BACKGROUND: We investigated whether the improved prognosis in relapsing-remitting multiple sclerosis (RRMS) was also reflected in socioeconomic milestones. METHODS: This 29-year nationwide cohort study linked the Danish...BACKGROUND: We investigated whether the improved prognosis in relapsing-remitting multiple sclerosis (RRMS) was also reflected in socioeconomic milestones. METHODS: This 29-year nationwide cohort study linked the Danish MS Registry with national registries on social transfer payments and income. We created two cohorts of all persons aged 18-63 with RRMS: a clinical onset-based cohort (onset 1995-2018; N = 10,894); and a diagnosis-based cohort (diagnosed 1995-2018; N = 11,392). Cohort entry years were grouped: 1995-2000; 2001-2006; 2007-2012; 2013-2018. Socioeconomic milestones included disability pension receipt, employment in protected employment scheme (flexi-job, introduced in 2000), and loss of income from paid work. Age- and sex adjusted Fine-Gray hazard models were applied. Diagnosis-based cohort analyses were further adjusted for baseline Extended Disability Status Scale score. RESULTS: Compared with the 1995-2000 onset group, persons with later onset had a lower risk of disability pension with HRs of 0.66 (95 %CI: 0.61-0.72), 0.46 (95 %CI: 0.42-0.51), and 0.33 (95 %CI: 0.30-0.38) in successive periods. HRs for income loss (0.78; 0.62; 0.49) and flexi-job (0.75; 0.64) also declined over time in a consistent exposure-response pattern. Diagnosis-based cohort results were similar. CONCLUSION: We found a lower risk of adverse socioeconomic milestones in recent compared to early cohorts of persons with RRMS, likely partly indicating improved workability throughout the disease course.
BACKGROUND: This scoping review aimed to identify and synthesize the types of virtual reality (VR) interventions and applications used in the rehabilitation of adults with multiple sclerosis (MS). METHODS: A comprehensiv...BACKGROUND: This scoping review aimed to identify and synthesize the types of virtual reality (VR) interventions and applications used in the rehabilitation of adults with multiple sclerosis (MS). METHODS: A comprehensive search was conducted across seven generic databases (MEDLINE/PubMed, Scopus, Cochrane Library, Web of Science Core Collection, EBSCOhost, CINAHL, and ProQuest) up to April 2026. The review followed PRISMA-ScR guidelines and the protocol was prospectively registered in OSF https://doi.org/10.17605/OSF.IO/G7R5X RESULTS: A total of 670 records were identified, and 33 studies met the inclusion criteria. The evidence showed a predominance of non-immersive and semi-immersive VR systems, whereas fully immersive and augmented/projection-based applications were less frequently reported. Applications were technologically heterogeneous and included commercial exergaming platforms, motion-sensing systems, specialized rehabilitation devices, immersive head mounted systems, telerehabilitation tools, and projection-based environments CONCLUSIONS: VR based rehabilitation in adults with MS is characterized by heterogeneous technologies and diverse clinical applications. Current evidence supports VR mainly as a feasible adjunctive rehabilitation tool, with non-immersive and semi-immersive systems predominating and fully immersive or augmented/projection-based approaches emerging as areas for further research.
PURPOSE: To develop a deep learning-based fully automated framework for segmenting multiple sclerosis (MS) lesions in the spinal cord (SC) using images derived from MP2RAGE acquisitions. MATERIALS AND METHODS: This retro...PURPOSE: To develop a deep learning-based fully automated framework for segmenting multiple sclerosis (MS) lesions in the spinal cord (SC) using images derived from MP2RAGE acquisitions. MATERIALS AND METHODS: This retrospective multicenter study included 472 MRI volumes from 422 subjects (mean age 52±12.5 years), comprising 402 patients with MS and 20 healthy controls, acquired at three centers using 3 T and 7 T MRI systems. MP2RAGE-UNI images were preprocessed and analyzed using the Spinal Cord Toolbox (SCT). The multicenter 3 T dataset was divided into training (60%), validation (20%), and testing (20%) subsets, while the 7 T dataset was reserved for testing. The proposed method (UNIseg), based on the nnU-Net v2 architecture, was trained on the multicenter dataset and compared with the current benchmark (seg_ms_lesion_mp2rage, available in SCT v6.3 and earlier versions), which was trained on single-center MP2RAGE-UNI data. Segmentation performance was evaluated using Dice coefficient and lesion-wise metrics by comparing both UNIseg and the benchmark against reference standard. Statistical comparisons were performed using the Wilcoxon signed-rank test. RESULTS: On the 3 T dataset, UNIseg achieved a mean Dice score of 0.67, significantly outperforming the benchmark (p ≤ 0.01). Lesion-wise sensitivity and precision were 0.81 and 0.92, respectively, with fewer false-positive segmentations. On the 7 T dataset, UNIseg also demonstrated significantly higher performance (p ≤ 0.001), although segmentation performance was lower than that observed at 3 T CONCLUSION: UNIseg provides a robust and efficient approach for segmentation of lesions, improving accuracy compared with existing methods, especially for 3 T data. The trained model and code are publicly available in SCT v6.4 and later.
Fingolimod is an immunosuppressive drug widely used to manage relapsing-remitting multiple sclerosis (RRMS), which is associated with increased rates of viral infections. We described 3 cases of viral skin infections rel...Fingolimod is an immunosuppressive drug widely used to manage relapsing-remitting multiple sclerosis (RRMS), which is associated with increased rates of viral infections. We described 3 cases of viral skin infections related to fingolimod therapy. One of them developed cervical dysplasia. The first case is a 26-year-old woman with RRMS who developed anogenital warts 11 and a half years after using fingolimod. The second case is a 44-year-old woman with RRMS who developed genital warts four years after the onset of receiving fingolimod. Pap smear testing confirmed low-grade squamous intraepithelial dysplasia, with positive human papillomavirus (HPV) types 18 and 45. A year later, she developed genital molluscum contagiosum. The third case is a 28-year-old man with RRMS after six years of starting fingolimod, who developed widespread molluscum contagiousum, which resolved with no recurrence after fingolimod cessation. In conclusion, fingolimod treatment is associated with an increased risk of molluscum contagiosum, HPV infections, and HPV-associated dysplasia in RRMS patients. Periodic clinical surveillance and HPV vaccination are recommended for patients receiving fingolimod therapy.
BACKGROUND/OBJECTIVES: Neurofilament light (NfL) is a biomarker of axonal damage, typically measured in CSF or venous blood. There is growing interest in the utility of remote sampling methods however limited studies of...BACKGROUND/OBJECTIVES: Neurofilament light (NfL) is a biomarker of axonal damage, typically measured in CSF or venous blood. There is growing interest in the utility of remote sampling methods however limited studies of feasibility exist. METHODS: 45 people with MS undergoing lumbar puncture were recruited and had at least one sample included. NfL levels from different biofluids and sampling methods were examined at baseline: CSF (n = 43), venous plasma (n = 29) and finger-prick dried plasma spots (fDPS, n = 39). Participants were then asked to self-collect fDPS at two, four and six months after enrolment. RESULTS: Levels of NfL were highest in CSF with a geometric mean of 449.78 pg/ml (95% CI 334.25-605.26) compared to plasma, 71.48 pg/ml (95% CI 57.04-89.57) or fDPS 4.02pg/ml (95% CI 3.03-5.36). There was a strong correlation between CSF and venous plasma NfL, (r = 0.78, r=0.61, p < 0.001); and venous plasma and fDPS NfL, (r = 0.71, r=0.50, p < 0.005); and a moderate correlation between CSF and fDPS, (r = 0.44, r=0.20, p < 0.05). CONCLUSION: Remote self-collection of fDPS was feasible in our study with NfL levels strongly correlating with plasma while capturing CSF trends. Additionally, NfL remained stable over six months in a clinically stable population, supporting the reliability of the assay.
INTRODUCTION: Brain structure deteriorates with aging as well as with neurodegenerative diseases such as multiple sclerosis (MS). While these brain changes are accompanied by deterioration of motor function, the associat...INTRODUCTION: Brain structure deteriorates with aging as well as with neurodegenerative diseases such as multiple sclerosis (MS). While these brain changes are accompanied by deterioration of motor function, the association between brain structures and motor function in older people with MS (pwMS) has been scarcely investigated, especially across a broad range of outcomes. OBJECTIVE: To investigate the association between a broad range of brain structures and motor function outcomes in older pwMS as well as in older, healthy controls (HC). METHODS: The present cross-sectional study included n = 41 older pwMS (≥60 years) and n = 27 age- and sex-matched HC. Assessments included volume and diffusivity of brain structures (evaluated via magnetic resonance imaging) and lower extremity motor function including neuromuscular function (muscle strength evaluated via leg press dynamometry; muscle power via chair rise test) and physical function (walking capacity evaluated via tests of walking speed, endurance, and balance/coordination). RESULTS: Associations between brain volumes and motor function were observed (generally weak, although moderate for lesion load), with more frequent and pronounced associations for walking capacity compared to neuromuscular function. Regarding brain diffusivity, associations were observed (generally weak-to-moderate), again with more frequent and pronounced associations for walking capacity compared to neuromuscular function. CONCLUSION: Neurodegeneration - specifically the changes in brain volumes and diffusivity - remains a primary driver of motor decline in older pwMS (as well as in age- and sex-matched HC). This appears particularly evident for lesion load and brain diffusivity, being critically linked to various motor outcomes, most notably walking capacity.
INTRODUCTION: Although word-finding difficulties (WFD) are prevalent in multiple sclerosis (MS), they remain poorly understood. This cross-sectional study aimed to identify several important practical and theoretical cha...INTRODUCTION: Although word-finding difficulties (WFD) are prevalent in multiple sclerosis (MS), they remain poorly understood. This cross-sectional study aimed to identify several important practical and theoretical challenges, including key knowledge gaps related to understanding and measuring aspects of language deficit in MS (i.e., WFD). Further investigations of possible correlates of deficits with other symptoms of MS (i.e., such as depression, fatigue and cognitive impairment) were also carried out as part of this study to find out if WFD is a standalone symptom or is a part of a broader and complex symptom of MS. METHODS: In this cohort study, all data from 586 consecutive Persons with MS (PwMS) (137 males and 449 females), with a mean age of 47.1 (SD±10.34) and a median EDSS score of 2.0, were included. A standardized naming task was used as part of a computerized cognitive assessment battery (CAB, NeuroTrax™) with computer-based administration and off-site scoring that has been validated for use in PwMS to determine the associations between cognitive impairment (CI), fatigue, and depression in WFD. RESULTS: A significant correlation (r = 0.327) was noted in this study between cognitive impairment and WFD (p < 0.001). PwMS with CI had a higher rate of WFD (i.e., 43.2%) as compared to individuals with WFD despite not having CI (i.e., 13.9%). Disability (EDSS), disease duration, depression and fatigue, were not correlated with WFD. CONCLUSION: WFD are most likely part of a larger underlying problem (i.e., CI), but there is a small group of persons with MS and WFD who have isolated WFD. Findings of this study have implications for activities of daily living (ADLs) and therapy for rehabilitation professionals working with PwMS.
BACKGROUND: Although oral cladribine received approval for treating relapsing-remitting multiple sclerosis (RRMS), real-world evidence regarding its long-term effectiveness and safety in the United Arab Emirates (UAE) re...BACKGROUND: Although oral cladribine received approval for treating relapsing-remitting multiple sclerosis (RRMS), real-world evidence regarding its long-term effectiveness and safety in the United Arab Emirates (UAE) remains limited. OBJECTIVE: To evaluate efficacy and safety outcomes of RRMS patients treated with cladribine tablets (CladT) and identify early predictors of response. METHODS: This is a multicenter, observational, retrospective study of RRMS patients treated with CladT from four tertiary MS centers in the UAE. Relapses, disability worsening, occurrence of new or enlarging T2-hyperintense magnetic resonance imaging (MRI) lesions and the proportion of patients achieving no-evidence-of-disease-activity-3 (NEDA-3) status were assessed. Safety outcomes included lymphocyte counts, infections and malignancy. The association between baseline characteristics and outcomes was tested to identify potential predictors of response. RESULTS: A total of 163 MS patients were included, 120 (73.6%) of whom were females. Patients were treated with CladT, with a median (IQR) follow-up of 2.0 (1.0-2.6) years. A total of 121 (74.2%) patients had received another disease-modifying therapy (DMT) before cladribine. By the end of follow-up, the mean annualized relapse rate decreased by 84.4% (p<0.001). Most patients (91.8%) showed no disability progression, 74.1% had no new MRI activity, and 70.5% achieved NEDA-3. The number of relapses prior to CladT was the only predictor of NEDA-3. Safety outcomes included 7 adverse events (2.5%), with no hospitalizations. One patient developed a malignancy (astrocytoma) 1.2 years after treatment initiation. CONCLUSION: Our study results confirm the safety and efficacy profiles of CladT reported in Phase 3 clinical trials and other real-world studies.
OBJECTIVES: To analyze mortality from multiple sclerosis (MS) in Spain from 1992 to 2022 by geographic region, age, and sex, while considering possible period and cohort effects. METHODS: This is a retrospective populati...OBJECTIVES: To analyze mortality from multiple sclerosis (MS) in Spain from 1992 to 2022 by geographic region, age, and sex, while considering possible period and cohort effects. METHODS: This is a retrospective population-based ecological study. Mortality data was obtained from the Spanish National Statistics Institute. Deaths with MS listed as the underlying cause were identified using the International Classification of Diseases (ICD): ICD-9 code 340 for 1992-1998 and ICD-10 code G35 for 1999-2022. They were analyzed using spatial Age-Period-Cohort models fitted with INLA Integrated Nested Laplace Approximation (INLA), and Joinpoint regression was applied to assess national trends in age-standardized mortality. RESULTS: During the period studied (1992-2022), a total of 6524 people died from MS in Spain (2701 males and 3823 females), with mortality exhibiting an annual increase of 1% in both sexes without statistically significant differences; the female-to-male ratio rose from 0.898 in 1992 to 1.472 in 2022, indicating a relative increase in mortality among females compared to males (though not statistically significant); a clear north-south gradient in MS mortality was identified, and the cohort at highest risk comprised individuals born between 1950 and 1960. CONCLUSION: MS mortality increased in both sexes over the 1992-2022 period, and a north-south gradient was observed in Spain. Although overall sex differences in the increase in age-standardized mortality were not statistically significant, the female-to-male ratio showed an upward tendency over time, a finding that should be interpreted as a population-level association rather than evidence of causality.
Interleukin-33 (IL-33) is an important regulator of immune and neuroinflammatory responses implicated in multiple sclerosis (MS), yet its genetic contribution to disease susceptibility remains unclear. In this study, we...Interleukin-33 (IL-33) is an important regulator of immune and neuroinflammatory responses implicated in multiple sclerosis (MS), yet its genetic contribution to disease susceptibility remains unclear. In this study, we examined three IL-33 variants (rs1157505, rs7044343, rs11792633) and circulating IL-33 levels in a Lithuanian case-control cohort (280 MS patients and 280 controls). No statistically significant associations were observed in the overall genetic analysis. However, exploratory sex and age stratified analyses identified subgroup-specific associations, with rs1157505 associated with increased odds of MS in women and with clinical parameters, whereas rs7044343 and rs11792633 showed associations in men. Genetic associations were observed only in participants older than 38 years. Circulating IL-33 levels were lower in MS patients than in controls. Taken together, these findings suggest that IL-33 variants may be associated with selected MS related characteristics in this Lithuanian cohort; however, the subgroup findings should be interpreted cautiously and require replication in larger independent studies.
Lopez-Alcalde J, Yan Y, Canella C
… +10 more, Barth J, Steinemann N, von Wyl V, Baum C, Bolt S, Haegele-Link S, Grob GR, Tietjen AK, Álvarez-Díaz N, Witt CM
BACKGROUND: A systematic visual presentation of clinical research on complementary therapies for people with multiple sclerosis (pwMS) can support clinical decisions and guide future research. OBJECTIVES: To identify the...BACKGROUND: A systematic visual presentation of clinical research on complementary therapies for people with multiple sclerosis (pwMS) can support clinical decisions and guide future research. OBJECTIVES: To identify the interventions and outcomes evaluated in systematic reviews (SRs) and randomized clinical trials (RCTs) of complementary therapies for pwMS. METHODS: Scoping review searching four databases for RCTs (any date) and SRs (since 2017). Results were presented in an evidence and gap map (EGM). RESULTS: The map displayed 63 complementary therapies, 30 outcomes of a core outcome set (COS) and 83 studies (46 SRs, 37 RCTs) published from 1977 to 2023. Most trials were small (26 (70.2%) had 100-200 participants) and conducted in Europe (n = 28; 75.6%). Natural products (n = 57 studies) and mind-body therapies (n = 12) were the most frequent groups of interventions. Cannabis (n = 24) and vitamins (n = 15) were the most frequent individual therapies. For 65.1% of the 63 listed interventions, there were no RCTs or SRs. Seventeen (56.7%) of the 30 core outcomes had fewer than five studies. Seven outcomes (23.3%) were not evaluated. The most frequent outcomes were ability to work/perform daily activities (n = 40 studies), safety (n = 37), health-related quality of life (n = 32), and fatigue (n = 31). CONCLUSIONS: This overview of RCTs and SRs of complementary therapies for pwMS indicates that the available research is scarce, with many interventions and outcomes unevaluated. Future RCTs should be adequately powered to assess outcomes relevant to pwMS. Efforts should be made to integrate research from non-Western studies to inform decisions.
Multiple sclerosis (MS) is a chronic immune-mediated CNS disorder marked by inflammation, demyelination, and neurodegeneration. Standard clinical evaluation, neurological exams, disability scoring, and MRI often miss sub...Multiple sclerosis (MS) is a chronic immune-mediated CNS disorder marked by inflammation, demyelination, and neurodegeneration. Standard clinical evaluation, neurological exams, disability scoring, and MRI often miss subclinical activity and poorly predict progression. Fluid biomarkers in cerebrospinal fluid (CSF) and blood provide objective, quantifiable indicators of disease activity, progression, and therapeutic response. Essential fluid biomarkers for monitoring MS include neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Chitinase-3-like protein 1 (CHI3L1), C-X-C Motif Chemokine 13 (CXCL13), osteopontin (OPN), leptin, brain-derived neurotrophic factor (BDNF), and copeptin. NfL reflects axonal injury and correlates with lesion burden, relapse frequency, and long-term disability. At the same time, GFAP and CHI3L1 track astroglial activation and neurodegeneration, which aid the differentiation between relapsing-progressive forms. CXCL13 and OPN also capture intrathecal immune activity. Ultrasensitive assays allow reliable detection of low-abundance CNS proteins in blood, enabling longitudinal monitoring. Altogether, integrating biomarker panels improves prognostication, guides treatment selection, and assesses the efficacy of disease-modifying therapy. Future studies should prioritize establishing robust reference ranges and accounting for demographic and physiological confounders to ensure accurate clinical application.
BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic autoimmune demyelinating diseases of the central nervous system (CNS) that frequently present with overlapping features,...BACKGROUND: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are chronic autoimmune demyelinating diseases of the central nervous system (CNS) that frequently present with overlapping features, including optic neuritis (ON). This study aimed to evaluate differences in retinal measurements obtained via optical coherence tomography (OCT) between people with multiple sclerosis (PwMS) and neuromyelitis optica spectrum disorder (PwNMOSD). METHODS: The PubMed/MEDLINE, Embase, Scopus, and Web of Science databases were systematically searched up to February 22, 2025, to identify relevant studies investigating retinal changes assessed by OCT in PwMS and PwNMOSD. A meta-analysis was conducted using R software version 4.4.0, applying a random-effects model to calculate pooled standardized mean differences (SMD) for OCT parameters between PwMS and PwNMOSD, as well as between eyes with and without a history of ON. RESULTS: This systematic review and meta-analysis included 60 studies with 3520 PwMS and 1463 PwNMOSD. OCT measurements differed significantly between PwNMOSD and PwMS, especially in ON-affected eyes. The most pronounced difference was found in peripapillary retinal nerve fiber layer (pRNFL) thickness, significantly thinner in PwNMOSD than PwMS (SMD = 0.61; 95% CI:0.44-0.79; p < 0.01), with the largest effect in ON eyes (SMD = 0.98; 95% CI:0.73-1.22; p < 0.05). Significant reductions were also seen in total foveal volume (TFV) (SMD = 1.15; p < 0.01), total macular volume (TMV) (SMD = 0.52; p < 0.01), and macular ganglion cell-inner plexiform layer (mGCIPL) thickness (SMD = 0.47; p < 0.01). CONCLUSION: OCT measurements, including pRNFL, mGCIPL, TFV, and TMV, are consistently reduced in PwNMOSD compared to PwMS, particularly in ON-affected eyes. Further studies should standardize imaging protocols and establish diagnostic criteria.