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"Lupus Myelitis" Revisited: A Retrospective Single-Center Study of Myelitis Associated With Rheumatologic Disease. "狼疮性脊髓炎 "重新审视:风湿病相关骨髓炎的单中心回顾性研究
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-23 DOI: 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.

背景和目的:以前报道的与风湿病相关的脊髓炎患者中可能有未被发现的水通道蛋白-4(AQP4)-IgG血清阳性神经脊髓炎视谱系障碍(NMOSD)或髓鞘少突胶质细胞糖蛋白(MOG)-IgG相关疾病(MOGAD)。我们从临床放射学和血清学的角度对与风湿病相关的脊髓炎患者进行了评估,评估是在可以使用MOG-IgG和更灵敏的AQP4-IgG细胞检测的时代进行的:通过电子病历(EMR)查询,确定了约翰霍普金斯医学院诊断为脊髓病和风湿病合并症的回顾性队列(2018-2023 年)。所有与典型多发性硬化症(MS)无关的脊髓炎患者都被纳入其中,并通过病历审查进行分析:在通过电子病历查询确定的 238 名患者中,有 197 人被排除在外(148 人不符合预先确定的纳入标准,49 人患有典型多发性硬化症),最终有 41 名患者接受了复查。脊髓炎发病时的平均年龄为 44 ± 15 岁,其中 39 人(95%)为女性。风湿病诊断包括 17 例(41.5%)系统性红斑狼疮(SLE)、10 例(24.3%)患有斯约格伦综合征(SS),6 人(15%)患有未分化结缔组织病(UCTD),5 人(12%)合并有系统性红斑狼疮/SS/UCTD 和抗磷脂抗体综合征,1 人(2.4%)患有类风湿性关节炎,1 人(2.4%)患有银屑病关节炎,1 人(2.4%)患有白塞病。20名患者(49%)被诊断为AQP4-IgG血清反应阳性的NMOSD,3名患者(7%)被诊断为MOGAD,18名患者(44%)患有 "双酮体阴性 "脊髓炎。在这18人中,3人被诊断为AQP4-IgG血清反应阴性的NMOSD,1人被诊断为神经-贝赫切特病,14人被诊断为其他(无法分类的)脊髓炎。除去1名神经-贝赫切特病患者,20名AQP4-IgG血清反应阳性患者中有18名(90%)有纵向广泛的脊髓病变,而17名 "双克隆阴性 "患者中有5名(29%;p < 0.001)和3名MOGAD患者中有2名(67%)有纵向广泛的脊髓病变。"双克隆阴性 "患者更常出现脑脊液限制性寡克隆带。大多数患者在最初确诊脊髓炎时接受了急性免疫治疗,中位随访时间为38个月(四分位间范围:9-74个月),至少部分康复:讨论:在与多发性硬化症无关的脊髓炎风湿病队列中,约有半数患者的AQP4-IgG血清反应呈NMOSD阳性,而MOGAD患者所占比例虽小,但具有临床意义。对于AQP4-IgG和MOG-IgG血清均阴性的脊髓炎患者,还需要进一步研究其病因。
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引用次数: 0
Microstructural Damage and Repair in the Spinal Cord of Patients With Early Multiple Sclerosis and Association With Disability at 5 Years. 早期多发性硬化症患者脊髓的微结构损伤和修复以及与 5 年后残疾的关系。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-21 DOI: 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.

背景和目的:多发性硬化症患者脊髓(SC)微结构损伤和修复的动态变化及其临床意义尚待探索。我们的目的是描述多发性硬化症确诊后第一年内患者脊髓微结构损伤和变化的特异性特征,并研究它们与5年后残疾和脊髓萎缩的关系:我们对复发缓解型多发性硬化症患者进行了一项纵向单中心队列研究:首次复发9例脑MRI上的T2病变和/或最初的脊髓炎。根据健康对照组的数据,计算出每位多发性硬化症患者的颈椎 SC MT 比值 z-score 图。微结构损伤指数的计算方法是:在基线时被归类为正常的体素在 1 年后被确定为损伤的体素所占的比例。同样,还计算了修复指数(基线时归类为受损的体素和 1 年后归类为正常的体素)。建立的线性模型包括这些指数和基线与 5 年之间残疾或 SC 横截面面积(CSA)的变化:结果:共纳入 37 名患者和 19 名 HC。我们观察到基线时 SC 微结构损伤程度存在很大差异(0%-58% 的 SC 体素)。我们还观察到一年内损伤和修复指数存在相当大的差异(0%-31% 和 0%-20%),其中 18 名患者以损伤为主,18 名患者以修复为主。微结构损伤指数与5年后的残疾状况扩展量表评分呈正相关(r = 0.504,p = 0.002),与CSA变化呈负相关(r = -0.416,p = 0.02),与基线SC病变体积无关:讨论:早期复发缓解型多发性硬化症患者的SC微结构损伤和修复情况各不相同。微结构损伤的进展与5年后的残疾进展和SC萎缩有关。这些结果表明,SC微结构修复有可能预防多发性硬化症患者的残疾进展。
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引用次数: 0
The Role of Complement Activation in IgM M-Protein-Associated Neuropathies. 补体激活在 IgM M 蛋白相关神经病中的作用
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-21 DOI: 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.

背景和目的:与免疫球蛋白 M(IgM)单克隆抗体病相关的多发性神经病的特征是缓慢进展的、主要是远端感觉运动障碍、感觉共济失调和脱髓鞘的电生理特征。大多数患者的血清中存在针对髓鞘相关糖蛋白(MAG)的 IgM 抗体。神经损伤很可能是由于抗MAG抗体与神经结合,然后补体激活的协同作用造成的。抗MAG抗体与补体激活的相互作用及其与临床特征的关系尚未得到详细研究。我们研究了抗 MAG 抗体滴度、补体激活和 IgM 相关性多发性神经病疾病严重程度之间的相关性:我们使用 101 位 IgM 相关性多发性神经病患者的血清样本,通过 ELISA 方法评估 IgM 抗 MAG 滴度,并使用基于 ELISA 的系统和基于灵长类动物外周神经切片细胞的系统评估抗体介导的补体沉积。我们研究了补体激活与抗 MAG ELISA 滴度和临床特征的相关性:IgM抗MAG滴度从阴性到强阳性不等。基于 ELISA 系统的补体沉积与抗 MAG 抗体滴度显著相关(Spearman rho 0.80; p < 0.0001),尽管抗 MAG 滴度相当的血清样本之间存在很大差异。这种变异性在基于细胞的检测中更大,在 IgM 抗 MAG 阴性患者中也显示出补体沉积,表明在 IgM 相关性多发性神经病患者中存在针对 MAG 以外表位的自身抗体。临床特征与抗MAG滴度或补体激活无关:讨论:抗 MAG 抗体滴度与 ELISA 和基于细胞的系统中的补体激活水平相关。然而,IgM 相关性多发性神经病的临床特征与滴度或补体沉积水平没有关联或仅有微弱关联。补体激活与临床特征之间缺乏明确的相关性,在现阶段并不支持使用补体抑制剂治疗 IgM 相关性多发性神经病。
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引用次数: 0
Proteomics Reveals Age as Major Modifier of Inflammatory CSF Signatures in Multiple Sclerosis. 蛋白质组学揭示年龄是多发性硬化症脑脊液炎症特征的主要修饰因素
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-13 DOI: 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.

背景和目的:多发性硬化症(MS)可分为复发性和进行性两种。虽然它们的临床特征和治疗反应各不相同,但它们的病理机制是否存在差异仍不确定。年龄对多发性硬化症表型和免疫疗法反应的显著影响已得到公认,但其潜在的病理生理学原因尚未完全阐明。我们的目的是通过全面的靶向蛋白质组分析,确定疾病特异性和与年龄相关的蛋白质组特征:在我们的回顾性队列研究中,我们使用靶向蛋白质组学分析了年龄匹配的复发性缓解型和原发性进展型多发性硬化症患者、神经系统对照组(NC)和神经源性多发性硬化症患者的脑脊液和血清蛋白质组,并在一个独立队列中验证了研究结果。蛋白质组学结果与临床和实验室协变量相结合:在2500个蛋白质中,47个CSF蛋白质在多发性硬化症患者(n = 60)和NC患者(n = 20)之间存在差异,其中一个子集也与神经源性疾病患者(n = 8)存在差异。我们确定了 MS 相关蛋白,包括 LY9 和 JCHAIN 等新型候选生物标记物,以及 SLAMF7、BCMA 和 IL5RA 等可能的治疗靶点,这些靶点的药物已在其他适应症中获得许可。复发性和进行性多发性硬化症患者的脑脊液蛋白质组差异很小,但50岁以上患者的脑脊液蛋白质组发生了重大变化,这表明多发性硬化症相关炎症蛋白特征向年龄相关蛋白特征转变。NEFL是唯一在多发性硬化症患者和对照组之间存在差异的血清蛋白:本研究揭示了多发性硬化症独特的脑脊液蛋白质组特征,提供了新的病理生理学见解,并确定了新的候选生物标记物和潜在的治疗靶点。我们的研究结果突显了复发性和进展性多发性硬化症相似的免疫机制,并强调了衰老对鞘内免疫反应的深远影响。这与所观察到的免疫疗法在老年人中疗效较低的情况相吻合,因此强调了在治疗 50 岁以上多发性硬化症患者时采用替代疗法的必要性。
{"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}
引用次数: 0
Missing Full Disclosures. 缺少全面披露。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-30 DOI: 10.1212/NXI.0000000000200342
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引用次数: 0
Obesity Affects Disease Activity and Progression, Cognitive Functioning, and Quality of Life in People With Multiple Sclerosis. 肥胖会影响多发性硬化症患者的病情活动和发展、认知功能和生活质量。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-13 DOI: 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。
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引用次数: 0
Pediatric MOG-Ab-Associated Encephalitis: Supporting Early Recognition and Treatment. 小儿 MOG-Ab 相关脑炎:支持早期识别和治疗。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1212/NXI.0000000000200348
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引用次数: 0
Proteomic Profiling and Pathophysiological Implications in Multiple Sclerosis. 多发性硬化症的蛋白质组分析和病理生理学意义
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-13 DOI: 10.1212/NXI.0000000000200341
Michael R Wilson, Ahmed Abdelhak
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引用次数: 0
Autoantibodies Against Dihydrolipoamide S-Acetyltransferase Are Not Associated With Immune-Mediated Neuropathies. 二氢脂酰胺S-乙酰转移酶自身抗体与免疫相关性神经病无关
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-18 DOI: 10.1212/NXI.0000000000200336
Alexandre Jentzer, Jérémie El-Bechir, Guillaume Taieb, Jérôme J Devaux

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.

研究目的二氢脂酰胺 S-乙酰转移酶(DLAT)是线粒体丙酮酸脱氢酶复合物(PDC-E2)的 E2 组份,最近被认为是慢性炎症性脱髓鞘性多发性神经病(CIDP)的生物标志物。它与 CIDP 的感觉变异型尤其相关。抗线粒体抗体对于诊断原发性胆汁性胆管炎非常重要,但迄今为止,只有两项研究报告了它与 CIDP 的关联。在这里,我们的目的是在一组法国免疫介导的神经病患者中验证这些观察结果:方法:使用酶联免疫吸附试验检测 PDC-E2/DLAT 的阳性率,并使用市售免疫 DOT 和间接免疫荧光法对胃、肾和肝切片进行确认:结果:20 名健康对照组、31 名格林-巴利综合征患者、102 名 CIDP 患者(包括 24 名感觉型 CIDP 患者)、26 名单克隆丙种球蛋白病患者、23 名 Charcot-Marie-Tooth 病患者和 20 名自身免疫性结节病患者均未出现针对 PDC-E2/DLAT 的 IgG:讨论:PDC-E2/DLAT是免疫介导的神经病变的目标抗原。
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引用次数: 0
Spectrum of Clinical and Imaging Features of Children With GFAP Astrocytopathy. GFAP星形细胞病儿童的临床和影像学特征谱。
IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-20 DOI: 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

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.

背景和目的:胶质纤维酸性蛋白(GFAP)抗体(abs)主要见于成人自身免疫介导的一系列疾病。在儿童中,有关自身免疫性 GFAP 星形胶质细胞病的临床和神经放射学特征的数据非常有限。本研究旨在描述GFAP-ab相关疾病患儿的临床和放射学特征:我们回顾性地从 13 个临床中心招募了 2020 年至 2023 年间的儿童,这些儿童(1)血清和/或 CSF 中 GFAP-ab 检测呈阳性;(2)有完整的临床和 MRI 数据集:我们确定并纳入了 15 名儿童(5 名女孩,10 名男孩)。发病年龄中位数为 9.9 岁(2-16 岁)。所有患儿均表现为AE或脑膜炎、急性小脑炎或横贯性脊髓炎。脑脊液多细胞常见(13/15,中位数为245个细胞/μL),15名患儿中有13名(87%)的脑脊液中含有GFAP-抗体,其中8名(53%)患儿的血清中未检测到GFAP-抗体。15名儿童中有15名(100%)核磁共振成像异常:具体病变包括脑桥或尾状核(11/15;73%)、脊髓周围(13/15;87%)和脊髓(6/10;60%)的汇合性病变。12名患儿的预后良好(mRS评分为 "讨论"):GFAP-ab相关疾病的临床表现范围很广,其磁共振成像特征与其他抗体介导的疾病或MOGAD明显不同。我们建议将血清和脑脊液中的 GFAP-abs 检测纳入 AE 患儿的检查中,尤其是在脑干受累的情况下。
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Neurology® Neuroimmunology & Neuroinflammation
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