Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Advanced Quantitative MRI Unveils Microstructural Thalamic Changes Reflecting Disease Progression in Multiple Sclerosis.","authors":"Alessandro Cagol,Mario Ocampo-Pineda,Po-Jui Lu,Matthias Weigel,Muhamed Barakovic,Lester Melie-Garcia,Xinjie Chen,Antoine Lutti,Pasquale Calabrese,Jens Kuhle,Ludwig Kappos,Maria Pia Sormani,Cristina Granziera","doi":"10.1212/nxi.0000000000200299","DOIUrl":"https://doi.org/10.1212/nxi.0000000000200299","url":null,"abstract":"BACKGROUND AND OBJECTIVESIn patients with multiple sclerosis (PwMS), thalamic atrophy occurs during the disease course. However, there is little understanding of the mechanisms leading to volume loss and of the relationship between microstructural thalamic pathology and disease progression. This cross-sectional and longitudinal study aimed to comprehensively characterize in vivo pathologic changes within thalamic microstructure in PwMS using advanced multiparametric quantitative MRI (qMRI).METHODSThalamic microstructural integrity was evaluated using quantitative T1, magnetization transfer saturation, multishell diffusion, and quantitative susceptibility mapping (QSM) in 183 PwMS and 105 healthy controls (HCs). The same qMRI protocol was available for 127 PwMS and 73 HCs after a 2-year follow-up period. Inclusion criteria for PwMS encompassed either an active relapsing-remitting MS (RRMS) or inactive progressive MS (PMS) disease course. Thalamic alterations were compared between PwMS and HCs and among disease phenotypes. In addition, the study investigated the relationship between thalamic damage and clinical and conventional MRI measures of disease severity.RESULTSCompared with HCs, PwMS exhibited substantial thalamic alterations, indicative of microstructural and macrostructural damage, demyelination, and disruption in iron homeostasis. These alterations extended beyond focal thalamic lesions, affecting normal-appearing thalamic tissue diffusely. Over the follow-up period, PwMS displayed an accelerated decrease in myelin volume fraction [mean difference in annualized percentage change (MD-ApC) = -1.50; p = 0.041] and increase in quantitative T1 (MD-ApC = 0.92; p < 0.0001) values, indicating heightened demyelinating and neurodegenerative processes. The observed differences between PwMS and HCs were substantially driven by the subgroup with PMS, wherein thalamic degeneration was significantly accelerated, even in comparison with patients with RRMS. Thalamic qMRI alterations showed extensive correlations with conventional MRI, clinical, and cognitive disease burden measures. Disability progression over follow-up was associated with accelerated thalamic degeneration, as reflected by enhanced diffusion (β = -0.067; p = 0.039) and QSM (β = -0.077; p = 0.027) changes. Thalamic qMRI metrics emerged as significant predictors of neurologic and cognitive disability even when accounting for other established markers including white matter lesion load and brain and thalamic atrophy.DISCUSSIONThese findings offer deeper insights into thalamic pathology in PwMS, emphasizing the clinical relevance of thalamic damage and its link to disease progression. Advanced qMRI biomarkers show promising potential in guiding interventions aimed at mitigating thalamic neurodegenerative processes.","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"9 1","pages":"e200299"},"PeriodicalIF":8.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256170","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":"IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.","authors":"Ronald Postuma,Nisa Vorasoot,Erik K St Louis,Amélie Pelletier,Miranda M Lim,Jonathan Elliott,Jean-Francois Gagnon,Ziv Gan-Or,Leah K Forsberg,Julie A Fields,Owen A Ross,Wolfgang Singer,Daniel E Huddleston,Donald L Bliwise,Alon Y Avidan,Michael Howell,Carlos H Schenck,Jennifer McLeland,Albert A Davis,Susan R Criswell,Aleksandar Videnovic,Emmanuel H During,Mitchell G Miglis,Bradley F Boeve,Yo-El S Ju,Andrew McKeon,","doi":"10.1212/nxi.0000000000200311","DOIUrl":"https://doi.org/10.1212/nxi.0000000000200311","url":null,"abstract":"BACKGROUND AND OBJECTIVESIdiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.METHODSParticipants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5.RESULTSOf 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease.DISCUSSIONOur finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings.TRIAL REGISTRATION INFORMATIONNCT03623672.","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"31 1","pages":"e200311"},"PeriodicalIF":8.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256260","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":"A Simple Score (MOG-AR) to Identify Individuals at High Risk of Relapse After MOGAD Attack.","authors":"Yun Xu,Huaxing Meng,Moli Fan,Linlin Yin,Jiali Sun,Yajun Yao,Yuzhen Wei,Hengri Cong,Huabing Wang,Tian Song,Chun-Sheng Yang,Jinzhou Feng,Fu-Dong Shi,Xinghu Zhang,De-Cai Tian","doi":"10.1212/nxi.0000000000200309","DOIUrl":"https://doi.org/10.1212/nxi.0000000000200309","url":null,"abstract":"BACKGROUND AND OBJECTIVESTo identify predictors for relapse in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to develop and validate a simple risk score for predicting relapse.METHODSIn China National Registry of Neuro-Inflammatory Diseases (CNRID), we identified patients with MOGAD from March 2023 and followed up prospectively to September 2023. The primary endpoint was MOGAD relapse, confirmed by an independent panel. Patients were randomly divided into model development (75%) and internal validation (25%) cohorts. Prediction models were constructed and internally validated using Andersen-Gill models. Nomogram and relapse risk score were generated based on the final prediction models.RESULTSA total of 188 patients (comprising 612 treatment episodes) were included in cohorts. Female (HR: 0.687, 95% CI 0.524-0.899, p = 0.006), onset age 45 years or older (HR: 1.621, 95% CI 1.242-2.116, p < 0.001), immunosuppressive therapy (HR: 0.338, 95% CI 0.239-0.479, p < 0.001), oral corticosteroids >3 months (HR 0.449, 95% CI 0.326-0.620, p < 0.001), and onset phenotype (p < 0.001) were identified as factors associated with MOGAD relapse. A predictive score, termed MOG-AR (Immunosuppressive therapy, oral Corticosteroids, Onset Age, Sex, Attack phenotype), derived in prediction model, demonstrated strong predictive ability for MOGAD relapse. MOG-AR score of 13-16 indicates a higher risk of relapse (HR: 3.285, 95% CI 1.473-7.327, p = 0.004).DISCUSSIONThe risk of MOGAD relapse seems to be predictable. Further validation of MOG-AR score developed from this cohort to determine appropriate treatment and monitoring frequency is warranted.TRIAL REGISTRATION INFORMATIONCNRID, NCT05154370, registered December 13, 2021, first enrolled December 15, 2021.","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"1 1","pages":"e200309"},"PeriodicalIF":8.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206374","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":"Serological Markers of Clinical Improvement in MuSK Myasthenia Gravis.","authors":"Gregorio Spagni,Angela Vincent,Bo Sun,Silvia Falso,Leslie W Jacobson,Sean Devenish,Amelia Evoli,Valentina Damato","doi":"10.1212/nxi.0000000000200313","DOIUrl":"https://doi.org/10.1212/nxi.0000000000200313","url":null,"abstract":"BACKGROUND AND OBJECTIVESIn this retrospective longitudinal study, we aimed at exploring the role of (a) MuSK-immunoglobulin G (IgG) levels, (b) predominant MuSK-IgG subclasses, and (c) antibody affinity as candidate biomarkers of severity and outcomes in MuSK-MG, using and comparing different antibody testing techniques.METHODSTotal MuSK-IgGs were quantified with radioimmunoassay (RIA), ELISA, flow cytometry, and cell-based assay (CBA) serial dilutions using HEK293 cells transfected with MuSK-eGFP. MuSK-IgG subclasses were measured by flow cytometry. SAffCon assay was used for determining MuSK-IgG affinity.RESULTSForty-three serum samples were obtained at different time points from 20 patients with MuSK-MG (median age at onset: 48 years, interquartile range = 27.5-72.5; women, 16/20), with 9 of 20 (45%) treated with rituximab. A strong correlation between MuSK-IgG levels measured by flow cytometry and RIA titers was found (rs = 0.74, 95% CI 0.41-0.89, p = 0.0003), as well as a moderate correlation between CBA end-point titers and RIA titers (rs = 0.47, 95% CI 0.01-0.77, p = 0.0414). A significant correlation was found between MuSK-IgG flow cytometry levels and disease severity (rs = 0.39, 95% CI 0.06-0.64, p = 0.0175; mixed-effects model estimate: 2.296e-06, std. error: 1.024e-06, t = 2.243, p = 0.032). In individual patients, clinical improvement was associated with decrease in MuSK-IgG levels, as measured by either flow cytometry or CBA end-point titration. In all samples, MuSK-IgG4 was the most frequent isotype (mean ± SD: 90.95% ± 13.89). A significant reduction of MuSK-IgG4 and, to a lesser extent, of MuSK-IgG2, was seen in patients with favorable clinical outcomes. A similar trend was confirmed in the subgroup of rituximab-treated patients. In a single patient, MuSK-IgG affinity increased during symptom exacerbation (KD values: 62 nM vs 0.6 nM) while total MuSK-IgG and IgG4 levels remained stable, suggesting that affinity maturation may be a driver of clinical worsening.DISCUSSIONOur data support the quantification of MuSK antibodies by flow cytometry. Through a multimodal investigational approach, we showed that total MuSK-IgG levels, MuSK-IgG4 and MuSK-IgG2 levels, and MuSK-IgG affinity may represent promising biomarkers of disease outcomes in MuSK-MG.","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"18 1","pages":"e200313"},"PeriodicalIF":8.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206381","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":"Relapsing-Remitting Immunotherapy Responsive Small-Fiber Neuropathy: Longitudinal Tracking Through 10 Years Including Pregnancies.","authors":"Anne Louise Oaklander, Julia Allen, Nadja Dietliker, Einar P Wilder-Smith","doi":"10.1212/NXI.0000000000200286","DOIUrl":"10.1212/NXI.0000000000200286","url":null,"abstract":"<p><strong>Objectives: </strong>To expand understanding of the pathogenesis, presentations, and treatment of initially idiopathic small fiber polyneuropathy (SFN).</p><p><strong>Methods: </strong>We longitudinally readministered validated metrics to track disease course and treatment responses in a previously healthy woman with acute, postinfectious, skin biopsy-confirmed, idiopathic SFN.</p><p><strong>Results: </strong>During 5 years, viral respiratory infections triggered 3 separated episodes of acute, disabling burning hand, foot, and face pain (erythromelalgia). The initial 2 resolved with high-dose prednisone, and the third responded to repeated immunoglobulin treatments. Pregnancy with miscarriage triggered a fourth exacerbation refractory to corticosteroids and cyclosporin. Immunoglobulins restored total remission for 2 months; then, 2 rituximab doses slightly improved later flaring. Subsequently, daratumumab initiated 100-day remission later maintained by belimumab, initiated to permit another pregnancy. Remission continued after gestational week 13 all-treatment withdrawal. A week 30 fifth flare responded to plasmapheresis, with healthy birth at week 40. At 11-week postpartum, as symptoms returned, restarting belimumab restored remission maintained during ≥19 months of breastfeeding.</p><p><strong>Discussion: </strong>This decade of tracking characterizes a relapsing-remitting course of SFN with initially separated monophasic episodes becoming more confluent, as with multiple sclerosis. This tempo and responsiveness to 5 immunotherapies suggest dysimmune causality. Validated metrics helped define the course and track treatment efficacy, particularly during pregnancy and breastfeeding.</p><p><strong>Classification of evidence: </strong>This is a single observational study without controls. This provides Class IV evidence.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200286"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760101","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":"REM and NREM Sleep Parasomnia in Anti-NMDA Receptor Encephalitis.","authors":"Luis Ribeiro, Dimitri Psimaras, Raphael Vollhardt, Jerome Honnorat, Aurélie Méneret, Sophie Demeret, Adam Celier, Nefeli E Valyraki, Louis Cousyn, Loic Le Guennec, Isabelle Arnulf, Ana Z Gales","doi":"10.1212/NXI.0000000000200203","DOIUrl":"10.1212/NXI.0000000000200203","url":null,"abstract":"<p><strong>Objectives: </strong>Encephalitis with anti-N-methyl-d-aspartate receptor antibodies (anti-NMDARe) is a rare disorder characterized by cognitive impairment, psychosis, seizures, and abnormal movements. Abnormal behaviors during REM sleep have not been described in anti-NMDARe.</p><p><strong>Methods: </strong>Patients were monitored by video-polysomnography on a first night followed by multiple sleep latency tests and 18 hours of bed rest.</p><p><strong>Results: </strong>Two patients with anti-NMDARe developed during the acute and postacute phase parasomnias including REM sleep behavior disorder and continuous finalistic quiet gesturing during a mixed N2/R sleep. The parasomnia disorder was improved by gabapentin and clonazepam.</p><p><strong>Discussion: </strong>Video-polysomnography avoids misdiagnosing these parasomnia behaviors for seizure or movement disorders and allows adequate treatment.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200203"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451087","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":"Frequency of Asymptomatic Optic Nerve Enhancement in 203 Patients With MOG Antibody-Associated Disease.","authors":"Deena Tajfirouz, Ajay Madhavan, Johann M Pacheco Marrero, Karl N Krecke, Kalli J Fautsch, Eoin P Flanagan, Sean J Pittock, Shailee Shah, M Tariq Bhatti, John J Chen","doi":"10.1212/NXI.0000000000200277","DOIUrl":"10.1212/NXI.0000000000200277","url":null,"abstract":"<p><strong>Background and objectives: </strong>Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI has not been explored in patients with MOGAD. An improved understanding of this would guide clinical practice and assessment of treatment efficacy. We aimed to determine the frequency of asymptomatic optic nerve enhancement in MOGAD.</p><p><strong>Methods: </strong>This was a retrospective review of patients evaluated at Mayo Clinic with MOGAD between January 1, 2000, and August 1, 2021 (median follow-up 1.6 [range 1-19] years). MRI studies were reviewed by masked neuroradiologists. Scans performed within 30 days of ON attack were classified as attack scans. Images obtained for routine surveillance, before ON attack, or at the time of non-ON attack were classified as interattack scans.</p><p><strong>Results: </strong>Five hundred sixty-six MRIs (203 unique patients, 53% female) were included. Interattack MRIs represented 341 (60%) of the scans (median 36 days post-ON [range -1,032 to 6,001]). Of the interattack scans, 43 of 341 (13%), 30 unique patients, showed optic nerve enhancement. The enhancement was located at prior sites of ON in 35 of 43 (81%). Among the 8 patients with enhancement in new optic nerve areas, 6 had acute disseminated encephalomyelitis without an eye examination at the time of the MRI and 2 had preceding ON without imaging. Long-term visual outcomes showed no significant difference between those with and without asymptomatic enhancement, with improved visual acuity in most patients.</p><p><strong>Discussion: </strong>Asymptomatic optic nerve enhancement occurred in 13% of interattack MRIs, the majority in patients with prior ON and occurring at prior sites of optic nerve enhancement. New asymptomatic optic nerve enhancement in areas without prior ON was rare. These findings are important for understanding the natural history of MOGAD, the interpretation of symptoms or response to treatment, and the adjudication of attacks in clinical trials.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200277"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458442","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":"Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.","authors":"Sarah K G Jensen, Susana Camposano, Anne Berens, Michael Waltz, Lauren B Krupp, Leigh Charvet, Anita L Belman, Gregory S Aaen, Leslie A Benson, Meghan Candee, Theron C Casper, Tanuja Chitnis, Jennifer Graves, Yolanda S Wheeler, Ilana Kahn, Timothy E Lotze, Soe S Mar, Mary Rensel, Moses Rodriguez, John W Rose, Jennifer P Rubin, Jan-Mendelt Tillema, Amy T Waldman, Bianca Weinstock-Guttman, Lisa F Barcellos, Emmanuelle Waubant, Mark P Gorman","doi":"10.1212/NXI.0000000000200282","DOIUrl":"10.1212/NXI.0000000000200282","url":null,"abstract":"<p><strong>Background and objectives: </strong>Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity.</p><p><strong>Methods: </strong>This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study. Cases (n = 381) were youth aged 3-21 years diagnosed with POMS or a clinically isolated demyelinating syndrome indicating high risk of MS. Frequency-matched controls (n = 611) aged 3-21 years were recruited from the same institutions. Prenatal and postnatal adversity and postnatal socioeconomic factors were assessed using retrospective questionnaires and zip code data. The primary outcome was MS diagnosis. Secondary outcomes were age at onset, relapse rate, and Expanded Disability Status Scale (EDSS). Predictors were maternal education, maternal prenatal stress events, child separation from caregivers during infancy and childhood, parental death during childhood, and childhood neighborhood disadvantage.</p><p><strong>Results: </strong>MS cases (64% female, mean age 15.4 years, SD 2.8) were demographically similar to controls (60% female, mean age 14.9 years, SD 3.9). Cases were less likely to have a mother with a bachelor's degree or higher (OR 0.42, 95% CI 0.22-0.80, <i>p</i> = 0.009) and were more likely to experience childhood neighborhood disadvantage (OR 1.04 for each additional point on the neighborhood socioeconomic disadvantage score, 95% CI 1.00-1.07; <i>p</i> = 0.025). There were no associations of the socioeconomic variables with age at onset, relapse rate, or EDSS, or of prenatal or postnatal adverse events with risk of POMS, age at onset, relapse rate, or EDSS.</p><p><strong>Discussion: </strong>Low socioeconomic status at the neighborhood level may increase the risk of POMS while high parental education may be protective against POMS. Although we did not find associations of other evaluated prenatal or postnatal adversities with POMS, future research should explore such associations further by assessing a broader range of stressful childhood experiences.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200282"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988495","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":"Different Patterns of Autoantibody Secretion by Peripheral Blood Mononuclear Cells in Autoimmune Nodopathies.","authors":"Sophia Rohrbacher, Sabine Seefried, Beate Hartmannsberger, Rosa Annabelle, Luise Appeltshauser, Friederike A Arlt, Dirk Brämer, Christian Dresel, Johannes Dorst, Zeynep Elmas, Christiana Franke, Christian Geis, Tobias Högen, Sabine Krause, Martin Marziniak, Mathias Mäurer, Harald Prüss, Florian Schoeberl, Bertold Schrank, Claudia Steen, Helena Teichtinger, Andrea Thieme, Lena Wessely, Alma Zernecke, Claudia Sommer, Kathrin Doppler","doi":"10.1212/NXI.0000000000200295","DOIUrl":"10.1212/NXI.0000000000200295","url":null,"abstract":"<p><strong>Background and objectives: </strong>Autoimmune nodopathies with antibodies against the paranodal proteins show a distinct phenotype of a severe sensorimotor neuropathy. In some patients, complete remission can be achieved after treatment with rituximab whereas others show a chronic course. For optimal planning of treatment, predicting the course of disease and therapeutic response is crucial.</p><p><strong>Methods: </strong>We stimulated peripheral blood mononuclear cells in vitro to find out whether secretion of specific autoantibodies may be a predictor of the course of disease and response to rituximab.</p><p><strong>Results: </strong>Three patterns could be identified: In most patients with anti-Neurofascin-155-, anti-Contactin-1-, and anti-Caspr1-IgG4 autoantibodies, in vitro production of autoantibodies was detected, indicating autoantigen-specific memory B cells and short-lived plasma cells/plasmablasts as the major source of autoantibodies. These patients generally showed a good response to rituximab. In a subgroup of patients with anti-Neurofascin-155-IgG4 autoantibodies and insufficient response to rituximab, no in vitro autoantibody production was found despite high serum titers, indicating autoantibody secretion by long-lived plasma cells outside the peripheral blood. In the patients with anti-pan-Neurofascin autoantibodies-all with a monophasic course of disease-no in vitro autoantibody production could be measured, suggesting a lack of autoantigen-specific memory B cells. In some of them, autoantibody production by unstimulated cells was detectable, presumably corresponding to high amounts of autoantigen-specific plasmablasts-well in line with a severe but monophasic course of disease.</p><p><strong>Discussion: </strong>Our data suggest that different B-cell responses may occur in autoimmune nodopathies and may serve as markers of courses of disease and response to rituximab.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200295"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036510","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 Alcohol Consumption and Disability Accumulation in Multiple Sclerosis.","authors":"Jing Wu, Tomas Olsson, Jan A Hillert, Lars Alfredsson, Anna Karin Hedström","doi":"10.1212/NXI.0000000000200289","DOIUrl":"10.1212/NXI.0000000000200289","url":null,"abstract":"<p><strong>Background and objectives: </strong>Previous studies have indicated that alcohol consumption is associated with multiple sclerosis (MS) disease progression. We aimed to study the influence of alcohol consumption habits on disease progression and health-related quality of life in MS.</p><p><strong>Methods: </strong>We categorized patients from 2 population-based case-control studies by alcohol consumption habits at diagnosis and followed them up to 15 years after diagnosis through the Swedish MS registry regarding changes in the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Impact Scale 29 (MSIS-29). We used Cox regression models with 95% confidence intervals (CIs) using 24-week confirmed disability worsening, EDSS 3, EDSS 4, and physical and psychological worsening from the patient's perspective as end points.</p><p><strong>Results: </strong>Our study comprised 9,051 patients with MS, with a mean age of 37.5 years at baseline/diagnosis. Compared with nondrinking, low and moderate alcohol consumption was associated with reduced risk of EDSS-related unfavorable outcomes (hazard ratios between 0.81 and 0.90) and with reduced risk of physical worsening. The inverse association was confined to relapsing-remitting MS and was more pronounced among women. High alcohol consumption did not significantly affect disease progression. The inverse relationship between low-moderate alcohol consumption and disability progression became stronger when we only included those who had not changed their alcohol consumption during follow-up (hazard ratios between 0.63 and 0.71). There were no differences in measures of disability at baseline between drinkers who continued drinking alcohol after diagnosis and those who later discontinued. Our findings speak against bias due to reverse causation.</p><p><strong>Discussion: </strong>Low and moderate alcohol consumption was associated with more favorable outcomes in relapsing-remitting MS, compared with nondrinking, while there was no significant influence of high alcohol consumption on disease outcomes.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 5","pages":"e200289"},"PeriodicalIF":7.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875480","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}