Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Conformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.","authors":"Stefano Masciocchi, Pietro Businaro, Giacomo Greco, Silvia Scaranzin, Antonio Malvaso, Chiara Morandi, Elisabetta Zardini, Mario Risi, Elisa Vegezzi, Luca Diamanti, Paola Bini, Sabrina Siquilini, Maria Pia Giannoccaro, Luana Morelli, Rocco Liguori, Francesco Patti, Valeria De Giuli, Emilio Portaccio, Chiara Zanetta, Stefania Bergamoni, Anna Maria Simone, Roberta Lanzillo, Giorgia Bruno, Antonio Gallo, Alvino Bisecco, Massimiliano Di Filippo, Flavia Pauri, Antonella Toriello, Paolo Barone, Francesco Tazza, Sebastiano Bucello, Paola Banfi, Martina Fabris, Irene Volonghi, Loredana Raciti, Maria Claudia Vigliani, Tommaso Bocci, Matteo Paoletti, Elena Colombo, Massimo Filippi, Anna Pichiecchio, Enrico Marchioni, Diego Franciotta, Matteo Gastaldi","doi":"10.1212/NXI.0000000000200359","DOIUrl":"10.1212/NXI.0000000000200359","url":null,"abstract":"<p><strong>Background and objectives: </strong>Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum.</p><p><strong>Methods: </strong>We devised a new live cell-based assay (CBA) for PLP1-IgG and used it to test 2 cohorts (retrospective exploratory, n = 284; prospective validation, n = 824) of patients with ADDs and controls (n = 177). Patients were classified as MS, neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and other ADDs. PLP1-IgG-positive samples were tested for IgG subclasses, DM20-IgG, and on rat brain tissue-based assay (TBA). Complement-dependent cytotoxicity (CDC) was assessed on a live CBA and antigen specificity and conformational binding through immunoadsorption/colocalization/fixation experiments.</p><p><strong>Results: </strong>PLP1-IgG were found in 0 of 177 controls and 42 of 1104 patients with ADDs mainly diagnosed as other ADDs (19/42) with frequent myelitis/encephalomyelitis (14/19) and coexisting PNS involvement (13/19). Four of 19 patients with other ADDs fulfilled the seronegative NMOSD criteria. PLP1-IgG were also found in patients with MOGAD (11/42), more frequently with PNS involvement (<i>p</i> = 0.01), and in patients with MS (12/42), more frequently with atypical features (<i>p</i> < 0.001). PLP1-IgG-positive MOGAD had higher EDSS scores (<i>p</i> < 0.001) and PLP1-IgG-positive MS had higher severity scores (MSSS, <i>p</i> < 0.001) compared with those PLP1-IgG-negative. Overall, PLP1-IgG were found in 24.1% of patients with CNS+PNS-ADD, 21.2% with atypical MS, 8.3% with MOGAD, 12.0% with seronegative NMOSD, and 1.4% with typical MS. Their frequency within each diagnostic subgroup was consistent between the exploratory and validation cohorts. PLP1-IgG a) colocalized with their target on CBA-TBA, where their binding was abolished after immunoadsorption and fixation-induced conformational epitope alteration; b) mostly pertained to the IgG1/IgG3 subclass (68.3%) and were able to induce CDC; and c) coreacted with DM20 in all 12 patients with PNS involvement tested.</p><p><strong>Discussion: </strong>Conformational PLP1-IgG predominantly identify patients with non-MS ADDs. They should be tested mainly in those with CNS + PNS ADD, coherently with DM20-IgG coreactivity. PLP1-IgG could also be investigated as disease modifiers and prognostic markers in MS and MOGAD. Preliminary evidence supports their pathogenic potential.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200359"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009111","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":"Clinical Manifestations and Treatment Responses in Pediatric Neurofascin 155-IgG4 Autoimmune Nodopathy.","authors":"Hebatallah R Rashed, Naveen Kumar Paramasivan, Duygu Selcen, P James B Dyck, Smathorn Thakolwiboon, Michelle L Mauermann, John Mills, Divyanshu Dubey","doi":"10.1212/NXI.0000000000200368","DOIUrl":"10.1212/NXI.0000000000200368","url":null,"abstract":"<p><strong>Background and objectives: </strong>While it is well characterized in adults, little is known about the clinical features of neurofascin 155-IgG4 autoimmune nodopathy (NF155-IgG4 AN) in the pediatric population. In this study, we aimed to describe the clinical features and treatment outcomes in children diagnosed with neurofascin 155-IgG4 autoimmune nodopathy (NF155-IgG4 AN).</p><p><strong>Methods: </strong>Pediatric and adult patients with NF155-IgG4 AN were identified retrospectively through the Mayo Clinic Neuroimmunology Laboratory database.</p><p><strong>Results: </strong>Eight pediatric and 20 adult patients with NF155-IgG4 AN were included with a median age at onset of 11 and 43 years, respectively. Pediatric patients (3/8) were often diagnosed initially with Guillain-Barre syndrome compared with adults (2/20) (<i>p</i> = 0.123). Six pediatric patients deteriorated beyond 2 months with rapid progression to disease nadir compared with adults (22 vs 52 weeks, <i>p</i> = 0.04). All had distal predominant weakness with paresthesias. Four patients had tremor, and one had cerebellar ataxia. Sensory ataxia was significantly less common in pediatric patients (4/8) compared with adults (18/20) (<i>p</i> = 0.038). Most pediatric patients (6/7) were IVIG refractory and responded to rituximab. Six patients had favorable outcomes after immunotherapy with improvement ≥1 in the Inflammatory Neuropathy Cause and Treatment disability score.</p><p><strong>Discussion: </strong>Pediatric patients with NF155-IgG4 AN display an aggressive disease course with rapid progression to disease nadir compared with adults. Sensory ataxia is less common in children, and they often respond to rituximab. It is crucial to consider autoimmune nodopathies in the differential diagnosis of pediatric patients with suspected inflammatory demyelinating polyneuropathy and to test for NF155-IgG4 antibodies because of their diagnostic and therapeutic implications.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence that in pediatric patients with NF155-IgG4 AN who are refractory to IVIG, rituximab treatment provided some benefit.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200368"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009110","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":"Cognitive Deficits in Anti-LGI1 Encephalitis Are Linked to Immunotherapy-Resistant White Matter Network Changes.","authors":"Stephan Krohn, Leonie Müller-Jensen, Joseph Kuchling, Amy Romanello, Katharina Wurdack, Sophia Rekers, Thorsten Bartsch, Frank Leypoldt, Friedemann Paul, Christoph J Ploner, Harald Prüss, Carsten Finke","doi":"10.1212/NXI.0000000000200360","DOIUrl":"10.1212/NXI.0000000000200360","url":null,"abstract":"<p><strong>Background and objectives: </strong>Cognitive deficits represent a major long-term complication of anti-leucine-rich, glioma-inactivated 1 encephalitis (LGI1-E). Although severely affecting patient outcomes, the structural brain changes underlying these deficits remain poorly understood. In this study, we hypothesized a link between white matter (WM) networks and cognitive outcomes in LGI1-E.</p><p><strong>Methods: </strong>In this cross-sectional study, we combined clinical assessments, comprehensive neuropsychological testing, diffusion tensor MRI, probabilistic WM tractography, and computational network analysis in patients with LGI1-E referred to Charité-Universitätsmedizin Berlin. Healthy individuals were recruited as control participants and matched to patients for age and sex with logistic regression propensity scores.</p><p><strong>Results: </strong>Twenty-five patients with LGI1-E (mean age = 63 ± 12 years, 76% male) and 25 healthy controls were enrolled. Eighty-eight percent of patients presented persistent cognitive symptoms at postacute follow-up (median: 12 months from onset, interquartile range: 6-23 months)-despite treatment with immunotherapy and good overall recovery (modified Rankin Scale [mRS] score at peak illness vs postacute: <i>z =</i> -4.1, <i>p</i> < 0.001, median mRS score at postacute visit: 1). Neuroimaging revealed that WM networks in LGI1-E are characterized by (1) a systematic reduction in whole-brain connectivity (<i>t =</i> -2.16, <i>p =</i> 0.036, <i>d =</i> -0.61), (2) a cortico-subcortical hypoconnectivity cluster affecting both limbic and extralimbic brain systems, and (3) a \"topological reorganization\" marked by a bidirectional shift in the relative importance of individual brain regions in the WM network. The extent of this WM reorganization was strongly associated with long-term deficits of verbal memory (<i>r =</i> -0.56), attention (<i>r =</i> -0.55), and executive functions (<i>r =</i> -0.60, all <i>p</i>_<i>FDR</i> = 0.017).</p><p><strong>Discussion: </strong>Although traditionally viewed as a form of limbic encephalitis, our study characterizes LGI1-E as a \"network disorder\" that affects the whole brain. Structural reorganization of WM networks was linked to long-term and multidomain cognitive impairment, which was not prevented by immunotherapy. These findings highlight the need for closer monitoring and improved treatment strategies to mitigate long-term cognitive impairment in LGI1-E.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200360"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067119","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":"Breast Cancer Specificities of Patients With Anti-Ri Paraneoplastic Neurologic Syndromes.","authors":"Elise Peter, Isabelle Treilleux, Valentin Wucher, Macarena Villagrán-García, Pauline Dumez, Daniel Pissaloux, Sandrine Paindavoine, Valéry Attignon, Geraldine Picard, Veronique Rogemond, Marine Villard, Laurie Tonon, Anthony Ferrari, Alain Viari, Bertrand Dubois, Jerome Honnorat, Virginie Desestret","doi":"10.1212/NXI.0000000000200367","DOIUrl":"10.1212/NXI.0000000000200367","url":null,"abstract":"<p><strong>Background and objectives: </strong>Breast cancers (BCs) of patients with paraneoplastic neurologic syndromes and anti-Yo antibodies (Yo-PNS) overexpress human epidermal growth factor receptor 2 (HER2) and display genetic alterations and overexpression of the Yo-onconeural antigens. They are infiltrated by an unusual proportion of B cells. We investigated whether these features were also observed in patients with PNS and anti-Ri antibodies (Ri-PNS).</p><p><strong>Methods: </strong>Using clinicopathologic data, DNA sequencing, and whole-transcriptome analysis, 28 BCs associated with Ri-PNS were characterized regarding oncological characteristics. Genetic alteration of the onconeural antigens and differential gene expression profiles were analyzed in the 12 available tumor samples and compared with those of 5 Yo-PNS tumors.</p><p><strong>Results: </strong>Ri-PNS BCs were mainly luminal B invasive carcinomas that did not overexpress HER2 and were a subtype of BCs different from the ones observed in Yo-PNS BCs. They had a low expression of wild-type <i>TP53</i> and deletions of 1p chromosome. Neither overexpression nor genetic alteration of the Ri onconeural antigens was found in Ri-PNS BCs. Conversely, the nature of the antitumor immune reaction in Ri-PNS BCs was similar to the one found in Yo-PNS BCs. Ri-BCs also had a high propension for early nodal regional metastasis.</p><p><strong>Discussion: </strong>BCs associated with Ri-PNS are uncommon and the tumor subtype and their molecular and oncological characteristics are different from those of Yo-PNS and controls. Overexpression or sequence variation in the gene of the onconeural antigen is not mandatory. Conversely, Ri-PNS-associated and Yo-PNS-associated BCs display the same atypical B-cell-mediated intratumoral immune response, and tumor escape in the lymph nodes is frequent.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200367"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055837","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":"Association Between Sun Exposure and Risk of Relapse in Pediatric-Onset Multiple Sclerosis.","authors":"Gina Chang, Prince Sebastian, Akash Virupakshaiah, Vinicius A Schoeps, Nicolas Cherbuin, T Charles Casper, Mark P Gorman, Leslie A Benson, Tanuja Chitnis, Mary Rensel, Aaron W Abrams, Tim Lotze, Soe S Mar, Teri L Schreiner, Yolanda S Wheeler, John W Rose, Jennifer Graves, Lauren B Krupp, Amy T Waldman, Robyn Lucas, Emmanuelle Waubant","doi":"10.1212/NXI.0000000000200375","DOIUrl":"10.1212/NXI.0000000000200375","url":null,"abstract":"<p><strong>Background and objectives: </strong>Low sun and ultraviolet radiation (UVR) exposures have been associated with increased risk of developing pediatric-onset multiple sclerosis (MS); however, their effect on disease course has not been well characterized. We primarily investigated whether there was an association between time spent in the sun in early childhood and risk of relapse in pediatric MS. We secondarily investigated the effect of sun exposure during more recent periods on risk of relapse.</p><p><strong>Methods: </strong>We conducted a multicenter cohort study of participants with pediatric-onset MS recruited from 18 pediatric MS clinics across the United States between November 1, 2011, and July 1, 2017. Relapses were identified prospectively after study enrollment; relapses preceding study enrollment were entered retrospectively. Time spent in the sun at various periods of life was measured using a detailed environmental questionnaire, and ambient UVR exposure was determined using zip codes. Multivariable Cox regression models were used to assess the association between time spent in the sun and UVR dose at specific periods of life and the risk of relapse. Models were adjusted for demographic, clinical, and sun exposure-related characteristics.</p><p><strong>Results: </strong>In our cohort of 334 children with MS, 206 (62%) experienced at least one relapse from disease onset to the end of the follow-up period. After adjustment, ≥30 minutes of daily sun exposure during the first summer of life was associated with a lower risk of relapse compared with <30 minutes (adjusted hazard ratio [aHR] 0.67, CI 0.48-0.92, <i>p</i> = 0.01). Greater time spent in the sun during the second trimester of pregnancy was also associated with reduced risk of relapse (aHR 0.68, CI 0.48-0.97, <i>p</i> = 0.04). UVR dose and time spent in the sun later in life were not significantly associated with relapse risk.</p><p><strong>Discussion: </strong>In this large cohort study of children with MS, greater early childhood and prenatal sun exposure time was associated with lower risk of relapse. Further investigation of sun exposure at other periods is needed to better characterize its impact on disease course and guide potential future interventions.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200375"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11820808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409511","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":"Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis.","authors":"Vinod K Gupta, Guneet S Janda, Heather K Pump, Nikhil Lele, Isabella Cruz, Inessa Cohen, William E Ruff, David A Hafler, Jaeyun Sung, Erin E Longbrake","doi":"10.1212/NXI.0000000000200355","DOIUrl":"10.1212/NXI.0000000000200355","url":null,"abstract":"<p><strong>Background and objectives: </strong>Gut microbial symbionts have been shown to influence the development of autoimmunity in multiple sclerosis (MS). Emerging research points to an important relationship between the microbial-IgA interface and MS pathophysiology. IgA-secreting B cells are observed in the MS brain, and shifts in gut bacteria-IgA binding have been described in some patients with MS. However, the relationships between the gut microbiome and the host immune response, particularly regarding B-cell-depleting immunomodulation, remain underexplored. This study aimed to evaluate the composition of the gut microbiome in patients with newly diagnosed MS at baseline and after B-cell depletion, using long-read sequencing for enhanced taxonomic resolution. We further aimed to investigate the host/microbiome interface by evaluating microbe/immunoglobulin A relationships.</p><p><strong>Methods: </strong>We collected stool samples from 43 patients with newly diagnosed, untreated MS and 42 matched healthy controls. Nineteen patients with MS initiated anti-CD20 monoclonal antibody treatment and donated additional stool samples after 6 months of treatment. We evaluated the host-microbial interface using bacterial flow cytometry and long-read 16S rRNA gene amplicon sequencing. We used Immune Coating Scores to compare the proportions of bacteria identified in the IgA-coated vs IgA-uncoated bacterial fractions.</p><p><strong>Results: </strong>Patients with untreated, newly diagnosed MS showed significant reductions in IgA-bound fecal microbiota compared with controls. Using multiple linear regression models adjusted for potential confounders, we observed significant (<i>p</i> < 0.05) changes in the abundance and prevalence of various strain-level gut bacteria amplicon sequence variants (ASVs) within both total and IgA-coated bacterial fractions. Some changes (e.g., decreased relative abundance of a <i>Faecalibacterium prausnitzii</i> variant in MS) were consistent with previous reports, while others (e.g., increased relative abundance and prevalence of <i>Monoglobus pectinyliticus</i> in MS) were novel. Immune Coating Scores identified subsets of organisms for which normal IgA-coating patterns were disrupted at the onset of MS, as well as those (particularly <i>Akkermansia muciniphila</i>) whose IgA-coating became more aligned with controls after therapy.</p><p><strong>Discussion: </strong>This analysis of gut microbial ASVs reveals shifts in taxonomic strains induced by immune modulation in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200355"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009109","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":"Profile and Usefulness of Serum Cytokines to Predict Prognosis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.","authors":"Javier Villacieros-Álvarez, Carmen Espejo, Georgina Arrambide, Alessandro Dinoto, Patricia Mulero, Laura Rubio-Flores, Pablo Nieto, Carmen Alcalá, Jose E Meca-Lallana, Jorge Millan-Pascual, Pedro Martínez-García, Raphael Bernard-Valnet, Inés González-Suárez, Aída Orviz, Raquel Téllez, Laura Navarro Cantó, Silvia Presas-Rodríguez, Sergio Martínez-Yélamos, Juan Pablo Cuello, Ana Alonso, Raquel Piñar Morales, Gary Álvarez Bravo, Lakhdar Benyahya, Sophie Trouillet-Assant, Virginie Dyon-Tafan, Caroline Froment Tilikete, Aurélie Ruet, Bertrand Bourre, Romain Deschamps, Caroline Papeix, Elisabeth Maillart, Philippe Kerschen, Xavier Ayrignac, Àlex Rovira, Cristina Auger, Bertrand Audoin, Xavier Montalban, Mar Tintore, Sara Mariotto, Alvaro Cobo-Calvo, Romain Marignier","doi":"10.1212/NXI.0000000000200362","DOIUrl":"10.1212/NXI.0000000000200362","url":null,"abstract":"<p><strong>Objectives: </strong>To characterize the serum cytokine profile in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at onset and during follow-up and assess their utility for predicting relapses and disability.</p><p><strong>Methods: </strong>This retrospective multicentric cohort study included patients aged 16 years and older meeting MOGAD 2023 criteria, with serum samples collected at baseline (≤3 months from disease onset) and follow-up (≥6 months from the baseline), and age-matched and time to sampling-matched patients with multiple sclerosis (MS). Eleven cytokines were assessed using the ELLA system. Data comparisons and statistical analyses between cytokine levels and clinical outcomes were performed.</p><p><strong>Results: </strong>Eighty-eight patients with MOGAD and 32 patients with MS were included. Patients with MOGAD showed higher IL6 (<i>p</i> = 0.036), IL8 (<i>p</i> = 0.012), and IL18 (<i>p</i> = 0.026) baseline levels compared with those with MS, in non-optic neuritis (ON) presentations. BAFF values increased over time, especially in patients with MOGAD treated with anti-CD20 (<i>p</i> = 0.002). Baseline BAFF, CXCL10, IL10, and IL8 levels correlated with disease severity at MOGAD onset (all <i>p</i> < 0.05). Finally, higher baseline BAFF levels predicted lower risk of relapses (hazard ratio 0.41 [0.19; 0.89], <i>p</i> = 0.024).</p><p><strong>Discussion: </strong>This study suggests a proinflammatory Th17-dominant profile in non-ON MOGAD patients, with a novel finding of a potential protective role of BAFF on relapses. These results shed new light on the pathogenesis of MOGAD, potentially guiding therapeutic decisions.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200362"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927655","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":"Modulator of VRAC Current 1 Is a Potential Target Antigen in Multiple Sclerosis.","authors":"Johannes Raffael Dahl, Alicia Weier, Christopher Winter, Maik Hintze, Veit Rothhammer, Thanos Tsaktanis, Anne-Katrin Proebstel, Tradite Neziraj, Elisabeth Poessnecker, Johanna Oechtering, Jens Kuhle, Boris-Alexander Kallmann, Gabriele Luber, Thorsten Heider, Luisa Klotz, Rittika Chunder, Stefanie Kuerten","doi":"10.1212/NXI.0000000000200374","DOIUrl":"10.1212/NXI.0000000000200374","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the CNS. Highlighted by the success of B-cell-depleting therapies such as the monoclonal anti-CD20 antibodies rituximab, ocrelizumab, and ofatumumab, B cells have been shown to play a central role in the immunopathology of the disease. Yet, the target antigens of the pathogenic B-cell response in MS remain unclear.</p><p><strong>Methods: </strong>We combined polyclonal B-cell stimulation of peripheral blood mononuclear cells with a human proteome-wide protein microarray to identify target antigens of MS by comparing samples from 20 patients with MS with 9 age-matched and sex-matched healthy controls. Results were verified by enzyme-linked immunosorbent assay (ELISA) in 3 independent validation cohorts (N = 47 patients with MS in remission; N = 20 patients with MS during relapse; N = 25 HCs; N = 30 patients with other noninflammatory neurologic diseases; N = 9 patients with other inflammatory neurologic diseases). Experimental autoimmune encephalomyelitis (EAE) was used as an animal model to evaluate the pathogenicity of the antibodies of choice.</p><p><strong>Results: </strong>Our results corroborate the existing concept of a highly diverse autoimmune response in MS. Yet, a significantly elevated antibody response against the membrane protein modulator of VRAC current 1 (MLC1) was noted in B-cell culture supernatants and serum samples of patients with MS. Furthermore, significantly elevated titers to MLC1 were observed in the CSF of patients with neuroinflammatory diseases other than MS. Neurons and astrocytes were identified as the main cell types expressing MLC1 in the brain of a patient with MS. Injection of anti-MLC1 antibodies into mice with EAE led to strong in vivo binding to cerebral cortical neurons and to the death of 4 of the 7 injected mice.</p><p><strong>Discussion: </strong>Future studies will have to address the diagnostic and prognostic value of MLC1-specific antibodies in neuroinflammatory disorders such as MS and characterize the functional role of MLC1 expression in neurons and astrocytes.</p><p><strong>Trial registration information: </strong>The study has been registered in the German Clinical Trials Register (study number DRKS00015528).</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200374"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399322","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":"Clinical Characterization and Prognostic Risk Factors of Susac Syndrome: A Retrospective Multicenter Study.","authors":"Lior Fuchs, Adi Wilf-Yarkoni, Hadar Kolb, Ifat Vigiser, Keren Regev, Dinah Zur, Zohar Habot-Wilner, Yahav Oron, Viktoria Furer, Nitai Shimon, Mark A Hellmann, Itay Lotan, Eitan Auriel, Robert Rennebohm, Ori Elkayam, Arnon Karni","doi":"10.1212/NXI.0000000000200357","DOIUrl":"10.1212/NXI.0000000000200357","url":null,"abstract":"<p><strong>Background and objectives: </strong>Susac syndrome (SuS) is a rare disorder characterized by encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss, often accompanied by vertigo. Recent updates to diagnostic criteria and treatment guidelines have been made. This study examines clinical manifestations; disease activity; and risk factors of disability, dependency, and return to work in patients with SuS.</p><p><strong>Methods: </strong>A retrospective multicenter study was conducted on 20 consecutive patients with SuS with at least 2 years of follow-up. Clinical and paraclinical activities were assessed and rated according to the severity at onset and the end of follow-up. Cognitive function was assessed using the Montreal Cognitive Assessment while disability and dependence in daily activities were measured using the modified Rankin Scale. Employment status was graded.</p><p><strong>Results: </strong>The mean age at onset was 38.9 years, with a mean follow-up of 55.9 months. The female-to-male ratio was 1.86, and 45% of patients had the complete clinical triad. Severe cerebral involvement at onset was associated with a higher risk of cerebral exacerbations within the first year and with an increased long-term disability and dependency. Cognitive function improved in 75% of patients during follow-up. At disease onset, hearing loss excluding low frequencies occurred in 46.7%. Relapse of hearing loss was associated with greater impairment in daily activities. Male sex and elevated CSF protein levels were linked to poorer prognosis. Cerebral and inner ear exacerbations were most common in the first year while retinal exacerbations occurred more frequently, mainly within the first 2 years. Approximately 50% of patients resumed employment while 25% did not return to work.</p><p><strong>Discussion: </strong>Current treatment strategies for SuS do not fully prevent relapses. Severe brain manifestation at onset, male sex, and high CSF protein levels are risk factors of a worse prognosis of disability and dependence, indicating the need for intensive treatment. High-frequency hearing loss does not exclude SuS diagnosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200357"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854877","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":"Clinical and Paraclinical Characterizations, Management, and Prognosis in DPPX Antibody-Associated Encephalitis: A Systematic Review.","authors":"Er-Chuang Li, Tian-Yi Zhang, Meng-Ting Cai, Sheng-Yao Su, Chun-Hong Shen, Qi-Lun Lai, Yin-Xi Zhang","doi":"10.1212/NXI.0000000000200350","DOIUrl":"10.1212/NXI.0000000000200350","url":null,"abstract":"<p><p>In dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, DPPX antibodies from serum and CSF target the extracellular subunit of the voltage-gated potassium channel 4.2. This targeting leads to a characteristic clinical triad comprising gastrointestinal symptoms (predominantly diarrhea), cognitive-psychiatric dysfunction, and manifestations of CNS hyperexcitability, with hyperekplexia being a more specific feature. This rare disease typically presents with a subacute or chronic course and often affects middle-aged and older individuals. Patients may have a weak association with certain hematologic malignancies, particularly lymphoma and chronic lymphocytic leukemia. Brain MRI typically shows normal findings or nonspecific white matter changes. DPPX antibody-associated encephalitis responds well to immunotherapy, and most patients ultimately present with a good prognosis. However, relapses can occur. To improve our understanding of this rare but treatable autoimmune encephalitis and avoid misdiagnosis, we conduct a systematic review and summarize the current knowledge of its clinical and paraclinical features, management, and prognosis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 2","pages":"e200350"},"PeriodicalIF":7.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854875","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}