Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Real-World Multicenter Cohort Study of Inebilizumab vs Low-Dose Rituximab in Neuromyelitis Optica Spectrum Disorders.","authors":"Qiao Xu, Linming Zhang, Xinyi Duan, Kai Zhou, Zhizhong Li, Xiaolin Yang, Jing Wang, Jinyu Jiang, Ke Xu, Gang Yu, Peng Zheng, Yongmei Li, Xinyue Qin, Jingyuan Li, Wen Ya Wang, He Zhao, Dehui Huang, Hao Qu, Haibing Xiao, Bin Li, Lei Wu, Jinzhou Feng","doi":"10.1212/NXI.0000000000200586","DOIUrl":"10.1212/NXI.0000000000200586","url":null,"abstract":"<p><strong>Background and objectives: </strong>Inebilizumab and rituximab (RTX) are anti-CD19 and anti-CD20 B cell-depleting antibodies, respectively. They are both used in the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, limited data on both drugs exist regarding real-world clinical applications. This study aimed to assess the efficacy and safety of inebilizumab vs low-dose RTX in NMOSD patients through a retrospective-prospective multicenter analysis.</p><p><strong>Methods: </strong>This study collected data on aquaporin-4 immunoglobulin G seropositive NMOSD patients from 6 cities in China among those receiving either inebilizumab or low-dose RTX (500 mg), with a 1-year follow-up. Analyses assessed outcomes using inverse probability of treatment weighting and doubly robust models.</p><p><strong>Results: </strong>We included a total of 229 patients, comprising 119 treated with inebilizumab and 110 with low-dose RTX. The cohort was predominantly female (217/229, 94.76%). The median follow-up duration was 12.0 months (range: 4.0-12.0) in the inebilizumab group and 12.0 months (range: 7.0-12.0) in the low-dose RTX group. Relapses occurred in 8/119 (6.72%) inebilizumab recipients vs 24/110 (21.82%) low-dose RTX recipients (hazard ratio [HR] 3.77, 95% confidence interval [CI] 1.56-9.14; <i>p</i> = 0.003). Adjusted annualized relapse rates were significantly lower in the inebilizumab group (0.06) than in the low-dose RTX group (0.24), corresponding to an incidence rate ratio (IRR) of 3.65 (95% CI 1.59-8.39; <i>p</i> = 0.003). Adverse events (AEs) occurred in 35 patients (29.42%) with inebilizumab, including 2 serious adverse events (SAEs; 1.68%), vs 44 patients (40.00%) with low-dose RTX (4 SAEs [3.64%]). Both AE and SAE rates showed no statistical difference between groups. The rate of patients with at least 1 infection in inebilizumab group was lower than that in the low-dose RTX group (<i>p</i> = 0.003).</p><p><strong>Discussion: </strong>In this short-term study, inebilizumab demonstrated greater efficacy in reducing relapse risk, along with significantly lower rates of key adverse events, compared with low-dose RTX in patients with NMOSD. These findings support the use of inebilizumab as an effective and well-tolerated therapeutic option in a broader NMOSD population.</p><p><strong>Classification of evidence: </strong>This short-term study with a 12-month observation period provides Class III evidence that in patients with NMOSD, inebilizumab is more effective than low-dose RTX in reducing relapses.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200586"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777167","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":"HTLV-1-Infected CD4⁺ T Cells Drive Spontaneous Lymphoproliferation and Virus-Specific CD8⁺ Cytotoxic T Lymphocyte Expansion in HAM/TSP.","authors":"Mika Dozono, Satoshi Nozuma, Takashi Yoshida, Daisuke Kodama, Toshio Matsuzaki, Eiji Matsuura, Masakazu Tanaka, Hiroshi Takashima, Ryuji Kubota","doi":"10.1212/NXI.0000000000200581","DOIUrl":"10.1212/NXI.0000000000200581","url":null,"abstract":"<p><strong>Background and objectives: </strong>Spontaneous lymphoproliferation (SP) is an ex vivo phenomenon where lymphocytes proliferate without exogenous stimulation in peripheral blood mononuclear cells (PBMCs) from patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). SP is thought to reflect spinal cord pathology in HAM/TSP, but its cellular mechanisms remain unclear.</p><p><strong>Methods: </strong>PBMCs from 30 patients with HAM/TSP, 12 asymptomatic HTLV-1 carriers, and 8 healthy controls (HCs) were labeled with a proliferation tracer and cultured for 6 days without exogenous stimulation. Flow cytometry was used to identify T-cell subsets, HTLV-1-infected cells, and HTLV-1-specific cytotoxic T lymphocytes (CTLs). Additional analyses included CTL antigen specificity, proviral load (PVL), phenotypic profiling (differentiation, activation, exhaustion markers), and cytokine/chemokine quantification in culture supernatants.</p><p><strong>Results: </strong>CD8⁺ T cells exhibited greater proliferation than CD4⁺ T cells during SP. Among proliferating CD4⁺ T cells, 38.15% were CADM1+, 61.84% were Tax+, and PVL analysis indicated that nearly all proliferating CD4⁺ T cells were HTLV-1 infected. The frequency of HTLV-1 Tax 301-309-specific CTLs among CD8⁺ T cells increased from 3.81% to 17.67% during SP. After a subsequent resting phase, IFN-γ responses were detected in 37.38% of CD8⁺ T cells to a Tax peptide mixture and in 33.42% to an HTLV-1 bZIP factor peptide mixture, together accounting for over 70% of proliferating CD8⁺ T cells. Sorted CD4⁺ T cells proliferated independently, whereas sorted CD8⁺ T cells did not; however, coculture with CD4⁺ T cells restored CD8⁺ T-cell proliferation. Proliferating infected cells exhibited a Th1 phenotype, and most proliferating T cells coexpressed activation and exhaustion markers with memory phenotypes. IL-6 and IFN-γ levels were significantly elevated in culture supernatants from patients with HAM/TSP compared with HCs. IFN-γ levels in SP supernatants correlated with CSF PVL. SP responses in HTLV-1 carriers were attenuated, with reduced proliferation compared with patients with HAM/TSP.</p><p><strong>Discussion: </strong>SP is driven by HTLV-1-infected CD4⁺ T cells, which are essential for sustaining HTLV-1-specific CD8⁺ CTL expansion. This phenomenon appears to recapitulate certain immunologic features of neuroinflammation in HAM/TSP. This ex vivo model may help evaluate therapies targeting HTLV-1-infected cells and immune-mediated pathology.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200581"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818393","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":"Clearance of Early Complement Protein From CSF After Aneurysmal Subarachnoid Hemorrhage and Influence on Neurologic Outcome.","authors":"Joseph R Geraghty, Eitan A Katz, Mitchell Butler, Fernando D Testai","doi":"10.1212/NXI.0000000000200582","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200582","url":null,"abstract":"<p><strong>Background and objectives: </strong>Aneurysmal subarachnoid hemorrhage (aSAH) triggers a robust inflammatory response, which has been associated with brain injury and poor outcome. The complement system is an integral part of the innate immune system activated after acute brain injury. The early complement proteins C1q and C3 have roles in glial-neuronal interactions and synaptic pruning. The objective of this study was to determine whether changes in CSF complement proteins over time after aSAH are associated with neurologic outcome.</p><p><strong>Methods: </strong>We performed an exploratory retrospective case-control study investigating the association of CSF levels and clearance of C1q and C3 with outcome in patients with aSAH and compared with controls with normal CSF. Clearance was defined as the percent change of complement protein levels between 2 time points corresponding to peaks of early (<72 hours) and delayed (5-7 days) brain injury after aSAH. The primary endpoint was functional outcome, assessed by Glasgow Outcome Scale (GOS; range 1-5 with higher scores denoting better outcome), at the time of discharge. Good functional outcome was defined as GOS 4-5. Complement protein clearance was adjusted by baseline differences, and receiver operating characteristic analysis was performed.</p><p><strong>Results: </strong>Early after aSAH, there was a robust increase in C1q (median 89.10 vs 6.42 ng/mL, <i>p</i> < 0.0001) and C3 (78.00 vs 8.72 µg/mL, <i>p</i> = 0.0001) in CSF of 20 patients with aSAH compared with 11 controls. Between early and late time points, both C1q (97.38 vs 47.85 ng/mL, <i>p</i> = 0.0326) and C3 (85.23 vs 23.10 µg/mL, <i>p</i> = 0.0004) decreased in those with good outcome. Percent clearance of C3 from CSF was larger in those with good vs poor neurologic outcome (median 74.85% vs 11.43% reduction over time, <i>p</i> = 0.0159). C3 clearance, particularly when adjusted by baseline Glasgow coma scale on admission, was a highly sensitive and specific marker of neurologic outcome after aSAH (area under curve = 0.990, 95% confidence interval 0.958-1.000, sensitivity 90.9%, specificity 100.0%).</p><p><strong>Discussion: </strong>Increased CSF clearance of C3 within the first week after aSAH appears to be associated with improved neurologic outcome. Future strategies to promote clearance of inflammatory mediators such as early complement proteins from CSF may, therefore, improve outcomes after aSAH.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 4","pages":"e200582"},"PeriodicalIF":7.5,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Hospital Incidence of Autoimmune Encephalitis During the COVID-19 Pandemic.","authors":"Jonathan Wickel, Ha-Yeun Chung, Franz Felix Konen, Rosa Rössling, Annikki Bertolini, Andrea Kraft, Kai Siebenbrodt, Stefan Bittner, Aleksandra Juranek, Mosche Brokbals, Saskia Räuber, Jaqueline Klausewitz, Lena K Pfeffer, André Scherag, Til Menge, Alexander Finke, Kathrin Doppler, Christian Urbanek, Christian G Bien, Thomas Seifert-Held, Frank Hoffmann, Klaus-Peter Wandinger, Simone C Tauber, Marie Süße, Jan Lewerenz, Marie Madlener, Kevin Rostasy, Harald Prüss, Kurt-Wolfram Sühs, Tania Kümpfel, Franziska S Thaler, Frank Leypoldt, Christian Geis","doi":"10.1212/NXI.0000000000200555","DOIUrl":"10.1212/NXI.0000000000200555","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to analyze changes in hospital incidence cases and disease severity of autoantibody-associated autoimmune encephalitis (AE) during the COVID-19 pandemic compared with the prepandemic period.</p><p><strong>Methods: </strong>A retrospective multicenter study analyzed data from 24 centers within the German Network for Research on Autoimmune Encephalitis (GENERATE). Patients with a new diagnosis of definite antibody-positive autoimmune encephalitis from 2017 to 2022 were included and divided into prepandemic (2017-2019) and pandemic (2020-2022) periods.</p><p><strong>Results: </strong>Among 392 patients, 227 were diagnosed before and 165 during the pandemic (mean 9.5 vs 6.9 per site, <i>p</i> = 0.04). A reduction was observed in cases with antibodies to neuronal surface antigens (174 vs 122 cases; mean 7.3 vs 5.1 per site, <i>p</i> = 0.02), while cases with antibodies against intracellular antigens remained stable (<i>p</i> = 0.40). No differences were observed in disease severity, age, or sex distribution between periods.</p><p><strong>Discussion: </strong>This study provides clinical data on antibody-positive AE before and during the COVID-19 pandemic. The findings do not support the hypothesis that SARS-CoV-2 infection triggers autoantibody-associated AE or increases disease severity.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200555"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195036","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":"Fulminant Amyloid β-Related Angiitis With Herniation and Rapid Response to Tocilizumab: A Case Report.","authors":"James V Nguyen, Emma M Byrne, Salina Yuan, Shamik Bhattacharyya, Mariel G Kozberg, Marshall Lukacs, Philippe A Bilodeau","doi":"10.1212/NXI.0000000000200559","DOIUrl":"10.1212/NXI.0000000000200559","url":null,"abstract":"<p><strong>Objectives: </strong>Amyloid β-related angiitis (ABRA) is a rare, inflammatory vasculopathy resulting from intravascular amyloid deposition. We describe a refractory presentation of ABRA and its response to tocilizumab.</p><p><strong>Methods: </strong>Single-patient, biopsy-confirmed ABRA with serial MRI and clinical outcomes. Treatments included high-dose IV methylprednisolone, hyperosmolar therapy, cyclophosphamide, and escalation to tocilizumab.</p><p><strong>Results: </strong>A 70-year-old woman presented with seizure and focal deficits. Initial MRI showed multifocal subcortical T2/FLAIR hyperintensities with cortical microhemorrhages without enhancement. Despite steroids, interval imaging showed progressive vasogenic edema, new leptomeningeal enhancement, and rising microhemorrhage burden. She developed severe headache and worsening hemiparesis; CT/MRI demonstrated marked edema with subfalcine/uncal herniation. Biopsy confirmed ABRA. Edema did not improve with steroids, maximal hyperosmolar therapy, or cyclophosphamide. After tocilizumab, MRI within 48 hours showed reduced edema and midline shift with near-resolution of sulcal enhancement; hemiparesis markedly improved without hemicraniectomy.</p><p><strong>Discussion: </strong>We expand the phenotypic spectrum of ABRA by presenting a herniation syndrome associated with fulminant disease and a clear clinicoradiographic natural history. The precipitous progression of microhemorrhage accrual suggests a pathophysiologically distinct mechanism of disease from cerebral amyloid angiopathy-related inflammation. IL-6 receptor blockade was associated with rapid clinical and radiographic improvement and stabilization, supporting prospective evaluation of tocilizumab in amyloid-related neuroinflammatory disorders.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200559"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369850","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":"Development of a Diagnostic Autoantibody Assay to a Consensus Motif for the Risk Prediction of Epstein-Barr Virus-Related Multiple Sclerosis.","authors":"Krista M McCutcheon, Aaron Bodansky, Thomas T Ngo, Colette Caspar, Sydney Quintana, James Asaki, Jing Zhou, Stacy J Caillier, Akshay Sharathchandra, Greer Waldrop, Ravi Dandekar, Kelsey Zorn, Asritha Tubati, Sasha Gupta, Joseph J Sabatino, Richard Cuneo, Jorge Oksenberg, Mitchell T Wallin, Bruce A C Cree, Stephen L Hauser, Samuel Pleasure, Joseph Derisi, Michael R Wilson","doi":"10.1212/NXI.0000000000200551","DOIUrl":"10.1212/NXI.0000000000200551","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is a chronic progressive, demyelinating autoimmune CNS disease. Autoantibodies to the motif P-(SA)-x-(SGA)-R-(SN)-(LRKH) are a class of predictive markers specific to MS that could add to emerging diagnostic criteria for MS. In this study, we describe the discovery of an MS patient-derived monoclonal antibody (mAb) specific to this motif from memory B cells, and we develop a proof-of-principle autoantibody test to report the prevalence of seropositivity, predict MS early in disease, and identify underlying tolerance-breaking antigens in Epstein-Barr virus (EBV) and the CNS.</p><p><strong>Methods: </strong>Peptide tetramers containing the motif were used to screen activated memory B cells, collected from a patient with MS, on the Beacon Optofluidic system. A mAb to the motif and serum samples from clinically diagnosed patients with MS and healthy controls were used to qualify a Luminex xMAP autoantibody serologic test. Antigen discovery methods included phage-immunoprecipitation sequencing (PhIP-Seq), biolayer interferometry, human protein microarrays, isoelectric focusing gels and blots, and immunofluorescence staining of mouse brain cell cultures.</p><p><strong>Results: </strong>A mAb cloned from an MS patient's memory B cells binds diverse peptides containing the MS signature motif with affinities ranging from 2 to 25 nM. Consensus peptides defined by alanine scanning PhIP-Seq were used to develop an autoimmune IgG test with a sensitivity equivalent to 0.5 ng/mL mAb, a precision of <11%, and a positivity rate of 11% among a cohort of 179 patients with MS (n = 91 healthy and n = 49 unrelated neurologic disease serum samples were negative). Utility of the assay for prodromal MS was demonstrated using retrospective, longitudinal samples from cases in the Department of Defense Serum Repository. The mAb identified EBV tegument protein BRRF2 as a tolerance-breaking antigen with nanomolar affinity, containing the motif with reactivity to oligoclonal bands in CSF from MS signature-positive patients. Immunocytochemical staining of mixed mouse neuronal cells showed the dominant cross-reactive human antigen to be vimentin.</p><p><strong>Discussion: </strong>We describe a test for MS signature autoantibodies that could be used to support MS diagnosis, prodromal research, and early interventions. The integration of this assay with other emerging biomarkers will advance progress toward a combined predictive risk score for MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200551"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12983327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147459074","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":"Generation of Monoclonal Autoantibodies From Myelin Oligodendrocyte Glycoprotein-Specific Human B Cells Using an Optofluidic-Based Platform.","authors":"Anjali J Panicker, Samuel S Hinman, Julie Perreau, Ava Aslanpour, Robyn L Williams, Stephan Steinke, Elizabeth Quinn, Amanda L Hernandez, Soumya S Yandamuri, Sarosh R Irani, Erin E Longbrake, Kevin C O'Connor","doi":"10.1212/NXI.0000000000200577","DOIUrl":"10.1212/NXI.0000000000200577","url":null,"abstract":"<p><strong>Objectives: </strong>Monoclonal antibodies (mAbs) are powerful tools for elucidating disease mechanisms. Capturing heterogeneity of patient responses-including clonality, somatic mutations, isotypes, and pathogenic potential-requires building large libraries of mAbs using high-throughput approaches. However, current techniques for identifying and isolating patient-derived mAbs targeting conformational epitopes on membrane proteins remain labor-intensive and inefficient. To address this challenge, we evaluated a cell-based optofluidic antibody discovery pipeline to generate patient-derived mAbs against myelin oligodendrocyte glycoprotein (MOG), a transmembrane autoantigen targeted in MOG antibody-associated disease (MOGAD).</p><p><strong>Methods: </strong>An optofluidic-based workflow incorporated mammalian display of human MOG (hMOG) in a live cell-based assay (CBA) format. B-cell receptor sequences from individual hMOG-binding B cells were cloned and expressed to generate mAbs from 3 patients. The hMOG binding specificity of these mAbs was validated in off-platform hMOG-CBAs.</p><p><strong>Results: </strong>hMOG-specific antibody-secreting cells in one patient represented 0.02% of all single B cells screened. From these low-frequency populations, one patient-derived IgG mAb was successfully generated and validated. This IgG mAb, characterized by a high frequency of V-region somatic mutations (5%-12.2%), bound hMOG at concentrations as low as 1 ng/mL.</p><p><strong>Discussion: </strong>This workflow enables rapid discovery of rare, patient-derived mAbs targeting conformational epitopes on membrane antigens, offering a scalable approach for dissecting autoantibody repertoires.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200577"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777639","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":"Neuromyelitis Optica Spectrum Disorders in Africa: A Systematic Review.","authors":"Abdu Kisekka Musubire, Judith Derdelinckx, Tatjana Reynders, David B Meya, Paul R Bohjanen, Patrick Cras, Barbara Willekens","doi":"10.1212/NXI.0000000000200572","DOIUrl":"10.1212/NXI.0000000000200572","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200572"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959725/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348660","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":"Outcome Predictors in Progressive Multifocal Leukoencephalopathy Associated With Multiple Sclerosis Treatments: A Multicenter Cohort Study.","authors":"Julie Céline Blant, Nicola De Rossi, Ralf Gold, Aude Maurousset, Markus Kraemer, Lucía Romero-Pinel, Tatsuro Misu, Jean-Christophe Ouallet, Maud Pallix Guyot, Simonetta Gerevini, Christos Bakirtzis, Raquel Piñar Morales, Benjamin Vlad, Panajotis Karypidis, Xavier Moisset, Tobias J Derfuss, Ilijas Jelcic, Guillaume Martin-Blondel, Ilya Ayzenberg, Corey McGraw, David Axel Laplaud, Christine Lebrun-Frenay, Renaud A Du Pasquier, Raphael Bernard-Valnet","doi":"10.1212/NXI.0000000000200558","DOIUrl":"10.1212/NXI.0000000000200558","url":null,"abstract":"<p><strong>Background and objectives: </strong>JC virus (JCV) reactivation causing progressive multifocal leukoencephalopathy (PML) is a complication in patients with multiple sclerosis (MS) treated with disease-modifying therapies (DMTs). Although natalizumab (NTZ) is most frequently involved, PML also occurs less commonly with sphingosine-1-phosphate receptor modulators (S1P-RM), dimethyl fumarate (DMF), and ocrelizumab. This study aimed to identify factors predicting worse outcomes, focusing on the influence of PML-immune reconstitution inflammatory syndrome (PML-IRIS), plasma exchange (PlEx), corticosteroids, and DMT reintroduction.</p><p><strong>Methods: </strong>This retrospective multicenter cohort study analyzed patients with MS who had JCV-associated pathology (PML or granule cell neuronopathy) from 42 centers (2009-2022). The primary outcome was disability at 12 months, measured by the modified Rankin Scale (mRS). Multivariable analyses identified predictors of poor outcomes, PML-IRIS development, and recurrent MS activity.</p><p><strong>Results: </strong>Of 96 identified patients, 94 were analyzed. Most cases occurred under NTZ (77%), followed by S1P-RM (22%) and DMF (1%). Twelve-month survival was 91.5%, with a median mRS of 3 [IQR: 2-4]. Multivariable analysis showed that higher pre-PML disability (OR: 1.95 [95% CI 1.46-2.60], <i>p</i> < 0.001), elevated CSF JCV viral load (OR: 2.45 [95% CI 1.55-3.87], <i>p</i> < 0.001), and symptomatic presentation at onset (OR: 3.93 [95% CI 1.23-12.55], <i>p</i> = 0.021) were associated with worse outcomes. Conversely, PML-IRIS was associated with better outcomes (OR: 0.28 [95% CI 0.09-0.86], <i>p</i> = 0.025). PlEx and corticosteroid use had no negative effect.</p><p><strong>Discussion: </strong>This study provides valuable insights into the management of iatrogenic PML in patients with MS. The findings may guide clinicians in making informed decisions, particularly regarding the use of PlEx, corticosteroids, and the management of PML-IRIS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200558"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258897","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":"Dynamics of Spinal Fluid Immune Cell Alterations Following Cladribine Tablet Treatment in Multiple Sclerosis.","authors":"Roman A Smirnov, Claudia Cantoni, Kenneth Lee, Rea A Agnihotri, Robert C Axtell, Amber Salter, Samantha Lancia, Michael A Paley, Brooke Hayward, Julie Korich, Emily Evans, Gabriel Pardo, Ahmed Z Obeidat, Olaf Stuve, Amit Bar-Or, Maxim N Artyomov, Anne H Cross, Brian T Edelson, Gregory F Wu","doi":"10.1212/NXI.0000000000200565","DOIUrl":"10.1212/NXI.0000000000200565","url":null,"abstract":"<p><strong>Background and objectives: </strong>Oral cladribine tablet (CladT) therapy is efficacious for relapsing multiple sclerosis (MS). However, the mechanisms by which cladribine exerts benefit in MS remain unclear, particularly regarding its effects on compartmentalized inflammation within the CSF.</p><p><strong>Methods: </strong>Transcriptional profiles along with T and B lymphocyte receptor repertoires from CSF and blood were obtained by single-cell sequencing methods from a single site participating in a phase IV clinical trial investigating the impact of cladribine treatment for MS. Blood and CSF samples from patients were obtained immediately before starting CladT therapy, and they were randomized to also provide additional samples at either 5 weeks, 10 weeks, 1 year, or 2 years after CladT therapy. Thirty-four samples from 13 individuals with relapsing MS before and after treatment were available to test the hypothesis that CladT alters the composition and phenotype of lymphocytes in the CSF, including paired baseline and post-CladT CSF samples obtained from 4 unique participants.</p><p><strong>Results: </strong>We found that treatment with CladT profoundly altered cellular composition, but not the transcriptional phenotype, of immune cells in the CSF. In particular, we identified a reduction in switched memory B cells but recovery of naive B cells in the CSF, similar to our findings in blood. In addition, populations of CD4 Treg cells emerged early after CladT therapy and remained elevated 1 year later in the CSF, but not in the blood. Antigen receptor sequencing revealed a moderate decrease in numbers of large clonally expanded CD8 T cell clones (>10 cells/clone) primarily in the CSF, but also in the blood after CladT treatment.</p><p><strong>Discussion: </strong>Our results identified unique cellular dynamics and changes in T cell and B cell clonality in both tissues, which can potentially explain long-term beneficial effects of CladT therapy in MS, including preservation of immune function and a relatively low number of side effects. Altogether, this study demonstrates that CladT treatment had a substantial impact not only on blood but also on the CSF compartment, highlighting the importance of cross-tissue analysis for better understanding of effect and the mechanism of action of disease-modifying therapies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200565"},"PeriodicalIF":7.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699344","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}