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The relationship between being overweight during early life and disease course in multiple sclerosis (MS) is unresolved. We investigated the association between being overweight or obese during early life (childhood and adolescence) and MS case status, age of first symptom onset and onset type in people with MS (pwMS) of the same birth year. We enrolled 363 PwMS and 125 healthy controls (HC) from Project Y, a Dutch population-based cross-sectional cohort study including all PwMS born in 1966 and age and sex-matched HC. The associations between weight during childhood and adolescence (non-overweight vs. overweight or obese) and MS, age at symptom onset and onset type (relapsing vs. progressive) were assessed using logistic and linear regressions. In addition, sex-separated associations were explored. Being overweight or obese during childhood (OR = 2.82, 95% CI 1.17–6.80) and adolescence (OR = 2.45, 95% CI 1.13–5.34) was associated with developing MS. Furthermore, being overweight or obese during adolescence was associated with a younger age of onset (β = −0.11, p = 0.041). Of all 47 patients with a primary progressive (PP) onset type, only one patient (2.1%) was overweight or obese during childhood, whereas 45 patients with a relapsing remitting (RR) onset (14.3%) were overweight or obese during childhood (PP vs. RR p = 0.017; PP vs. HC p = 0.676; RR vs. HC, p = 0.015). However, using logistic regression analysis we did not find evidence of a significant association. In a nationwide population-based birth year cohort, being overweight or obese during childhood or adolescence is associated with MS prevalence and an earlier age of onset, but does not seem to associate with the type of onset. [ABSTRACT FROM AUTHOR]

Background: Suboptimal performance during neuropsychological testing frequently occurs in multiple sclerosis (MS), leading to unreliable cognitive outcomes. Neurophysiological alterations correlate with MS-related cognitive impairment, but studies have not yet considered performance validity. Objectives: To investigate neurophysiological markers of cognitive impairment in MS, while explicitly addressing performance validity. Methods: Magnetoencephalography recordings, neuropsychological assessments, and performance validity testing were obtained from 90 MS outpatients with cognitive complaints. Spectral and resting-state functional connectivity (rsFC) properties were compared between cognitively impaired (CI), cognitively preserved (CP), and suboptimally performing (SUB) patients using regression models and permutation testing. Results: CI had higher power in low-frequency bands and lower power in high bands compared to CP, indicating neuronal slowing. CI also showed lower beta power compared to SUB. Overall power spectra visually differed between CI and CP, and SUB showed overlap with both groups. CI had lower rsFC than CP and SUB patients. CP and SUB patients showed no differences. Conclusion: Neuronal slowing and altered rsFC can be considered cognitive markers in MS. Patients who performed suboptimally showed resemblance with patients with and without cognitive impairments, and although their overall neurophysiological profile was more similar to patients without impairments, it suggests heterogeneity regarding their pathophysiology. [ABSTRACT FROM AUTHOR]

Up to 65% of people with multiple sclerosis (PwMS) develop cognitive deficits, which hampers participation in day-to-day life and ultimately reduces quality of life (QoL). Treatment of symptoms at a late stage can lead to cognitive impairment and unemployment, highlighting the need for preventative interventions in PwMS. Presenting a combination of exercise and cognitive training early might postpone cognitive decline. This study highlights one intervention of the Don't be late! study, which aims to evaluate the (cost-)effectiveness of an innovative preventative intervention, aimed at postponing cognitive decline, compared to enhanced usual care in improving health-related QoL (HRQoL). Randomised controlled trial including 270 PwMS with mild cognitive impairment, who have paid employment ≥ 12 hours per week and are able to participate in physical exercise (Expanded Disability Status Scale < 6.0). Participants are assigned to either a lifestyle intervention combining one-on-one personal fitness, mental coaching, dietary advice, and cognitive training, adjusted to the goals and level of the participant or a control group receiving general information about cognitive impairment in MS and receiving care as usual. Intervention duration is four months, with short-term and long-term follow-up measurements at 10 and 16 months, respectively. The overarching study also includes a work-focused intervention. The primary outcome measure will be HRQoL. Secondary outcomes include cognition, structural and functional brain changes, work related outcomes, physical functioning, psychological functioning, and societal costs. Semi-structured interviews and focus groups with stakeholders will be organised to qualitatively reflect on the process and outcome of the interventions. This study seeks to prevent (further) cognitive decline due to MS by introducing tailor-made interventions at an early stage of cognitive symptoms, thereby maintaining or improving HRQoL. Qualitative analyses will be performed to allow successful implementation into clinical practice. [ABSTRACT FROM AUTHOR]

In this observational study, 159 patients with multiple sclerosis received personalized dosing of ocrelizumab incentivized by the COVID-19 pandemic. Re-dosing was scheduled when CD19 B-cell count was ⩾10 cells/µL (starting 24 weeks after the previous dose, repeated 4-weekly). Median interval until re-dosing or last B-cell count was 34 [30–38] weeks. No clinical relapses were reported and a minority of patients showed Expanded Disability Status Scale (EDSS) progression. Monthly serum neurofilament light levels remained stable during extended intervals. Two (1.9%) of 107 patients with a follow-up magnetic resonance imaging (MRI) scan showed radiological disease activity. Personalized dosing of ocrelizumab could significantly extend intervals with low short-term disease activity incidence, encouraging future research on long-term safety and efficacy. [ABSTRACT FROM AUTHOR]

Interferon-β (IFN-β) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-β in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN-β was effective in reducing EAE symptoms induced by T helper type 1 ([T.sub.H]1) cells but exacerbated disease induced by [T.sub.H]17 cells. Effective treatment in [T.sub.H]1-induced EAE correlated with increased interleukin-10 (IL-10) production by splenocytes. In [T.sub.H]17-induced disease, the amount of IL-10 was unaltered by treatment, although, unexpectedly, IFN-β treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-γ. In the absence of IFN-γ signaling, IFN-β therapy was ineffective in EAE. In RRMS patients, IFN-β nonresponders had higher IL-17F concentrations in serum compared to responders. Nonresponders had worse disease with more steroid usage and more relapses than did responders. Hence, IFN-β is proinflammatory in [T.sub.H]17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-β., IFN-β is widely prescribed for the treatment of RRMS. However, only about two thirds of patients with RRMS respond to treatment (1). Furthermore, IFN-β can exacerbate symptoms in some individuals [...]

In women with very active multiple sclerosis (MS), natalizumab can be continued during pregnancy to prevent rebound disease activity. Our aim was to evaluate changes in serum natalizumab trough concentrations during pregnancy. Blood samples of 3 patients were collected before, during, and after pregnancy. Natalizumab trough concentrations gradually decreased during pregnancy. The patient with the lowest trough concentrations during the third trimester was treated with extended interval dosing (EID). After delivery, natalizumab concentrations increased to similar levels as before pregnancy. All patients remained clinically and radiologically stable. MS neurologists should be aware of decreasing natalizumab concentrations during pregnancy, especially in patients with low initial trough concentrations and patients with EID. [ABSTRACT FROM AUTHOR]

Background: Cognitive decline remains difficult to predict as structural brain damage cannot fully explain the extensive heterogeneity found between MS patients. Objective: To investigate whether functional brain network organization measured with magnetoencephalography (MEG) predicts cognitive decline in MS patients after 5 years and to explore its value beyond structural pathology. Methods: Resting-state MEG recordings, structural MRI, and neuropsychological assessments were analyzed of 146 MS patients, and 100 patients had a 5-year follow-up neuropsychological assessment. Network properties of the minimum spanning tree (i.e. backbone of the functional brain network) indicating network integration and overload were related to baseline and longitudinal cognition, correcting for structural damage. Results: A more integrated beta band network (i.e. smaller diameter) and a less integrated delta band network (i.e. lower leaf fraction) predicted cognitive decline after 5 years ( R adj 2 = 15 %), independent of structural damage. Cross-sectional analyses showed that a less integrated network (e.g. lower tree hierarchy) related to worse cognition, independent of frequency band. Conclusions: The level of functional brain network integration was an independent predictive marker of cognitive decline, in addition to the severity of structural damage. This work thereby indicates the promise of MEG-derived network measures in predicting disease progression in MS. [ABSTRACT FROM AUTHOR]