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Psychometric validation of PROMIS-Fatigue-MS-8a and MSIS-29v2 questionnaires in relapsing multiple sclerosis participants enrolled in a phase 2 trial of frexalimab 在参加frexalimab 2期试验的复发性多发性硬化症参与者中,对允诺-疲劳- ms -8a和MSIS-29v2问卷的心理测量学验证
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-02-22 DOI: 10.1016/j.msard.2026.107090
Patrick Vermersch , Lita Araujo , Samuel Gourlain , Natalia Hakimi-Hawken , Stephane Saubadu , Philippe Truffinet , Benoit Arnould , Jerome Msihid

Background

There are limited psychometric studies conducted using the Patient-Reported Outcomes Measurement Information System Adult Short Form-Fatigue-Multiple Sclerosis 8a (PROMIS-Fatigue-MS-8a) and Multiple Sclerosis Impact Scale-29 version 2 (MSIS-29v2) questionnaires.

Methods

Data were collected from a phase 2 trial (NCT04879628) investigating frexalimab in adults with relapsing multiple sclerosis (RMS). Reliability, convergent validity, construct validity, and sensitivity to change were assessed on PROMIS-Fatigue-MS-8a and MSIS-29v2 using Cronbach’s alpha coefficient, intraclass correlation coefficient, Spearman’s or polyserial correlation coefficients, analysis of variance, and analysis of covariance, respectively. Analyses were conducted using baseline and Week 12 data from pooled treatment arms.

Results

Item-to-item correlations were acceptable (0.4–0.9) for most of the items for both patient-reported outcomes (PROs) at baseline and Week 12. Internal consistency was excellent (Cronbach’s alpha >0.90) for both PROs at baseline and Week 12. Additionally, good test–retest reliability was observed for PROMIS-Fatigue-MS-8a and the physical and psychological domains of MSIS-29v2. Convergent validity was supported by high correlations (r>0.50) between the PROMIS-Fatigue-MS-8a T-score and the MSIS-29v2 and the Patient Global Impression of Severity (PGIS)-Fatigue at baseline and Week 12. Construct validity was supported by significant differences between groups defined by the PGIS-Fatigue scores at baseline and Week 12 for both PROs (p<0.0001). Sensitivity to change was demonstrated by statistically significant differences in the mean change from baseline at Week 12 among groups defined by the PGIS-Fatigue and the Patient Global Impression of Change-Fatigue.

Conclusions

PROMIS-Fatigue-MS-8a and MSIS-29v2 are valid and reliable measures for evaluating treatment benefits in clinical trials of RMS.
背景:使用患者报告结果测量信息系统成人短表格疲劳-多发性硬化症8a(允诺-疲劳- ms -8a)和多发性硬化症影响量表-29第2版(MSIS-29v2)问卷进行了有限的心理测量研究。方法:数据收集自一项研究frexalimab治疗复发性多发性硬化症(RMS)成人的2期试验(NCT04879628)。采用Cronbach′s α系数、类内相关系数、Spearman′s或多序列相关系数、方差分析和协方差分析,分别对promisi -疲劳- ms -8a和MSIS-29v2的信度、收敛效度、结构效度和变化敏感性进行评估。使用合并治疗组的基线和第12周数据进行分析。结果:在基线和第12周,大多数项目的患者报告结果(PROs)的项目与项目之间的相关性是可接受的(0.4-0.9)。在基线和第12周,PROs的内部一致性都很好(Cronbach's alpha >0.90)。此外,promise - fatigue - ms -8a和MSIS-29v2的生理和心理领域具有良好的重测信度。在基线和第12周时,promisi -Fatigue- ms -8a t评分和MSIS-29v2与患者严重程度总体印象(PGIS)-疲劳之间的高相关性(r>0.50)支持了收敛效度。通过基线和第12周的pgis -疲劳评分来定义两组之间的显著差异,结构效度得到了支持。结论:在RMS临床试验中,允诺-疲劳- ms -8a和MSIS-29v2是评估治疗效果的有效和可靠的指标。
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引用次数: 0
Non-invasive Assessment of Glymphatic System Function in Patients with Anti-LGI1 Encephalitis 抗lgi1脑炎患者淋巴系统功能的无创评估。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-02-05 DOI: 10.1016/j.msard.2026.107053
Ziyao Liu , Lizhang Han , Ruiqi Li , Houyuan Zhu , Jianping Qiao , Jiaxiang Xin , Dandan Zhang , Linlin Zhai , Xinjuan Jin , Jingli Shan , Shengjun Wang , Anning Li

Background and purpose

Cognitive impairment is a core deficit in anti-LGI1 encephalitis, yet its underlying mechanisms remain incompletely understood. The glymphatic system (GS), a brain waste clearance pathway, is implicated in cognitive dysfunction in other neuroinflammatory conditions. However, its role in anti-LGI1 encephalitis is unknown. We hypothesized that GS dysfunction is a key mechanism contributing to cognitive deficits in this disease. This study aimed to investigate GS function using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) and other MRI indices, and evaluate its association with hippocampal/amygdala volumes and cognition.

Materials and Methods

This prospective study enrolled 42 healthy controls (HCs) and 40 patients with a confirmed diagnosis of anti-LGI1 encephalitis who underwent brain MRI and neurocognitive assessment. Clinical and neuropsychological data were collected, including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Modified Rankin Scale (mRS), and Clinical Assessment Scale for Autoimmune Encephalitis (CASE). Patients were stratified into three cognitive subgroups based on MoCA scores: LGI1-NCI (no cognitive impairment, MoCA ≥ 26), LGI1-MCI (mild cognitive impairment, MoCA 18–25), and LGI1-SCI (moderate-to-severe cognitive impairment, MoCA < 18). Imaging-derived biomarkers included the DTI-ALPS index, hippocampal and amygdala volumes extracted from 3D T1-weighted images, perivascular space (PVS) volume fraction, and free water fraction with in white matter (FW-WM).

Results

Key imaging biomarkers showed significant differences between patients and HCs. Specifically, the DTI-ALPS index was significantly decreased in patients (1.483 vs. 1.671, p_FDR= 0.011), whereas the FW-WM was significantly increased (0.210 vs. 0.174, p_FDR=0.007). Subgroup analysis demonstrated a progressive decline in the DTI-ALPS index (LGI1-SCI: 1.3813 vs. HCs: 1.6706, p_FDR=0.004) and concomitant elevation in FW-WM (LGI1-SCI: 0.2258 vs. HCs: 0.1743, p_FDR=0.001) associated with increasing cognitive impairment severity. Unilateral hippocampal atrophy was also observed, with a significantly reduced volumes in the left hippocampus (2.942 vs. 3.216 cm³, p_FDR=0.049).

Conclusion

We observed glymphatic dysfunction and left hippocampal atrophy in anti-LGI1 encephalitis, with both features showing trends of greater severity in patients with more pronounced cognitive impairment. Longitudinal observations indicate that recovery of these pathological features lags behind clinical improvement, suggesting independent underlying mechanisms.
背景与目的:认知障碍是抗lgi1脑炎的核心缺陷,但其潜在机制尚不完全清楚。淋巴系统(GS),脑废物清除途径,涉及认知功能障碍在其他神经炎症条件。然而,其在抗lgi1脑炎中的作用尚不清楚。我们假设GS功能障碍是导致该疾病认知缺陷的关键机制。本研究旨在利用沿血管周围空间扩散张量成像(DTI-ALPS)等MRI指标研究GS功能,并评估其与海马/杏仁核体积和认知的关系。材料和方法:这项前瞻性研究纳入了42名健康对照(hc)和40名确诊为抗lgi1脑炎的患者,他们接受了脑MRI和神经认知评估。收集临床和神经心理学资料,包括蒙特利尔认知评估(MoCA)、简易精神状态检查(MMSE)、改良Rankin量表(mRS)和自身免疫性脑炎临床评估量表(CASE)。根据MoCA评分将患者分为三个认知亚组:LGI1-NCI(无认知障碍,MoCA≥26),LGI1-MCI(轻度认知障碍,MoCA 18-25)和LGI1-SCI(中重度认知障碍,MoCA < 18)。成像衍生的生物标志物包括DTI-ALPS指数、从3D t1加权图像中提取的海马和杏仁核体积、血管周围空间(PVS)体积分数和白质游离水分数(FW-WM)。结果:关键成像生物标志物在患者和hc之间存在显著差异。具体来说,患者的DTI-ALPS指数显著降低(1.483 vs. 1.483)。1.671, p_FDR= 0.011),而FW-WM显著增加(0.210 vs. 0.011)。0.174, p_FDR = 0.007)。亚组分析显示DTI-ALPS指数(LGI1-SCI: 1.3813 vs。HCs: 1.6706, p_FDR=0.004)和FW-WM伴发升高(LGI1-SCI: 0.2258 vs。HCs: 0.1743, p_FDR=0.001)与认知障碍严重程度增加相关。单侧海马萎缩也被观察到,左侧海马体积明显减少(2.942 vs。3.216 cm³,p_FDR=0.049)。结论:我们观察到抗lgi1脑炎患者淋巴功能障碍和左海马萎缩,且这两种特征在认知功能障碍更明显的患者中表现出更严重的趋势。纵向观察表明,这些病理特征的恢复滞后于临床改善,提示独立的潜在机制。
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引用次数: 0
Risk of postpartum disease activity with subcutaneous versus intravenous Natalizumab in pregnant women with multiple sclerosis 在患有多发性硬化症的孕妇中,皮下注射与静脉注射Natalizumab治疗产后疾病活动的风险
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-02-20 DOI: 10.1016/j.msard.2026.107086
Vito AG Ricigliano , Doriana Landi , Marine Boudot de la Motte , Jonathan Ciron , Bertrand Bourre , Olivier Casez , Silvia Bartolomeo , Giangaetano D'Aleo , Roberta Fantozzi , Matteo Foschi , Francesca Napoli , Caroline Papeix , Girolama Alessandra Marfia , Elisabeth Maillart

Background

Intravenous (IV) Natalizumab (NTZ) extended-interval dosing (EID) in women with multiple sclerosis (WwMS) is safe and effective in controlling disease activity during pregnancy. Recently, a subcutaneous (SC) form of the drug has become available.

Objectives

To assess clinical/radiological relapses in postpartum comparing IV and SC NTZ EID in two groups of pregnant WwMS.

Methods

We retrospectively collected data on pregnancies across French and Italian MS centers. We assessed clinical/radiological activity in postpartum, accounting for the number of administrations during pregnancy and the duration of NTZ washout. Fisher’s exact test, followed by multivariable logistic regression to adjust for confounders, were used to compare outcomes by administration route. Group differences in the odds of disease activity were expressed as odds ratios (OR).

Results

56 pregnancies were identified (35IV, 21SC). Relapses were rare and not different between groups (p=0.88). Postpartum radiological activity was observed in 10/21 WwMS with SC NTZ (47.6%), versus 5/35 with IV NTZ (14,3%) (p=0.012; OR=5.32[CI:1.41-20.06]). Notably, 50% of all reactivations with SC NTZ occurred with washout between 10 and 12 weeks.

Conclusions

Our study suggests a higher risk of postpartum radiological activity in pregnant WmMS treated with SC NTZ EID, prompting for adaptation of the administration schedule to control disease reactivation.
背景:静脉注射(IV) Natalizumab (NTZ)延长间隔给药(EID)对多发性硬化症(WwMS)妇女在妊娠期间控制疾病活动安全有效。最近,一种皮下(SC)形式的药物已经可用。目的:比较两组妊娠期WwMS患者IV和SC NTZ EID的临床/影像学复发情况。方法:我们回顾性收集了法国和意大利MS中心的妊娠数据。我们评估了产后的临床/放射活性,考虑了妊娠期间的给药次数和NTZ洗脱的持续时间。采用Fisher精确检验,然后采用多变量逻辑回归来调整混杂因素,比较不同给药途径的结果。疾病活动几率的组间差异用比值比(OR)表示。结果:56例妊娠(35IV, 21SC)。复发罕见,两组间无差异(p=0.88)。在10/21 WwMS中,SC NTZ(47.6%)与5/35 IV NTZ(14.3%)相比(p=0.012; OR=5.32[CI:1.41-20.06])观察到产后放射活动。值得注意的是,50%的SC NTZ再激活发生在10 - 12周的洗脱期。结论:我们的研究表明,SC NTZ EID治疗妊娠WmMS的产后放射性活动风险较高,提示调整给药计划以控制疾病再激活。
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引用次数: 0
Randomized controlled trial of a remotely-delivered exercise training program in older adults with multiple sclerosis: Secondary effects on cognition, symptoms, and quality of life 老年多发性硬化症患者远程运动训练项目的随机对照试验:对认知、症状和生活质量的继发影响
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-03-01 DOI: 10.1016/j.msard.2026.107105
Peixuan Zheng , Sydney R. DeJonge , Noah G. DuBose , Ariel Kidwell-Chandler , Trevor B. Martin , Trinh L.T. Huynh , Robert W. Motl

Background

Older adults with multiple sclerosis (MS) experience co-occurring effects of aging and disease progression, resulting in worsening cognition, symptoms, and quality of life (QOL). There is limited research examining approaches for improving those outcomes in older adults with MS.

Objectives

We examined the efficacy of a 16-week home-based exercise training program for improving secondary study outcomes of cognition, symptoms, and QOL in older adults with MS.

Methods

This phase-Ib, randomized controlled trial (RCT) included 51 participants (60.5±6.6 years, 78% females) who were randomized into exercise training (aerobic and resistance) or active control (stretching) conditions. Participants completed laboratory assessments before and after the 16-week programs. Cognitive function was measured using the NIH Toolbox Cognitive Battery. Symptoms of fatigue, depression, anxiety, and pain were assessed using the Fatigue Severity Scale, Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale, and Short-form McGill Pain Questionnaire, respectively. QOL was measured by the 29-item Multiple Sclerosis Impact Scale and the 36-Item Short Form Health Survey.

Results

Forty-one participants (80.4 %) completed the conditions, with outcome data obtained from 20 exercise and 16 control participants. There were statistically significant improvements in executive function, processing speed, fatigue, and health-related QOL in the exercise group (p < 0.05, d = 0.48–0.66). No significant changes were observed in the control group (p>0.05).

Conclusions

We provide preliminary evidence on the benefits of exercise training for improving cognition, reducing fatigue impact, and enhancing QOL in older adults with MS who had moderate disability.
背景:老年多发性硬化症(MS)患者经历衰老和疾病进展的共同作用,导致认知、症状和生活质量(QOL)恶化。目的:我们研究了16周的家庭运动训练计划对改善老年ms患者认知、症状和生活质量的次要研究结果的有效性。这项ib期随机对照试验(RCT)包括51名参与者(60.5±6.6岁,78%为女性),他们被随机分为运动训练(有氧和阻力)和主动控制(拉伸)两组。参与者在为期16周的项目前后完成了实验室评估。使用NIH工具箱认知电池测量认知功能。分别采用疲劳严重程度量表、修正疲劳影响量表、医院焦虑抑郁量表和短格式McGill疼痛问卷对疲劳、抑郁、焦虑和疼痛的症状进行评估。生活质量由29项多发性硬化症影响量表和36项简短健康调查来衡量。结果:41名参与者(80.4%)完成了条件,结果数据来自20名运动参与者和16名对照参与者。运动组在执行功能、处理速度、疲劳和健康相关生活质量方面均有统计学意义的改善(p < 0.05, d = 0.48-0.66)。对照组无明显变化(p < 0.05)。结论:我们提供了初步证据,证明运动训练可以改善中度残疾的老年MS患者的认知能力,减少疲劳影响,提高生活质量。
{"title":"Randomized controlled trial of a remotely-delivered exercise training program in older adults with multiple sclerosis: Secondary effects on cognition, symptoms, and quality of life","authors":"Peixuan Zheng ,&nbsp;Sydney R. DeJonge ,&nbsp;Noah G. DuBose ,&nbsp;Ariel Kidwell-Chandler ,&nbsp;Trevor B. Martin ,&nbsp;Trinh L.T. Huynh ,&nbsp;Robert W. Motl","doi":"10.1016/j.msard.2026.107105","DOIUrl":"10.1016/j.msard.2026.107105","url":null,"abstract":"<div><h3>Background</h3><div>Older adults with multiple sclerosis (MS) experience co-occurring effects of aging and disease progression, resulting in worsening cognition, symptoms, and quality of life (QOL). There is limited research examining approaches for improving those outcomes in older adults with MS.</div></div><div><h3>Objectives</h3><div>We examined the efficacy of a 16-week home-based exercise training program for improving secondary study outcomes of cognition, symptoms, and QOL in older adults with MS.</div></div><div><h3>Methods</h3><div>This phase-Ib, randomized controlled trial (RCT) included 51 participants (60.5±6.6 years, 78% females) who were randomized into exercise training (aerobic and resistance) or active control (stretching) conditions. Participants completed laboratory assessments before and after the 16-week programs. Cognitive function was measured using the NIH Toolbox Cognitive Battery. Symptoms of fatigue, depression, anxiety, and pain were assessed using the Fatigue Severity Scale, Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale, and Short-form McGill Pain Questionnaire, respectively. QOL was measured by the 29-item Multiple Sclerosis Impact Scale and the 36-Item Short Form Health Survey.</div></div><div><h3>Results</h3><div>Forty-one participants (80.4 %) completed the conditions, with outcome data obtained from 20 exercise and 16 control participants. There were statistically significant improvements in executive function, processing speed, fatigue, and health-related QOL in the exercise group (<em>p</em> &lt; 0.05, <em>d</em> = 0.48–0.66). No significant changes were observed in the control group (<em>p</em>&gt;0.05).</div></div><div><h3>Conclusions</h3><div>We provide preliminary evidence on the benefits of exercise training for improving cognition, reducing fatigue impact, and enhancing QOL in older adults with MS who had moderate disability.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107105"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355940","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
Effect of laughter yoga on fatigue, sleep quality and psychological well-being in people with multiple sclerosis: A randomized controlled trial 笑瑜伽对多发性硬化症患者疲劳、睡眠质量和心理健康的影响:一项随机对照试验。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-02-26 DOI: 10.1016/j.msard.2026.107098
Nurgül Kaplan , Mehtap Tan , Dürdane Aksoy

Background and purpose

Symptoms such as fatigue, sleep disturbances, and impaired psychological well-being are common in individuals Multiple Sclerosis (MS). However, studies on the use of laughter yoga, a non-invasive intervention method, are very limited in the literature. The aim of this study was to evaluate the effects of laughter yoga on fatigue, sleep quality and psychological well-being in individuals with MS.

Materials and methods

In this randomized controlled trial, 42 people with MS were randomly assigned to intervention or control group. The intervention group received a total of 12 sessions of laughter yoga. Descriptive Information Form, Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI) and Psychological Well-Being Scale (PWBS) were used to collect data.

Results

Laughter yoga was associated with improvements in fatigue and sleep outcomes. Fatigue severity decreased substantially in the intervention group (Cohen’s d = 2.785), with no meaningful change observed in the control group. Sleep quality improved in the intervention group, as indicated by reduced Pittsburgh Sleep Quality Index scores (p < 0.001, d = 2.921). Psychological well-being increased within the intervention group (d = -1.505); however, the between-group effect at post-test was small (d = 0.485).

Conclusion

Laughter yoga showed statistically significant results in terms of decreasing fatigue level, increasing sleep quality and psychological well-being in individuals with MS. The findings suggest that laughter yoga is a low-cost and effective complementary psycho-social intervention that can be used in clinical settings within the scope of nursing practice. This intervention offers an evidence-based approach that can be integrated into nursing care to manage fatigue and sleep problems and improve psychological well-being in individuals with MS. For the generalizability of the effects of laughter yoga, studies with larger samples are needed.
背景和目的:疲劳、睡眠障碍和心理健康受损等症状在多发性硬化症(MS)个体中很常见。然而,关于大笑瑜伽这种非侵入性干预方法的研究在文献中非常有限。本研究的目的是评估笑瑜伽对多发性硬化症患者疲劳、睡眠质量和心理健康的影响。材料和方法:在本随机对照试验中,42例多发性硬化症患者随机分为干预组和对照组。干预组总共接受了12次笑声瑜伽。采用描述性信息表、疲劳严重程度量表(FSS)、匹兹堡睡眠质量指数(PSQI)和心理健康量表(PWBS)收集数据。结果:笑瑜伽与改善疲劳和睡眠结果有关。干预组疲劳程度显著降低(Cohen’s d = 2.785),对照组无显著变化。干预组的睡眠质量得到改善,匹兹堡睡眠质量指数得分降低(p < 0.001, d = 2.921)。干预组患者的心理幸福感增加(d = -1.505);但后测组间效应较小(d = 0.485)。结论:笑瑜伽在缓解多发性硬化症患者的疲劳水平、提高睡眠质量和心理健康方面具有显著的统计学效果。研究结果表明,笑瑜伽是一种低成本、有效的心理社会辅助干预方法,可在临床护理实践范围内应用。这种干预提供了一种基于证据的方法,可以整合到护理中,以管理疲劳和睡眠问题,改善多发性硬化症患者的心理健康。为了使笑瑜伽的效果具有普遍性,需要进行更大样本的研究。
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引用次数: 0
Voice analysis as a digital biomarker: A machine learning approach for automated multiple sclerosis classification 语音分析作为数字生物标志物:多发性硬化症自动分类的机器学习方法。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-03-01 DOI: 10.1016/j.msard.2026.107109
Jonathan Delgado Hernández , Moisés Betancort Montesinos , Tatiana Romero Arias , Miguel Ángel Hernández Pérez

Background/Objectives

Voice analysis is a non-invasive tool that can capture subtle motor impairments in Multiple Sclerosis (MS). The objective of this study was to develop and validate a machine learning (ML) framework for the automated classification of MS through acoustic voice analysis.

Methods

A cohort of 300 gender-balanced participants (200 with MS and 100 healthy controls) provided sustained vocal recordings. Fifteen acoustic features were extracted. An elastic network model first identified the most relevant parameters from the development cohort (n = 200), which were then used to train five supervised ML classifiers. During the variable selection and ML model training phase, the sample was divided into an 80/20 split and cross-validation was used to minimize overfitting. The best-performing model was subsequently validated in an independent, unknown clinical cohort (n = 100).

Results

The Random Forest model demonstrated robust performance, which was confirmed in the independent validation (ROC AUC = 0.85 [95% CI=0.76-0.93] and balanced accuracy = 0.80), showing strong discriminative ability independent of sample prevalence.

Conclusion

Voice analysis combined with ML presents a non-invasive, low-cost, and effective method for MS discrimination, offering significant potential as a classification support tool.
背景/目的:语音分析是一种非侵入性工具,可以捕捉多发性硬化症(MS)中细微的运动损伤。本研究的目的是开发和验证一个机器学习(ML)框架,通过声学语音分析对多发性硬化症进行自动分类。方法:300名性别平衡的参与者(200名多发性硬化症患者和100名健康对照)提供持续的录音。提取了15个声学特征。弹性网络模型首先从开发队列(n = 200)中识别出最相关的参数,然后将其用于训练五个监督ML分类器。在变量选择和ML模型训练阶段,样本被分成80/20的分割,并使用交叉验证来最小化过拟合。随后在一个独立的未知临床队列(n = 100)中验证了表现最佳的模型。结果:随机森林模型具有较强的鲁棒性,在独立验证中得到证实(ROC AUC = 0.85 [95% CI=0.76-0.93],平衡精度= 0.80),具有较强的独立于样本患病率的判别能力。结论:语音分析结合机器学习是一种无创、低成本、有效的多发性硬化症鉴别方法,作为一种分类支持工具具有很大的潜力。
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引用次数: 0
Chronic lesion expansion as an imaging biomarker in multiple sclerosis 慢性病变扩张作为多发性硬化症的影像学生物标志物。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-02-23 DOI: 10.1016/j.msard.2026.107093
Michael T G Hayes , Heidi N Beadnall , Daniel Merlo , Mastura Monif , Samuel Klistorner , Chao Zhu , Anneke van der Walt , Helmut Butzkueven
The pathophysiological processes that drive disability progression in multiple sclerosis (MS) are not adequately captured by clinically available imaging biomarkers. Slowly expanding lesions (SELs) are a novel magnetic resonance imaging (MRI) biomarker proposed to reflect histopathologically defined chronic active lesions, which are associated with disease progression. SELs are identified through complex MRI analysis pipelines that measure volume changes in chronic MS lesions across serial MRI scans. This review provides a comprehensive overview of SELs, covering their proposed histopathological correlates, associations with clinical outcomes and response to disease-modifying therapies (DMTs). A distinguishing aim of this review is to provide the reader with a clear understanding of different SEL analysis techniques, particularly the two most established automated approaches, including their respective strengths and limitations. Each technique is compatible with conventional clinical MRI sequences, making clinical translation feasible. Current DMTs have modest effects on SELs, paralleling their limited efficacy in progressive MS. SELs may become a key outcome measure in clinical trials of DMTs for progressive MS. However, further research is needed to ascertain the optimal parameters for identifying clinically meaningful chronic lesion expansion with each analysis technique, and to clarify which SEL measures are most strongly associated with disability progression.
驱动多发性硬化症(MS)残疾进展的病理生理过程没有被临床可用的成像生物标志物充分捕获。慢扩张病变(slow expansion lesion, SELs)是一种新的磁共振成像(MRI)生物标志物,用于反映与疾病进展相关的组织病理学定义的慢性活动性病变。通过复杂的MRI分析管道,通过连续MRI扫描测量慢性MS病变的体积变化来识别SELs。这篇综述提供了SELs的全面概述,包括其提出的组织病理学相关性,与临床结果的关联以及对疾病改善治疗(dmt)的反应。这篇综述的一个显著目的是让读者清楚地了解不同的SEL分析技术,特别是两种最成熟的自动化方法,包括它们各自的优势和局限性。每种技术都与常规的临床MRI序列兼容,使临床翻译成为可能。目前的dmt对SEL的影响不大,与它们在进展性ms中的有限疗效相当。SELs可能成为dmt治疗进展性ms临床试验的关键结果指标。然而,需要进一步的研究来确定每种分析技术用于识别临床有意义的慢性病变扩展的最佳参数,并明确哪些SEL指标与残疾进展最密切相关。
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引用次数: 0
Poincaré feature-based classification of electroencephalography signals for multiple sclerosis diagnosis 基于特征的脑电图信号分类在多发性硬化症诊断中的应用。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-02-23 DOI: 10.1016/j.msard.2026.107092
Umut Aslan, Mehmet Feyzi Akşahin

Background

As one of the most widespread neurodegenerative disorders, Multiple Sclerosis (MS) is a progressive neuroinflammatory disorder affecting millions of individuals worldwide. Although magnetic resonance imaging (MRI) techniques are commonly employed for diagnosis, there is an increasing emphasis on electroencephalogram (EEG) signal processing to diagnose neurodegenerative disorders.

Methods

This study explores the use of Poincaré plot–derived features from EEG signals to differentiate MS patients from healthy individuals. EEG recordings from 50 subjects (25 MS, 25 Healthy controls) have been analyzed. EEG data were segmented into epochs, and four quantitative Poincaré features were extracted from each segment. These features were used as inputs to various classifiers, including traditional machine learning methods, k-Nearest Neighbors (KNN), Decision Tree (DT), Random Forest (RF), and ensemble models, and deep learning architectures such as Multilayer Perceptron (MLP), Convolutional Neural Network combined with Long Short-Term Memory (CNN+LSTM), and LSTM combined with Gated Recurrent Units (LSTM+GRU). Additionally, sub-frequency bands of EEG signals were analyzed separately to evaluate the discriminative potential of each band.

Results

The results demonstrated that Poincaré-based features effectively distinguished MS patients from healthy individuals. This yielded accuracies, sensitivities, and specificities of 99.8%, 100%, and 99.7%, respectively. Moreover, classification based on the Beta band consistently exhibited the highest discriminative power in differentiating MS patients. However, given the limited sample size, these results should be interpreted as preliminary and warrant further validation.

Conclusions

The results indicate that EEG-based Poincaré feature analysis offers a promising, low-cost, and noninvasive approach for assisting in MS diagnosis. While the observed classification performance is encouraging, larger and more diverse datasets, along with rigorous validation strategies, are required to confirm the robustness and clinical applicability of the proposed approach. Integrating this method with clinical workflows may enhance diagnostic accuracy and provide new insights into MS-related alterations in brain dynamics.
背景:作为最广泛的神经退行性疾病之一,多发性硬化症(MS)是一种进行性神经炎症性疾病,影响着全世界数百万人。虽然磁共振成像(MRI)技术通常用于诊断,但越来越重视脑电图(EEG)信号处理来诊断神经退行性疾病。方法:本研究探讨利用脑电图信号中的poincar图衍生特征来区分多发性硬化症患者与健康个体。分析了50名受试者(25名MS, 25名健康对照)的脑电图记录。将脑电数据进行分段,每个分段提取4个定量庞卡罗特征。这些特征被用作各种分类器的输入,包括传统的机器学习方法、k近邻(KNN)、决策树(DT)、随机森林(RF)和集成模型,以及多层感知器(MLP)、卷积神经网络结合长短期记忆(CNN+LSTM)、LSTM结合门控循环单元(LSTM+GRU)等深度学习架构。此外,对脑电信号的子频段进行单独分析,评价各频段的判别电位。结果:基于poincar的特征能有效区分MS患者和健康个体。其准确度、灵敏度和特异性分别为99.8%、100%和99.7%。此外,基于Beta波段的分类在鉴别MS患者方面始终表现出最高的鉴别能力。然而,考虑到有限的样本量,这些结果应该被解释为初步的,需要进一步的验证。结论:基于脑电图的poincar特征分析为辅助MS诊断提供了一种有前景的、低成本的、无创的方法。虽然观察到的分类性能令人鼓舞,但需要更大、更多样化的数据集,以及严格的验证策略,来确认所提出方法的稳健性和临床适用性。将这种方法与临床工作流程相结合可以提高诊断的准确性,并为ms相关的脑动力学改变提供新的见解。
{"title":"Poincaré feature-based classification of electroencephalography signals for multiple sclerosis diagnosis","authors":"Umut Aslan,&nbsp;Mehmet Feyzi Akşahin","doi":"10.1016/j.msard.2026.107092","DOIUrl":"10.1016/j.msard.2026.107092","url":null,"abstract":"<div><h3>Background</h3><div>As one of the most widespread neurodegenerative disorders, Multiple Sclerosis (MS) is a progressive neuroinflammatory disorder affecting millions of individuals worldwide. Although magnetic resonance imaging (MRI) techniques are commonly employed for diagnosis, there is an increasing emphasis on electroencephalogram (EEG) signal processing to diagnose neurodegenerative disorders.</div></div><div><h3>Methods</h3><div>This study explores the use of Poincaré plot–derived features from EEG signals to differentiate MS patients from healthy individuals. EEG recordings from 50 subjects (25 MS, 25 Healthy controls) have been analyzed. EEG data were segmented into epochs, and four quantitative Poincaré features were extracted from each segment. These features were used as inputs to various classifiers, including traditional machine learning methods, k-Nearest Neighbors (KNN), Decision Tree (DT), Random Forest (RF), and ensemble models, and deep learning architectures such as Multilayer Perceptron (MLP), Convolutional Neural Network combined with Long Short-Term Memory (CNN+LSTM), and LSTM combined with Gated Recurrent Units (LSTM+GRU). Additionally, sub-frequency bands of EEG signals were analyzed separately to evaluate the discriminative potential of each band.</div></div><div><h3>Results</h3><div>The results demonstrated that Poincaré-based features effectively distinguished MS patients from healthy individuals. This yielded accuracies, sensitivities, and specificities of 99.8%, 100%, and 99.7%, respectively. Moreover, classification based on the Beta band consistently exhibited the highest discriminative power in differentiating MS patients. However, given the limited sample size, these results should be interpreted as preliminary and warrant further validation.</div></div><div><h3>Conclusions</h3><div>The results indicate that EEG-based Poincaré feature analysis offers a promising, low-cost, and noninvasive approach for assisting in MS diagnosis. While the observed classification performance is encouraging, larger and more diverse datasets, along with rigorous validation strategies, are required to confirm the robustness and clinical applicability of the proposed approach. Integrating this method with clinical workflows may enhance diagnostic accuracy and provide new insights into MS-related alterations in brain dynamics.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107092"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308246","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
Distinct microstructural white matter alterations in demyelinating diseases: Insights from myelin- and axon-sensitive MRI 脱髓鞘疾病中明显的微结构白质改变:髓磷脂和轴突敏感MRI的见解。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-02-16 DOI: 10.1016/j.msard.2026.107078
Yasunobu Hoshino , Akifumi Hagiwara , Yuji Tomizawa , Naohisa Hara , Moto Nakaya , Junko Kikuta , Satoru Kamio , Hanna Okada , Koji Kamagata , Shigeki Aoki , Nobutaka Hattori

Objectives

We aimed to compare microstructural white matter alterations in multiple sclerosis (MS), anti–aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) using advanced quantitative MRI.

Methods

This retrospective study included 84 participants (24 MS, 18 AQP4-NMOSD, 20 MOGAD, and 22 healthy controls). Quantitative MR relaxometry and multi-shell diffusion-weighted imaging were acquired at 3 T to derive myelin volume fraction (MVF), axonal volume fraction, g-ratio, and diffusion tensor metrics. Normal-appearing white matter (NAWM) was analyzed in all patients, and plaque-based analyses were performed in patients with focal white matter lesions (20 MS, 8 AQP4-NMOSD, 8 MOGAD). Diagnostic performance was assessed using receiver operating characteristic (ROC) analyses.

Results

In NAWM, MS showed significantly lower fractional anisotropy than MOGAD or controls (P < 0.05), and AQP4-NMOSD exhibited lower MVF than MOGAD (P < 0.05). Among patients with lesions, plaques in MS had significantly lower MVF and higher g-ratio than those in AQP4-NMOSD (P < 0.0001) and MOGAD (P < 0.05). Plaques in AQP4-NMOSD showed a lower g-ratio than MOGAD (P < 0.01). Univariate ROC analyses revealed that plaque g-ratio distinguished AQP4-NMOSD from MS (AUC 0.92 [95%CI, 0.82–1.00], sensitivity 100.0%, specificity 75.0%) and from MS + MOGAD (AUC 0.88 [0.77–0.99], sensitivity 100.0%, specificity 75.0%). A multivariate model combining NAWM and plaque metrics further improved discrimination (AUC 0.95 [0.88–1.00], sensitivity 75.0%, specificity 95.0%, and AUC 0.91 [0.81–1.00], sensitivity 50.0%, specificity 92.9%).

Conclusion

Quantitative MRI metrics—especially MVF and g-ratio—demonstrate distinct microstructural profiles among MS, AQP4-NMOSD, and MOGAD, enabling improved disease differentiation.
目的:我们旨在利用先进的定量MRI比较多发性硬化症(MS)、抗水通道蛋白-4抗体阳性的视神经脊髓炎谱系障碍(AQP4-NMOSD)和髓鞘少突胶质细胞糖蛋白抗体相关疾病(MOGAD)的微结构白质改变。方法:回顾性研究共纳入84例受试者(MS 24例,AQP4-NMOSD 18例,MOGAD 20例,健康对照22例)。在3 T时进行定量MR松弛测量和多壳扩散加权成像,得出髓磷脂体积分数(MVF)、轴突体积分数、g比和扩散张量指标。对所有患者进行外观正常的白质(NAWM)分析,对局灶性白质病变患者(20 MS, 8 AQP4-NMOSD, 8 MOGAD)进行基于斑块的分析。采用受试者工作特征(ROC)分析评估诊断表现。结果:在NAWM中,MS的分数各向异性明显低于MOGAD和对照组(P < 0.05), AQP4-NMOSD的MVF明显低于MOGAD (P < 0.05)。病变患者中,MS斑块的MVF明显低于AQP4-NMOSD (P < 0.0001), g-ratio明显高于MOGAD (P < 0.05)。AQP4-NMOSD斑块的g比值低于MOGAD (P < 0.01)。单因素ROC分析显示,斑块g-ratio将AQP4-NMOSD与MS (AUC 0.92 [95%CI, 0.82-1.00],敏感性100.0%,特异性75.0%)和MS + MOGAD (AUC 0.88[0.77-0.99],敏感性100.0%,特异性75.0%)区分开来。结合NAWM和斑块指标的多变量模型进一步提高了识别能力(AUC为0.95[0.88-1.00],灵敏度为75.0%,特异性为95.0%;AUC为0.91[0.81-1.00],灵敏度为50.0%,特异性为92.9%)。结论:定量MRI指标-特别是MVF和g-ratio-显示MS, AQP4-NMOSD和MOGAD之间不同的微观结构特征,有助于改善疾病分化。
{"title":"Distinct microstructural white matter alterations in demyelinating diseases: Insights from myelin- and axon-sensitive MRI","authors":"Yasunobu Hoshino ,&nbsp;Akifumi Hagiwara ,&nbsp;Yuji Tomizawa ,&nbsp;Naohisa Hara ,&nbsp;Moto Nakaya ,&nbsp;Junko Kikuta ,&nbsp;Satoru Kamio ,&nbsp;Hanna Okada ,&nbsp;Koji Kamagata ,&nbsp;Shigeki Aoki ,&nbsp;Nobutaka Hattori","doi":"10.1016/j.msard.2026.107078","DOIUrl":"10.1016/j.msard.2026.107078","url":null,"abstract":"<div><h3>Objectives</h3><div>We aimed to compare microstructural white matter alterations in multiple sclerosis (MS), anti–aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) using advanced quantitative MRI.</div></div><div><h3>Methods</h3><div>This retrospective study included 84 participants (24 MS, 18 AQP4-NMOSD, 20 MOGAD, and 22 healthy controls). Quantitative MR relaxometry and multi-shell diffusion-weighted imaging were acquired at 3 T to derive myelin volume fraction (MVF), axonal volume fraction, g-ratio, and diffusion tensor metrics. Normal-appearing white matter (NAWM) was analyzed in all patients, and plaque-based analyses were performed in patients with focal white matter lesions (20 MS, 8 AQP4-NMOSD, 8 MOGAD). Diagnostic performance was assessed using receiver operating characteristic (ROC) analyses.</div></div><div><h3>Results</h3><div>In NAWM, MS showed significantly lower fractional anisotropy than MOGAD or controls (P &lt; 0.05), and AQP4-NMOSD exhibited lower MVF than MOGAD (P &lt; 0.05). Among patients with lesions, plaques in MS had significantly lower MVF and higher g-ratio than those in AQP4-NMOSD (P &lt; 0.0001) and MOGAD (P &lt; 0.05). Plaques in AQP4-NMOSD showed a lower g-ratio than MOGAD (P &lt; 0.01). Univariate ROC analyses revealed that plaque g-ratio distinguished AQP4-NMOSD from MS (AUC 0.92 [95%CI, 0.82–1.00], sensitivity 100.0%, specificity 75.0%) and from MS + MOGAD (AUC 0.88 [0.77–0.99], sensitivity 100.0%, specificity 75.0%). A multivariate model combining NAWM and plaque metrics further improved discrimination (AUC 0.95 [0.88–1.00], sensitivity 75.0%, specificity 95.0%, and AUC 0.91 [0.81–1.00], sensitivity 50.0%, specificity 92.9%).</div></div><div><h3>Conclusion</h3><div>Quantitative MRI metrics—especially MVF and g-ratio—demonstrate distinct microstructural profiles among MS, AQP4-NMOSD, and MOGAD, enabling improved disease differentiation.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107078"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308259","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
Altered network recruitment in multiple sclerosis patients during resting state 多发性硬化症患者静息状态下网络募集的改变。
IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Pub Date : 2026-05-01 Epub Date: 2026-03-03 DOI: 10.1016/j.msard.2026.107111
Annika Lüttjohann , Saskia Räuber , Melanie Korsen , Alice G. Willison , Saskia Elben , Christina B. Schroeter , Tobias Ruck , Philipp Albrecht , Marc Pawlitzki , Albrecht Stroh , Nico Melzer , Thomas Budde , Sven G. Meuth

Background

Electroencephalography (EEG) allows a versatile recording of neuronal activity in neurological disorders. Signal analytical techniques like time-frequency analysis (TFA) can uncover latent information in the EEG of patients. Classically, EEG and TFA analysis relies on predefined frequency bands. Cluster-based permutation statistics provides an unbiased statistical comparison of high dimensional neurophysiological data, stabilizing the measured effect size and increasing the probability of uncovering the main effect present.

Methods

Resting state surface EEG recordings from 51 Multiple Sclerosis (MS) and 51 control patients were analyzed using TFA and compared by cluster-based permutation statistics. We further correlated results with disease characteristics, retinal nerve fiber layer (RNFL) thickness assessed by optical coherence tomography, evoked potentials (EPs), and neuropsychological data.

Results

We detected increased power in the low and high beta frequency bands in MS compared to control patients in a subset of recording sites. Spectral power in the high beta band of resting state EEG recorded at O1 negatively correlated with the RNFL thickness. Furthermore, differences in low and high beta power were dependent on the EP score of MS patients.

Conclusion

Our results suggest a more desynchronized EEG activity in MS patients compared to controls, correlating with clinical markers of disease severity. The findings indicate differential brain network recruitment that may be the result of compensatory mechanisms and the basis for clinical impairment in MS.
背景:脑电图(EEG)允许在神经系统疾病的神经元活动的多功能记录。信号分析技术如时频分析(TFA)可以揭示患者脑电图中的潜在信息。通常,EEG和TFA分析依赖于预定义的频带。基于聚类的排列统计提供了高维神经生理数据的无偏统计比较,稳定了测量的效应大小,增加了发现当前主要效应的概率。方法:采用TFA对51例多发性硬化症(MS)患者和51例对照组的静息状态表脑电图记录进行分析,并采用聚类排列统计进行比较。我们进一步将结果与疾病特征、光学相干断层扫描评估的视网膜神经纤维层(RNFL)厚度、诱发电位(EPs)和神经心理学数据相关联。结果:我们检测到在记录部位的一个子集中,MS患者的低频段和高频段的功率比对照患者增加。O1时静息状态脑电图高β带频谱功率与RNFL厚度呈负相关。此外,低β功率和高β功率的差异取决于MS患者的EP评分。结论:我们的研究结果表明,与对照组相比,MS患者的脑电图活动更加非同步,与疾病严重程度的临床标志物相关。研究结果表明,不同的脑网络招募可能是代偿机制的结果,也是MS临床损伤的基础。
{"title":"Altered network recruitment in multiple sclerosis patients during resting state","authors":"Annika Lüttjohann ,&nbsp;Saskia Räuber ,&nbsp;Melanie Korsen ,&nbsp;Alice G. Willison ,&nbsp;Saskia Elben ,&nbsp;Christina B. Schroeter ,&nbsp;Tobias Ruck ,&nbsp;Philipp Albrecht ,&nbsp;Marc Pawlitzki ,&nbsp;Albrecht Stroh ,&nbsp;Nico Melzer ,&nbsp;Thomas Budde ,&nbsp;Sven G. Meuth","doi":"10.1016/j.msard.2026.107111","DOIUrl":"10.1016/j.msard.2026.107111","url":null,"abstract":"<div><h3>Background</h3><div>Electroencephalography (EEG) allows a versatile recording of neuronal activity in neurological disorders. Signal analytical techniques like time-frequency analysis (TFA) can uncover latent information in the EEG of patients. Classically, EEG and TFA analysis relies on predefined frequency bands. Cluster-based permutation statistics provides an unbiased statistical comparison of high dimensional neurophysiological data, stabilizing the measured effect size and increasing the probability of uncovering the main effect present.</div></div><div><h3>Methods</h3><div>Resting state surface EEG recordings from 51 Multiple Sclerosis (MS) and 51 control patients were analyzed using TFA and compared by cluster-based permutation statistics. We further correlated results with disease characteristics, retinal nerve fiber layer (RNFL) thickness assessed by optical coherence tomography, evoked potentials (EPs), and neuropsychological data.</div></div><div><h3>Results</h3><div>We detected increased power in the low and high beta frequency bands in MS compared to control patients in a subset of recording sites. Spectral power in the high beta band of resting state EEG recorded at O1 negatively correlated with the RNFL thickness. Furthermore, differences in low and high beta power were dependent on the EP score of MS patients.</div></div><div><h3>Conclusion</h3><div>Our results suggest a more desynchronized EEG activity in MS patients compared to controls, correlating with clinical markers of disease severity. The findings indicate differential brain network recruitment that may be the result of compensatory mechanisms and the basis for clinical impairment in MS.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107111"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378079","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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