Ultra-processed foods are increasingly recognised as drivers of adverse health outcomes, yet their implications for multiple sclerosis remain underexamined. Emerging evidence suggests that ultra-processed food-rich dietary patterns are associated with greater central adiposity, pro-inflammatory metabolic signatures, microbiota disruption and adverse neuroimmune profiles relevant to multiple sclerosis. Major conceptual pitfalls, including the heterogeneity of ultra-processed foods and the scarcity of longitudinal or interventional studies addressing neuroimmune outcomes, continue to limit interpretation. Ultra-processed food-driven comorbidities, such as obesity, hypertension, dyslipidaemia, insulin resistance and depression, may further accelerate disability accumulation and reduce treatment efficacy in multiple sclerosis, underscoring the need for integrated dietary-immune models. This review integrates evidence from epidemiology, mechanistic studies, microbiome research and exposome science to provide a coherent framework for interpreting ultra-processed food-multiple sclerosis interactions. Recognising ultra-processed food exposure as a potentially modifiable contributor to multiple sclerosis activity may inform future preventive and therapeutic strategies.
BACKGROUND:The Atlas of MS provides a dataset on multiple sclerosis. This analysis updates the global prevalence (including separate estimates for pediatric multiple sclerosis) and incidence of multiple sclerosis, and examines changes over time using data from 2013, 2020, and 2024. METHODS:Countries participating in the 2024 Atlas update confirmed or updated epidemiological data. Global prevalence was estimated using submitted case counts supplemented with pooled subregional rates and, for 2020 and 2024, literature-based imputation. RESULTS:Experts in 133 countries representing 93% of the global population participated. Prevalence data were provided by 118 countries. Global multiple sclerosis prevalence per 100,000 rose from 24.8 (95% confidence interval: 24.73-24.80) in 2013 to 38.1 (95% confidence interval: 38.09-38.17) in 2024 and most regions showed rising prevalence; 3.1 million people now live with multiple sclerosis globally. Higher-income countries reported higher prevalence than lower-income countries. The number of reported pediatric multiple sclerosis cases increased from 7,000 in 2013 to >40,000 in 2024. Incidence data provided by 91 countries estimated that 120,000 new diagnoses occur annually. CONCLUSION:Global multiple sclerosis prevalence continues to rise. Strengthened and equitable data collection is essential as diagnostic criteria evolve, and these findings provide a benchmark before widespread adoption of the 2024 McDonald criteria.
BACKGROUND:Pregnant women with multiple sclerosis have higher Cesarean section (C-section) rates than controls. Whether these are occurring prior to 39 weeks' gestation is unclear and important, as C-sections <39 weeks are associated with increased neonatal morbidity and are not recommended unless medically indicated. OBJECTIVES:Determine whether pregnant women with multiple sclerosis experience higher rates of non-medically indicated C-sections <39 weeks and whether these were attributed to multiple sclerosis. METHODS:We conducted a retrospective, population-based case-control study of pregnancies ⩾20 weeks' gestation among pregnant women with multiple sclerosis and 2:1 matched controls (1 January 2009-30 June 2024). Electronic health records identified C-sections <39 weeks and were manually reviewed for outcomes and covariates. RESULTS:Among 600 MS pregnancies and 1199 controls, C-sections <39 weeks were more frequent in pregnant women with multiple sclerosis (15.2% vs 9.8%, p = 0.0007). However, non-medically indicated C-sections <39 weeks were uncommon and did not differ significantly between groups (pregnant women with multiple sclerosis 3.7% vs controls 2.8%, p = 0.3386). The higher proportion of medically indicated C-sections <39 weeks in pregnant women with multiple sclerosis (11.5% vs 6.9%, p = 0.001) was driven by high-risk myomectomy and stalled labor. Multiple sclerosis was documented as a pregnancy complication in 24.2% of cases. CONCLUSIONS:C-sections <39 weeks were more common in pregnant women with multiple sclerosis but were attributable to standard obstetric indications rather than multiple sclerosis. Documentation of multiple sclerosis as a pregnancy complication suggests persistent provider misconceptions.
BACKGROUND:Modifiable factors that contribute to racial disparities in healthcare have been highlighted in multiple clinical settings; however, the role of these factors in individuals with multiple sclerosis has not been well examined. OBJECTIVES:In this study, we quantify disparities in multiple sclerosis care among non-Hispanic Black and non-Hispanic White patients. METHODS:Longitudinal data across four encounters obtained via retrospective chart review were analyzed for non-Hispanic Black and non-Hispanic White patients across two multiple sclerosis centers. Variables included demographics, multiple sclerosis characteristics, and clinical care factors. RESULTS:In total, 150 non-Hispanic Black and 150 non-Hispanic White patients were included (mean age = 49.3 vs 53.6). Non-Hispanic Black patients had longer time gaps between encounters with their multiple sclerosis clinician versus non-Hispanic White (mean months = 10.3 vs 8.8; adjusted mean difference = 1.53 months (95% confidence interval = 0.59, 2.47; p = 0.001)). Non-Hispanic Black patients less frequently received comprehensive/longer encounters, evaluations for a recent relapse, or had magnetic resonance imaging findings discussed during encounters relative to non-Hispanic White, although these findings were not statistically significant. CONCLUSIONS:Gaps in multiple sclerosis care metrics, including lower levels of care and greater time between encounters, were observed for non-Hispanic Black compared to non-Hispanic White patients with multiple sclerosis, all of which may contribute to disparities in multiple sclerosis. Further research is needed to assess contributing clinician, patient, and systemic factors.
BACKGROUND:Left-truncation is an unrecorded interval between multiple sclerosis (MS) onset and initial data in observational studies. This delay may bias estimates of disease-modifying therapy (DMT) effectiveness, especially when determined by patient or disease characteristics. OBJECTIVES:To examine whether causal effect estimates of DMTs over the full disease course can be reliably derived from left-truncated registry data. METHODS:We analysed data from MSBase (144 centres, 41 countries) to assess the impact of left-truncation on causal treatment effect estimates. Cox marginal structural models (MSMs) estimated hazard ratios (HRs) for relapses, disability worsening and improvement, considering left-truncation at random and not-at-random. Fixed-time truncation and multivariable adjustment were applied to remediate bias. RESULTS:The study included 5588 patients tracked from true MS onset. The null model, without left-truncation, estimated the DMT effect on relapse risk (HR = 0.64; 95% confidence interval (CI) = 0.54-0.77). Left-truncation inflated this estimate. Shorter random truncation (1 year) produced greater bias (HR = 0.34), decreasing with longer durations (3-year HR = 0.48). Truncation not-at-random biased relapse estimates (HR = 0.37). Disability outcomes were less sensitive. CONCLUSION:MSMs can reliably estimate DMT effectiveness in left-truncated MS registry data, although accuracy depends on truncation mechanism and duration. Both random and not-at-random truncation impact relapse estimates. Disability outcomes appear less sensitive. Fixed-time truncation and covariate adjustment mitigated bias.
BACKGROUND:To optimize the care of people with multiple sclerosis in Europe, the European Multiple Sclerosis Platform aimed to gather vital evidence from people with multiple sclerosis to understand prevalence, burden, and symptom management. METHODS:An online survey was distributed by 24 European Multiple Sclerosis Platform-associated multiple sclerosis organizations across 22 countries. Descriptive statistics were applied. RESULTS:Data from 17,151 people with multiple sclerosis revealed a mean of 13.7 symptoms. The five most prevalent symptoms included fatigue, sensory problems, sleep disturbances, cognitive impairment, and balance problems (range = 75%-93%). Respondents utilized a mean of 5.6 concurrent care modalities/strategies for symptom management, and 86% of them received disease-modifying drugs. They consulted a mean of 4.2 healthcare professionals for symptom management, with 50% experiencing coordination of care. Overall, 50% of respondents expressed satisfaction with their symptom management. However, satisfaction levels varied depending on the specific symptom: people with multiple sclerosis were twice as likely to report satisfaction with managing mobility, bladder control, and spasticity compared to managing sexual problems, fatigue, and cognitive impairment. CONCLUSION:This survey provides evidence of the high prevalence, burden, and impact of symptoms in people with multiple sclerosis, highlighting the need for multifaceted care strategies. The results call for a change in healthcare policies and practices.
BACKGROUND:The concept of affective reserve has been proposed, but not operationalized, as a buffer designed to regulate mood and behavior in response to adverse events. This study derived a residual-based metric of affective reserve and evaluated whether it mediated associations between having multiple sclerosis and subjective well-being in older adults. METHODS:Sociodemographics and brain pathology metrics were regressed against a composite mood, extraversion, and consciousness variable to derive affective reserve in a sample of older adults with multiple sclerosis (n = 107) and without (n = 104). Linear regressions were run to examine the associations between affective reserve and well-being, measured with the Short Form-12 Mental Composite Summary and Physical Composite Summary. Hayes' PROCESS was used to evaluate affective reserve as a mediator between group status and well-being. RESULTS:Affective reserve was positively associated with both Mental Composite Summary and Physical Composite Summary. After covariate adjustments, affective reserve fully mediated the relationship between having multiple sclerosis and Mental Composite Summary (b = 1.350, 95% confidence interval: 0.142-2.591) and partially mediated the association between multiple sclerosis and Physical Composite Summary (b = 0.915, 95% confidence interval: 0.073-1.906). CONCLUSION:This residual-based metric offers a novel approach for measuring affective reserve. Not only is it associated with both physical and mental well-being, but it explained the relationship between the latter and the presence of multiple sclerosis.
BACKGROUND/OBJECTIVES:The long-term implications of multiple sclerosis (MS) disease-modifying therapies (DMTs) on gynecologic health remain understudied. We leverage a multicenter database to evaluate whether DMTs are associated with such complications. METHODS:We propensity-score 1:1 matched women with MS on (1) any versus no or (2) moderate- to high- (vs low-) immunosuppressive DMT by age, marital status, race, ethnicity, tobacco use, body mass index, human papilloma virus (HPV) vaccination, and gynecologic examinations/screenings. We then compared matched cohorts with risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS:After matching, we analyzed 115,522 women with MS. The DMT (vs no DMT) group had increased risks of HPV positivity (RR: 1.52, 95% CI: 1.35-172), cervical dysplasia (RR: 1.40, 95% CI: 1.31-1.49), cervical cancer (RR: 1.23, 95% CI: 1.03-1.46), cervicitis (RR: 1.25, 95% CI: 1.10-1.41), herpes simplex virus positivity (RR: 1.29, 95% CI: 1.14-1.45), vulvovaginitis (RR: 1.30, 95% CI: 1.23-1.37), and Bartholin cysts/abscesses (RR: 1.37, 95% CI: 1.07-1.76). Moderate- to high- (vs low-) immunosuppressive. DISCUSSION:MS DMTs, especially more immunosuppressive ones, are associated with increased risks of several gynecologic complications. Clinicians should recognize these potential sequelae of DMTs and integrate gynecological counseling/screening into MS care.
OBJECTIVES:To assess vaccine effectiveness (VE) of the recombinant zoster vaccine (RZV) in adults with multiple sclerosis (MS). METHODS:This retrospective study included adults aged ⩾18 years with MS insured by Medicare or one of seven United States (US) commercial health insurers from January 2018 to September 2023. Adults receiving two RZV doses ⩾28 days apart were matched with four or less unvaccinated comparators on insurer, sex, and age. Adjusted hazard ratios (HRs) of incident herpes zoster (HZ) ⩾ 31 days after the second RZV dose were estimated using Cox models with inverse probability of treatment weighting applied to the matched cohorts to balance potential confounders. VE was calculated as (1 - HR) × 100. RESULTS:The Medicare cohort included 8705 vaccinated and 34,407 unvaccinated patients; the commercially insured cohort included 6025 vaccinated and 22,685 unvaccinated patients. Most patients in both cohorts were aged ⩾50 years. Crude HZ incidence in unvaccinated patients was 13.7 and 12.7/1000 person-years in the Medicare and commercially insured cohorts, while crude incidence among vaccinated patients was 4.6 and 2.4/1000 person-years. Weighted analyses demonstrated VE of 64% (95% confidence interval [CI]: 51%-74%) in Medicare and 81% (95% CI: 70%-88%) in commercially insured patients. CONCLUSION:RZV demonstrated robust VE, preventing 64%-81% of HZ cases in this MS population predominantly aged 50 years or older.
BACKGROUND:Juxtacortical paramagnetic rims (JPRs) have emerged as potential biomarkers of cortical pathology in multiple sclerosis (MS), yet their susceptibility characteristics and clinical significance remain unclear. OBJECTIVES:To characterize the heterogeneity of cortical lesions (CLs), with a particular focus on JPRs and clinical relevance. METHODS:Sixty-four patients underwent 3T magnetic resonance imaging (MRI), including structural imaging, multi-echo gradient echo, and Magnetic Resonance Image Compilation (MAGiC) sequences. Paramagnetic (χpara) and diamagnetic (χdia) maps were reconstructed using subvoxel quantitative susceptibility mapping. CLs were identified, and those with JPRs were defined as JPR-associated CLs. Susceptibility metrics were compared across lesion subtypes and correlated with clinical and imaging measures. RESULTS:Among 499 CLs, 15% were JPR-associated CLs, which exhibited elevated χpara measurements and reduced χdia measurements. Patients with JPRs had a higher number of paramagnetic rim lesions (95% CI [2.445, 4.738], p < 0.001), annualized relapse rates (95% CI [0.130, 0.297], p < 0.001), and lower digit span test scores (95% CI [-2.504, -0.473], p = 0.004). The absolute χpara and χdia values in all CLs were correlated with longer disease duration (r = -0.461, p = 0.001; r = 0.457, p = 0.001). CONCLUSION:JPRs are a characteristic feature of CLs associated with greater clinical and radiological burden in MS.
BACKGROUND:Emergency department (ED) visits represent a substantial component of healthcare use. Although increased utilization has been reported before multiple sclerosis (MS) recognition, ED use and its clinical context remain poorly characterized. METHODS:In this population-based matched cohort study, we used linked administrative health data from British Columbia, Canada. Persons with multiple sclerosis (PwMS) were identified using a validated case definition and matched to individuals without MS by age, sex and postal code. ED encounters in the 5 years preceding the index date (first demyelinating disease claim) were examined. Annual ED visit rates were compared using adjusted negative binomial models; discharge diagnoses were assessed using adjusted logistic regression. RESULTS:The cohort included 2383 PwMS and 11,896 matched individuals (mean age = 44.1 years; 69.2% female). ED visit rates were higher among PwMS across all five pre-index years, rising from an adjusted rate ratio (aRR) of 1.38 (95% confidence interval (CI) = 1.07-1.77) at 5 years pre-index to 3.40 (95% CI = 3.07-3.76) in the year immediately pre-index. Excess visits were observed for gastrointestinal, genitourinary, musculoskeletal, respiratory, mental health, and ill-defined conditions. PwMS had higher odds of a non-specific discharge diagnosis (adjusted odds ratio (aOR) = 1.36; 95% CI = 1.22-1.53). CONCLUSIONS:ED utilization was consistently elevated in the 5 years before MS recognition (index date), predominantly involving non-neurologic and non-specific presentations.
BACKGROUND:Individuals with multiple sclerosis (MS) often report fatigue and motor impairments, which may affect how accurately they assess physical exertion. Recent work with healthy individuals suggests that motor variability can distort judgments of exertion (i.e. feelings of effort); however, this relationship has not been explored in individuals with MS. OBJECTIVE:To determine how variability in physical exertion affects subjective effort assessment in individuals with MS compared with healthy participants. METHODS:Individuals with MS and age-matched healthy controls exerted varying levels of physical exertion and retrospectively assessed the feelings of effort associated with their exertion. Hierarchical linear models were used to compare motor performance and effort assessment metrics between cohorts. RESULTS:In total, 29 patients with MS and 22 healthy controls were included. Individuals with MS exhibited increased exertion variability compared with healthy participants (β=1.00, 95%CI=[0.32,1.68]). Increased exertion variability was associated with less accurate subjective effort assessment (β=3.16, 95%CI=[1.34,4.98]), and this effect was more pronounced in individuals with more advanced MS (β=1.49, 95%CI=[0.16,∞]).Conclusion:These results suggest a possible mechanism through which motor variability may be associated with inflated perceptions of effort in MS, highlighting a potential account of why exertion feels particularly costly to people living with MS.
BACKGROUND:Vascular risk factors (VRFs) are associated with diffuse brain damage in multiple sclerosis (MS). We investigated VRFs' impact on motor performance and sensorimotor network (SMN) structural integrity in MS patients. METHODS:In this retrospective cross-sectional study, 268 MS patients and 180 healthy controls were classified according to VRF presence (VRF[+]) or absence (VRF[-]). Clinical measures included Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk test, and 9-Hole Peg Test. SMN integrity was assessed using white matter lesion volumes, cortical thickness of primary motor and somatosensory cortices, normalized deep gray matter volume (NDGMV), anterior (ACMA) and posterior cerebellar motor area volumes, mean upper cervical cord area, and diffusion metrics of the middle and superior cerebellar peduncles, medial lemniscus (ML), and corticospinal tracts. Group differences and MS-VRF interactions were examined. In MS, associations between clinical and magnetic resonance imaging (MRI) measures were explored, focusing on VRF influence. RESULTS:MS-VRF[+] patients showed higher EDSS scores and worse motor performance than MS-VRF[-] (false discovery rate p value [pFDR] ⩽ 0.004). Significant MS-VRF interactions were observed for motor performance, ML mean diffusivity, NDGMV, and ACMA volumes (pFDR ⩽ 0.039). In MS, EDSS was associated with the VRF × ML fractional anisotropy interaction term (β = 1.931, p = 0.042). CONCLUSIONS:VRFs may contribute to increased disability, motor impairment, and region-specific SMN structural damage in MS patients.
BACKGROUND:Studies on early cognitive impairment (CI) in pediatric multiple sclerosis (MS) are heterogeneous and data on pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are scarce. OBJECTIVES:To evaluate early cognitive dysfunction in both diseases and delineate disease-specific neurocognitive profiles. METHODS:A cross-sectional study of children with MS and MOGAD assessed neurocognition within 2 years after disease onset using a comprehensive test battery. Test results were converted to Z-scores. CI was defined as Z-scores below -1.5 in ⩾2 domains. Children were compared by CI status and domain deficits quantified with composite Z-scores. RESULTS:Sixty-seven participants were analyzed (MS n = 36, MOGAD n = 31). Despite normal full-scale intelligence quotient, 47% of MS children and 43% of MOGAD children (acute disseminated encephalomyelitis excluded) met criteria for CI. Domain-specific impairments were prominent in complex attention, with significantly reduced composite Z-scores (MS: -1.24, p < 0.001; MOGAD: -1.12, p = 0.019). MS children additionally showed lower scores on tasks of visuospatial processing and visual memory. Only fatigue was significantly associated with the presence of CI (PedsQL fatigue Z-score: -2.61 vs -0.75, p = 0.005). CONCLUSION:In both pediatric MS and MOGAD, early CI is prevalent with difficulties in complex attention. Visuospatial cognition appears to be an additional vulnerable area for children with MS.
INTRODUCTION:People with multiple sclerosis (pwMS) have a lower reported risk of colorectal cancer, which may reflect reduced access to colorectal cancer screening (CCS). OBJECTIVES:Compare CCS in pwMS and the general population and identify barriers and facilitators using mixed methods. METHODS:In 2022-2024, PwMS aged 50-74 years and matched controls (3:1) were selected. Overall and age-stratified CCS coverage rates were computed. In pwMS, multivariable mixed-effects logistic models identified factors associated with CCS ⩾ 80%. Semi-structured interviews were carried out with 20 pwMS. RESULTS:The cohort included 63,509 pwMS and 190,527 controls (72.0% women, mean age 59.2 years). Annual CCS coverage was 41.2% in pwMS and 42.4% in controls (p < 0.001). In pwMS, CCS was higher in the 50-54 years (+1.5%, p < 0.001) and lower in the ⩾65 years group (-1.6% to -6.2%, p < 0.001). Male sex (odds ratio = 0.90; 95% CI = [0.86-0.93]) and lower ecological socioeconomic status (0.81 [0.76-0.86]) were associated with lower CCS, while disease-modifying therapies (1.12 [1.08-1.16]) and high healthcare use with higher CCS. Qualitative barriers included motor or digestive MS symptoms and feelings of disgust. Facilitators included health system trust and prevention awareness. CONCLUSION:CCS is lower among older pwMS and remains suboptimal in both pwMS and controls.
