Samuel F. Hunter , John W. Lindsey , Benjamin Osborne , Bethany Schreiber , Filipe Branco , Seth Levin , James B. Lewin , Matthew Scaramozza , Zhe Tian , Ariel Antezana
{"title":"Safety, tolerability, and efficacy of diroximel fumarate in a cohort of Black patients with multiple sclerosis from the phase 3 EVOLVE-MS-1 study","authors":"Samuel F. Hunter , John W. Lindsey , Benjamin Osborne , Bethany Schreiber , Filipe Branco , Seth Levin , James B. Lewin , Matthew Scaramozza , Zhe Tian , Ariel Antezana","doi":"10.1016/j.msard.2024.105912","DOIUrl":"10.1016/j.msard.2024.105912","url":null,"abstract":"<div><h3>Background</h3><div>Multiple sclerosis (MS) has not been well studied in racial and ethnic minorities, as these populations are typically underrepresented in clinical trials. Black or African Americans comprise ∼13 % of the US population, yet are represented by as little as 5 % in clinical trials. Differences in disease course and progression have been reported between races and ethnicities, so there is a need to understand the safety and efficacy of disease-modifying therapies (DMTs) in Black patients, to inform evidence-based approaches to treatment in this population.</div></div><div><h3>Methods</h3><div>EVOLVE-MS-1 (NCT0234307) was an open-label, single-arm, phase 3 study assessing the long-term safety, tolerability, and efficacy of diroximel fumarate (DRF) over 96 weeks in adults with relapsing-remitting multiple sclerosis (RRMS). Patients were either newly initiated to DRF or rolled over from completing EVOLVE-MS-2 (NCT03093324). In this post-hoc analysis of the phase 3 EVOLVE-MS-1 study, we evaluate the safety and exploratory efficacy outcomes for DRF in Black and non-Black patient subgroups.</div></div><div><h3>Results</h3><div>Of 1057 patients enrolled, 72 (6.8 %) were Black. In Black vs non-Black patients, mean age was 42 vs 43 years and 75 % vs 72 % were female, respectively. In both groups, median (range) duration of DRF exposure was 1.8 (0.0–2.0) years and mean Expanded Disability Status Scale (EDSS) was 2.7. The most common prior DMTs for both Black vs non-Black patients were interferons (47 % vs 37 %) and glatiramer acetate (36 % vs 24 %). DRF treatment was discontinued in 33 (46 %) Black and 224 (23 %) non-Black patients; most common reasons for discontinuation were withdrawal by patient (<em>n</em> = 11, 15.3 %), adverse events (AEs; <em>n</em> = 7, 9.7 %), and lost to follow-up (<em>n</em> = 7, 9.7 %) in Black patients; AEs (8.2 %) and withdrawal by patient (7.0 %) in non-Black patients. AEs were reported in 90 % Black and 89 % non-Black patients; most AEs were mild or moderate in both groups. Gastrointestinal (GI) AEs were reported in 36 % Black and 32 % non-Black patients; no Black patients discontinued due to GI AEs, vs 7 (0.7 %) non-Black patients. The most commonly reported AE was flushing (18 % Black and 28 % non-Black patients). No AEs of lymphopenia were reported in Black patients compared with 13 % of non-Black patients. Mean absolute lymphocyte count declined from baseline to week 48 by 15 % in Black patients and 29 % in non-Black patients, then plateaued and remained above the lower limit of normal (LLN; 0.91 × 10<sup>9</sup>/L). Adjusted annualized relapse rate (95 % confidence interval) was reduced by 78.2 % (54.6 − 89.5; <em>p</em> < 0.0001) in Black patients, from 12 months before to 96 weeks after DRF treatment; similar to 81.7 % (78.5 − 84.5 %; <em>p</em> < 0.0001) reduction in non-Black patients. Mean number of patients free from confirmed disability progression was 93.4 % by week 48, then 86.2 %","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105912"},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammed Arish , Meisam Sargazi , Mohammad Sedigh Dakkali , Sepide Mohammadzamani , Saeid Rasouli , Mahdi Asani
{"title":"Effect of brimonidine on visual indices in patients with acute optic neuritis: A single blind randomized clinical trial","authors":"Mohammed Arish , Meisam Sargazi , Mohammad Sedigh Dakkali , Sepide Mohammadzamani , Saeid Rasouli , Mahdi Asani","doi":"10.1016/j.msard.2024.105913","DOIUrl":"10.1016/j.msard.2024.105913","url":null,"abstract":"<div><h3>Purpose</h3><div>This study investigates brimonidine's potential effect on visual functions, particularly contrast sensitivity (CS), an indicator of retinal ganglion cell function.</div></div><div><h3>Methods</h3><div>In this single-blind, randomized clinical trial, 60 patients (aged 23–56) with first-episode acute optic neuritis within seven days of symptom onset were randomly assigned to brimonidine or control groups. The intervention group received brimonidine three times daily for three months, while the control group received synthetic tears with the same dosage and frequency. Primary outcomes were changes in CS, visual acuity (VA), and color vision at one and three months post-treatment. Repeated measures ANOVA was used to assess statistically significant and partial eta squared (η2) values, mean differences, and clinically significance important were reported.</div></div><div><h3>Results</h3><div>All participants completed the study without complications. VA improved significantly in both groups by follow-up end (<em>p</em> < 0.001), with significant improvement from first to third month only in the brimonidine group (<em>p</em> < 0.001). The mean VA difference between groups was not statistically and clinically significant. CS showed statistically significant improvement within both groups (<em>p</em> < 0.001) and between groups (<em>p</em> < 0.001), with a large effect size (partial η2 = 0.28). The mean CS difference between groups (14.5) was clinically considerable. No significant changes in color vision were observed between groups (<em>p</em> = 0.96).</div></div><div><h3>Conclusion</h3><div>Brimonidine significantly improved contrast sensitivity compared to placebo and was well-tolerated. Its neuroprotective effects suggest it may be beneficial in treating optic neuritis and preserving retinal ganglion cell function.</div></div><div><h3>Trial registration</h3><div>Prospectively registered at Iranian Clinical Trial Registration; Registration date 3 December 2022; Registration number: IRCT20221127056631N1</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105913"},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391925","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}
Hyun Ji Lyou , Ha Young Shin , Hye Lim Lee , Young Nam Kwon , Seong-il Oh , Jeeyoung Oh , Eun Bin Cho , Sunyoung Kim , Seol-Hee Baek , Byung-Jo Kim , Eunhee Sohn , Jin Myoung Seok , Ju-Hong Min , Seung Woo Kim , Byoung Joon Kim
{"title":"Quality of life in patients with myelin oligodendrocyte glycoprotein antibody associated disease compared to patients with AQP4-IgG positive neuromyelitis optica spectrum disorders: A Korean multicenter study","authors":"Hyun Ji Lyou , Ha Young Shin , Hye Lim Lee , Young Nam Kwon , Seong-il Oh , Jeeyoung Oh , Eun Bin Cho , Sunyoung Kim , Seol-Hee Baek , Byung-Jo Kim , Eunhee Sohn , Jin Myoung Seok , Ju-Hong Min , Seung Woo Kim , Byoung Joon Kim","doi":"10.1016/j.msard.2024.105914","DOIUrl":"10.1016/j.msard.2024.105914","url":null,"abstract":"<div><h3>Background</h3><div>Little is known about the quality of life (QOL) of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We compared QOL and associated factors in patients with MOGAD and aquaporin4 IgG (AQP4-IgG) positive neuromyelitis optica spectrum disorder (NMOSD).</div></div><div><h3>Methods</h3><div>This multicenter questionnaire study compared the QOL of 41 patients with MOGAD and 78 with AQP4-IgG positive NMOSD. Patients who were positive for AQP4-IgG or MOG antibodies were included. WHO Quality of Life Scale Brief Version was used to assess QOL in physical, psychological, social, and environmental domains. QOL, sleep quality, pain, fatigue, and depression were compared between the two groups. The factors associated with QOL in each group and the entire cohort were analyzed.</div></div><div><h3>Results</h3><div>The proportion of patients with poor QOL was not significantly different between MOGAD (51.22 %) and AQP4-IgG positive NMOSD (58.97 %, <em>p</em> = 0.054). In the MOGAD group, the pain score (β=-1.032, <em>p</em> = 0.001) and depression score (β=-0.694, <em>p</em> = 0.007) were negatively associated with physical and psychological QOL, respectively. Sleep quality was negatively associated with physical (β=-1.506, <em>p</em> = 0.034) and psychological (β =-2.064, <em>p</em> = 0.033) QOL. When the entire cohort was analyzed, a positive MOG antibody was independently associated with worse psychological QOL (β=-8.998, <em>p</em> = 0.013) compared to positive AQP4-Ab after adjustment for sleep quality, depression, fatigue, and pain.</div></div><div><h3>Conclusions</h3><div>The overall QOL of the patients of MOGAD was comparable to that of AQP4-IgG positive NMOSD. Patients with MOGAD were experiencing sleep disorder, fatigue, and depression at similar degrees to those of patients with AQP4-IgG positive NMOSD. Further consideration of sleep quality and psychological QOL is required to improve QOL in patients with MOGAD.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105914"},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381298","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}
Yanping Wang , Xiangyun Guo , Lin Zhang , Ying Hua , Miao Jing , Xiaoyue Hu , Xiaochun Fan , Mingxia Sun , Yanshan Liu , Jianbiao Wang
{"title":"Clinical characteristics analysis of 24 cases of pediatric MOG antibody-associated diseases","authors":"Yanping Wang , Xiangyun Guo , Lin Zhang , Ying Hua , Miao Jing , Xiaoyue Hu , Xiaochun Fan , Mingxia Sun , Yanshan Liu , Jianbiao Wang","doi":"10.1016/j.msard.2024.105911","DOIUrl":"10.1016/j.msard.2024.105911","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the clinical characteristics of children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on the clinical data, antibody tests, imaging, and factors associated with recurrence in 24 children diagnosed with MOGAD at Wuxi Children's Hospital from December 2017 to December 2023.</div></div><div><h3>Results</h3><div>Among the 24 included children, the clinical characteristics at the onset of the first episode included fever (12 cases), headache (8), decreased vision (7), drowsiness (6), convulsions (5), ataxia (3), paralysis of both lower limbs (2), urinary and fecal incontinence (2), and central facial palsy (1). Among them, one case started with paralysis of both lower limbs and urinary retention, and electromyography suggested the involvement of peripheral nerves, leading to the diagnosis of MOG antibody-associated central and peripheral demyelinating syndrome (MOGAD-CCPD). Cranial MRI abnormalities were observed in 20 children, and spinal MRI abnormalities were noted in 6 children. All children responded well to corticosteroids and intravenous immunoglobulin, but 7 children experienced a relapse. Among them, 3 children achieved disease control after the addition of mycophenolate mofetil (CellCept), with no further relapses observed during follow-up.</div></div><div><h3>Conclusion</h3><div>The disease course of MOGAD can be monophasic or relapsing. Most children have a good response to acute phase treatments. For those who relapse, immunosuppressants can be added as maintenance therapy, and the clinical prognosis is generally good. This article reports the first highly rare case in China of MOGAD-CCPD in childhood, suggesting that MOG IgG may serve as a potential biomarker associated with CCPD.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105911"},"PeriodicalIF":2.9,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivan Kiselev , Olga Kulakova , Olga Baturina , Marsel Kabilov , Alexey Boyko , Olga Favorova
{"title":"Different genome-wide DNA methylation patterns in CD4+ T lymphocytes and CD14+ monocytes characterize relapse and remission of multiple sclerosis: Focus on GNAS","authors":"Ivan Kiselev , Olga Kulakova , Olga Baturina , Marsel Kabilov , Alexey Boyko , Olga Favorova","doi":"10.1016/j.msard.2024.105910","DOIUrl":"10.1016/j.msard.2024.105910","url":null,"abstract":"<div><h3>Background</h3><div>Relapsing-remitting multiple sclerosis (RRMS) is a most common form of multiple sclerosis in which periods of neurological worsening are followed by periods of clinical remission. RRMS relapses are caused by an acute autoimmune inflammatory process, which can occur in any area of the central nervous system. Although development of exacerbation cannot yet be accurately predicted, various external factors are known to affect its risk. These factors may trigger the pathological process through epigenetic mechanisms of gene expression regulation, first of all, through changes in DNA methylation.</div></div><div><h3>Methods</h3><div>In the present work, we for the first time analyzed genome-wide DNA methylation patterns in CD4+ <em>T</em> lymphocytes and CD14+ monocytes of the same RRMS patients in relapse and remission. The effects of the differential methylation on gene expression were studied using qPCR.</div></div><div><h3>Results</h3><div>We found 743 differentially methylated CpG positions (DMPs) in CD4+ cells and only 113 DMPs in CD14+ cells. They were mostly hypermethylated in RRMS relapse in both cell populations. However, the proportion of hypermethylated DMPs (as well as DMPs located within or in close proximity to CpG islands) was significantly higher in CD4+ <em>T</em> lymphocytes. In CD4+ and CD14+ cells we identified 469 and 67 DMP-containing genes, respectively; 25 of them were common for two cell populations. When we conducted a search for differentially methylated genomic regions (DMRs), we found a CD4+ specific DMR hypermethylated in RRMS relapse (adj. <em>p</em> = 0.03) within the imprinted <em>GNAS</em> locus. Total level of the protein-coding <em>GNAS</em> transcripts in CD4+ <em>T</em> cells decreased significantly in the row from healthy control to RRMS remission and then to RRMS relapse (adj. <em>p</em> = 3.1 × 10<sup>–7</sup> and 0.011, respectively).</div></div><div><h3>Conclusion</h3><div>Our findings suggest that the epigenetic mechanism of DNA methylation in immune cells contributes to the development of RRMS relapse. Further studies are now required to validate these results and shed light on the molecular mechanisms underlying the observed <em>GNAS</em> methylation and expression changes.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105910"},"PeriodicalIF":2.9,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381296","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}
E. Coerver , L. Schoof , L. Hogenboom , M. Wessels , P. van Ruyven , A. van Samkar , J. Mostert , Z. van Kempen , B.W. van Oosten , B.H. Wokke , E. Tallantyre , KM. Myhr , O. Torkildsen , J. Killestein , I. Smets , E. Strijbis
{"title":"The recurrence of disease activity after ocrelizumab discontinuation in multiple sclerosis","authors":"E. Coerver , L. Schoof , L. Hogenboom , M. Wessels , P. van Ruyven , A. van Samkar , J. Mostert , Z. van Kempen , B.W. van Oosten , B.H. Wokke , E. Tallantyre , KM. Myhr , O. Torkildsen , J. Killestein , I. Smets , E. Strijbis","doi":"10.1016/j.msard.2024.105900","DOIUrl":"10.1016/j.msard.2024.105900","url":null,"abstract":"<div><h3>Introduction</h3><div>Ocrelizumab (OCR) is a highly effective treatment of multiple sclerosis (MS), and B cell repopulation profiles suggest that it might be used as an immune reconstitution therapy. However, data on disease recurrence after stopping treatment with OCR are scarce. Our objective was to evaluate the recurrence of disease activity after OCR discontinuation.</div></div><div><h3>Methods</h3><div>In this multicenter retrospective cohort study, we included MS patients who discontinued OCR, without switching to another treatment, for twelve months or more, after having received at least one full dosage of 600 mg. We defined focal inflammation as the occurrence of a clinical relapse or significant MRI activity (≥3 new T2 lesions or ≥2 contrast-enhancing lesions).</div></div><div><h3>Results</h3><div>We included 53 MS patients; 41 relapsing remitting (RRMS), 5 secondary progressive (SPMS) and 7 primary progressive (PPMS) patients. Median follow-up period after OCR discontinuation was 16 months. We only observed focal inflammation after discontinuation in RRMS patients; 2.4 % (1/41) patients presented with significant MRI activity and matching clinical symptoms, and 7.3 % (3/41) patients presented with a suspected clinical relapse without radiological activity: a total of 9.8 % (4/41) at a median time of 17 months after the last infusion.</div></div><div><h3>Discussion</h3><div>We found focal inflammation after discontinuation of OCR in 4 (9.8 %) of the RRMS patients, of which 1 was radiologically confirmed. Our observations highlight that recurrence of focal inflammation seems low but discontinuation may not be appropriate for everyone. Further larger studies are important to determine the immune reconstitution therapy potential of OCR.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105900"},"PeriodicalIF":2.9,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cognitive behavioural therapy for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis","authors":"Henry L.T. Vo , Sandra Elias , Todd A. Hardy","doi":"10.1016/j.msard.2024.105908","DOIUrl":"10.1016/j.msard.2024.105908","url":null,"abstract":"<div><h3>Background</h3><div>Treatment of fatigue is important for many patients with multiple sclerosis (MS). While pharmacological options have not shown consistent benefit, psychological interventions offer another avenue of treatment. Cognitive behavioural therapy (CBT) involves strategies to change maladaptive cognition and illness behaviours that modulate how patients with MS respond to fatigue. The aim of this study was to perform a systematic review and meta-analysis to determine the effectiveness of CBT for the treatment of fatigue in patients with MS.</div></div><div><h3>Methods</h3><div>Five databases (Cochrane Central Register of Controlled Trials, MEDLINE/PubMed, Embase, Emcare and PsycINFO) were searched up until 31 July 2023. Randomised controlled trials involving adult patients with MS and fatigue, comparing CBT with another intervention or usual treatment were included. Studies were required to measure fatigue severity and/or the impact of fatigue as the primary outcome(s). Each study was assessed for bias using the Cochrane Risk of Bias tool version 2. Studies with sufficient data were used for meta-analysis to quantify the short- and long-term effects of CBT on MS-related fatigue. The level of certainty provided by the body of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework.</div></div><div><h3>Results</h3><div>Eight studies were included in the review and six studies contributed to the meta-analysis. Most studies had a low overall risk of bias. CBT interventions differed in the number, duration and frequency of sessions, mode of delivery and therapist. There were significant short- (standardised mean difference (SMD) -0.58, 95% confidence interval (95%CI) -0.85 to -0.31, P-value < 0.0001) and long-term (SMD -0.36, 95%CI -0.52 to -0.19, P-value < 0.0001) effects supporting CBT. The evidence provided a low level of certainty for the short-term effect because of heterogeneity of results and possible publication bias, while there was high certainty for the long-term result.</div></div><div><h3>Conclusion</h3><div>The study provides secondary evidence that CBT has moderate short-term and small long-term effects in reducing fatigue in patients with MS. CBT should be regarded as a viable evidence-based intervention, particularly in the absence of established alternatives. Future research should identify the ideal characteristics of a fatigue-specific CBT intervention, patient factors that predict treatment response and strategies to maintain initial improvements over time.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105908"},"PeriodicalIF":2.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jörn Nielsen , Sarah Görtz , Ellen Aschermann , Jochen Saliger , Eva Hennecken , Mareike Eschweiler , Hans Karbe , Elke Kalbe , Ann-Kristin Folkerts
{"title":"Exploring humor as a coping factor against depressive mood and fear of progression in people with multiple sclerosis with moderate disability: A cross-sectional analysis of a rehabilitation cohort","authors":"Jörn Nielsen , Sarah Görtz , Ellen Aschermann , Jochen Saliger , Eva Hennecken , Mareike Eschweiler , Hans Karbe , Elke Kalbe , Ann-Kristin Folkerts","doi":"10.1016/j.msard.2024.105906","DOIUrl":"10.1016/j.msard.2024.105906","url":null,"abstract":"<div><h3>Background</h3><div>People with multiple sclerosis (pwMS) face disease-related stress throughout their lives, often resulting in depressive mood and fear of progression (FoP). People with a pronounced sense of humor demonstrate greater resilience to stress and tend to perceive threats as challenges. This research investigates whether humor can be identified as a relevant coping factor in pwMS regarding depressive mood and FoP.</div></div><div><h3>Methods</h3><div>Participants were 77 German inpatients aged 25–64 years with predominantly relapsing-remitting MS. Blockwise regression analyses were conducted to examine the relationship between <em>humor skills</em> (Sense of Humor Scale, SHS), <em>depressive mood</em> (Centre for Epidemiologic Studies Depression Scale, CES-D), and <em>fear of progression</em> (Fear of Progression-Questionnaire, FoP-Q), adjusting for demographic, disease-specific, and self-management variables. Correlational and moderator analyses were conducted to evaluate the impact of <em>humor styles</em> (Comic Style Markers, CSM) and <em>self-observation</em> (as a self-distancing measure, Questionnaire to Assess Resources and Self-Management Skills) on these relationships.</div></div><div><h3>Results</h3><div>The summed SHS score was found to be a significant unique determinant for less depressive mood (CES-D, RΔ = 0.05, <em>p</em> = .005), low FoP (FoP-Q sum score, RΔ = 0.06, <em>p</em> = .004), and greater anxiety coping (FoP-Q anxiety coping, RΔ = 0.06, <em>p</em> = .007). Only <em>light humor style</em> was associated with specific FoP-Q scales; the variable <em>dark humor style</em> was not correlated with any study variable. The subscale <em>self-observation</em> failed to moderate between SHS and emotional disorders.</div></div><div><h3>Conclusion</h3><div>Data indicate that humor skills in pwMS are associated with less depression and FoP, which argues for incorporating adaptive humor as a coping resource into psychosocial interventions for pwMS. However, further validation is needed through larger and longitudinal trials.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105906"},"PeriodicalIF":2.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Manifestations of walking fatigability in people with multiple sclerosis based on gait quality and distance walked during the six minutes walking test","authors":"Felipe Balistieri Santinelli , Zuhal Abasıyanık , Cintia Ramari , Griet Gysemberg , Daphne Kos , Massimiliano Pau , Alon Kalron , Pieter Meyns , Serkan Ozakbas , Peter Feys","doi":"10.1016/j.msard.2024.105909","DOIUrl":"10.1016/j.msard.2024.105909","url":null,"abstract":"<div><h3>Background</h3><div>Distance walking fatigability (DWF) in people with multiple sclerosis (pwMS) is defined as a decrease in the distance walking over time. However, declines in gait quality (i.e., gait quality fatigability- GQF) may occur independently or alongside DWF.</div></div><div><h3>Objective</h3><div>i) to investigate how walking fatigability manifests and its prevalence in pwMS; ii) to describe the temporal pattern of the changes of specific gait characteristics during the 6-minute walking test (6MWT)</div></div><div><h3>Methods</h3><div>Eighty-eight pwMS (EDSS 4[0–6.5], 49[21–70] years) and 47 healthy controls (HC- 46[25–60] years) performed the 6MWT wearing inertial measurement units. Gait characteristics (stride length, sensor-based gait speed, cadence, double support, step duration, stance phase, step duration asymmetry, step duration variability, foot-strike, toe-off, and leg circumduction) and walking distance were recorded in 1-minute intervals. A fatigability index was calculated by comparing the last and first minute of the 6MWT to identify abnormal worsening based on cutoff scores. The manifestation of walking fatigability was counted. The temporal pattern of worsening of gait characteristics during the 6MWT was examined in pwMS exceeding the cutoff values, compared to pwMS without abnormal changes and HC, using a two-way ANOVA (group vs. minutes)</div></div><div><h3>Results</h3><div>Thirty-five pwMS presented both DWF and GQF, 2 presented isolated DWF, 27 presented isolated GQF, and 24 presented non-walking fatigability. PwMS having GQF presented worsening in gait characteristics (cadence, step duration, step duration variability, or toe-off angle) from minute 2 onwards of the 6MWT, while HCs and pwMS without abnormal changes stabilized gait from minute 2 towards the end of the 6MWT.</div></div><div><h3>Conclusion</h3><div>Walking fatigability in pwMS manifests not only as a decrease in walking distance but also as changes in gait quality. Understanding changes in gait characteristics during walking can help tailor rehabilitation interventions.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105909"},"PeriodicalIF":2.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375654","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}
Alfonso Delgado-Álvarez , Laura Hernández-Lorenzo , T. Rune Nielsen , María Díez-Cirarda , Constanza Cuevas , Paloma Montero-Escribano , Cristina Delgado-Alonso , María Valles-Salgado , María José Gil-Moreno , Jorge Matias-Guiu , Jordi A Matias-Guiu
{"title":"European cross-cultural neuropsychological test battery (CNTB) for the assessment of cognitive impairment in multiple sclerosis: Cognitive phenotyping and classification supported by machine learning techniques","authors":"Alfonso Delgado-Álvarez , Laura Hernández-Lorenzo , T. Rune Nielsen , María Díez-Cirarda , Constanza Cuevas , Paloma Montero-Escribano , Cristina Delgado-Alonso , María Valles-Salgado , María José Gil-Moreno , Jorge Matias-Guiu , Jordi A Matias-Guiu","doi":"10.1016/j.msard.2024.105907","DOIUrl":"10.1016/j.msard.2024.105907","url":null,"abstract":"<div><h3>Background</h3><div>The European Cross-Cultural Neuropsychological Test Battery (CNTB) has been proposed as a comprehensive battery for cognitive assessment, reducing the potential impact of cultural variables. In this validation study, we aimed to evaluate the diagnostic capacity of CNTB for the assessment of participants with multiple sclerosis (pwMS) compared to the Neuronorma battery (NN) according to the International Classification of Cognitive Disorders in MS criteria, and to develop machine learning (ML) algorithms to improve the diagnostic capacity of CNTB and to select the most relevant tests.</div></div><div><h3>Methods</h3><div>Sixty pwMS and 60 healthy controls (HC) with no differences in sex, age, or years of education were enrolled. All participants completed the CNTB and pwMS were also examined with NN, depression, and fatigue scales. Impaired domains and cognitive phenotypes were defined following IC<img>CoDiMS based on CNTB scores and compared to NN, according to -1SD and -1.5SD cutoff scores. To select the most relevant tests, random forest (RF) was performed for different binary classifications.</div></div><div><h3>Results</h3><div>PwMS showed a lower performance compared to HC with medium-large effect sizes, in episodic memory, executive function, attention, and processing speed, in accordance with their characteristic cognitive profile. There were no differences in impaired domains or cognitive phenotypes between CNTB and NN, highlighting the role of episodic memory, executive function, attention, and processing speed tests. The most relevant tests identified by RF were consistent with inter-group comparisons and allowed a better classification than SD cutoff scores.</div></div><div><h3>Conclusion</h3><div>CNTB is a valid test for cognitive diagnosis in pwMS, including key tests for the most frequently impaired cognitive domains in MS. The use of ML techniques may also be useful to improve diagnosis, especially in some tests with lower sensitivity.</div></div>","PeriodicalId":18958,"journal":{"name":"Multiple sclerosis and related disorders","volume":"91 ","pages":"Article 105907"},"PeriodicalIF":2.9,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375653","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}