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Influence of FCGR2A (rs1801274) and FCGR3A (rs396991) polymorphisms on natalizumab response on multiple sclerosis FCGR2A (rs1801274)和FCGR3A (rs396991)多态性对纳他珠单抗治疗多发性硬化疗效的影响
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-06 DOI: 10.1016/j.msard.2025.106912
Rafaella de C Cardoso , Matheus D de Matos , Larissa A Duarte , Bárbara D Guimenes , Giovanni K Pavani , Elisa Gouvea Gutman , Helena França Alcaraz Ferreira , Valéria Coelho Santa Rita Pereira , Vinícius B Domingues , João G D Farinhas , Kamilla A Fernandez , Felipe R Schmidt , Guilherme C Montes , Soniza V Alves-Leon , Fabrícia L Fontes-Dantas

Background

Genetic variants in Fc gamma receptors (FcγRs) have been implicated in the therapeutic failure of monoclonal antibodies. Natalizumab (NTZ), a monoclonal antibody widely used in the treatment of multiple sclerosis (MS), prevents immune cell migration into the central nervous system, thereby reducing inflammation and demyelination. Despite its high efficacy, a subset of patients does not respond to NTZ, with single nucleotide polymorphisms (SNPs) in FcγRs emerging as potential pharmacogenetic biomarkers.

Methods

In this study, we evaluated patients with relapsing-remitting MS diagnosed according to the McDonald criteria and treated with NTZ. Genotyping of FCGR2A (rs1801274) and FCGR3A (rs396991) was performed using TaqMan-PCR allelic discrimination. Cytokine levels were quantified using x-MAP technology.

Results

Of the 116 patients analyzed, 13 were classified as non-responders. Logistic regression adjusted for sex and age revealed that the FCGR2A AG genotype was significantly associated with a reduced risk of therapeutic failure (OR = 0.044; p = 0.014), while for FCGR3A, the AC genotype was also associated with a protective effect (OR = 0.077; p = 0.025). No significant effects of age or sex were observed in either model. Receiver Operating Characteristic (ROC) analysis showed that the FCGR2A rs1801274 GG genotype had weak predictive value for therapeutic failure, whereas FCGR3A rs396991 AA had modest discriminatory power. Additionally, these genotypes were associated with reduced levels of specific pro-inflammatory cytokines.

Conclusion

The FCGR2A AG and FCGR3A AC genotypes were associated with a lower risk of NTZ treatment failure, suggesting that FcγR polymorphisms may serve as biomarkers for therapeutic response in MS.
Fcγ受体(Fcγ rs)的遗传变异与单克隆抗体的治疗失败有关。Natalizumab (NTZ)是一种广泛用于多发性硬化症(MS)治疗的单克隆抗体,它可以阻止免疫细胞迁移到中枢神经系统,从而减少炎症和脱髓鞘。尽管NTZ疗效很高,但仍有一部分患者对NTZ没有反应,FcγRs中的单核苷酸多态性(snp)正成为潜在的药物遗传生物标志物。方法在本研究中,我们评估了根据McDonald标准诊断并接受NTZ治疗的复发缓解型MS患者。采用TaqMan-PCR等位基因鉴别技术对FCGR2A (rs1801274)和FCGR3A (rs396991)进行基因分型。使用x-MAP技术定量细胞因子水平。结果116例患者中,13例无反应。经性别和年龄调整后的Logistic回归显示,FCGR2A AG基因型与治疗失败风险降低显著相关(OR = 0.044; p = 0.014),而FCGR3A的AC基因型也与保护作用相关(OR = 0.077; p = 0.025)。在两种模型中均未观察到年龄或性别的显著影响。受试者工作特征(Receiver Operating Characteristic, ROC)分析显示,FCGR2A rs1801274 GG基因型对治疗失败的预测价值较弱,而FCGR3A rs396991 AA基因型对治疗失败的预测能力中等。此外,这些基因型与特异性促炎细胞因子水平降低有关。结论FCGR2A AG和FCGR3A AC基因型与较低的NTZ治疗失败风险相关,提示FcγR多态性可能是MS治疗反应的生物标志物。
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引用次数: 0
Employment status in people with multiple sclerosis: Profile, dynamic changes and determinants over time 多发性硬化症患者的就业状况:概况、动态变化和决定因素
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-06 DOI: 10.1016/j.msard.2025.106911
Carolyn A Young , David Rog , Radu Tanasescu , Basil Sharrack , Seema Kalra , Roger Mills , Alan Tennant , TONiC study group

Aim

In a large UK multiple sclerosis (MS) cohort, we examined work status and how it changed over follow-up, identifying demographic, clinical and other factors associated with these transitions.

Methods

Participants of the Trajectories of Outcome in Neurological Conditions-MS study completed questionnaires on demographics, work instability, disability, fatigue, mood and quality of life at baseline and follow-up to explore work disability (stopping), discontinuity (retiring early) and drift (downgrading). Regression and Classification and Regression Tree (CART) analysis examined predictive factors.

Results

Among 1035 subjects aged 20–60 years in paid work at baseline with mean follow-up 22.7 months, net annual increases were 4.0 % for work disability, 3.1 % for discontinuity and 1.8 % for drift. Risk of work disability was increased by age, work instability and for part-time work, female sex. The risk of drift was 3.9 times higher for females; work instability increased drift for all subjects. Reverse work disability and drift were also observed, i.e. returning to employment or upgrading work. Discontinuity was influenced by secondary progressive subtype, impaired cognition, more comorbidities, and reduced by disease modifying therapy use. CART analysis showed that risk of job loss could be predicted using age, EDSS and sickness absence information, and of medical retirement using the above three factors and MS subtype.

Conclusions

Screening for people with MS at greater risk of losing employment could be readily done in clinical practice, facilitating further discussion with the multidisciplinary team and referral to support services as appropriate.
在英国一个大型多发性硬化症(MS)队列中,我们检查了工作状态及其在随访中的变化,确定了与这些转变相关的人口统计学、临床和其他因素。方法神经系统疾病结局轨迹- ms研究的参与者在基线时完成人口统计、工作不稳定性、残疾、疲劳、情绪和生活质量的问卷调查,并随访调查工作残疾(停止)、不连续(提前退休)和漂移(降级)。回归和分类回归树(CART)分析检验了预测因素。结果1035名年龄在20-60岁的有薪工作对象,平均随访22.7个月,工作残疾的年净增长率为4.0%,工作中断的年净增长率为3.1%,工作漂移的年净增长率为1.8%。因年龄、工作不稳定以及兼职工作的女性而导致工作残疾的风险增加。女性的漂移风险是男性的3.9倍;工作不稳定增加了所有受试者的漂移。还观察到反向工作残疾和漂移,即重返就业或升级工作。不连续性受继发性进展亚型、认知受损、更多合并症的影响,并因使用疾病修饰疗法而减少。CART分析显示,年龄、EDSS和缺勤信息可以预测失业风险,医疗退休风险可以利用以上三个因素和MS亚型进行预测。结论在临床实践中,对失业风险较大的多发性硬化症患者进行筛查是很容易的,可以促进与多学科团队的进一步讨论,并酌情转介到支持服务机构。
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引用次数: 0
Investigating the causality and pathogenesis of multiple sclerosis in breast cancer via bioinformatics analysis 通过生物信息学分析探讨乳腺癌多发性硬化的因果关系和发病机制
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-05 DOI: 10.1016/j.msard.2025.106898
Yanfeng Wang , Haitao Ji , Huxia Wang , Zhangjun Song

Background

Breast cancer (BC) is one of the most prevalent cancers among women in the worldwide. Multiple sclerosis (MS) plays an important role not only in pathogenesis but also in the antitumour response. Therefore, we investigated the causal relationship and pathogenesis between BC and MS via integrated Mendelian randomization (MR) and bioinformatics analysis.

Methods

We performed MR analyses to investigate the potential causal relationship between BC and MS via the IEU database. A comprehensive strategy among least absolute shrinkage and selection operator regression, support vector machine, univariate and multivariate Cox regression analysis, time ROC regression, and survival analysis was adopted to construct and validate the prognostic model. Immune cell infiltration and chemotherapy sensitivity were used to evaluate the prognostic model.

Results

MR analysis revealed that MS was causally associated with the incidence risk of BC. Patients in the high-risk group were related to worse survival, immune infiltration, and increased sensitivity to paclitaxel, methotrexate, doxorubicin, gemcitabine, and sunitinib. Furthermore, KLRC1 was expressed at low levels in BC tissues and correlated with poor prognosis and immune cell infiltration.

Conclusions

Our findings suggest a potential causal association between MS and BC. KLRC1 is a robust and promising biomarker for predicting the prognosis of patients with MS and BC.
乳腺癌(breast cancer, BC)是世界范围内最常见的女性癌症之一。多发性硬化症(MS)不仅在发病机制中起重要作用,而且在抗肿瘤反应中起重要作用。因此,我们通过综合孟德尔随机化(MR)和生物信息学分析来研究BC和MS之间的因果关系和发病机制。方法通过IEU数据库进行MR分析,探讨BC与MS之间的潜在因果关系。采用最小绝对收缩和选择算子回归、支持向量机、单变量和多变量Cox回归分析、时间ROC回归、生存分析等综合策略构建和验证预后模型。采用免疫细胞浸润和化疗敏感性评价预后模型。结果smr分析显示MS与BC发病风险呈正相关。高危组患者生存率较差,免疫浸润,对紫杉醇、甲氨蝶呤、阿霉素、吉西他滨和舒尼替尼的敏感性增加。此外,KLRC1在BC组织中低水平表达,与预后不良和免疫细胞浸润相关。结论研究结果提示MS与BC之间存在潜在的因果关系。KLRC1是预测多发性硬化症和BC患者预后的强大且有前景的生物标志物。
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引用次数: 0
Nutritional status and taste impairment in adult patients with multiple sclerosis and dysphagia. A pilot study 成人多发性硬化症和吞咽困难患者的营养状况和味觉障碍。一项初步研究。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-05 DOI: 10.1016/j.msard.2025.106909
N.V. Franchina-Vergel , J. Molina-López , E. Planells

Introduction

Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune, and demyelinating disease of the central nervous system. Disease progression increases dysphagia, raising risks of malnutrition, dehydration, and respiratory complications, directly impacting nutrition management.

Objectives

(I) To analyse the anthropometric profiles and body composition of adults with MS; (II) to determine the prevalence of dysphagia according to disease duration; (III) to examine dietary intake and eating habits; (IV) to identify potential alterations in taste perception.

Methodology

A descriptive-analytical study included 14 MS patients (7 women, 7 men; median age 46.9 ± 13.5 years) from Granada. Anthropometry and body composition were assessed using bioelectrical impedance analysis (TANITA). Dysphagia risk was evaluated using the Yale Swallow protocol, TWST, and TOMASS protocols, and basic taste perception was examined. Dietary intake was recorded over 3-day (24-hour recall) and food frequency questionnaire (FFQ); data were processed with Dietowin® software.

Results

A total of 66.7 % presented with overweight or obesity (median BMI 28.1 kg/m²). The prevalence of mixed dysphagia was 71.4 %, with no significant differences according to disease duration, except for mixed dysphagia (p = 0.018). Over 70 % of patients had insufficient intake of energy, fibre, and micronutrients (calcium, iron, potassium, magnesium). Taste alterations were observed in 57.1 % of patients, particularly in the perception of sweetness (78.6 %).

Conclusions

Patients with MS and dysphagia exhibit a high prevalence of overweight, inadequate dietary intake, and taste alterations. These findings highlight the need for comprehensive, multidisciplinary interventions involving speech therapy and nutritional support, to optimise nutritional status and quality of life.
简介:多发性硬化症(MS)是一种慢性、炎症性、自身免疫性和脱髓鞘性中枢神经系统疾病。疾病进展会增加吞咽困难,增加营养不良、脱水和呼吸系统并发症的风险,直接影响营养管理。目的:(1)分析成人多发性硬化症患者的人体测量特征和身体组成;(二)根据病程确定吞咽困难的发生率;(三)检查膳食摄入量和饮食习惯;(四)识别味觉感知的潜在变化。方法:一项描述性分析研究包括来自格拉纳达的14例MS患者(7女7男,中位年龄46.9±13.5岁)。采用生物电阻抗分析(TANITA)评估人体测量和身体成分。使用耶鲁吞咽法、TWST法和TOMASS法评估吞咽困难风险,并检查基本味觉。记录3天内的膳食摄入量(24小时回忆)和食物频率问卷(FFQ);数据用Dietowin®软件处理。结果:66.7%的患者表现为超重或肥胖(中位BMI为28.1 kg/m²)。混合性吞咽困难的患病率为71.4%,除混合性吞咽困难外,不同病程间差异无统计学意义(p = 0.018)。超过70%的患者能量、纤维和微量营养素(钙、铁、钾、镁)摄入不足。在57.1%的患者中观察到味觉改变,特别是对甜味的感知(78.6%)。结论:多发性硬化症和吞咽困难患者表现出超重、饮食摄入不足和味觉改变的高患病率。这些发现强调需要综合的、多学科的干预措施,包括语言治疗和营养支持,以优化营养状况和生活质量。
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引用次数: 0
Towards practical management of the Marburg variant of multiple sclerosis 马尔堡变异体多发性硬化症的实际管理
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-05 DOI: 10.1016/j.msard.2025.106908
Mašan Sredanović , Branka Bunoza , Ivan Lehman , Maja Jurin , Nataša Nenadić Baranašić , Gabriela Plosnić , Petra Grđan Stevanović , Miroslav Weiss , Ivan Jovanović , Ivana Brnadić , Katarina Tešija , Ernest Bilić , Daniel Turudić , Magdalena Krbot Skorić , Mario Habek

Objectives

The Marburg variant of multiple sclerosis (MvMS) is a rare, rapidly progressive demyelinating disorder characterized by an acute, monophasic onset with early, severe disability or death within weeks to months. In this systematic review, we aimed to: (I) describe patient characteristics and therapies used; (II) categorize outcomes; and (III) synthesize therapy–outcome relationships to guide practical management.

Methods

We performed a PRISMA-guided systematic review of published MvMS cases reporting treatment and outcomes, and present an illustrative pediatric case from our center.

Results

Across databases, 144 records were identified (PubMed 34; Scopus 74; WoS 36), out of which 22 articles met inclusion criteria. Among the 23 patients synthesized (22 published cases plus our pediatric case), median age was 32 years (range 14–63), with a female predominance (78 %). Nearly all patients received high-dose corticosteroids (22/23; 96 %). Additional therapies were common and variably combined: plasma exchange (14/23; 61 %), IVIg (8/23; 35 %), cyclophosphamide (10/23; 43 %), mitoxantrone (7/23; 30 %), any cytotoxic (cyclophosphamide and/or mitoxantrone) (15/23; 65 %), B-cell–depleting therapy (rituximab/ocrelizumab) (4/23; 17 %), alemtuzumab (1/23; 4 %), and natalizumab (1/23; 4 %); doses were inconsistently reported across studies, and order/timing of therapies varied widely. Overall outcomes were death in 6/23 (26 %), stable deficit in 4/23 (17 %), improvement in 9/23 (39 %), and near-complete recovery in 4/23 (17 %). We also propose a set of pragmatic, evidence-based diagnostic criteria. These criteria classify cases as Definite, Probable, or Possible Marburg variant MS based on fulminant clinical course, characteristic MRI patterns, CSF/serologic exclusion of mimics, and—when available—pathological confirmation.

Conclusion

While no single regimen was uniformly effective, our three-group analysis suggests a stepwise strategy: steroids ± plasma exchange alone were often insufficient; adding a cytotoxic agent with dual B- and T-cell activity (cyclophosphamide or mitoxantrone) was associated with more frequent improvement; and the highest proportion of improvement occurred when dual-arm cytotoxic therapy was combined with a B-cell–directed/lymphocyte-depleting agent.
马尔堡变异型多发性硬化症(MvMS)是一种罕见的、快速进展的脱髓鞘疾病,其特征是急性、单阶段发病,早期、严重残疾或在数周至数月内死亡。在本系统综述中,我们的目的是:(1)描述患者特征和使用的治疗方法;(II)对结果进行分类;(3)综合治疗-结果关系,指导实际管理。方法:我们对已发表的MvMS病例进行了prisma引导的系统回顾,报告了治疗和结果,并提出了我们中心的一例说明性儿科病例。结果共检索到144篇文献(PubMed 34; Scopus 74; WoS 36),其中22篇文献符合纳入标准。在合成的23例患者中(22例已发表病例加上我们的儿科病例),中位年龄为32岁(范围14-63岁),以女性为主(78%)。几乎所有患者都接受了大剂量皮质类固醇治疗(22/23;96%)。其他治疗是常见的和不同的联合治疗:血浆置换(14/23;61%)、IVIg(8/23; 35%)、环磷酰胺(10/23;43%)、米托蒽醌(7/23;30%)、任何细胞毒性(环磷酰胺和/或米托蒽醌)(15/23;65%)、b细胞消耗治疗(利妥昔单抗/奥crelizumab)(4/23; 17%)、阿仑单抗(1/23;4%)和那他珠单抗(1/23;4%);各研究报告的剂量不一致,治疗顺序/时间差异很大。总体结果为6/23患者死亡(26%),4/23患者病情稳定恶化(17%),9/23患者病情改善(39%),4/23患者近乎完全康复(17%)。我们还提出了一套实用的、基于证据的诊断标准。这些标准根据暴发性临床病程、特征性MRI模式、脑脊液/血清学排除模拟物以及病理证实,将病例分为明确、可能或可能马尔堡变异型MS。结论:虽然没有单一的治疗方案是一致有效的,但我们的三组分析建议采用渐进式策略:单独使用类固醇+血浆置换往往不够;添加具有双重B细胞和t细胞活性的细胞毒性药物(环磷酰胺或米托蒽醌)与更频繁的改善相关;当双臂细胞毒治疗与b细胞导向/淋巴细胞消耗药物联合使用时,改善的比例最高。
{"title":"Towards practical management of the Marburg variant of multiple sclerosis","authors":"Mašan Sredanović ,&nbsp;Branka Bunoza ,&nbsp;Ivan Lehman ,&nbsp;Maja Jurin ,&nbsp;Nataša Nenadić Baranašić ,&nbsp;Gabriela Plosnić ,&nbsp;Petra Grđan Stevanović ,&nbsp;Miroslav Weiss ,&nbsp;Ivan Jovanović ,&nbsp;Ivana Brnadić ,&nbsp;Katarina Tešija ,&nbsp;Ernest Bilić ,&nbsp;Daniel Turudić ,&nbsp;Magdalena Krbot Skorić ,&nbsp;Mario Habek","doi":"10.1016/j.msard.2025.106908","DOIUrl":"10.1016/j.msard.2025.106908","url":null,"abstract":"<div><h3>Objectives</h3><div>The Marburg variant of multiple sclerosis (MvMS) is a rare, rapidly progressive demyelinating disorder characterized by an acute, monophasic onset with early, severe disability or death within weeks to months. In this systematic review, we aimed to: (I) describe patient characteristics and therapies used; (II) categorize outcomes; and (III) synthesize therapy–outcome relationships to guide practical management.</div></div><div><h3>Methods</h3><div>We performed a PRISMA-guided systematic review of published MvMS cases reporting treatment and outcomes, and present an illustrative pediatric case from our center.</div></div><div><h3>Results</h3><div>Across databases, 144 records were identified (PubMed 34; Scopus 74; WoS 36), out of which 22 articles met inclusion criteria. Among the 23 patients synthesized (22 published cases plus our pediatric case), median age was 32 years (range 14–63), with a female predominance (78 %). Nearly all patients received high-dose corticosteroids (22/23; 96 %). Additional therapies were common and variably combined: plasma exchange (14/23; 61 %), IVIg (8/23; 35 %), cyclophosphamide (10/23; 43 %), mitoxantrone (7/23; 30 %), any cytotoxic (cyclophosphamide and/or mitoxantrone) (15/23; 65 %), B-cell–depleting therapy (rituximab/ocrelizumab) (4/23; 17 %), alemtuzumab (1/23; 4 %), and natalizumab (1/23; 4 %); doses were inconsistently reported across studies, and order/timing of therapies varied widely. Overall outcomes were death in 6/23 (26 %), stable deficit in 4/23 (17 %), improvement in 9/23 (39 %), and near-complete recovery in 4/23 (17 %). We also propose a set of pragmatic, evidence-based diagnostic criteria. These criteria classify cases as Definite, Probable, or Possible Marburg variant MS based on fulminant clinical course, characteristic MRI patterns, CSF/serologic exclusion of mimics, and—when available—pathological confirmation.</div></div><div><h3>Conclusion</h3><div>While no single regimen was uniformly effective, our three-group analysis suggests a stepwise strategy: steroids ± plasma exchange alone were often insufficient; adding a cytotoxic agent with dual B- and T-cell activity (cyclophosphamide or mitoxantrone) was associated with more frequent improvement; and the highest proportion of improvement occurred when dual-arm cytotoxic therapy was combined with a B-cell–directed/lymphocyte-depleting agent.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"106 ","pages":"Article 106908"},"PeriodicalIF":2.9,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Expert consensus on the clinical use of cladribine tablets for treating relapsing multiple sclerosis in the asia-pacific region 专家对亚太地区临床使用克拉西宾片治疗复发性多发性硬化症的共识
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.msard.2025.106897
Ho Jin Kim , Suzanne J. Hodgkinson , Long-Sun Ro , Rocksy Fransisca V Situmeang , Sasitorn Siritho , Kevin Tan , Hoang Tien Trong Nghia , Shanthi Viswanathan , Lau Yuk Lun Alexander , Hannah Loke , Ru Jin Tay , Karim Taha , Maya Zeineddine , Bassem Yamout

Background

Cladribine Tablets (CladT) have emerged as a potent disease-modifying therapy (DMT) for relapsing multiple sclerosis (Pittock et al., 2019. While their efficacy and safety profiles have been well-documented in Western populations, there is a paucity of region-specific guidelines for their use in the Asia-Pacific context. This manuscript presents a consensus developed by Asia-Pacific experts, aiming to provide practical recommendations for the clinical application of CladT in this region.

Methods

A steering committee (SC) comprising four multiple sclerosis (Pittock et al., 2019one international and three from the APAC region—led an advisory board and developed 16 clinical questions regarding the practical use of CladT. To address these questions, statements were formulated based on available evidence, expert insights, and perspectives from the SC, along with input from an extended faculty of six MS experts representing in total nine APAC countries. Consensus on the recommendations was established when at least 75 % of respondents rated their agreement between 7 and 9 on a 9-point scale.

Results

A total of 16 clinical statements were drafted, and consensus was reached on 15 of them. The recommendations covered key aspects of CladT use, including indications for treatment initiation in both treatment-naïve and previously treated patients, strategies for managing disease activity over time, long-term safety considerations, and the role of CladT in special populations. CladT were recognized as an effective high-efficacy therapy for both highly and moderately active RMS, with robust long-term efficacy and safety profiles. It was also identified as a suitable option for patients requiring minimal hospital visits and those with limited access to healthcare facilities. While there was strong agreement on its use in treatment-naïve and early MS patients as well as a switch therapy, no consensus was reached on using CladT as a first-switch option for patients experiencing breakthrough disease on high-efficacy therapies. Recommendations also emphasized the importance of lymphocyte monitoring, appropriate patient selection, and the possibility of additional treatment courses beyond Year 5 in selected cases.

Conclusion

The consensus encompasses patient selection criteria, therapeutic strategies, monitoring protocols, and safety considerations, tailored to the unique demographic and healthcare landscapes of APAC countries.
背景克拉德滨片(CladT)已成为治疗复发性多发性硬化症的有效疾病修饰疗法(DMT) (Pittock et al., 2019)。虽然它们在西方人群中的有效性和安全性已经得到了充分的证明,但在亚太地区的使用中缺乏针对特定区域的指导方针。本文提出了亚太地区专家达成的共识,旨在为CladT在该地区的临床应用提供实用建议。方法由4名多发性硬化症患者(Pittock et al., 2019)、1名国际患者和3名亚太地区患者组成的指导委员会(SC)领导了一个咨询委员会,并制定了16个关于CladT实际应用的临床问题。为了解决这些问题,我们根据现有的证据、专家的见解和SC的观点,以及来自亚太地区9个国家的6名MS专家的意见,制定了声明。当至少75%的受访者在9分制中对他们的同意进行7到9分的评分时,就建立了对这些建议的共识。结果共起草临床陈述16份,达成共识15份。这些建议涵盖了CladT使用的关键方面,包括treatment-naïve和先前治疗过的患者开始治疗的适应症,长期管理疾病活动的策略,长期安全性考虑以及CladT在特殊人群中的作用。CladT被认为是一种有效的治疗高度和中度活性RMS的高效疗法,具有强大的长期疗效和安全性。它还被确定为需要最少住院次数的患者和获得保健设施的机会有限的患者的合适选择。虽然对于在treatment-naïve和早期MS患者中使用CladT以及作为一种转换疗法已经达成了强烈的共识,但对于使用CladT作为在高效疗法中经历突破性疾病的患者的第一转换选择,尚未达成共识。建议还强调了淋巴细胞监测的重要性,适当的患者选择,以及在选定病例中超过5年的额外治疗课程的可能性。结论共识包括患者选择标准、治疗策略、监测方案和安全考虑,针对亚太地区国家独特的人口统计学和医疗保健景观量身定制。
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引用次数: 0
The brainstem signature of multiple sclerosis: predictable lesions, consistent syndromes 多发性硬化症的脑干特征:可预测的病变,一致的症状。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.msard.2025.106894
Mohammad Wafa , Khalid Nuh , Gavin Giovannoni , Klaus Schmierer , Sharmilee Gnanapavan , Ruth Dobson , Monical Marta , Maria Papachatzaki , Benjamin Turner , Thomas Campion , Ashok Adams , Anant Krishnan , Alexandros Chatzistefanou , Bader Mohamed , Ahmed Hashish

Background

Integrating clinical findings with neuroradiological changes is a crucial skill in neurology, particularly for diagnosis. Multiple Sclerosis (MS) lesions in the brainstem are rarely asymptomatic, leading to unique and often localised clinical syndromes. MS lesions exhibit a characteristic perivenular distribution, which in the brainstem is imprinted by the consistent topography of the penetrating veins.

Objective

This review provides an integrative perspective on the anatomical patterns of MS lesions in the brainstem (midbrain, pons, and medulla). It correlates specific clinical syndromes with radiological appearances, aiding in both diagnosis and functional localisation.

Methods

We searched the available literature using keywords related to the three brainstem sections (midbrain, pons, medulla) and eloquent anatomical locations (medial longitudinal fasciculus, cerebellar peduncle, nerve fascicle, aqueduct, area postrema), aiming to correlate specific radiological patterns of MS lesions with their consistent clinical syndromes as reported in the literature.

Summary of Key Findings

Brainstem MS lesions often cause irritative symptoms rather than full functional loss. Unlike other conditions, visible MS lesions on MRI rarely disappear and usually remain as silent lesions following an acute event. The consistent venous architecture creates specific radiological patterns that link to distinct clinical presentations. In contrast, inflammatory disorders like NMOSD and MOGAD cause more aggressive and extensive dysfunction.

Conclusion

The visual details of MS brainstem lesions reflect their close relationship to venous anatomy, which can be anticipated even when the central vein sign is not directly visualised. Recognising these specific clinical-radiological syndromes provides a unique and insightful diagnostic tool for MS, underscoring the value of strong functional and radiological-anatomical interpretation skills in clinical neurology.
背景:将临床表现与神经影像学改变相结合是神经病学的一项关键技能,尤其是在诊断方面。多发性硬化症(MS)病变在脑干很少是无症状的,导致独特的,往往是局部临床综合征。多发性硬化症病变表现为特征性的静脉周围分布,其在脑干中表现为穿透静脉的一致地形。目的:本文综述了多发性硬化症脑干(中脑、脑桥和脑髓)病变的解剖学模式。它将特定的临床综合征与影像学表现联系起来,有助于诊断和功能定位。方法:以脑干3个部位(中脑、脑桥、脑髓)及相关解剖部位(内侧纵束、小脑脚、神经束、输水管、后脑区)为关键词,检索相关文献,将MS病变的特定影像学表现与文献报道的一致临床症状联系起来。主要发现总结:脑干MS病变通常引起刺激症状,而不是完全功能丧失。与其他疾病不同,MRI上可见的MS病变很少消失,通常在急性事件后保持沉默。一致的静脉结构创造了特定的放射学模式,与不同的临床表现相联系。相比之下,炎性疾病如NMOSD和MOGAD会导致更严重和广泛的功能障碍。结论:MS脑干病变的视觉细节反映了其与静脉解剖的密切关系,即使没有直接看到中央静脉征象,也可以预见到这一点。认识到这些特定的临床-放射学综合征为MS提供了独特而深刻的诊断工具,强调了临床神经病学中强大的功能和放射-解剖解释技能的价值。
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引用次数: 0
Dynamics of plasma fibrinogen unveils hepatic initiating role in the pathogenesis of multiple sclerosis 血浆纤维蛋白原的动态变化揭示了肝脏在多发性硬化症发病中的起始作用。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.msard.2025.106896
Jiaji Lin , Xinyan Han , Chuanping Zhao , Yanan Bai , Weitai He , Xiaoli Liu , Daidi Zhao , Hongzeng Li , Jun Guo

Background

Fibrinogen deposition in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS), but its peripheral dynamics and hepatic contribution remain unclear.

Methods

We integrated a retrospective analysis of 100 MS patients with longitudinal proteomic and transcriptomic profiling of experimental autoimmune encephalomyelitis (EAE) mice, validated by flow cytometry, western blotting, and AAV8-mediated liver-specific fibrinogen overexpression.

Results

MS patients during relapse showed reduced plasma fibrinogen (2.43 ± 0.61 vs. 2.79 ± 0.60 g/L, P < 0.001) and altered hepatic indices. In EAE, fibrinogen chains and complement–coagulation cascades peaked at the pre-onset phase but declined at peak disease, coinciding with hepatic transcriptional exhaustion. Cross-tissue analysis identified hepatic activity as a major driver of plasma proteome remodeling (Variable importance in projection (VIP) = 1.32) with increased hepatic CD45⁺Ly6G⁺CD11b⁺ neutrophils. Liver-specific fibrinogen overexpression induced intrahepatic neutrophil recruitment and CNS fibrinogen deposition.

Conclusions

Hepatic fibrinogen synthesis precedes CNS deposition, revealing a liver–CNS axis in early neuroinflammation.
背景:纤维蛋白原沉积在中枢神经系统(CNS)是多发性硬化症(MS)的标志,但其外周动力学和肝脏贡献尚不清楚。方法:我们整合了100例MS患者的纵向蛋白质组学和实验性自身免疫性脑脊髓炎(EAE)小鼠的转录组学分析,通过流式细胞术、western blotting和aav8介导的肝脏特异性纤维蛋白原过表达进行了验证。结果:复发期MS患者血浆纤维蛋白原降低(2.43±0.61比2.79±0.60 g/L, P < 0.001),肝脏指标改变。在EAE中,纤维蛋白原链和补体-凝血级联在发病前达到峰值,但在疾病高峰期下降,与肝脏转录衰竭相一致。跨组织分析发现肝脏活性是血浆蛋白质组重塑的主要驱动因素(投影变量重要性(VIP) = 1.32),肝脏CD45 + Ly6G + CD11b +中性粒细胞增加。肝脏特异性纤维蛋白原过表达诱导肝内中性粒细胞募集和中枢神经系统纤维蛋白原沉积。结论:肝纤维蛋白原合成先于中枢神经系统沉积,揭示了早期神经炎症的肝-中枢神经系统轴。
{"title":"Dynamics of plasma fibrinogen unveils hepatic initiating role in the pathogenesis of multiple sclerosis","authors":"Jiaji Lin ,&nbsp;Xinyan Han ,&nbsp;Chuanping Zhao ,&nbsp;Yanan Bai ,&nbsp;Weitai He ,&nbsp;Xiaoli Liu ,&nbsp;Daidi Zhao ,&nbsp;Hongzeng Li ,&nbsp;Jun Guo","doi":"10.1016/j.msard.2025.106896","DOIUrl":"10.1016/j.msard.2025.106896","url":null,"abstract":"<div><h3>Background</h3><div>Fibrinogen deposition in the central nervous system (CNS) is a hallmark of multiple sclerosis (MS), but its peripheral dynamics and hepatic contribution remain unclear.</div></div><div><h3>Methods</h3><div>We integrated a retrospective analysis of 100 MS patients with longitudinal proteomic and transcriptomic profiling of experimental autoimmune encephalomyelitis (EAE) mice, validated by flow cytometry, western blotting, and AAV8-mediated liver-specific fibrinogen overexpression.</div></div><div><h3>Results</h3><div>MS patients during relapse showed reduced plasma fibrinogen (2.43 ± 0.61 vs. 2.79 ± 0.60 g/L, <em>P</em> &lt; 0.001) and altered hepatic indices. In EAE, fibrinogen chains and complement–coagulation cascades peaked at the pre-onset phase but declined at peak disease, coinciding with hepatic transcriptional exhaustion. Cross-tissue analysis identified hepatic activity as a major driver of plasma proteome remodeling (Variable importance in projection (VIP) = 1.32) with increased hepatic CD45⁺Ly6G⁺CD11b⁺ neutrophils. Liver-specific fibrinogen overexpression induced intrahepatic neutrophil recruitment and CNS fibrinogen deposition.</div></div><div><h3>Conclusions</h3><div>Hepatic fibrinogen synthesis precedes CNS deposition, revealing a liver–CNS axis in early neuroinflammation.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"107 ","pages":"Article 106896"},"PeriodicalIF":2.9,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145834452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuropsychologic impact of MOGAD: A patient reported outcomes study MOGAD的神经心理影响:一项患者报告的结果研究
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.msard.2025.106873
Bruna Leles , Yihan Zhang , Philippe A. Bilodeau , Anastasia Vishnevetsky , Takahisa Mikami , Monique Anderson , Rebecca Gillani , Mattia Wruble Clark , Rebecca Salky , Gabriela Romanow , Michael Levy , Giovanna S. Manzano

Background

Myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system with monophasic or relapsing courses. While acute outcomes are well described, long-term patient-reported effects on cognition, fatigue, mood, and vision remain understudied.

Objective

To evaluate the feasibility of implementing patient-reported outcome measures (PROMs) in MOGAD and to characterize 12-month changes in quality of life, cognition, fatigue, anxiety, depression, and visual function.

Methods

Twenty-two adults meeting 2023 MOGAD criteria were enrolled from Massachusetts General Hospital, Brigham and Women’s Hospital, and Mass Eye and Ear Infirmary. PROMs were administered at baseline, and at 3-, 6-, 9-, and 12-month intervals via REDCap, including PROMIS10 Global Physical and Mental Health, PROMIS Cognitive Abilities v2.0, PHQ-9, ASQ, MFIS, and NEI-VFQ-25. Mixed-effects models tested longitudinal effects, and cross-sectional analyses examined associations with phenotype, MOG-IgG titer, relapse, maintenance therapy, and psychiatric comorbidities.

Results

ASQ (H(1)=3.77, p = 0.05) and VFQ-25 (H(1)=4.96, p = 0.03) scores were lower in patients with optic neuritis, while other phenotypes showed no PROM differences. No significant longitudinal changes were observed in any PROM. MOG-IgG titer and relapse status did not predict baseline scores. Patients receiving maintenance therapy had lower PROMIS10 Mental scores at baseline (44.9 vs. 48.3; p = 0.02). Mean ASQ rose from 96.6 to 130.8 over 12 months, exceeding reference values for anxiety; the same three patients with elevated ASQ also had PHQ-9 scores >10, indicating depression.

Conclusions

PROM implementation in MOGAD is feasible and highlights persistent fatigue, mood, and visual impairment, supporting routine use for patient-centered care.
髓鞘少突胶质细胞糖蛋白抗体相关疾病(MOGAD)是一种单相或反复发作的中枢神经系统自身免疫性脱髓鞘疾病。虽然急性结果已被很好地描述,但患者报告的对认知、疲劳、情绪和视力的长期影响仍未得到充分研究。目的评估在MOGAD中实施患者报告结果测量(PROMs)的可行性,并描述12个月生活质量、认知、疲劳、焦虑、抑郁和视觉功能的变化。方法从马萨诸塞州总医院、布里格姆妇女医院和大众眼耳医院纳入符合2023年MOGAD标准的22名成年人。通过REDCap在基线、3个月、6个月、9个月和12个月间隔进行PROMs,包括PROMIS10全球身心健康、PROMIS认知能力v2.0、PHQ-9、ASQ、MFIS和NEI-VFQ-25。混合效应模型检验了纵向效应,横断面分析检验了与表型、MOG-IgG滴度、复发、维持治疗和精神合并症的关系。结果视神经炎患者asq (H(1)=3.77, p = 0.05)和VFQ-25 (H(1)=4.96, p = 0.03)评分较低,其他表型无统计学差异。在任何PROM中未观察到明显的纵向变化。MOG-IgG滴度和复发状态不能预测基线评分。接受维持治疗的患者在基线时的PROMIS10 Mental评分较低(44.9比48.3;p = 0.02)。平均ASQ在12个月内从96.6上升到130.8,超过焦虑的参考值;这三名ASQ升高的患者也有PHQ-9得分[gt;10],表明患有抑郁症。结论在MOGAD中实施prom是可行的,并突出了持续性疲劳、情绪和视力障碍,支持以患者为中心的常规护理。
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引用次数: 0
The association between objective measures of sleep and physical activity in individuals with multiple sclerosis 多发性硬化症患者客观睡眠测量与身体活动之间的关系
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2025-12-02 DOI: 10.1016/j.msard.2025.106895
Adi Einav-Farber , Shay Menascu , Tali Drori , Alon Kalron
Sleep disturbances are common yet often overlooked in people with multiple sclerosis (pwMS), significantly impacting their quality of life. Although previous studies have explored the link between sleep and physical activity in pwMS, many lacked adequate control for key confounders such as depression, mobility impairments, and balance difficulties, which are independently associated with both sleep and activity. Additionally, reliance on self-reported data has limited the accuracy of findings. Understanding this relationship using objective measures is crucial, as poor sleep can exacerbate fatigue and further reduce quality of life. This study examined the association between objective sleep metrics and physical activity in pwMS while controlling for key confounders. A cross-sectional study was conducted with 50 pwMS (30 women, 20 men) aged 25–55 years, who wore an ActiGraph accelerometer for seven days to measure physical activity and sleep. Additional assessments included mobility (Timed Up and Go, Four Square Step Test, MS Walking Scale-12), fatigue (Modified Fatigue Impact Scale), and mental health (Hospital Anxiety and Depression Scale). Pearson’s correlations and multiple linear regression models were used for analysis. Results showed that sleep efficiency was significantly associated with daily step counts and the maximum consecutive steps. Sleep measures accounted for 16–17 % of the variance in physical activity metrics, increasing to 30–35 % after adjusting for mobility and disability. These findings suggest a positive association between physical activity and sleep quality in pwMS, indicating that promoting physical activity may have potential benefits for sleep.
睡眠障碍在多发性硬化症(pwMS)患者中很常见,但往往被忽视,严重影响了他们的生活质量。虽然以前的研究已经探索了睡眠和身体活动之间的联系,但许多研究缺乏对抑郁症、行动障碍和平衡困难等关键混杂因素的充分控制,这些因素与睡眠和活动独立相关。此外,对自我报告数据的依赖限制了研究结果的准确性。用客观的方法来理解这种关系是至关重要的,因为睡眠质量差会加剧疲劳,进一步降低生活质量。本研究在控制关键混杂因素的情况下,检验了pwMS患者客观睡眠指标与身体活动之间的关系。对50名年龄在25-55岁的pwMS(30名女性,20名男性)进行了一项横断面研究,他们佩戴ActiGraph加速计7天以测量身体活动和睡眠。额外的评估包括活动能力(计时起身和行走,四方步测试,MS步行量表-12),疲劳(修正疲劳影响量表)和心理健康(医院焦虑和抑郁量表)。采用Pearson相关和多元线性回归模型进行分析。结果表明,睡眠效率与每日步数和最大连续步数显著相关。睡眠指标占体力活动指标差异的16 - 17%,在调整了活动能力和残疾因素后,这一比例增加到30 - 35%。这些发现表明,在pwMS患者中,身体活动与睡眠质量之间存在正相关,表明促进身体活动可能对睡眠有潜在的好处。
{"title":"The association between objective measures of sleep and physical activity in individuals with multiple sclerosis","authors":"Adi Einav-Farber ,&nbsp;Shay Menascu ,&nbsp;Tali Drori ,&nbsp;Alon Kalron","doi":"10.1016/j.msard.2025.106895","DOIUrl":"10.1016/j.msard.2025.106895","url":null,"abstract":"<div><div>Sleep disturbances are common yet often overlooked in people with multiple sclerosis (pwMS), significantly impacting their quality of life. Although previous studies have explored the link between sleep and physical activity in pwMS, many lacked adequate control for key confounders such as depression, mobility impairments, and balance difficulties, which are independently associated with both sleep and activity. Additionally, reliance on self-reported data has limited the accuracy of findings. Understanding this relationship using objective measures is crucial, as poor sleep can exacerbate fatigue and further reduce quality of life. This study examined the association between objective sleep metrics and physical activity in pwMS while controlling for key confounders. A cross-sectional study was conducted with 50 pwMS (30 women, 20 men) aged 25–55 years, who wore an ActiGraph accelerometer for seven days to measure physical activity and sleep. Additional assessments included mobility (Timed Up and Go, Four Square Step Test, MS Walking Scale-12), fatigue (Modified Fatigue Impact Scale), and mental health (Hospital Anxiety and Depression Scale). Pearson’s correlations and multiple linear regression models were used for analysis. Results showed that sleep efficiency was significantly associated with daily step counts and the maximum consecutive steps. Sleep measures accounted for 16–17 % of the variance in physical activity metrics, increasing to 30–35 % after adjusting for mobility and disability. These findings suggest a positive association between physical activity and sleep quality in pwMS, indicating that promoting physical activity may have potential benefits for sleep.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"106 ","pages":"Article 106895"},"PeriodicalIF":2.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Multiple sclerosis and related disorders
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