Pub Date : 2025-01-01Epub Date: 2024-10-23DOI: 10.1212/NXI.0000000000200329
Jonathan D Krett, Angeliki G Filippatou, Paula Barreras, Carlos A Pardo, Allan C Gelber, Elias S Sotirchos
Background and objectives: Previous reports of patients with myelitis associated with rheumatologic disease may have had unrecognized aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD). We clinicoradiologically and serologically characterized patients with myelitis associated with rheumatologic disease evaluated in the era of availability of MOG-IgG and more sensitive AQP4-IgG cell-based assays.
Methods: A retrospective cohort (2018-2023) at Johns Hopkins Medicine with diagnoses of myelopathy and rheumatologic comorbidity was identified by electronic medical record (EMR) query. All patients with myelitis unrelated to typical multiple sclerosis (MS) were included and analyzed by chart review.
Results: Of 238 patients identified by EMR query, 197 were excluded (148 not meeting prespecified inclusion criteria, 49 had typical MS), resulting in 41 patients for review. The mean age at myelitis onset was 44 ± 15 years; 39 (95%) were female. Rheumatologic diagnoses included 17 (41.5%) with systemic lupus erythematosus (SLE), 10 (24.3%) Sjögren syndrome (SS), 6 (15%) undifferentiated connective tissue disease (UCTD), 5 (12%) combinations of SLE/SS/UCTD with antiphospholipid antibody syndrome, 1 (2.4%) rheumatoid arthritis, 1 (2.4%) psoriatic arthritis, and 1 (2.4%) Behçet disease. 20 patients (49%) were diagnosed with AQP4-IgG seropositive NMOSD, 3 (7%) with MOGAD, and 18 (44%) had "double-seronegative" myelitis. Of these 18, 3 were diagnosed with AQP4-IgG seronegative NMOSD, 1 neuro-Behçet disease, and 14 other (unclassifiable) myelitis. Excluding 1 patient with neuro-Behçet disease, 18 (90%) of 20 AQP4-IgG seropositive patients had longitudinally extensive cord lesions compared with 5 (29%; p < 0.001) of 17 "double-seronegative" patients and 2 (67%) of 3 with MOGAD. "Double-seronegative" patients more commonly had CSF-restricted oligoclonal bands. Functional outcomes did not differ by diagnosis, and most patients received acute immunotherapy at the time of initial myelitis diagnosis with at least partial recovery over a median follow-up of 38 (interquartile range: 9-74) months.
Discussion: Approximately half of our rheumatologic disease cohort with myelitis unrelated to MS had AQP4-IgG seropositive NMOSD while MOGAD accounted for a small but clinically relevant proportion of patients. Further research is needed to characterize myelitis etiology in patients who are seronegative for both AQP4-IgG and MOG-IgG.
{"title":"\"Lupus Myelitis\" Revisited: A Retrospective Single-Center Study of Myelitis Associated With Rheumatologic Disease.","authors":"Jonathan D Krett, Angeliki G Filippatou, Paula Barreras, Carlos A Pardo, Allan C Gelber, Elias S Sotirchos","doi":"10.1212/NXI.0000000000200329","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200329","url":null,"abstract":"<p><strong>Background and objectives: </strong>Previous reports of patients with myelitis associated with rheumatologic disease may have had unrecognized aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD). We clinicoradiologically and serologically characterized patients with myelitis associated with rheumatologic disease evaluated in the era of availability of MOG-IgG and more sensitive AQP4-IgG cell-based assays.</p><p><strong>Methods: </strong>A retrospective cohort (2018-2023) at Johns Hopkins Medicine with diagnoses of myelopathy and rheumatologic comorbidity was identified by electronic medical record (EMR) query. All patients with myelitis unrelated to typical multiple sclerosis (MS) were included and analyzed by chart review.</p><p><strong>Results: </strong>Of 238 patients identified by EMR query, 197 were excluded (148 not meeting prespecified inclusion criteria, 49 had typical MS), resulting in 41 patients for review. The mean age at myelitis onset was 44 ± 15 years; 39 (95%) were female. Rheumatologic diagnoses included 17 (41.5%) with systemic lupus erythematosus (SLE), 10 (24.3%) Sjögren syndrome (SS), 6 (15%) undifferentiated connective tissue disease (UCTD), 5 (12%) combinations of SLE/SS/UCTD with antiphospholipid antibody syndrome, 1 (2.4%) rheumatoid arthritis, 1 (2.4%) psoriatic arthritis, and 1 (2.4%) Behçet disease. 20 patients (49%) were diagnosed with AQP4-IgG seropositive NMOSD, 3 (7%) with MOGAD, and 18 (44%) had \"double-seronegative\" myelitis. Of these 18, 3 were diagnosed with AQP4-IgG seronegative NMOSD, 1 neuro-Behçet disease, and 14 other (unclassifiable) myelitis. Excluding 1 patient with neuro-Behçet disease, 18 (90%) of 20 AQP4-IgG seropositive patients had longitudinally extensive cord lesions compared with 5 (29%; <i>p</i> < 0.001) of 17 \"double-seronegative\" patients and 2 (67%) of 3 with MOGAD. \"Double-seronegative\" patients more commonly had CSF-restricted oligoclonal bands. Functional outcomes did not differ by diagnosis, and most patients received acute immunotherapy at the time of initial myelitis diagnosis with at least partial recovery over a median follow-up of 38 (interquartile range: 9-74) months.</p><p><strong>Discussion: </strong>Approximately half of our rheumatologic disease cohort with myelitis unrelated to MS had AQP4-IgG seropositive NMOSD while MOGAD accounted for a small but clinically relevant proportion of patients. Further research is needed to characterize myelitis etiology in patients who are seronegative for both AQP4-IgG and MOG-IgG.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200329"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504995","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}
Pub Date : 2025-01-01Epub Date: 2024-11-21DOI: 10.1212/NXI.0000000000200333
Malo Gaubert, Benoit Combès, Elise Bannier, Arthur Masson, Vivien Caron, Gaëlle Baudron, Jean-Christophe Ferré, Laure Michel, Emmanuelle Le Page, Bruno Stankoff, Gilles Edan, Benedetta Bodini, Anne Kerbrat
Background and objectives: The dynamics of microstructural spinal cord (SC) damage and repair in people with multiple sclerosis (pwMS) and their clinical relevance have yet to be explored. We set out to describe patient-specific profiles of microstructural SC damage and change during the first year after MS diagnosis and to investigate their associations with disability and SC atrophy at 5 years.
Methods: We performed a longitudinal monocentric cohort study among patients with relapsing-remitting MS: first relapse <1 year, no relapse <1 month, and high initial severity on MRI (>9 T2 lesions on brain MRI and/or initial myelitis). pwMS and age-matched healthy controls (HCs) underwent cervical SC magnetization transfer (MT) imaging at baseline and at 1 year for pwMS. Based on HC data, SC MT ratio z-score maps were computed for each person with MS. An index of microstructural damage was calculated as the proportion of voxels classified as normal at baseline and identified as damaged after 1 year. Similarly, an index of repair was also calculated (voxels classified as damaged at baseline and as normal after 1 year). Linear models including these indices and disability or SC cross-sectional area (CSA) change between baseline and 5 years were implemented.
Results: Thirty-seven patients and 19 HCs were included. We observed considerable variability in the extent of microstructural SC damage at baseline (0%-58% of SC voxels). We also observed considerable variability in damage and repair indices over 1 year (0%-31% and 0%-20%), with 18 patients showing predominance of damage and 18 predominance of repair. The index of microstructural damage was associated positively with the Expanded Disability Status Scale score (r = 0.504, p = 0.002) and negatively with CSA change (r = -0.416, p = 0.02) at 5 years, independent of baseline SC lesion volume.
Discussion: People with early relapsing-remitting MS exhibited heterogeneous profiles of microstructural SC damage and repair. Progression of microstructural damage was associated with disability progression and SC atrophy 5 years later. These results indicate a potential for microstructural repair in the SC to prevent disability progression in pwMS.
{"title":"Microstructural Damage and Repair in the Spinal Cord of Patients With Early Multiple Sclerosis and Association With Disability at 5 Years.","authors":"Malo Gaubert, Benoit Combès, Elise Bannier, Arthur Masson, Vivien Caron, Gaëlle Baudron, Jean-Christophe Ferré, Laure Michel, Emmanuelle Le Page, Bruno Stankoff, Gilles Edan, Benedetta Bodini, Anne Kerbrat","doi":"10.1212/NXI.0000000000200333","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200333","url":null,"abstract":"<p><strong>Background and objectives: </strong>The dynamics of microstructural spinal cord (SC) damage and repair in people with multiple sclerosis (pwMS) and their clinical relevance have yet to be explored. We set out to describe patient-specific profiles of microstructural SC damage and change during the first year after MS diagnosis and to investigate their associations with disability and SC atrophy at 5 years.</p><p><strong>Methods: </strong>We performed a longitudinal monocentric cohort study among patients with relapsing-remitting MS: first relapse <1 year, no relapse <1 month, and high initial severity on MRI (>9 T2 lesions on brain MRI and/or initial myelitis). pwMS and age-matched healthy controls (HCs) underwent cervical SC magnetization transfer (MT) imaging at baseline and at 1 year for pwMS. Based on HC data, SC MT ratio <i>z</i>-score maps were computed for each person with MS. An index of microstructural damage was calculated as the proportion of voxels classified as normal at baseline and identified as damaged after 1 year. Similarly, an index of repair was also calculated (voxels classified as damaged at baseline and as normal after 1 year). Linear models including these indices and disability or SC cross-sectional area (CSA) change between baseline and 5 years were implemented.</p><p><strong>Results: </strong>Thirty-seven patients and 19 HCs were included. We observed considerable variability in the extent of microstructural SC damage at baseline (0%-58% of SC voxels). We also observed considerable variability in damage and repair indices over 1 year (0%-31% and 0%-20%), with 18 patients showing predominance of damage and 18 predominance of repair. The index of microstructural damage was associated positively with the Expanded Disability Status Scale score (<i>r</i> = 0.504, <i>p</i> = 0.002) and negatively with CSA change (<i>r</i> = -0.416, <i>p</i> = 0.02) at 5 years, independent of baseline SC lesion volume.</p><p><strong>Discussion: </strong>People with early relapsing-remitting MS exhibited heterogeneous profiles of microstructural SC damage and repair. Progression of microstructural damage was associated with disability progression and SC atrophy 5 years later. These results indicate a potential for microstructural repair in the SC to prevent disability progression in pwMS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200333"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687545","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}
Pub Date : 2025-01-01Epub Date: 2024-11-21DOI: 10.1212/NXI.0000000000200339
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
Background and objectives: 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.
Methods: 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.
Results: 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; p < 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.
Discussion: 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.
{"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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-11-13DOI: 10.1212/NXI.0000000000200322
Friederike Held, Christine Makarov, Christiane Gasperi, Martina Flaskamp, Verena Grummel, Achim Berthele, Bernhard Hemmer
Background and objectives: 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.
Methods: 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.
Results: 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.
Discussion: 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.
{"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}
Pub Date : 2025-01-01Epub Date: 2024-11-13DOI: 10.1212/NXI.0000000000200334
Jing Wu, Lars Alfredsson, Tomas Olsson, Jan A Hillert, Anna Karin Hedström
Background and objectives: 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.
Methods: 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.
Results: 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.
Discussion: 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.
背景和目的:虽然肥胖是多发性硬化症(MS)发病的一个已知风险因素,但其对 MS 疾病进展的影响仍不清楚。我们旨在研究体重指数(BMI)对多发性硬化症患者的疾病活动和进展、认知能力以及与健康相关的生活质量的影响:方法:根据诊断时的体重指数状况对一项基于人群的病例对照研究中的患者(n = 3249)进行分类,并在诊断后通过瑞典多发性硬化症登记处进行随访。结果包括扩展残疾状态量表(EDSS)、多发性硬化影响量表29和符号数字模型测试的变化。平均随访时间为 10.6 年(标清 6.1)。线性混合模型用于分析长期变化,而 Cox 回归模型则用于评估 24 周证实的残疾恶化风险、达到 EDSS 3 分和 EDSS 4 分的时间、核磁共振成像出现新病灶、患者报告的身体和心理恶化以及处理速度恶化:与健康体重相比,肥胖与EDSS评分每年增加0.02分有关(EDSS评分×时间的β值为0.02,95% CI为0.00-0.04)。此外,肥胖与达到 EDSS 3 级(HR 1.43,95% CI 1.17-1.75)和 EDSS 4 级(HR 1.40,95% CI 1.07-1.73)的风险较高以及身体和心理恶化的风险增加有关。与体重健康者相比,超重和肥胖者在核磁共振成像上出现新病灶的频率更高(HR 分别为 1.21,95% CI 1.02-1.44 和 HR 1.29,95% CI 1.03-1.62)。在随访期间体重指数未发生变化的人群中,肥胖与不利结果之间的关联更加明显,与非肥胖参与者相比,肥胖者认知障碍恶化的HR为1.51(95% CI 1.09-2.09):讨论:在多发性硬化症患者中,肥胖与疾病进展更快、健康相关生活质量更差和认知能力下降更快有关。超重和肥胖都与较高的磁共振成像活动有关。
{"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}
Pub Date : 2025-01-01Epub Date: 2024-11-13DOI: 10.1212/NXI.0000000000200341
Michael R Wilson, Ahmed Abdelhak
{"title":"Proteomic Profiling and Pathophysiological Implications in Multiple Sclerosis.","authors":"Michael R Wilson, Ahmed Abdelhak","doi":"10.1212/NXI.0000000000200341","DOIUrl":"10.1212/NXI.0000000000200341","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200341"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624800","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}
Objectives: Dihydrolipoamide S-acetyltransferase (DLAT), the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), has recently been suggested to be a biomarker of chronic inflammatory demyelinating polyneuropathy (CIDP). It was particularly associated with sensory variants of CIDP. Antimitochondrial antibodies are important for the diagnosis of primary biliary cholangitis, but insofar, only 2 studies have reported an association with CIDP. Here, we aimed to validate these observations in a cohort of French patients with immune-mediated neuropathy.
Methods: The positivity against PDC-E2/DLAT was examined using ELISA and confirmed using commercially available immuno-DOT and by indirect immunofluorescence on stomach, kidney, and liver sections.
Results: None of the 20 healthy controls, 31 patients with Guillain-Barré syndrome, 102 patients with CIDP (including 24 patients with sensory CIDP), 26 patients with monoclonal gammopathy, 23 patients with Charcot-Marie-Tooth disease, or 20 patients with autoimmune nodopathy showed IgG against PDC-E2/DLAT.
Discussion: PDC-E2/DLAT is accurately a target antigen in immune-mediated neuropathies.
{"title":"Autoantibodies Against Dihydrolipoamide S-Acetyltransferase Are Not Associated With Immune-Mediated Neuropathies.","authors":"Alexandre Jentzer, Jérémie El-Bechir, Guillaume Taieb, Jérôme J Devaux","doi":"10.1212/NXI.0000000000200336","DOIUrl":"10.1212/NXI.0000000000200336","url":null,"abstract":"<p><strong>Objectives: </strong>Dihydrolipoamide S-acetyltransferase (DLAT), the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), has recently been suggested to be a biomarker of chronic inflammatory demyelinating polyneuropathy (CIDP). It was particularly associated with sensory variants of CIDP. Antimitochondrial antibodies are important for the diagnosis of primary biliary cholangitis, but insofar, only 2 studies have reported an association with CIDP. Here, we aimed to validate these observations in a cohort of French patients with immune-mediated neuropathy.</p><p><strong>Methods: </strong>The positivity against PDC-E2/DLAT was examined using ELISA and confirmed using commercially available immuno-DOT and by indirect immunofluorescence on stomach, kidney, and liver sections.</p><p><strong>Results: </strong>None of the 20 healthy controls, 31 patients with Guillain-Barré syndrome, 102 patients with CIDP (including 24 patients with sensory CIDP), 26 patients with monoclonal gammopathy, 23 patients with Charcot-Marie-Tooth disease, or 20 patients with autoimmune nodopathy showed IgG against PDC-E2/DLAT.</p><p><strong>Discussion: </strong>PDC-E2/DLAT is accurately a target antigen in immune-mediated neuropathies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200336"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668551","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}
Pub Date : 2025-01-01Epub Date: 2024-11-20DOI: 10.1212/NXI.0000000000200327
Simon Sommer, Andreas Panzer, Annikki Bertolini, Robert Cleaveland, Vivek Jain, Tugba Kapanci, Ute Derichs, Tobias Geis, Axel Neu, Christa Löhr-Nilles, Rahel Aeschimann-Huhn, Marina Flotats-Bastardas, Kumaran Deiva, Thais Armangue, Gemma Olivé-Cirera, Sudheeran Kannoth, Anne Koy, Hadas Meirson, Aviva Fattal-Valevski, Esther Ganelin-Cohen, Heike Losch, Annacarin Horne, Ronny Wickström, Justina Dargvainiene, Frank Leypoldt, Kevin Rostasy
Background and objectives: Glial fibrillary acidic protein (GFAP) antibodies (abs) have been described primarily in adults with a spectrum of autoimmune-mediated diseases. In children, data on clinical and neuroradiologic features of children with autoimmune GFAP astrocytopathy are limited. The aim of this study was to describe the clinical and radiologic features in children with GFAP-ab-associated diseases.
Methods: We retrospectively recruited children from 13 clinical centers between 2020 and 2023 who (1) tested positive for GFAP-ab in serum and/or CSF and (2) of whom a complete clinical and MRI data set was available.
Results: We identified and included 15 children (5 girls, 10 boys). The median age at onset was 9.9 years (range: 2-16 years). All children presented with features of AE or meningitis, acute cerebellitis, or transverse myelitis. CSF pleocytosis was common (13/15, median 245 cells/μL), and 13 (87%) of 15 harbored GFAP-abs in their CSF, 8 (53%) of whom did not have detectable GFAP-abs in their serum. MRI was abnormal in 15 (100%) of 15 children: Specific patterns included confluent lesions in the pons or caudate nucleus (11/15; 73%), peri-aqueductal regions (13/15; 87%), and spinal cord (6/10; 60%). 12 children had a favorable outcome (mRS score of = 1). Two patients died in the acute phase or during follow-up.
Discussion: GFAP-ab-associated diseases encompass a wide spectrum of clinical presentation associated with a particular set of MRI features clearly distinct to other antibody-mediated diseases or MOGAD. We recommend that testing for GFAP-abs in serum and CSF be included in the workup of children with AE, particularly if brainstem involvement occurs.
{"title":"Spectrum of Clinical and Imaging Features of Children With GFAP Astrocytopathy.","authors":"Simon Sommer, Andreas Panzer, Annikki Bertolini, Robert Cleaveland, Vivek Jain, Tugba Kapanci, Ute Derichs, Tobias Geis, Axel Neu, Christa Löhr-Nilles, Rahel Aeschimann-Huhn, Marina Flotats-Bastardas, Kumaran Deiva, Thais Armangue, Gemma Olivé-Cirera, Sudheeran Kannoth, Anne Koy, Hadas Meirson, Aviva Fattal-Valevski, Esther Ganelin-Cohen, Heike Losch, Annacarin Horne, Ronny Wickström, Justina Dargvainiene, Frank Leypoldt, Kevin Rostasy","doi":"10.1212/NXI.0000000000200327","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200327","url":null,"abstract":"<p><strong>Background and objectives: </strong>Glial fibrillary acidic protein (GFAP) antibodies (abs) have been described primarily in adults with a spectrum of autoimmune-mediated diseases. In children, data on clinical and neuroradiologic features of children with autoimmune GFAP astrocytopathy are limited. The aim of this study was to describe the clinical and radiologic features in children with GFAP-ab-associated diseases.</p><p><strong>Methods: </strong>We retrospectively recruited children from 13 clinical centers between 2020 and 2023 who (1) tested positive for GFAP-ab in serum and/or CSF and (2) of whom a complete clinical and MRI data set was available.</p><p><strong>Results: </strong>We identified and included 15 children (5 girls, 10 boys). The median age at onset was 9.9 years (range: 2-16 years). All children presented with features of AE or meningitis, acute cerebellitis, or transverse myelitis. CSF pleocytosis was common (13/15, median 245 cells/μL), and 13 (87%) of 15 harbored GFAP-abs in their CSF, 8 (53%) of whom did not have detectable GFAP-abs in their serum. MRI was abnormal in 15 (100%) of 15 children: Specific patterns included confluent lesions in the pons or caudate nucleus (11/15; 73%), peri-aqueductal regions (13/15; 87%), and spinal cord (6/10; 60%). 12 children had a favorable outcome (mRS score of </= 1). Two patients died in the acute phase or during follow-up.</p><p><strong>Discussion: </strong>GFAP-ab-associated diseases encompass a wide spectrum of clinical presentation associated with a particular set of MRI features clearly distinct to other antibody-mediated diseases or MOGAD. We recommend that testing for GFAP-abs in serum and CSF be included in the workup of children with AE, particularly if brainstem involvement occurs.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200327"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682163","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}