Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"CSF Leukocytes Transiently Increase Before Onset of Huntington Disease in Association With a Stage-Specific CSF Cytokine/Chemokine Pattern.","authors":"Yu Gao, Birna Ásbjörnsdóttir, Tua Vinther-Jensen, Marina Rode Von Essen, Marie Nathalie Nickelsen Hellem, Lena E Hjermind, Patrick Ejlerskov, G Bernhard Landwehrmeyer, Finn Sellebjerg, Joergen Erik Nielsen, Jan Lewerenz","doi":"10.1212/NXI.0000000000200632","DOIUrl":"10.1212/NXI.0000000000200632","url":null,"abstract":"<p><strong>Background and objectives: </strong>CSF inflammatory biomarkers in Huntington disease (HD), a neurodegenerative CAG-triplet expansion disorder, usually increase with disease progression. CSF leukocytes as an inflammatory marker have not been explored in HD. We explored high-precision CSF-leukocyte counts across different HD stages in the multicenter prospective biosample HD study HDClarity and their association with CSF neurofilament light chain (NFL) and cytokine and chemokine patterns.</p><p><strong>Methods: </strong>A cross-sectional case-control study of the first average CSF leukocyte count of HDClarity study control participants (N = 94) and those carrying a repeat-expanded Huntingtin (<i>HTT</i>) allele (N = 335) categorized as having successive stages of presymptomatic and motor manifest HD as predefined by the HDClarity protocol (early presymptomatic [N = 48]: disease burden score [DBS] <250; late presymptomatic [N = 93]: DBS ≥ 250; early manifest HD [N = 171]: total functional capacity [TFC] 7-11; and late motor manifest HD [N = 23]: TFC < 11) was performed. CSF-NFL was available in 165. Results were juxtaposed with an independent single-center data set of 18 CSF cytokines and chemokines (57 CSFs, 19 control, 6 early and 8 late presymptomatic HD CSFs, and 19 manifest HD CSFs).</p><p><strong>Results: </strong>CSF leukocytes peaked in late premanifest (median, interquartile range: 1.0/µL, 0.33-1.33/µL) when compared with early premanifest (0.0/µL, 0.0-1.0/µL) but also early (0.33/µL, 0.0-1.0/µL) and late manifest HD (0.0/µL, 0.0-0.67/µL). CSF leukocytes in late premanifest HD were higher than in controls (0.0/µL, 0.0-1.0/µL). A CSF-leukocyte peak at a DBS between 256 and 344 closely corresponded to the late premanifest HD peak. Higher CSF leukocytes in late premanifest HD were associated with higher CSF-NFL levels. Exploratory analysis of CSF cytokine and chemokine levels revealed that low interleukin (IL)-7 but high vascular endothelial growth factor (VEGF) and C-C motif chemokine ligand (CCL)22 levels may distinguish HD from control CSF; high VEGF, IL-6, and IL-15 early from late premanifest HD CSF; and low CCL2, CCL17, and IL-8 late premanifest from manifest HD CSF. When consecutively applied, these patterns identified late premanifest HD participants with a 75% sensitivity (95% CI 41%-96%) and 90% specificity (78%-96%).</p><p><strong>Discussion: </strong>CSF leukocytes peaking in late premanifest HD, their association with increased CSF-NFL, and the corresponding stage-specific chemokine/cytokine changes indicate a temporally dynamic, probably neurotoxic inflammatory signaling network in HD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200632"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795637","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":"Bispecific Antibodies Are Associated With Progressive Multifocal Leukoencephalopathy.","authors":"Avi Gadoth, Yael Paran, Yair Mina, Ofir Levy, Tamir Shragai, Yael C Cohen, Nir Weigert, Orit Wolfovitz Barchad, Yitzhak Friedman, Hila Magen, Michal Dekel, Tal Freund, Yifat Alcalay, Orna Aizenstein, Ronen Ben Ami, Ron Ram, David Hagin","doi":"10.1212/NXI.0000000000200633","DOIUrl":"10.1212/NXI.0000000000200633","url":null,"abstract":"<p><strong>Background and objectives: </strong>Bispecific antibodies (BisAbs) have transformed the management of relapsed and refractory multiple myeloma (MM), achieving high response rates in heavily pretreated patients. However, these therapies induce profound immune perturbation, including plasma cell aplasia, hypogammaglobulinemia, and T-cell exhaustion, predisposing patients to serious infections. Progressive multifocal leukoencephalopathy (PML) has rarely been reported in this setting.</p><p><strong>Methods: </strong>We report on 5 patients with MM who developed PML following BisAbs therapy. Clinical presentation, prior treatments, imaging, CSF studies, pathology, and outcomes were reviewed. In addition, T-cell immunophenotyping and antiviral T-cell responses were evaluated.</p><p><strong>Results: </strong>Five patients (median age 63 years; range 60-77; 3 male) developed PML after treatment with elranatamab (1) or teclistamab (4), with (3) or without (1) talquetamab (1). All patients were under BCMA-directed BisAbs treatment at the time of PML diagnosis. Patients had received a median of 5 prior treatment lines (range 2-7) and 4 had undergone autologous stem cell transplantation. All demonstrated significant immune compromise. Median time from BisAbs initiation to PML diagnosis was 12 months (range 6-24; mean 15.4 months). One patient developed PML after only 2 prior therapies. Three of 5 patients had positive PCR for JC virus (JCV) in the CSF, while the other 2 were positive for JCV on brain biopsy. Clinical manifestations included dysarthria, ataxia, cognitive decline, and focal weakness. Although all patients demonstrated significant immune compromise (lymphopenia and hypogammaglobulinemia), 2 of 4 tested, showed specific anti-JCV/BKV T-cell response.</p><p><strong>Discussion: </strong>PML represents a rare but serious, life-threatening complication of BisAbs therapy in MM. Although most patients were heavily pretreated, occurrence after limited prior therapies and the presence of specific anti-JCV T cells in 2 patients suggests BisAbs-related immune modulation may contribute independently to the risk. Duration of exposure may also be relevant. Given emerging therapeutic options such as immune check point inhibitors and anti-JCV-specific T-cell therapies, early recognition is critical. PML should be considered in patients receiving BisAbs therapy who develop new neurologic symptoms, and prompt evaluation is warranted.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200633"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13436855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670176","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":"Neuronal Antibodies in Patients With Atypical Parkinsonism.","authors":"Jeroen Kerstens, Elise G P Dopper, Laura Donker Kaat, Lieke H Meeter, Esther De Graaff, Juna M de Vries, Yvette S Crijnen, Robin W Van Steenhoven, Sharon Veenbergen, Nina Fransen, Suzanne C Franken, Mariska M P Nagtzaam, Ece Erdag Turgeon, Harro Seelaar, John C Van Swieten, Maaike A Hoogland, Marcel M Verbeek, Bastiaan R Bloem, Peter A E Sillevis Smitt, Agnita J W Boon, Bart P C van de Warrenburg, Maarten J Titulaer","doi":"10.1212/NXI.0000000000200631","DOIUrl":"10.1212/NXI.0000000000200631","url":null,"abstract":"<p><strong>Background and objectives: </strong>Patients with antibody-associated movement disorders sometimes lack specific features of autoimmune diseases and can therefore be misdiagnosed, for example, as neurodegenerative diseases. A well-known example is anti-IgLON5 disease, which may mimic atypical parkinsonian (AP) syndromes. Our objectives were (1) to test different cohorts of patients with suspected AP for anti-IgLON5 and other neuronal antibodies and (2) to describe the characteristics of AP in anti-IgLON5 disease.</p><p><strong>Methods: </strong>We performed a retrospective observational cohort study in which we screened 5 cohorts of patients with AP syndromes for antibodies by immunohistochemistry. Positive results were evaluated with additional techniques including human live neurons. We also reviewed all Dutch patients with anti-IgLON5 disease for parkinsonian features.</p><p><strong>Results: </strong>We identified 719 patients with AP syndromes, of which 532 had available serum or CSF. Seven (1.3%) had antibody-associated disorders (2 anti-IgLON5, 1 anti-IgLON5/anti-NMDAR, 1 anti-Caspr2, 1 anti-CV2, 1 anti-Hu, and 1 anti-CV2/anti-Hu). All but 1 of these patients were already suspected of an autoimmune cause.Furthermore, we identified 30 Dutch patients with anti-IgLON5 disease. Twelve (40%) had AP features, but 11 of the 12 patients also had additional features that differentiated them from classical AP (prominent sleep apnea in 10, neuromuscular symptoms in 6, and chorea in 3). The phenotype of the last patient was clinically indistinguishable from idiopathic Parkinson disease (with probable concurrent mild anti-IgLON5 disease). We also found 8 patient cases falsely identified as anti-IgLON5 positive using a commercial cell-based assay.</p><p><strong>Discussion: </strong>Routine testing for anti-IgLON5 or other neuronal antibodies in AP is not recommended. Rather, careful clinical phenotyping is essential to uncover additional features that might suggest an underlying antibody-associated disease in selected patient cases.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200631"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813754","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":"Long-Term Ravulizumab Efficacy and Safety in AQP4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder: Final CHAMPION-NMOSD Results.","authors":"Sean J Pittock, Michael H Barnett, Jeffrey L Bennett, Achim Berthele, Jérôme de Sèze, Michael Levy, Ichiro Nakashima, Celia Oreja-Guevara, Jacqueline Palace, Friedemann Paul, Carlo Pozzilli, Ritu Pathak, Kerstin Allen, Becky Parks, Ho Jin Kim","doi":"10.1212/NXI.0000000000200609","DOIUrl":"10.1212/NXI.0000000000200609","url":null,"abstract":"<p><strong>Background and objectives: </strong>Ravulizumab, a complement component 5 inhibitor, was approved for the treatment of adults with anti-aquaporin-4 antibody-positive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) based on results of the primary treatment period (PTP) of CHAMPION-NMOSD, a phase 3, open-label, external placebo-controlled trial. Here, we report the final efficacy and safety results of CHAMPION-NMOSD (PTP and the long-term extension [LTE]).</p><p><strong>Methods: </strong>Adult patients with AQP4-Ab+ NMOSD received an IV, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. After completion of the PTP (up to 2.5 years), patients could enter the LTE. The primary endpoint was time to first adjudicated on-trial relapse. The placebo group of the eculizumab phase 3 trial PREVENT was used as an external comparator because eculizumab availability at CHAMPION-NMOSD initiation precluded the use of concurrent placebo control.</p><p><strong>Results: </strong>Of 58 patients enrolled in the trial, 56 entered and 55 completed the LTE. The overall median (range) follow-up was 170.3 (11.0-243.0) weeks, with 100.8 (53-137) weeks during the LTE. No patient receiving ravulizumab had an adjudicated on-trial relapse throughout the PTP (84.0 patient-years) and LTE (105.7 patient-years); relative reduction in risk of relapse vs placebo (n = 47) was 98.9% (95% CI 91.8-100; <i>p</i> < 0.0001). Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 94.8% and 27.6% of patients, respectively, during the PTP and LTE. Most TEAEs were grade 1 and unrelated to ravulizumab. One patient discontinued ravulizumab because of TEAEs. Two cases of meningococcal infection occurred during the PTP; none occurred in the LTE. One death due to hypertensive heart disease (unrelated to ravulizumab) occurred during the LTE.</p><p><strong>Discussion: </strong>Long-term ravulizumab treatment (median follow-up, >3 years) continued to show significant relapse risk reduction in patients with AQP4-Ab+ NMOSD, and the safety profile was consistent with the known safety profile for ravulizumab.</p><p><strong>Trial registration information: </strong>ClinicalTrials.gov, NCT04201262; EudraCT: 2019-003352-37. Submitted December 11, 2019. First patient enrolled: December 13, 2019. clinicaltrials.gov/study/NCT04201262.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that long-term ravulizumab treatment, as compared with placebo, decreases the probability of clinical relapse in patients with AQP4-Ab+ NMOSD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200609"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437375","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":"MOGAD-Like Encephalitic Syndromes Without MOG Antibodies in Children.","authors":"Gemma Olivé-Cirera, Elianet Gisell Fonseca, Mar Guasp, Ludovica Falcioni, Anna Fetta, Raquel Ruiz García, Elisabet Poyatos, Ana Beatriz Serafim, Maria Gual, Gianni Ippoliti, Armando Reques, Laura Naranjo Rondán, Marianna Spatola, Yolanda Blanco, Eugenia Martinez-Hernandez, Francesc Graus, Maria Sepulveda, Romana Höftberger, Lidia Sabater, Albert Saiz, Josep Dalmau, Thais Armangue","doi":"10.1212/NXI.0000000000200635","DOIUrl":"10.1212/NXI.0000000000200635","url":null,"abstract":"<p><strong>Background and objectives: </strong>Although acute disseminated encephalomyelity (ADEM) can be myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) positive or negative, it is unclear whether other MOG-antibody-associated disease (MOGAD)-like encephalitis syndromes occur without MOG-IgG. We aimed to define the frequency, clinico-radiologic features, outcomes, and antibody associations of such cases in children.</p><p><strong>Methods: </strong>Prospective cohort study of children (<18 years) with encephalitis meeting clinico-radiologic MOGAD criteria, regardless of MOG-IgG status. Serum from all patients and CSF when available were tested by live cell-based assays (CBA-IIF, CBA-FACS) at 2 laboratories. Brain MRIs were centrally reviewed for MOGAD-like patterns (ADEM, cortical encephalitis, isolated/predominant central gray matter). Additional testing included CBAs for MOG-IgA, MOG-IgM, PLP1-IgG, glial fibrillary acidic protein-IgG, and AQP4-IgG, along with rat brain immunohistochemistry.</p><p><strong>Results: </strong>Among 160 patients with MOGAD-like encephalitis, 120 were MOG-IgG positive and 40 negative (20 ADEM, 11 cortical encephalitis, 9 isolated/predominant central gray matter encephalitis). Clinical-radiologic features were broadly comparable between groups, including lesion distribution, frequency of associated longitudinally extensive transverse myelitis, lesion resolution, and functional outcomes. Relapses were more frequent in MOG-IgG-positive patients (22, 18% vs 1, 3%; <i>p</i> = 0.017). Immunohistochemistry revealed myelin immunostaining in 14 (12%) MOG-IgG-positive cases (CBA confirmed cross-reactivity with rodent MOG-epitopes) and 10 (25%) MOG-IgG-negative patients (no cross-reactivity with rodent MOG-epitopes); this included a fulminant case with autopsy showing perivenous demyelination and C4d complement deposition, suggesting autoantibodies against an unknown myelin antigen. MOG-IgA, MOG-IgM, or PLP1-IgG occurred in 36/111 (32%) MOG-IgG-positive and 7/37 (19%) MOG-IgG-negative cases, without clinical differences between groups.</p><p><strong>Discussion: </strong>Children can develop the full spectrum of MOGAD-like encephalitis without MOG-IgG. Clinical features and immunotherapy response are similar to MOGAD, but relapses are uncommon.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200635"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813705","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":"Myelin Oligodendrocyte Glycoprotein Antibodies in Breast Milk in a Lactating Woman With Severe Enterovirus-Associated MOGAD.","authors":"Stefan Kammermeier, Suzette Heck, Hanna Zimmermann, Daniel Engels, Markus Reindl, Tania Kümpfel","doi":"10.1212/NXI.0000000000200637","DOIUrl":"10.1212/NXI.0000000000200637","url":null,"abstract":"<p><strong>Objectives: </strong>Myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) is a distinct neuroinflammatory disorder, which may be preceded by infections. Transmission of MOG-IgG from blood into breast milk has not been reported previously.</p><p><strong>Methods: </strong>We present the case of a 38-year-old lactating woman with a severe manifestation of MOGAD after enterovirus gastroenteritis, who was still lactating at that time. Alongside with detailed clinical characteristics, we measured MOG-IgG in breast milk and serum from the breast-fed infant.</p><p><strong>Results: </strong>Our patient experienced a severe progressive episode of CNS inflammation, affecting the optic nerve, brain, and spinal cord, before which she was partially breastfeeding. Her condition rapidly worsened to coma with status epilepticus, requiring intensive care admission. High serum MOG-IgG titers were detected and prompt attack therapy initiated with high-dose glucocorticosteroids followed by plasma exchange, which led to rapid clinical improvement. The patient's breast milk tested positive for MOG-IgG, whereas the serum of the breastfed infant was negative.</p><p><strong>Discussion: </strong>Early diagnosis and therapeutic intervention at acute onset of MOGAD is important for attack remission. MOG-IgG may be detected in breast milk of lactating woman with MOGAD, but is probably not transmitted to the infant in detectable quantities.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 5","pages":"e200637"},"PeriodicalIF":8.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13510213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819002","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":"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}