Functional assessments of mobility are crucial for managing the symptoms of people with Multiple Sclerosis(pwMS). Impairment in dual-task skills, which is seen in pwMS, can have a negative effect on daily living activities. The purpose of this study was to determine validity and the intra-rater and inter-rater reliability of the L-test under dual-task conditions in pwMS. In total, 47 pwMS were included in the study. The L-test with single and dual task was administered along with the timed up and go (TUG) test, 25-foot walk (T25-FW) test by two rater. The tests were repeated seven to ten days later. According to the results of the study; the intra-rater and inter-rater reliabilities of the L-test under dual-task conditions were excellent (intraclass correlation coefficient intra-rater= 0.915, 0.922 and inter-rater= 0.96, 0.970), a significant positive relationship was found between the L test in dual-task conditions and the TUG (p < 0.001, r = 0.673), the T25-FW (p = 0.024, r = 0.328), and the L test with single and the TUG and the T25-FW (p < 0.001, r = 0.743, p= 0.002, r = 0.432) The L test under dual-task conditions is a reliable and valid tool for the assessment of cognitive ability on functional mobility in PwMS.
{"title":"Reliability and concurrent validity of L test under dual-task conditions in people with multiple sclerosis","authors":"Meltem Uzun , Hakan Polat , Zekiye İpek Katirci Kirmaci , Yasemin Ekmekyapar Firat , Suat Erel","doi":"10.1016/j.msard.2026.107085","DOIUrl":"10.1016/j.msard.2026.107085","url":null,"abstract":"<div><div>Functional assessments of mobility are crucial for managing the symptoms of people with Multiple Sclerosis(pwMS). Impairment in dual-task skills, which is seen in pwMS, can have a negative effect on daily living activities. The purpose of this study was to determine validity and the intra-rater and inter-rater reliability of the L-test under dual-task conditions in pwMS. In total, 47 pwMS were included in the study. The L-test with single and dual task was administered along with the timed up and go (TUG) test, 25-foot walk (T25-FW) test by two rater. The tests were repeated seven to ten days later. According to the results of the study; the intra-rater and inter-rater reliabilities of the L-test under dual-task conditions were excellent (intraclass correlation coefficient intra-rater= 0.915, 0.922 and inter-rater= 0.96, 0.970), a significant positive relationship was found between the L test in dual-task conditions and the TUG (p < 0.001, r = 0.673), the T25-FW (p = 0.024, r = 0.328), and the L test with single and the TUG and the T25-FW (p < 0.001, r = 0.743, p= 0.002, r = 0.432) The L test under dual-task conditions is a reliable and valid tool for the assessment of cognitive ability on functional mobility in PwMS.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107085"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344664","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}
Pub Date : 2026-05-01Epub Date: 2026-02-26DOI: 10.1016/j.msard.2026.107100
Andreas Wanitschek , Barbara Seebacher , Barbara Linert , Andreas Mühlbacher , Robert Hatschenberger , Nicole Kranawetter , Lisa Tischler , Monika Scarpatetti , Verena Walder , Alexandra Holzinger , Bernhard Haider , Doris Hörtenhuber , Eva Kronberger-Schaffer , Viktoria Mangold , Christian Brenneis , Rainer Ehling
Background
Improved understanding of effective therapeutic interventions (TI) is required to optimise mobility outcomes in people with multiple sclerosis (pwMS) undergoing multidisciplinary neurological rehabilitation (MNR). The primary objective was to explore clinically meaningful effects of active TI on mobility during inpatient MNR. Secondary objectives were to assess mobility-related goal attainment and to develop and evaluate a standardised TI documentation catalogue.
Methods
A TI catalogue and manual were developed and refined based on moderate interrater reliability from 12 video-recorded therapy sessions rated by eight clinicians. Usability was assessed by 47 physiotherapists using the System Usability Scale (SUS). Mobility outcomes included the 12-item Multiple Sclerosis Walking Scale (MSWS-12), 2-Minute Walk Test (2 MWT), Five Times Sit-to-Stand Test (5-TSTS), and Timed 25-Foot Walk. Effect sizes were calculated for individual and group-based TI. Goal attainment was measured using Goal Attainment Scaling.
Results
The TI catalogue showed good usability (mean SUS score 72.3). Significant improvements were observed across all mobility outcomes, with clinically meaningful changes for MSWS-12, 2MWT and 5-TSTS. Gait training variants, robot-assisted gait training, strength, task-oriented, dual-task, endurance, coordination, and balance training showed medium-to-large effect sizes. Goal achievers demonstrated significantly greater improvements in walking perception, speed, and distance than non-achievers, with no difference in sit-to-stand performance. Over 88% of 255 pwMS achieved or exceeded their therapy goals.
Conclusions
The TI catalogue is a reliable and practical tool for documenting TI in routine MNR. Several interventions, particularly stair gait training, strength training, and robot-assisted gait training, were associated with clinically meaningful mobility improvements in pwMS.
Trial registration
The study was prospectively registered with the German Clinical Trials Register (DRKS00025216 and DRKS00030391).
{"title":"Development and validation of a practical documentation of inpatient rehabilitation goals, therapy content and outcomes for improving mobility in people with multiple sclerosis in Austria: A multicentre single-arm pragmatic clinical trial","authors":"Andreas Wanitschek , Barbara Seebacher , Barbara Linert , Andreas Mühlbacher , Robert Hatschenberger , Nicole Kranawetter , Lisa Tischler , Monika Scarpatetti , Verena Walder , Alexandra Holzinger , Bernhard Haider , Doris Hörtenhuber , Eva Kronberger-Schaffer , Viktoria Mangold , Christian Brenneis , Rainer Ehling","doi":"10.1016/j.msard.2026.107100","DOIUrl":"10.1016/j.msard.2026.107100","url":null,"abstract":"<div><h3>Background</h3><div>Improved understanding of effective therapeutic interventions (TI) is required to optimise mobility outcomes in people with multiple sclerosis (pwMS) undergoing multidisciplinary neurological rehabilitation (MNR). The primary objective was to explore clinically meaningful effects of active TI on mobility during inpatient MNR. Secondary objectives were to assess mobility-related goal attainment and to develop and evaluate a standardised TI documentation catalogue.</div></div><div><h3>Methods</h3><div>A TI catalogue and manual were developed and refined based on moderate interrater reliability from 12 video-recorded therapy sessions rated by eight clinicians. Usability was assessed by 47 physiotherapists using the System Usability Scale (SUS). Mobility outcomes included the 12-item Multiple Sclerosis Walking Scale (MSWS-12), 2-Minute Walk Test (2 MWT), Five Times Sit-to-Stand Test (5-TSTS), and Timed 25-Foot Walk. Effect sizes were calculated for individual and group-based TI. Goal attainment was measured using Goal Attainment Scaling.</div></div><div><h3>Results</h3><div>The TI catalogue showed good usability (mean SUS score 72.3). Significant improvements were observed across all mobility outcomes, with clinically meaningful changes for MSWS-12, 2MWT and 5-TSTS. Gait training variants, robot-assisted gait training, strength, task-oriented, dual-task, endurance, coordination, and balance training showed medium-to-large effect sizes. Goal achievers demonstrated significantly greater improvements in walking perception, speed, and distance than non-achievers, with no difference in sit-to-stand performance. Over 88% of 255 pwMS achieved or exceeded their therapy goals.</div></div><div><h3>Conclusions</h3><div>The TI catalogue is a reliable and practical tool for documenting TI in routine MNR. Several interventions, particularly stair gait training, strength training, and robot-assisted gait training, were associated with clinically meaningful mobility improvements in pwMS.</div></div><div><h3>Trial registration</h3><div>The study was prospectively registered with the German Clinical Trials Register (DRKS00025216 and DRKS00030391).</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107100"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348633","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}
Pub Date : 2026-05-01Epub Date: 2026-03-01DOI: 10.1016/j.msard.2026.107106
Alexandra Balshi , Madelyn Esser , John P. Dempsey , Ursela Baber , Jacob A. Sloane
Background
Although appendicitis is one of the most common surgical emergencies and is related to immune function, its relation to multiple sclerosis (MS) disease-modifying therapies (DMTs) is unclear.
Objective
To determine which, if any, MS DMTs are associated with disproportionally high appendicitis reporting using real-world data from the FDA Adverse Event Reporting System (FAERS).
Results
We identified 965 reports of appendicitis associated with MS DMTs. A pooled analysis of all DMTs showed disproportionately high appendicitis reporting compared to all other FAERS medications (reporting odds ratio, 2.83; 95% confidence interval, 2.63–3.06; χ (Bhangu et al., 2015), 787.54). Ocrelizumab, ofatumumab, natalizumab, alemtuzumab, dimethyl and diroximel fumarate, cladribine, and peg- and interferon beta-1a all individually exhibited disproportionally high appendicitis reporting.
Conclusion
Patient counseling on early appendicitis warning signs and indications for urgent evaluation may be warranted for people with MS on DMTs.
背景：虽然阑尾炎是最常见的外科急症之一，且与免疫功能有关，但其与多发性硬化症（MS）疾病改善治疗（DMTs）的关系尚不清楚。目的：利用FDA不良事件报告系统（FAERS）的真实数据，确定哪些（如果有的话）MS DMTs与不成比例的高阑尾炎报告相关。结果：我们确定了965例阑尾炎与MS DMTs相关的报告。对所有dmt的汇总分析显示，与所有其他FAERS药物相比，报告阑尾炎的比例高得不成比例（报告优势比为2.83；95%可信区间为2.63-3.06;χ (Bhangu et al., 2015), 787.54）。Ocrelizumab, ofatumumab, natalizumab, alemtuzumab, dimethyl and diroximel fumarate, cladribine， peg-和干扰素β -1a都单独显示出不成比例的高阑尾炎报告。结论：对MS患者进行早期阑尾炎预警信号和紧急评估的适应症咨询可能是有必要的。
{"title":"Appendicitis and multiple sclerosis disease-modifying therapies: a disproportionality analysis of the FDA adverse event reporting system","authors":"Alexandra Balshi , Madelyn Esser , John P. Dempsey , Ursela Baber , Jacob A. Sloane","doi":"10.1016/j.msard.2026.107106","DOIUrl":"10.1016/j.msard.2026.107106","url":null,"abstract":"<div><h3>Background</h3><div>Although appendicitis is one of the most common surgical emergencies and is related to immune function, its relation to multiple sclerosis (MS) disease-modifying therapies (DMTs) is unclear.</div></div><div><h3>Objective</h3><div>To determine which, if any, MS DMTs are associated with disproportionally high appendicitis reporting using real-world data from the FDA Adverse Event Reporting System (FAERS).</div></div><div><h3>Results</h3><div>We identified 965 reports of appendicitis associated with MS DMTs. A pooled analysis of all DMTs showed disproportionately high appendicitis reporting compared to all other FAERS medications (reporting odds ratio, 2.83; 95% confidence interval, 2.63–3.06; χ (Bhangu et al., 2015), 787.54). Ocrelizumab, ofatumumab, natalizumab, alemtuzumab, dimethyl and diroximel fumarate, cladribine, and peg- and interferon beta-1a all individually exhibited disproportionally high appendicitis reporting.</div></div><div><h3>Conclusion</h3><div>Patient counseling on early appendicitis warning signs and indications for urgent evaluation may be warranted for people with MS on DMTs.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107106"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365634","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}
Pub Date : 2026-05-01Epub Date: 2026-03-01DOI: 10.1016/j.msard.2026.107104
Ashley M. Whitaker , Emily Zhou , Brooke K. Iwamoto , Benjamin N. Vogel , Saba Jafarpour , Lina Nguyen , Nusrat Ahsan , Laura E. Saucier , Sharon H. O’Neil , Jonathan D. Santoro
Background
Disease-modifying therapies (DMTs) may mitigate well-documented cognitive challenges in pediatric-onset multiple sclerosis (POMS) by slowing disease progression and promoting production of neurotrophic factors, though studies are limited, especially in children. This study assessed cognitive proficiency in patients with POMS treated with DMTs.
Method
The sample (n = 26; x̄ age at diagnosis = 14.6 years) was treated with dimethyl fumarate, natalizumab, or B-cell depletion therapies. Neuropsychological outcomes included attention/working memory (WM) and processing speed (PS) as measured by Digit Span (DS) and Rapid Automatized Naming (RAN) subtests.
Results
Both WM and PS were clinically average for the sample (WM x̄ = 8.7; PS x̄ = 8.5). There were differences between DMT groups in PS, RAN F(2,23) = 7.9, p = 0.002, though not WM. Patients treated with natalizumab (DS x̄ = 6.8; RAN x̄ = 5.8) demonstrated low average to below average performance, clinically lower than average performance across those treated with dimethyl fumarate (DS x̄ = 8.6; RAN x̄ = 9.0) or B-cell depletion (DS x̄ = 9.3; RAN x̄ = 9.4).
Conclusion
In this cross-sectional cohort, all patients treated with B-cell depletion therapies performed within the average to high average range. While those treated with dimethyl fumarate displayed more variability, their mean/median scores fell within the average range. In contrast, patients treated with natalizumab demonstrated low average to below average scores, suggesting immune-modulating therapeutics such as dimethyl fumarate and B-cell depletion may potentially be more beneficial than therapies that only prevent immune cell ingress into the central nervous system.
{"title":"Effects of disease modifying therapy on cognitive proficiency in pediatric-onset multiple sclerosis (POMS)","authors":"Ashley M. Whitaker , Emily Zhou , Brooke K. Iwamoto , Benjamin N. Vogel , Saba Jafarpour , Lina Nguyen , Nusrat Ahsan , Laura E. Saucier , Sharon H. O’Neil , Jonathan D. Santoro","doi":"10.1016/j.msard.2026.107104","DOIUrl":"10.1016/j.msard.2026.107104","url":null,"abstract":"<div><h3>Background</h3><div>Disease-modifying therapies (DMTs) may mitigate well-documented cognitive challenges in pediatric-onset multiple sclerosis (POMS) by slowing disease progression and promoting production of neurotrophic factors, though studies are limited, especially in children. This study assessed cognitive proficiency in patients with POMS treated with DMTs.</div></div><div><h3>Method</h3><div>The sample (<em>n</em> = 26; x̄ age at diagnosis = 14.6 years) was treated with dimethyl fumarate, natalizumab, or B-cell depletion therapies. Neuropsychological outcomes included attention/working memory (WM) and processing speed (PS) as measured by Digit Span (DS) and Rapid Automatized Naming (RAN) subtests.</div></div><div><h3>Results</h3><div>Both WM and PS were clinically average for the sample (WM x̄ = 8.7; PS x̄ = 8.5). There were differences between DMT groups in PS, RAN <em>F</em>(2,23) = 7.9, <em>p</em> = 0.002, though not WM. Patients treated with natalizumab (DS x̄ = 6.8; RAN x̄ = 5.8) demonstrated low average to below average performance, clinically lower than average performance across those treated with dimethyl fumarate (DS x̄ = 8.6; RAN x̄ = 9.0) or B-cell depletion (DS x̄ = 9.3; RAN x̄ = 9.4).</div></div><div><h3>Conclusion</h3><div>In this cross-sectional cohort, all patients treated with B-cell depletion therapies performed within the average to high average range. While those treated with dimethyl fumarate displayed more variability, their mean/median scores fell within the average range. In contrast, patients treated with natalizumab demonstrated low average to below average scores, suggesting immune-modulating therapeutics such as dimethyl fumarate and B-cell depletion may potentially be more beneficial than therapies that only prevent immune cell ingress into the central nervous system.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107104"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372892","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}
Pub Date : 2026-05-01Epub Date: 2026-02-21DOI: 10.1016/j.msard.2026.107088
Irene Schiavetti , Pietro Annovazzi , Cinzia Cordioli , Mattia Pozzato , Sarah Rasia , Elisabetta Signoriello , Giacomo Lus , Livia Pasquali , Beatrice Giovannini , Alice Laroni , Alessio Carbone , Paola Cavalla , Sara La Gioia , Valentina Torri Clerici , Chiara Zecca , Francesca Caleri , Alessia Di Sapio , Maria Pia Sormani
Introduction and objective
The introduction of follow-on formulations of glatiramer acetate (GA) has raised questions regarding their equivalence to the originator in real-world practice. This study aimed to evaluate the clinical effectiveness and safety of switching from originator GA to its follow-on product, Copemyl® (CO), in people with multiple sclerosis (MS).
Methods
A multicenter, retrospective observational study was conducted, including patients with MS treated for at least two years with GA followed by at least two years with CO. The primary outcome was the annualized relapse rate (ARR), whereas secondary outcomes included disability progression assessed by the Expanded Disability Status Scale (EDSS), MRI activity, and adverse events (AEs).
Results
A total of 138 patients were included. The ARR was very low and comparable across treatments (GA: 0.028; CO: 0.019), with a mean paired difference of –0.009 (95 % CI –0.028 to 0.010; p = 0.38), falling within the predefined equivalence margin. Disability progression over six months occurred in 6.0 % of GA and 7.3 % of CO periods (HR 1.53; 95 % CI 0.74–3.16; p = 0.26). No significant difference was found in MRI activity (52.2 % vs 60.1 %, p = 0.14). Safety profiles were comparable, with mostly mild to moderate AEs; four serious AEs occurred under CO, two of them possibly treatment-related.
Conclusions
Switching from originator GA to CO did not influence clinical outcomes or safety. These findings support the therapeutic equivalence of the two formulations in real-world clinical practice, by supporting previous evidence from randomized trials.
前言和目的：醋酸格拉替默（GA）的后续配方的介绍引起了关于它们在实际应用中与原药等效性的问题。本研究旨在评估多发性硬化症（MS）患者从初始产品GA切换到后续产品Copemyl®（CO）的临床有效性和安全性。方法：进行了一项多中心、回顾性观察性研究，包括接受GA治疗至少两年的MS患者，随后接受CO治疗至少两年。主要结果是年化复发率（ARR），而次要结果包括通过扩展残疾状态量表（EDSS）评估的残疾进展、MRI活性和不良事件（ae）。结果：共纳入138例患者。不同处理的ARR非常低且具有可比性（GA: 0.028; CO: 0.019），平均配对差异为-0.009 (95% CI -0.028至0.010;p = 0.38)，落在预定义的等效范围内。6个月的残疾进展发生在6.0%的GA期和7.3%的CO期（HR 1.53; 95% CI 0.74-3.16; p = 0.26）。MRI活动无显著差异（52.2% vs 60.1%, p = 0.14）。安全性具有可比性，大多数为轻度至中度ae；4例严重不良反应在CO治疗期间发生，其中2例可能与治疗有关。结论：从初始GA切换到CO不影响临床结果或安全性。这些发现通过支持先前随机试验的证据，支持了两种配方在实际临床实践中的治疗等效性。
{"title":"Real-world evaluation of the transition between originator and follow-on glatiramer acetate in people with multiple sclerosis: the “GA transition” study","authors":"Irene Schiavetti , Pietro Annovazzi , Cinzia Cordioli , Mattia Pozzato , Sarah Rasia , Elisabetta Signoriello , Giacomo Lus , Livia Pasquali , Beatrice Giovannini , Alice Laroni , Alessio Carbone , Paola Cavalla , Sara La Gioia , Valentina Torri Clerici , Chiara Zecca , Francesca Caleri , Alessia Di Sapio , Maria Pia Sormani","doi":"10.1016/j.msard.2026.107088","DOIUrl":"10.1016/j.msard.2026.107088","url":null,"abstract":"<div><h3>Introduction and objective</h3><div>The introduction of follow-on formulations of glatiramer acetate (GA) has raised questions regarding their equivalence to the originator in real-world practice. This study aimed to evaluate the clinical effectiveness and safety of switching from originator GA to its follow-on product, Copemyl® (CO), in people with multiple sclerosis (MS).</div></div><div><h3>Methods</h3><div>A multicenter, retrospective observational study was conducted, including patients with MS treated for at least two years with GA followed by at least two years with CO. The primary outcome was the annualized relapse rate (ARR), whereas secondary outcomes included disability progression assessed by the Expanded Disability Status Scale (EDSS), MRI activity, and adverse events (AEs).</div></div><div><h3>Results</h3><div>A total of 138 patients were included. The ARR was very low and comparable across treatments (GA: 0.028; CO: 0.019), with a mean paired difference of –0.009 (95 % CI –0.028 to 0.010; <em>p</em> = 0.38), falling within the predefined equivalence margin. Disability progression over six months occurred in 6.0 % of GA and 7.3 % of CO periods (HR 1.53; 95 % CI 0.74–3.16; <em>p</em> = 0.26). No significant difference was found in MRI activity (52.2 % vs 60.1 %, <em>p</em> = 0.14). Safety profiles were comparable, with mostly mild to moderate AEs; four serious AEs occurred under CO, two of them possibly treatment-related.</div></div><div><h3>Conclusions</h3><div>Switching from originator GA to CO did not influence clinical outcomes or safety. These findings support the therapeutic equivalence of the two formulations in real-world clinical practice, by supporting previous evidence from randomized trials.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107088"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308261","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}
Pub Date : 2026-05-01Epub Date: 2026-02-21DOI: 10.1016/j.msard.2026.107087
Tuba Denkçeken , Elif Onur
Objective
Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and axonal degeneration, with relapsing-remitting MS (RRMS) representing its most prevalent clinical phenotype. This study aimed to investigate hub-genes and hub-miRNAs that were differentially expressed in peripheral blood mononuclear cell (PBMC) samples from RRMS patients and validate the hub-genes in cerebrospinal fluid (CSF) to assess their potential clinical diagnostic value.
Methods
All mRNA and miRNA expression profiling studies of RRMS in PBMC samples were downloaded from the GEO and ArrayExpress databases and differentially expressed mRNAs (DEGs) and miRNAs (DEMs) were determined. The regulation patterns of DEGs and DEMs were determined by fold change. Target genes of DEMs and common-gene clusters were defined, and then other bioinformatic approaches were applied. External validation of hub-genes was performed in CSF samples to confirm biological relevance beyond PBMCs and to evaluate their applicability as clinically accessible biomarkers.
Results
mRNA datasets 228 control and 209 RRMS, and miRNA datasets included 93 control and 84 RRMS PBMC samples. It was found that ATM, CREB1, ST8SIA4, hsa-miR-19b-3p, and hsa-miR-181c-5p are dysregulated in RRMS patients' PBMC samples. Then, hub-genes were validated and ST8SIA4 ROC analysis provided a sensitivity of 83.9% and specificity of 88% in discriminating RRMS from controls with an accuracy of 85.7%.
Conclusion
ST8SIA4 is regulated in the same direction in PBMC and CSF samples from RRMS patients and can discriminate between the RRMS and control groups with high sensitivity. It can be concluded that the high diagnostic accuracy of ST8SIA4 has the potential to be used as a novel biomarker alongside existing clinical and laboratory parameters to distinguish RRMS from controls during clinical examinations.
{"title":"ST8SIA4 as a candidate diagnostic biomarker: Blood–cerebrospinal fluid signature in RRMS","authors":"Tuba Denkçeken , Elif Onur","doi":"10.1016/j.msard.2026.107087","DOIUrl":"10.1016/j.msard.2026.107087","url":null,"abstract":"<div><h3>Objective</h3><div>Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and axonal degeneration, with relapsing-remitting MS (RRMS) representing its most prevalent clinical phenotype. This study aimed to investigate hub-genes and hub-miRNAs that were differentially expressed in peripheral blood mononuclear cell (PBMC) samples from RRMS patients and validate the hub-genes in cerebrospinal fluid (CSF) to assess their potential clinical diagnostic value.</div></div><div><h3>Methods</h3><div>All mRNA and miRNA expression profiling studies of RRMS in PBMC samples were downloaded from the GEO and ArrayExpress databases and differentially expressed mRNAs (DEGs) and miRNAs (DEMs) were determined. The regulation patterns of DEGs and DEMs were determined by fold change. Target genes of DEMs and common-gene clusters were defined, and then other bioinformatic approaches were applied. External validation of hub-genes was performed in CSF samples to confirm biological relevance beyond PBMCs and to evaluate their applicability as clinically accessible biomarkers.</div></div><div><h3>Results</h3><div>mRNA datasets 228 control and 209 RRMS, and miRNA datasets included 93 control and 84 RRMS PBMC samples. It was found that ATM, CREB1, ST8SIA4, hsa-miR-19b-3p, and hsa-miR-181c-5p are dysregulated in RRMS patients' PBMC samples. Then, hub-genes were validated and ST8SIA4 ROC analysis provided a sensitivity of 83.9% and specificity of 88% in discriminating RRMS from controls with an accuracy of 85.7%.</div></div><div><h3>Conclusion</h3><div>ST8SIA4 is regulated in the same direction in PBMC and CSF samples from RRMS patients and can discriminate between the RRMS and control groups with high sensitivity. It can be concluded that the high diagnostic accuracy of ST8SIA4 has the potential to be used as a novel biomarker alongside existing clinical and laboratory parameters to distinguish RRMS from controls during clinical examinations.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107087"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308274","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}
Multiple Sclerosis (MS) is the leading cause of non-traumatic disability in young adults, burdening patients, caregivers, and healthcare systems. In Portugal, annual direct healthcare costs for MS are estimated between €12,303 and €16,451, with total costs reaching €34,400 per patient. This study aims to characterize MS patients in Coimbra, focusing on demographic, clinical, and economic aspects to assess the disease's socioeconomic impact.
Methods
A cost-of-illness study with cross-sectional and retrospective components was conducted between 2021 and 2022 at the single referral center for MS in Coimbra. Patients completed a survey assessing sociodemographic, clinical, and economic data. Descriptive and comparative non-parametric analyses stratified by MS severity (mild EDSS 0–3.5, moderate 4–6.5, severe above 6.5) were performed.
Results
Among 163 patients (69.9 % female, mean age 48), 87.1 % had relapsing-remitting MS. Higher education was common (69.3 %), 45.4 % were married. Employment declined with disease severity; 9.4 % of mild EDSS patients were unemployed, while severe EDSS patients were retired. Average annual direct healthcare costs were €12,406, increasing with severity (€12,267 in mild MS to €16,020 in severe MS). Disease-modifying therapies accounted for most direct costs, although these declined in advanced stages, with hospitalization costs rising. Total costs per patient were €14,954 (mild MS), €28,289 (moderate MS), and €35,557 (severe MS), with relapses adding €3277 annually.
Conclusion
This study underscores the substantial economic burden of MS, particularly as disease severity progresses. Rising hospitalization and relapse costs highlight the need for cost-effective strategies and policies reducing MS-related socioeconomic impacts. Effective management could help mitigate these costs while improving outcomes.
{"title":"Socioeconomic burden of multiple sclerosis: Insights from a cohort in Coimbra, Portugal","authors":"Inês Correia , Carolina Cunha , Catarina Bernardes , Gonçalo Carvalho , Alex Xavier , Carla Nunes , Carmo Macário , Lívia Sousa , Sónia Batista","doi":"10.1016/j.msard.2026.107083","DOIUrl":"10.1016/j.msard.2026.107083","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple Sclerosis (MS) is the leading cause of non-traumatic disability in young adults, burdening patients, caregivers, and healthcare systems. In Portugal, annual direct healthcare costs for MS are estimated between €12,303 and €16,451, with total costs reaching €34,400 per patient. This study aims to characterize MS patients in Coimbra, focusing on demographic, clinical, and economic aspects to assess the disease's socioeconomic impact.</div></div><div><h3>Methods</h3><div>A cost-of-illness study with cross-sectional and retrospective components was conducted between 2021 and 2022 at the single referral center for MS in Coimbra. Patients completed a survey assessing sociodemographic, clinical, and economic data. Descriptive and comparative non-parametric analyses stratified by MS severity (mild EDSS 0–3.5, moderate 4–6.5, severe above 6.5) were performed.</div></div><div><h3>Results</h3><div>Among 163 patients (69.9 % female, mean age 48), 87.1 % had relapsing-remitting MS. Higher education was common (69.3 %), 45.4 % were married. Employment declined with disease severity; 9.4 % of mild EDSS patients were unemployed, while severe EDSS patients were retired. Average annual direct healthcare costs were €12,406, increasing with severity (€12,267 in mild MS to €16,020 in severe MS). Disease-modifying therapies accounted for most direct costs, although these declined in advanced stages, with hospitalization costs rising. Total costs per patient were €14,954 (mild MS), €28,289 (moderate MS), and €35,557 (severe MS), with relapses adding €3277 annually.</div></div><div><h3>Conclusion</h3><div>This study underscores the substantial economic burden of MS, particularly as disease severity progresses. Rising hospitalization and relapse costs highlight the need for cost-effective strategies and policies reducing MS-related socioeconomic impacts. Effective management could help mitigate these costs while improving outcomes.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107083"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308238","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}
Pub Date : 2026-05-01Epub Date: 2026-02-13DOI: 10.1016/j.msard.2026.107074
Felipe Colmeneiro dos Santos , Cláudia Tarragô Candotti , Luciano Palmeiro Rodrigues
Introduction
Multiple Sclerosis (MS) is a chronic neurological condition that frequently compromises upper limb (UL) function. Despite its functional relevance, few instruments validated in Brazilian Portuguese are specific to this population. The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) was originally developed in Dutch to measure this function in individuals with MS.
Objective
To translate, cross-culturally adapt, and validate the AMSQ for Brazilian Portuguese.
Methods
The study was approved by the HCPA Research Ethics Committee (CAAE: 82069424.0.0000.5327) and followed international guidelines, including translation, synthesis, back-translation, content validation and reliability. The Content Validity Index (CVI) was calculated. In the reliability stage, 50 individuals with MS answered the AMSQ at two time points, with an interval of 3–5 days. Internal consistency was assessed using Cronbach’s alpha, and test-retest reproducibility was evaluated by the Intraclass Correlation Coefficient (ICC 2,1).
Results
The questionnaire was well understood by the participants, confirming its cultural appropriateness. The AMSQ-BR showed a CVI above 90% for all items and presented excellent reproducibility (ICC = 0.932) and internal consistency (α = 0.984).
Conclusion
The Brazilian version of the AMSQ-BR is valid and reliable for the assessment of upper limb function in individuals with multiple sclerosis. It presents content validity, test-retest reproducibility, and internal consistency, making it a relevant tool for clinical and research use in the Brazilian context.
{"title":"Translation, cross-cultural adaptation, validation, reliability, and reproducibility of the arm function in multiple sclerosis questionnaire (AMSQ) for upper limb function assessment in individuals with multiple sclerosis in Brazilian Portuguese","authors":"Felipe Colmeneiro dos Santos , Cláudia Tarragô Candotti , Luciano Palmeiro Rodrigues","doi":"10.1016/j.msard.2026.107074","DOIUrl":"10.1016/j.msard.2026.107074","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple Sclerosis (MS) is a chronic neurological condition that frequently compromises upper limb (UL) function. Despite its functional relevance, few instruments validated in Brazilian Portuguese are specific to this population. The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) was originally developed in Dutch to measure this function in individuals with MS.</div></div><div><h3>Objective</h3><div>To translate, cross-culturally adapt, and validate the AMSQ for Brazilian Portuguese.</div></div><div><h3>Methods</h3><div>The study was approved by the HCPA Research Ethics Committee (CAAE: 82069424.0.0000.5327) and followed international guidelines, including translation, synthesis, back-translation, content validation and reliability. The Content Validity Index (CVI) was calculated. In the reliability stage, 50 individuals with MS answered the AMSQ at two time points, with an interval of 3–5 days. Internal consistency was assessed using Cronbach’s alpha, and test-retest reproducibility was evaluated by the Intraclass Correlation Coefficient (ICC 2,1).</div></div><div><h3>Results</h3><div>The questionnaire was well understood by the participants, confirming its cultural appropriateness. The AMSQ-BR showed a CVI above 90% for all items and presented excellent reproducibility (ICC = 0.932) and internal consistency (α = 0.984).</div></div><div><h3>Conclusion</h3><div>The Brazilian version of the AMSQ-BR is valid and reliable for the assessment of upper limb function in individuals with multiple sclerosis. It presents content validity, test-retest reproducibility, and internal consistency, making it a relevant tool for clinical and research use in the Brazilian context.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107074"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308257","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}
Pub Date : 2026-05-01Epub Date: 2026-02-23DOI: 10.1016/j.msard.2026.107091
Benjamin Michael Bloom , Olivia Payne , Ester Valero-Hernandez , Angray S. Kang , Bavneet Kaur Singh , David Baker , Kathryn Harris , Teresa Cutino-Moguel , Ian Butler , David L. Selwood , Louisa K. James , Gavin Giovannoni
Group A streptococcus (GAS) or Streptococcus pyogenes, which typically causes a purulent pharyngitis, is the established cause of acute rheumatic fever (ARF) and several other autoimmune diseases. Primary prevention, achieved by treating acute pharyngitis with antibiotics, prevents ARF. After an initial attack of ARF, secondary prevention, using long-term prophylactic antibiotics, prevents further attacks and chronic end-organ damage or chronic rheumatic heart disease. Infection with the Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS). EBV-associated infectious mononucleosis (IM) is a significant risk factor for developing MS. Reasoning by analogy, similar to the role of GAS in ARF, we hypothesise that treating IM with effective antivirals will prevent or at least reduce the incidence of MS. Similarly, once MS is established, the chronic administration of effective EBV antivirals will prevent further MS attacks and prevent end-organ damage or disability in people with MS. Treating IM and preventing EBV latent-lytic cycling in patients with MS needs to be explored as strategies to prevent and treat MS, respectively.
{"title":"Multiple sclerosis and autoimmunity: learnings from post-streptococcal autoimmunity","authors":"Benjamin Michael Bloom , Olivia Payne , Ester Valero-Hernandez , Angray S. Kang , Bavneet Kaur Singh , David Baker , Kathryn Harris , Teresa Cutino-Moguel , Ian Butler , David L. Selwood , Louisa K. James , Gavin Giovannoni","doi":"10.1016/j.msard.2026.107091","DOIUrl":"10.1016/j.msard.2026.107091","url":null,"abstract":"<div><div>Group A streptococcus (GAS) or <em>Streptococcus pyogenes</em>, which typically causes a purulent pharyngitis, is the established cause of acute rheumatic fever (ARF) and several other autoimmune diseases. Primary prevention, achieved by treating acute pharyngitis with antibiotics, prevents ARF. After an initial attack of ARF, secondary prevention, using long-term prophylactic antibiotics, prevents further attacks and chronic end-organ damage or chronic rheumatic heart disease. Infection with the Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS). EBV-associated infectious mononucleosis (IM) is a significant risk factor for developing MS. Reasoning by analogy, similar to the role of GAS in ARF, we hypothesise that treating IM with effective antivirals will prevent or at least reduce the incidence of MS. Similarly, once MS is established, the chronic administration of effective EBV antivirals will prevent further MS attacks and prevent end-organ damage or disability in people with MS. Treating IM and preventing EBV latent-lytic cycling in patients with MS needs to be explored as strategies to prevent and treat MS, respectively.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107091"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326702","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}
Pub Date : 2026-05-01Epub Date: 2026-02-17DOI: 10.1016/j.msard.2026.107081
Marie Lynning , Ida Skytt , Philipp Trénel , Anne Frølich , Sanne Lykke Lundstrøm , Nana Folmann Hempler , Lasse Skovgaard
Objectives
This national cross-sectional survey study aimed to investigate the prevalence and clustering of co-occurring diseases in persons with multiple sclerosis (MS) in Denmark. The study also examined the associations between socio-demographic and MS-specific characteristics and multimorbidity clusters.
Methods
The survey, conducted by the Danish MS Society, was carried out among 3,114 persons with MS (PwMS). The survey included information on 27 diseases, socio-demographic factors, and MS-specific factors. Weighted principal component analysis and K-means cluster analysis were used to identify multimorbidity clusters. Multinomial regression analyses were conducted to explore the associations between cluster membership and background variables.
Results
Seventy-five percent of the respondents reported having one or more diseases in addition to MS. The most common coexisting diseases were hypertension (25.1%), hyperlipidemia (18.4%), allergy (18.2%), slipped disc/other spine disorders (17.9%), and osteoarthritis (17.9%). Five multimorbidity clusters were identified: “None-to-low multimorbidity”, “Gastrointestinal, Musculoskeletal”, “Cardiovascular, Diabetes”, “Asthma, Allergy”, and “Mental Illness”. The clusters differed in terms of socio-demographic and MS-specific factors.
Conclusions
Understanding the patterns and clusters of multimorbidity, along with their links to socio-demographic and MS-specific characteristics, can help guide healthcare providers in assessing the healthcare needs of PwMS and in developing preventive strategies.
{"title":"Multimorbidity patterns among persons with multiple sclerosis in Denmark: A national cross-sectional survey study","authors":"Marie Lynning , Ida Skytt , Philipp Trénel , Anne Frølich , Sanne Lykke Lundstrøm , Nana Folmann Hempler , Lasse Skovgaard","doi":"10.1016/j.msard.2026.107081","DOIUrl":"10.1016/j.msard.2026.107081","url":null,"abstract":"<div><h3>Objectives</h3><div>This national cross-sectional survey study aimed to investigate the prevalence and clustering of co-occurring diseases in persons with multiple sclerosis (MS) in Denmark. The study also examined the associations between socio-demographic and MS-specific characteristics and multimorbidity clusters.</div></div><div><h3>Methods</h3><div>The survey, conducted by the Danish MS Society, was carried out among 3,114 persons with MS (PwMS). The survey included information on 27 diseases, socio-demographic factors, and MS-specific factors. Weighted principal component analysis and K-means cluster analysis were used to identify multimorbidity clusters. Multinomial regression analyses were conducted to explore the associations between cluster membership and background variables.</div></div><div><h3>Results</h3><div>Seventy-five percent of the respondents reported having one or more diseases in addition to MS. The most common coexisting diseases were hypertension (25.1%), hyperlipidemia (18.4%), allergy (18.2%), slipped disc/other spine disorders (17.9%), and osteoarthritis (17.9%). Five multimorbidity clusters were identified: “None-to-low multimorbidity”, “Gastrointestinal, Musculoskeletal”, “Cardiovascular, Diabetes”, “Asthma, Allergy”, and “Mental Illness”. The clusters differed in terms of socio-demographic and MS-specific factors.</div></div><div><h3>Conclusions</h3><div>Understanding the patterns and clusters of multimorbidity, along with their links to socio-demographic and MS-specific characteristics, can help guide healthcare providers in assessing the healthcare needs of PwMS and in developing preventive strategies.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107081"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321776","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}
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