Multiple sclerosis and related disorders最新文献

{"title":"Appendicitis and multiple sclerosis disease-modifying therapies: a disproportionality analysis of the FDA adverse event reporting system","authors":"Alexandra Balshi ,&nbsp;Madelyn Esser ,&nbsp;John P. Dempsey ,&nbsp;Ursela Baber ,&nbsp;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}

{"title":"Effects of disease modifying therapy on cognitive proficiency in pediatric-onset multiple sclerosis (POMS)","authors":"Ashley M. Whitaker ,&nbsp;Emily Zhou ,&nbsp;Brooke K. Iwamoto ,&nbsp;Benjamin N. Vogel ,&nbsp;Saba Jafarpour ,&nbsp;Lina Nguyen ,&nbsp;Nusrat Ahsan ,&nbsp;Laura E. Saucier ,&nbsp;Sharon H. O’Neil ,&nbsp;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}

{"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 ,&nbsp;Pietro Annovazzi ,&nbsp;Cinzia Cordioli ,&nbsp;Mattia Pozzato ,&nbsp;Sarah Rasia ,&nbsp;Elisabetta Signoriello ,&nbsp;Giacomo Lus ,&nbsp;Livia Pasquali ,&nbsp;Beatrice Giovannini ,&nbsp;Alice Laroni ,&nbsp;Alessio Carbone ,&nbsp;Paola Cavalla ,&nbsp;Sara La Gioia ,&nbsp;Valentina Torri Clerici ,&nbsp;Chiara Zecca ,&nbsp;Francesca Caleri ,&nbsp;Alessia Di Sapio ,&nbsp;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}

{"title":"ST8SIA4 as a candidate diagnostic biomarker: Blood–cerebrospinal fluid signature in RRMS","authors":"Tuba Denkçeken ,&nbsp;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}

{"title":"Socioeconomic burden of multiple sclerosis: Insights from a cohort in Coimbra, Portugal","authors":"Inês Correia ,&nbsp;Carolina Cunha ,&nbsp;Catarina Bernardes ,&nbsp;Gonçalo Carvalho ,&nbsp;Alex Xavier ,&nbsp;Carla Nunes ,&nbsp;Carmo Macário ,&nbsp;Lívia Sousa ,&nbsp;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}

{"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 ,&nbsp;Cláudia Tarragô Candotti ,&nbsp;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}

{"title":"Multiple sclerosis and autoimmunity: learnings from post-streptococcal autoimmunity","authors":"Benjamin Michael Bloom ,&nbsp;Olivia Payne ,&nbsp;Ester Valero-Hernandez ,&nbsp;Angray S. Kang ,&nbsp;Bavneet Kaur Singh ,&nbsp;David Baker ,&nbsp;Kathryn Harris ,&nbsp;Teresa Cutino-Moguel ,&nbsp;Ian Butler ,&nbsp;David L. Selwood ,&nbsp;Louisa K. James ,&nbsp;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}

{"title":"Multimorbidity patterns among persons with multiple sclerosis in Denmark: A national cross-sectional survey study","authors":"Marie Lynning ,&nbsp;Ida Skytt ,&nbsp;Philipp Trénel ,&nbsp;Anne Frølich ,&nbsp;Sanne Lykke Lundstrøm ,&nbsp;Nana Folmann Hempler ,&nbsp;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}

{"title":"Psychometric validation of PROMIS-Fatigue-MS-8a and MSIS-29v2 questionnaires in relapsing multiple sclerosis participants enrolled in a phase 2 trial of frexalimab","authors":"Patrick Vermersch ,&nbsp;Lita Araujo ,&nbsp;Samuel Gourlain ,&nbsp;Natalia Hakimi-Hawken ,&nbsp;Stephane Saubadu ,&nbsp;Philippe Truffinet ,&nbsp;Benoit Arnould ,&nbsp;Jerome Msihid","doi":"10.1016/j.msard.2026.107090","DOIUrl":"10.1016/j.msard.2026.107090","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 &gt;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 (<em>r</em>&gt;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 (<em>p</em>&lt;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.</div></div><div><h3>Conclusions</h3><div>PROMIS-Fatigue-MS-8a and MSIS-29v2 are valid and reliable measures for evaluating treatment benefits in clinical trials of RMS.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107090"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355807","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}

{"title":"Non-invasive Assessment of Glymphatic System Function in Patients with Anti-LGI1 Encephalitis","authors":"Ziyao Liu ,&nbsp;Lizhang Han ,&nbsp;Ruiqi Li ,&nbsp;Houyuan Zhu ,&nbsp;Jianping Qiao ,&nbsp;Jiaxiang Xin ,&nbsp;Dandan Zhang ,&nbsp;Linlin Zhai ,&nbsp;Xinjuan Jin ,&nbsp;Jingli Shan ,&nbsp;Shengjun Wang ,&nbsp;Anning Li","doi":"10.1016/j.msard.2026.107053","DOIUrl":"10.1016/j.msard.2026.107053","url":null,"abstract":"<div><h3>Background and purpose</h3><div>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.</div></div><div><h3>Materials and Methods</h3><div>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 &lt; 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).</div></div><div><h3>Results</h3><div>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).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"109 ","pages":"Article 107053"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372938","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}