Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Neurofilament Light Chain as a Discriminator of Disease Activity Status in MOG Antibody-Associated Disease.","authors":"Ana Beatriz Ayroza Galvão Ribeiro Gomes, Su-Hyun Kim, Roxanne Pretzsch, Laila Kulsvehagen, Sabine Schaedelin, Jasmine Lerner, Nora Sandrine Wetzel, Pascal Benkert, Aleksandra Maleska Maceski, Jae-Won Hyun, Anne-Catherine Lecourt, Patrick Lipps, Vinicius Andreoli Schoeps, Aline De Moura Brasil Matos, Natalia Trombini Mendes, Samira Luisa Apóstolos-Pereira, Matthias Mehling, Tobias Derfuss, Ludwig Kappos, Dagoberto Callegaro, Jens Kuhle, Ho Jin Kim, Anne-Katrin Pröbstel","doi":"10.1212/NXI.0000000000200347","DOIUrl":"10.1212/NXI.0000000000200347","url":null,"abstract":"<p><strong>Background and objectives: </strong>In patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), acute disease activity is generally identified through medical history, neurologic examination, and imaging. However, these may be insufficient for detecting disease activity in specific conditions. This study aimed to investigate the dynamics of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) after clinical attacks and to assess their utility in discriminating attacks from remission in patients with MOGAD.</p><p><strong>Methods: </strong>We conducted a multicenter, retrospective, longitudinal study including 239 sera from 62 MOGAD patients assessed from 1995 to 2023 in a discovery and validation setup. Sera were measured for sNfL and sGFAP with a single-molecule array assay and for MOG-IgG with a live cell-based assay. sNfL and sGFAP Z scores and percentiles adjusted for age, body mass index, and sex (sGFAP) were calculated from a healthy control normative database. Mixed-effects regression models were used to characterize biomarkers' dynamics and to investigate associations between serum biomarkers, clinical variables, and disease activity status.</p><p><strong>Results: </strong>Among the 62 study participants, 29 (46.8%) were female, with a median age at baseline of 40.0 years (interquartile range [IQR] 29.5-49.8) and a median duration of follow-up of 20.0 months (IQR 3.0-62.8). sNfL and sGFAP Z scores were nonlinearly associated with time from attack onset (<i>p</i> < 0.001 and = 0.002, respectively). During attacks, both biomarkers presented higher median values (sNfL Z score 2.9 [IQR 1.4-3.5], 99.8th; sGFAP Z score 0.4 [IQR -0.5 to 1.5], 65.5th) compared with remission (sNfL Z score 0.9 [IQR -0.1 to 1.6], 81.6th, <i>p</i> < 0.001; sGFAP Z score -0.2 [IQR -0.8 to 0.5], 42.1th; <i>p</i> < 0.001) across all clinical phenotypes. sNfL values consistently discriminated disease activity status in the discovery and validation cohorts, showing a 3.5-fold increase in the odds of attacks per Z score unit (odds ratio 3.5, 95% confidence interval 2.3-5.1; <i>p</i> < 0.001). Logistic models incorporating sNfL Z scores demonstrated favorable performance in discriminating disease activity status across both cohorts.</p><p><strong>Discussion: </strong>sNfL Z scores may serve as a biomarker for monitoring disease activity in MOGAD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200347"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869688","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":"Temporal Dynamics of Plasma Neurofilament Light in Blood Donors With Preclinical Multiple Sclerosis.","authors":"Josefine Britze, Margit Hørup Larsen, Anders Gorm Pedersen, Susanne Rosthøj, Helle Bach Søndergaard, Melinda Magyari, Ole Birger Pedersen, Bitten Aagaard Jensen, Sisse Rye Ostrowski, Christian Erikstrup, Henrik Ullum, Jette Lautrup Frederiksen Battistini, Finn Sellebjerg, Signe Modvig","doi":"10.1212/NXI.0000000000200335","DOIUrl":"10.1212/NXI.0000000000200335","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is a CNS disease, characterized by demyelination, inflammation, and neurodegeneration. Recent advances in technology allow measurement of the axonal damage marker neurofilament light chain in peripheral blood. Two studies have shown that patients with MS have elevated neurofilament light levels before their first symptom, but longitudinal studies are lacking. We aimed to investigate the intraindividual neurofilament light dynamics during the presymptomatic phase of MS.</p><p><strong>Methods: </strong>The Danish Blood Donor Study (DBDS) has stored plasma samples from blood donors for more than 10 years. We identified DBDS participants, who had subsequently been diagnosed with MS, and included all samples donated before their first demyelinating symptom (median 5.00 samples per case). As controls, we included 2 healthy donors per case. Plasma levels of neurofilament light were measured and compared with quality-of-life data. We used a Bayesian approach to derive estimates for the percentage of cases with presymptomatic increased neurofilament light levels.</p><p><strong>Results: </strong>We observed that 12 (17%, 95% CI 9%-28%) of 69 presymptomatic MS donors had intermittently increased neurofilament light levels preclinically. Increased levels were present up to 9 years before clinical onset, also in primary progressive MS. Healthy donors and presymptomatic MS donors with and without increased neurofilament light levels reported equally high physical and mental well-being. Model-based estimates suggested that 55% of cases (95% credible interval [28%-87%]) had experienced increased presymptomatic neurofilament light levels.</p><p><strong>Discussion: </strong>Patients with MS periodically sustain axonal injury up to 9 years before clinical onset, even in primary progressive disease. This most likely represents asymptomatic disease activity. Some or even all patients are affected by this intermittent axonal injury, prompting the need for further studies of the presymptomatic phase in relation to prognosis and as a therapeutic window of opportunity.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200335"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739923","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":"Pregnancy and Infant Outcomes in Women With Multiple Sclerosis Treated With Ocrelizumab.","authors":"Sandra Vukusic, Riley Bove, Ruth Dobson, Thomas McElrath, Celia Oreja-Guevara, Carlo Pietrasanta, Chien-Ju Lin, Germano Ferreira, Licinio Craveiro, Dusanka Zecevic, Noemi Pasquarelli, Kerstin Hellwig","doi":"10.1212/NXI.0000000000200349","DOIUrl":"10.1212/NXI.0000000000200349","url":null,"abstract":"<p><strong>Background and objectives: </strong>Ocrelizumab labeling advises contraception for women during treatment and for 6-12 months thereafter. Because pregnancies may occur during this time, it is critical to understand pregnancy and infant outcomes in women with multiple sclerosis (MS) after ocrelizumab exposure.</p><p><strong>Methods: </strong>Pregnancy cases reported to Roche global pharmacovigilance until 12 July 2023 were analyzed. In utero exposure was defined if the last ocrelizumab infusion occurred in the 3 months before the last menstrual period or during pregnancy. Breastfeeding exposure was defined if at least one infusion occurred while breastfeeding. Fetal death was termed spontaneous abortion (SA) if < 22 complete gestational weeks (GWs) and stillbirth if later. Live births (LBs) were preterm if < 37 complete GWs. Major congenital anomalies (MCAs), infant outcomes, and maternal complications were also analyzed.</p><p><strong>Results: </strong>In total, 3,244 pregnancies were reported in women with MS receiving ocrelizumab. The median maternal age was 32 years (Q1-Q3: 29-35 years), and most women had relapsing MS (65.6%). Of 2,444 prospectively reported pregnancies, 855 were exposed to ocrelizumab in utero (512 with a known outcome), 574 were nonexposed, and the remaining 1,015 had unknown timing of exposure. Most (83.6%; 956/1,144) of the pregnancies with a known outcome resulted in LBs (exposed, 84.2%; nonexposed, 88.3%). The exposed and nonexposed groups had similar proportions of other important pregnancy outcomes (preterm births, 9.5% vs 8.7%; SA, 7.4% vs 9.1%). Elective abortions were more frequent in the exposed group (7.4%, vs 1.7% in the nonexposed group). The proportion of LBs with MCAs was similar between the exposed and nonexposed groups (2.1% vs 1.9%) and within epidemiologic background rates. In the exposed group, one stillbirth and one neonatal death were prospectively reported.</p><p><strong>Discussion: </strong>In this analysis of a large pregnancy outcome dataset for an anti-CD20 in MS, in utero exposure to ocrelizumab was not associated with an increased risk of adverse pregnancy or infant outcomes. These data will enable neurologists and women with MS to make more informed decisions around family planning, balancing safety risks to the fetus/infant against the importance of disease control in the mother.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200349"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Complement Activation in IgM M-Protein-Associated Neuropathies.","authors":"Johannes P M van de Mortel, Kevin Budding, Kim Dijkxhoorn, Monique C Minnema, Alexander F J E Vrancken, Nicolette C Notermans, W Ludo van der Pol","doi":"10.1212/NXI.0000000000200339","DOIUrl":"10.1212/NXI.0000000000200339","url":null,"abstract":"<p><strong>Background and objectives: </strong>Polyneuropathy associated with an immunoglobulin M (IgM) monoclonal gammopathy is characterized by slowly progressive, predominantly distal sensorimotor deficits, sensory ataxia, and electrophysiologic features of demyelination. IgM antibodies against myelin-associated glycoprotein (MAG) are present in serum from most patients. Nerve damage most likely results from the concerted action of binding of anti-MAG antibodies to nerves, followed by complement activation. The interaction of anti-MAG antibodies with complement activation and their relation to clinical characteristics have not been studied in detail. We studied the correlation among anti-MAG antibody titers, complement activation, and IgM-associated polyneuropathy disease severity.</p><p><strong>Methods: </strong>We used serum samples from 101 patients with IgM-associated polyneuropathy to assess IgM anti-MAG titers by ELISA and antibody-mediated complement deposition using both an ELISA-based system and a cell-based system of primate peripheral nerve slides. We studied correlations of complement activation with anti-MAG ELISA titers and clinical characteristics.</p><p><strong>Results: </strong>IgM anti-MAG titers varied from negative to strongly positive. Complement deposition in the ELISA-based system correlated significantly with anti-MAG antibody titer (Spearman rho 0.80; <i>p</i> < 0.0001) despite large variability between serum samples with comparable anti-MAG titers. This variability was even larger in the cell-based assay, which also showed complement deposition in IgM anti-MAG negative patients, indicating the presence of autoantibodies directed against epitopes other than MAG in a subset of patients with IgM-associated polyneuropathy. Clinical characteristics did not correlate with anti-MAG titers or complement activation.</p><p><strong>Discussion: </strong>Anti-MAG antibody titers correlate with the level of complement activation in both ELISA and cell-based systems. However, clinical characteristics of IgM-associated polyneuropathy do not or only weakly correlate with titers or the level of complement deposition. The lack of clear correlations between complement activation and clinical characteristics does, at this stage, not support the use of complement inhibitors in the treatment of IgM-associated polyneuropathy.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200339"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687583","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":"Distinguishing Transient From Persistent Brain Structural Changes in Pediatric Patients With Acute Disseminated Encephalomyelitis.","authors":"Jason Michael Millward, Elias Pilgrim, Matthias Baumann, Eva-Maria Wendel, Ines El Naggar, Annikki Bertolini, Frederik Bartels, Carsten Finke, Friedemann Paul, Thoralf Niendorf, Kevin Rostásy, Sonia Waiczies","doi":"10.1212/NXI.0000000000200337","DOIUrl":"10.1212/NXI.0000000000200337","url":null,"abstract":"<p><strong>Background and objectives: </strong>Pediatric patients with acute disseminated encephalomyelitis (ADEM) are at risk of impaired brain growth, with long-term neuropsychiatric consequences. We previously reported transient expansions of cerebral ventricle volume (VV) in experimental autoimmune encephalomyelitis, which subsequently normalized. In this study, we investigated changes in VV in ADEM in relation to other brain structures and clinical outcomes.</p><p><strong>Methods: </strong>We investigated brain MRI scans acquired in routine clinical practice from a multicenter cohort of 61 pediatric patients with ADEM, of whom 39 were myelin oligodendrocyte glycoprotein (MOG) antibody-positive. Patients were compared with 1,219 pediatric healthy controls (HCs). Volumes of multiple brain structures were computed using a contrast-agnostic machine learning-based tool and analyzed with mixed-effect models regarding other clinical parameters.</p><p><strong>Results: </strong>Patients with ADEM had larger VV than HCs at initial clinical presentation, before immune therapy. Most of the patients showed further VV increases within 2 months after disease onset. Patients had smaller brain volumes than HCs, with specific reductions in deep gray matter structures. These changes were more pronounced in MOG antibody-negative patients.Of the patients with more than 2 MRI scans, 12 of 22 resolved their VV expansion back to within 15% of baseline values while 10 of 22 had persistently increased VV at the last available MRI within 1 year from onset. Patients with persistent VV expansion had greater reductions in volumes of other brain structures at the <i>last MRI</i> than patients whose VV resolved and were more likely to have residual neurologic signs. The VV <i>resolving</i> and <i>nonresolving</i> patients did not differ regarding age, sex, elevated CSF cell counts at baseline, or occurrence of relapses. However, patients with a larger magnitude of VV expansion-≥90% of baseline volume-were more likely to be in the <i>nonresolving</i> group.</p><p><strong>Discussion: </strong>We could distinguish between 2 outcomes of VV changes in ADEM: one in which the VV expanded but ultimately returned to normal and one in which the expansions continued after disease onset and treatment but failed to resolve. The latter was associated with reduced brain volume, particularly in deep gray matter structures. This highlights the necessity for patients with ADEM to undergo regular MRI scans to assess whether developing VV expansions indicate a greater risk of permanent brain atrophy.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200337"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11676258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882624","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":"Proteomics Reveals Age as Major Modifier of Inflammatory CSF Signatures in Multiple Sclerosis.","authors":"Friederike Held, Christine Makarov, Christiane Gasperi, Martina Flaskamp, Verena Grummel, Achim Berthele, Bernhard Hemmer","doi":"10.1212/NXI.0000000000200322","DOIUrl":"10.1212/NXI.0000000000200322","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) can start as relapsing or progressive. While their clinical features and treatment responses are distinct, it has remained uncertain whether their pathomechanisms differ. A notable age-related effect on MS phenotype and response to immunotherapies is well acknowledged, but the underlying pathophysiologic reasons are yet to be fully elucidated. We aimed to identify disease-specific and age-related proteomic signatures using a comprehensive targeted proteomic analysis.</p><p><strong>Methods: </strong>In our retrospective cohort study, we analyzed the CSF and serum proteome of age-matched individuals with treatment-naïve relapsing-remitting and primary progressive MS, neurologic controls (NC), and individuals with neuroborreliosis using targeted proteomics and validated findings in an independent cohort. Proteomic results were integrated with clinical and laboratory covariates.</p><p><strong>Results: </strong>Among 2,500 proteins, 47 CSF proteins were distinct between individuals with MS (n = 60) and NC (n = 20), with a subset also differing from those with neuroborreliosis (n = 8). We identified MS-associated proteins, including novel candidate biomarkers such as LY9 and JCHAIN, and putative treatment targets, such as SLAMF7, BCMA, and IL5RA, for which drugs are already licensed in other indications. The CSF proteome differences between relapsing and progressive MS were minimal, but major changes were noted in individuals older than 50 years, indicating a shift from MS-associated inflammatory to age-related protein signature. NEFL was the only serum protein that differed between individuals with MS and controls.</p><p><strong>Discussion: </strong>This study unveils a unique CSF proteomic signature in MS, providing new pathophysiologic insights and identifying novel biomarker candidates and potential therapeutic targets. Our findings highlight similar immunologic mechanisms in relapsing and progressive MS and underscore aging's profound effect on the intrathecal immune response. This aligns with the observed lower efficacy of immunotherapies in the elderly, thus emphasizing the necessity for alternative therapeutic approaches in treating individuals with MS beyond the age of 50.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200322"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624802","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":"Missing Full Disclosures.","authors":"","doi":"10.1212/NXI.0000000000200342","DOIUrl":"10.1212/NXI.0000000000200342","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200342"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546603","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":"Complement Activation Profiles Predict Clinical Outcomes in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.","authors":"Javier Villacieros-Álvarez, Jan D Lunemann, Maria Sepulveda, Adrián Valls-Carbó, Alessandro Dinoto, Victoria Fernández, Andreu Vilaseca, Mireia Castillo, Georgina Arrambide, Luca Bollo, Carmen Espejo, Sara Llufriu, Yolanda Blanco, Thais Armangue, Gary Álvarez Bravo, Ana Quiroga-Varela, Lluís Ramió Torrentà, Alvaro Cobo-Calvo, Mar Tintore, Sara Mariotto, Xavier Montalban, Manuel Comabella","doi":"10.1212/NXI.0000000000200340","DOIUrl":"10.1212/NXI.0000000000200340","url":null,"abstract":"<p><strong>Background and objectives: </strong>The role of the complement system in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is not completely understood, and studies exploring its potential utility for diagnosis and prognosis are lacking. We aimed to investigate the value of complement factors (CFs) as diagnostic and prognostic biomarkers in patients with MOGAD.</p><p><strong>Methods: </strong>Multicentric retrospective cohort study including patients with MOGAD, multiple sclerosis (MS) and aquaporin-4 seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD) with available paired serum and CSF samples. A panel of CFs were measured by multiplex ELISA, and the levels were compared between the 3 conditions. Univariable and multivariable analyses were performed to evaluate the association between levels of CFs and relapse and disability outcomes in MOGAD patients.</p><p><strong>Results: </strong>Ninety-four patients (MOGAD, n = 60; MS, n = 18; AQP4-NMOSD, n = 16) were included. Mean (SD) age at sampling was 39.4 (16.7), 40.7 (7.0), and 43.3 (21.0), respectively. Female were predominant, especially in AQP4-NMOSD (88%). Combination of the serum levels of C3a, C4a, and C3a/C3 ratio showed excellent potential to discriminate MOGAD from patients with MS (area under the curve [AUC] [95% CI] 0.95 [0.90-0.99]) and from AQP4-NMOSD (AUC 0.88 [0.76-1.00]). In patients with MOGAD, CSF levels of CFs of the classical/lectin pathway influenced relapse-related outcomes, and lower C4 levels were associated with higher number of relapses during follow-up (incidence rate ratio [95% CI] 0.88 [0.78-0.99]; <i>p</i> = 0.04 in multivariable analysis), and a high C4a/C4 ratio was associated with increased risk of second relapse during the first year (hazard ratio [95% CI] 3.68 [1.26-10.78]; <i>p</i> = 0.02 in multivariable analysis). Time to second relapse was shorter in patients with MOGAD with a high CSF C4a/C4 ratio (log-rank <i>p</i> = 0.01). CSF levels of the membrane attack complex SC5b9 influenced disability-related outcomes, and baseline CSF SC5b9 levels were higher in patients who reached the final Expanded Disability Status Scale (EDSS) ≥ 3.0 (<i>p</i> = 0.002), and elevated SC5b9 levels were associated with increased risk of reaching EDSS ≥ 3.0 (odds ratio [95% CI] 1.79 [1.16-3.67]; <i>p</i> = 0.04 in multivariable analyses).</p><p><strong>Discussion: </strong>Our results suggest that serum and CSF levels of CFs have diagnostic and prognostic value respectively in patients with MOGAD. These findings support the use of complement inhibitors as a therapeutic approach in these patients.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200340"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813867","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":"Obesity Affects Disease Activity and Progression, Cognitive Functioning, and Quality of Life in People With Multiple Sclerosis.","authors":"Jing Wu, Lars Alfredsson, Tomas Olsson, Jan A Hillert, Anna Karin Hedström","doi":"10.1212/NXI.0000000000200334","DOIUrl":"10.1212/NXI.0000000000200334","url":null,"abstract":"<p><strong>Background and objectives: </strong>While obesity is a known risk factor of the development of multiple sclerosis (MS), its impact on MS disease progression remains unclear. We aimed to investigate the influence of body mass index (BMI) on disease activity and progression, cognitive performance, and health-related quality of life in patients with MS.</p><p><strong>Methods: </strong>Patients from an incident population-based case-control study (n = 3,249) were categorized based on BMI status at diagnosis and followed up after diagnosis through the Swedish MS registry. Outcomes included changes in the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale 29, and Symbol Digit Modalities Test. The mean follow-up time was 10.6 years (SD 6.1). Linear mixed models were used to analyze long-term changes while Cox regression models assessed the risk of 24-week confirmed disability worsening, time to reach EDSS score 3 and EDSS score 4, the appearance of new lesions on MRI, patient-reported physical and psychological worsening, and processing speed worsening.</p><p><strong>Results: </strong>Obesity, compared with healthy weight, was associated with a 0.02-point faster annual increase in the EDSS score (β for EDSS score x time 0.02, 95% CI 0.00-0.04). In addition, obesity was linked to a higher risk of reaching EDSS score 3 (HR 1.43, 95% CI 1.17-1.75) and EDSS score 4 (HR 1.40, 95% CI 1.07-1.73) and an increased risk of physical and psychological worsening. New lesions on MRI were more frequent among those with overweight and obesity, compared with those with healthy weight (HR 1.21, 95% CI 1.02-1.44 and HR 1.29, 95% CI 1.03-1.62, respectively). Among those who had not changed BMI group during follow-up, the associations between obesity and unfavorable outcomes became more pronounced, and the HR of cognitive disability worsening was 1.51 (95% CI 1.09-2.09) among those with obesity, compared with nonobese participants.</p><p><strong>Discussion: </strong>In participants with MS, obesity was associated with faster disease progression, poorer health-related quality of life, and more rapid cognitive decline. Both overweight and obesity were associated with higher MRI activity.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200334"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624798","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":"Pediatric MOG-Ab-Associated Encephalitis: Supporting Early Recognition and Treatment.","authors":"","doi":"10.1212/NXI.0000000000200348","DOIUrl":"10.1212/NXI.0000000000200348","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200348"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668554","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}