Sleep disturbance is common in aquaporin-4 immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), but its clinical and neurobiological correlates remain incompletely characterized; prior studies used single-modality assessments. In this exploratory cross-sectional study we characterized sleep-wake patterns in clinically stable AQP4-IgG-positive NMOSD and explored volume-sleep associations. Patients and controls underwent questionnaires, 7-day wrist actigraphy and structural MRI; intracranial volume-normalized regional volumes and within-patient volume-sleep associations were examined, with Benjamini-Hochberg false discovery rate (FDR) correction. Twenty-four patients and 26 controls were enrolled; 20 patients and 20 database-derived controls contributed MRI. Patients were older than controls (49.7 versus 33.0 years; g = 1.40); analyses were adjusted for age and body mass index (BMI). After adjustment, patients showed longer time in bed (+58 min) and total sleep time (+50 min), whereas sleep efficiency and wake after sleep onset did not differ. Higher BMI was associated with lower sleep efficiency (r = -0.44) and longer sleep onset latency. Subjective sleep disturbance and pain-related quality of life were worse in NMOSD. After FDR correction, volume reductions were observed in bilateral hippocampal molecular-layer subfields and all five corpus callosum segments, with suggestive thalamic reductions; no volume-sleep association survived. Sleep disturbance in clinically stable AQP4-IgG-positive NMOSD was characterized by greater subjective sleep burden and altered sleep-wake timing, with associations observed with clinical and metabolic factors. These hypothesis-generating findings are consistent with a multifactorial pattern of associations and highlight the need for longitudinal studies integrating objective sleep measurement, neuroimaging and biomarkers.
Background Respiratory dysfunction may occur in multiple sclerosis, and respiratory complications are the most common cause of death. There is limited evidence to guide assessment and management of respiratory dysfunction in people with advanced multiple sclerosis. Objective The aim of this study was to evaluate the assessment and management of respiratory dysfunction in people with advanced multiple sclerosis as part of their routine out-patient care. Methods The medical records of 105 people with multiple sclerosis with Expanded Disability Status Scale (EDSS) score ≥ 8.0 assessed in a multidisciplinary clinic from April 2021 to January 2024 were retrospectively reviewed. Clinical details including age, sex, EDSS score, dysphagia status, respiratory symptoms and planned respiratory interventions were recorded. Results Sixty-four people (61%) reported at least one symptom suggestive of respiratory dysfunction including hypophonia, weak cough, difficulty in breathing, difficulty clearing airway secretions, chest infection and sleep apnoea. Forty-seven people (44.8%) received or were referred for respiratory interventions. Respiratory symptoms and interventions increased with advancing disability, respectively reported in 94% and 76% of those with EDSS ≥9.0. Conclusion Respiratory dysfunction is very common in people with advanced multiple sclerosis and increases with higher EDSS. Screening for respiratory dysfunction can be easily incorporated into routine clinical care by asking about respiratory symptoms. Referral for further assessment and intervention may be required, but this may be constrained by a lack of respiratory services for people with multiple sclerosis.
Background : Artificial intelligence (AI) has been applied across many aspects of multiple sclerosis (MS) theragnostics, from lesion detection in magnetic resonance imaging (MRI), gait assessment and treatment response prediction to drug repurposing. However, a considerable number of models characterized by high technical performance have yet to be translated into a clinical setting. Objective : To investigate the translational barriers between AI-based theragnostic applications and their clinical implementation in MS. Key Messages : Many AI-based models have been trained using retrospective data from a single-center source and are rarely externally validated in larger independent populations. Major barriers to translation include technical issues, limited prospective validation, and multi-modality data, poor interoperability, clinical utility, and ethical concerns. In MS particularly, models must remain reliable across various MS phenotypes and disease modifying therapies making translation even more challenging. Conclusion : High technical performance alone is not sufficient for clinical implementation. Meaningful translation of AI-based theragnostic approaches in MS will require multicenter datasets representative of larger populations, further external validation and transparency. Only through these measures can AI-driven theragnostic approaches evolve from promising research models into clinically meaningful tools for MS care.
BACKGROUND:Multiple sclerosis (MS) is a major cause of chronic neurological disability, and its burden has shifted from premature mortality toward long-term disability. Italy, with its marked north-south gradients and the exceptional epidemiology of Sardinia, offers a unique setting to examine whether this transition has occurred uniformly across regions and sexes. METHODS:Using Global Burden of Disease 2023 subnational estimates, we analysed MS burden in Italy from 1990 to 2023 across five macro-areas. Age-standardized disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and the YLL/YLD ratio were evaluated by sex. Temporal trends were quantified using log-linear regression to estimate annual percentage change (EAPC). Non‑linearities were assessed using Joinpoint regression. We assessed sex-specific differences, changes in proportional composition of DALYs, and heterogeneity of trends across macro-areas. RESULTS:DALY rates increased in all macro-areas, with the steepest rises in Sardinia and South+Sicily, and the smallest increase in the Center. YLDs rose faster than YLLs everywhere, producing a consistent decline in the YLL/YLD ratio and confirming a shift toward disability-dominated burden. EAPCs were positive for DALYs and YLDs in all regions and sexes, highest in Sardinia. Joinpoint regression revealed multiple inflection points. Sex differences were present but smaller than geographic differences. Global interaction tests showed significant heterogeneity across macro-areas for all outcomes. CONCLUSIONS:MS burden in Italy has increased substantially, consistent with a rising population‑level disability burden, which may reflect higher prevalence, longer survival, and evolving epidemiological dynamics. Differences across macro‑areas require continued region‑specific epidemiological monitoring.
BACKGROUND:Cognitive impairments are consistently associated with the actual number of falls and future fall risk in people with multiple sclerosis (PwMS), but their influence and predictive usefulness regarding fear of falling (FoF) are not well understood. Since FoF can greatly affect a patient's lived experience and is essential for evaluating overall fall risk in PwMS, we aimed to explore how cognitive performance relates to, and forecasts, individuals' perceptions of their fall risk, and whether disease severity impacts this relationship. METHODS:FoF (Modified Falls Efficacy Scale, MFES) and neurocognitive function (NeuroTrax computerized cognitive assessment battery) were assessed in 188 PwMS. The NeuroTrax battery provided index scores for global cognition and specific cognitive domains such as memory, executive function, attention, processing speed, visuo-spatial, verbal function, and motor skills. The predictive value of cognitive performance on FoF was examined through hierarchical regression models. RESULTS:Poorer performance on tests of executive function (β = 0.32, p = 0.023) and motor skills (β = 0.24, p = 0.009) were significantly predictive of greater FoF in our broader MS sample. Subgroup analyses showed that for participants with low-to-moderate disease disability, impairment in executive function (β = 0.38, p = 0.023) remained the only significant predictor of FoF in PwMS. Conversely, motor skill impairment (β = 0.38, p = 0.026) was a significant predictor of FoF in participants with higher disease disability. Participants with three or more (n = 47) domains of cognitive impairment had a higher FoF than those with 1-2 (n = 57, p = 0.02) or 0 (n = 76, p < 0.001) impaired domains (F(2, 104.55) = 9.15, p < 0.001). CONCLUSION:FoF in PwMS can affect day-to-day planning and quality of life but is often overlooked as a meaningful aspect of the patient's lived experience. Our findings suggest that cognitive deficits are associated with greater FoF, and that the cognitive domain related to FoF varies as a function of disability level. Deficits in executive functioning and motor skills, in particular, may indicate broader disease impact on the patient's perception of their physical capabilities.
OBJECTIVE:This systematic review synthesized evidence from intervention studies published over the past 25 years that aimed to improve coping and psychosocial well-being among individuals early in the multiple sclerosis (MS) disease course. The goal was to evaluate intervention characteristics, theoretical foundations, and psychosocial outcomes, and to identify gaps for future research. METHODS:Following PRISMA guidelines, a comprehensive search was conducted across PubMed, CINAHL, PsycINFO, and Web of Science (2000-2025). Eligible studies included quantitative or mixed-methods interventions that addressed coping or psychosocial well-being among adults newly diagnosed with MS. Data extraction and quality assessment were completed independently by multiple reviewers using the Joanna Briggs Institute Critical Appraisal Tools. RESULTS:Seven studies (n = 345) met inclusion criteria, representing cognitive-behavioral therapy, mindfulness, acceptance-based, and nurse- or peer-delivered interventions. The interval between diagnosis and intervention enrollment ranged from 14 days to >4 years, suggesting different phases of adjustment. All interventions produced significant short-term improvements in at least one psychosocial domain (e.g., anxiety, depression, stress, coping, or illness acceptance). However, sustained effects beyond 6-12 months were inconsistent. Common mechanisms across interventions included enhancing self-efficacy, stress management, and adaptive coping. CONCLUSIONS:The available evidence suggests that brief psychosocial interventions for adults in the early years after MS diagnosis are feasible and may provide short-term benefits for selected psychosocial outcomes. However, the evidence base remains limited, heterogeneous, and preliminary. Future studies should more clearly define diagnosis timing, use adequately powered designs and longer follow-up, and examine mechanisms of change.
Background Ublituximab(UTX) is a novel, glycoengineered anti-CD20 monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) that enables efficient B-cell depletion at lower doses and shorter infusion times compared to other anti-CD20 therapies. This critical review synthesizes evidence on the long-term efficacy and safety of UTX in relapsing forms of multiple sclerosis (MS). Objective To critically evaluate ublituximab's long-term efficacy and safety in relapsing MS via clinical evidence synthesis. Methods We reviewed peer-reviewed literature, clinical trials, extension studies, observational reports, and recent conference posters/abstracts, providing a qualitative overview. Results UTX shows sustained disease control, including reduced relapses and MRI activity, over extended periods in relapsing MS patients. B-cell depletion remains effective long-term, with a safety profile typical of anti-CD20 therapies, including manageable infusion reactions and stable monitoring for infections and immunoglobulins. Conclusions UTX represents a potent, efficient disease-modifying therapy for relapsing MS with robust, durable efficacy comparable to other anti-CD20 agents. Its primary clinical advantage is the streamlined one-hour maintenance infusion every 24 weeks. While the absence of head-to-head trials against other high-efficacy agents and knowledge gaps regarding long-term safety in diverse populations remain limitations, current evidence supports ublituximab's position in aggressive early-treatment strategies, provided that clinical vigilance for cumulative risks such as hypogammaglobulinemia is maintained. Future research should prioritize comparative trials, investigation in progressive MS phenotypes, and validation of optimized dosing strategies.
