ALS.</p><p><strong>Methods: </strong>Using this platform, we measured a targeted panel of 131 biomarkers in cohorts of patients with C9orf72-associated ALS, sporadic ALS (sALS), and matched healthy controls.</p><p><strong>Results: </strong>The 6 markers neurofilament heavy chain (NEFH) and neurofilament light chain (NEFL), chitinases-particularly chitotriosidase-1 (CHIT1) and chitinase-3-like protein-1 (CHI3L1), and chemokines CCL2 and CCL3 were significantly elevated in both ALS groups compared with controls. These biomarkers correlated with disease progression and demonstrated strong diagnostic performance when combined into aggregate scores, as reflected by a high area under the receiver operating characteristic curve for ALS. Notably, C9orf72-ALS patients exhibited higher levels of the oxidative stress-related markers PRDX6 and ENO2, compared with sALS patients, suggesting a genotype-specific molecular signature.</p><p><strong>Discussion: </strong>Overall, our findings support the use of a multiplexed panel of diverse, inflammatory, glial, and neurodegeneration-associated biomarkers as a complementary diagnostic and prognostic tool alongside established measurements of neurofilaments. This approach may enhance biomarker robustness while minimizing CSF volume requirements, thereby improving clinical feasibility in ALS research and care.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200618"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471774","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":"Kappa Free Light Chain for Diagnosis and Neurofilament Light Chain for Prognosis in Autoimmune Encephalitis.","authors":"Franz Felix Konen, Erda Bucak, Franziska Bachhuber, Justina Dargvainiene, Mar Guasp, Juliette Brenner, Anna Lena Streichert, Dominica Hudasch, Lina Marie Albers, Saskia Räuber, Jonathan Wickel, Kai Siebenbrodt, Michael Khalil, Klaus-Peter Wandinger, Marie Süße, Jan Lewerenz, Christian Geis, Christine S Falk, Nico Melzer, Sven G Meuth, Philipp Schwenkenbecher, Thomas Skripuletz, Hayrettin Tumani, Franziska S Thaler, Tania Kümpfel, Maarten J Titulaer, Jan D Lünemann, Frank Leypoldt, Kurt-Wolfram Sühs","doi":"10.1212/NXI.0000000000200630","DOIUrl":"10.1212/NXI.0000000000200630","url":null,"abstract":"<p><strong>Background and objectives: </strong>Reliable biomarkers for autoimmune encephalitis (AE) are limited, and emerging CSF markers are not incorporated into current diagnostic criteria. Prognostic tools remain insufficient, highlighting the need for biomarkers that support both early diagnosis and assessment of disease severity and prognosis.</p><p><strong>Methods: </strong>In this multicenter prospective cohort study, we analyzed clinical data and paired CSF-serum samples from adults with definite AE enrolled in the German Network for Research on Autoimmune Encephalitis registry and the CSF biobank of Hannover Medical School. Of 2,330 screened individuals, 92 patients with anti-N-methyl-d-aspartate receptor (NMDAR, n = 53), anti-leucine-rich glioma-inactivated 1 (LGI1, n = 20), or anti-contactin-associated protein-like 2 (CASPR2, n = 19) encephalitis were included and followed longitudinally for a median of 38 months. Control groups comprised patients with relapsing multiple sclerosis, varicella-zoster virus encephalitis, and noninflammatory neurologic conditions (each n = 30), as well as antibody-positive patients without AE (n = 15), with the groups frequency-matched for age and sex. Kappa free light chain (KFLC), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and cytokines were measured in paired CSF-serum samples obtained at baseline and during follow-up. Disease severity and disability were assessed using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score and the modified Rankin Scale (mRS).</p><p><strong>Results: </strong>Intrathecal synthesis of KFLC was detected in 94% of anti-NMDAR, 50% of anti-LGI1, and 53% of anti-CASPR2 encephalitis cases, demonstrating higher diagnostic sensitivity than CSF-restricted oligoclonal bands or pleocytosis. Diagnostic specificity across pooled control groups was moderate at 44% but reached 90% when compared with noninflammatory neurologic controls. CSF NfL z-score levels were strongly associated with baseline disease severity, with each 1-standard deviation increase corresponding to an approximately 10-point higher CASE score, independent of clinical covariates (β = 0.61). Longitudinal changes in NfL concentrations in CSF and serum were associated with disease severity and neurologic disability at follow-up (CASE score: adjusted <i>R</i>² = 0.401; mRS score: adjusted <i>R</i>² = 0.203). GFAP and cytokines showed limited diagnostic or prognostic utility.</p><p><strong>Discussion: </strong>Intrathecal KFLC synthesis represents a highly sensitive CSF marker that supports early suspicion of autoimmune encephalitis and prompts antibody testing. NfL provides robust biochemical information on baseline disease severity and longitudinal changes that may aid prognostic assessment across AE subtypes.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200630"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13470964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670163","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":"Cerebellar Atrophy in Pediatric-Onset Opsoclonus-Myoclonus-Ataxia Syndrome: A Large International Cohort Study.","authors":"Rebecca MacRae, Kierstin Hederstedt, Christopher Cortina, Kumaran Deiva, Andrea Klein, Ming Lim, Thomas Rossor, Elizabeth A Sokol, Yasmin Khakoo, Nikita Malani Shukla, Timothy E Lotze, Wendy G Mitchell, Sarah Hopkins, Bo Zhang, Mark P Gorman","doi":"10.1212/NXI.0000000000200619","DOIUrl":"10.1212/NXI.0000000000200619","url":null,"abstract":"<p><strong>Background and objectives: </strong>Pediatric-onset opsoclonus-myoclonus-ataxia syndrome (POOMAS) is a rare, neuroinflammatory syndrome that targets the cerebellum and can cause irreversible cerebellar structural changes, namely cerebellar atrophy. We investigated the frequency of cerebellar atrophy, as well as associated risk factors and functional outcome measures, using the largest active POOMAS registry.</p><p><strong>Methods: </strong>This was a retrospective observational study of participants with POOMAS with disease onset from 1995 to 2025 using data from the multinational, multicenter POOMAS registry. Variables were compared between the cerebellar atrophy subgroups using the Fisher exact test or Wilcoxon rank-sum test.</p><p><strong>Results: </strong>Of participants with follow-up imaging, cerebellar atrophy developed in 9.5% (6/63) of those with an MRI scan obtained at least 6 months after disease onset and 12.5% (3/24) with an MRI scan obtained at least 48 months after disease onset. Half of the participants who developed cerebellar atrophy (3/6) were identified more than 48 months after disease onset. Cerebellar atrophy was associated with older age at diagnosis (<i>p</i> = 0.023), but not with other demographic or clinical characteristics. There were no statistically significant differences in functional outcome measures or educational setting.</p><p><strong>Discussion: </strong>The overall frequency of cerebellar atrophy was likely underestimated in this study because of the lack of standardized MRI timing and the large number of patients without MRI scans beyond 48 months.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200619"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471797","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}