Stress and Multiple Sclerosis - Systematic review and meta-analysis of the association with disease onset, relapse risk and disability progression.

OBJECTIVE: This systematic review and meta-analysis address the evidence on the association of psychological stressors with onset of multiple sclerosis, inflammatory disease activity (relapses or new disease activity on magnetic resonance imaging, MRI) and disability progression. METHODS: PubMed was searched from 1946 to 15 July 2022. Studies and certain stressors were selected when they assessed stressors independent from stress elicited by the disease process itself. Risk of bias was assessed by the CASP Case Control Study Checklist and the CASP Cohort Study Checklist. Normal-Normal Hierarchical Model (NNHM) for random-effects meta-analysis was used in the Bayesian framework. RESULTS: 30 studies reporting data from 26 cohorts reporting on 24.781 cases could be identified. Ten studies addressed stressors and MS disease onset showing a weak to modest effect of psychological stressors. A meta-analysis of three studies investigating diagnosed stress disorders and MS risk showed a 1.87-fold (CI 1.061 to 3.429) increased MS risk. Stress and MS relapse risk were addressed in 19 heterogeneous studies. Meta-analyses from two independent cohorts investigating the same military threat of a population showed a threefold increased risk for relapses in association with war (relapse rate: 3.0, CI 1.56 to 5.81). In addition, two studies confirmed an association of stressful life events and MRI activity. Three studies of stressors and disease progression were included indicating some effect on disease progression. CONCLUSIONS: Taken together studies indicate a minor to modest impact of psychological stressors on disease onset, inflammatory activity and progression of MS. Possible case-selection bias and lack of confounder analysis were present in many studies.

Short-term interval aerobic exercise training does not improve memory functioning in relapsing-remitting multiple sclerosis-a randomized controlled trial.

BACKGROUND: Only few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in multiple sclerosis. OBJECTIVE AND METHODS: This randomized controlled trial with 34 patients in the intervention group (IG) (mean: 38.2 years (±9.6)) and 34 patients in the control group (CG) (mean: 39.6 years (±9.7)) aimed to determine the effects of aerobic exercise on cognition in relapsing-remitting multiple sclerosis (RRMS). The primary outcome was verbal learning assessed by the verbal learning and memory test (VLMT). Patients were randomized to an IG or a waitlist CG. Patients in the IG exercised according to an individually tailored training schedule (with two to three sessions per week for 12 weeks). The primary analysis was carried out using the intention-to-treat (ITT) sample with ANCOVA adjusting for baseline scores. RESULTS: A total of 77 patients with RRMS were screened and 68 participants randomized (CG n = 34; IG n = 34). The sample comprised 68% females, had a mean age of 39 years, a mean disease duration of 6.3 years, and a mean expanded disability status scale of 1.8. No significant effects were detected in the ITT analysis for the primary endpoint VLMT or any other cognitive measures. Moreover, no significant treatment effects were observed for quality of life, fatigue, or depressive symptoms. CONCLUSION: This study failed to demonstrate beneficial effects of aerobic exercise on cognition in RRMS. The trial was prospectively registered at clinicaltrials.gov (NCT02005237).

Prolactin stimulation in multiple sclerosis--an indicator of disease subtypes and activity?

Prolactin (PRL) belongs to the growth and lactogenic hormone family and has potent immunomodulating properties. Mild hyperprolactinemia has been found to enhance several autoimmune diseases and increased PRL plasma levels have been described in the experimental multiple sclerosis (MS) model while the PRL antagonist bromocriptine was able to suppress the disease. As studies of PRL serum levels in MS have led to conflicting results we investigated further the question of prolactin alterations in MS. We correlated PRL baseline values in a large sample of 132 MS patients with disease course and activity. Furthermore, inhibitory (bromocriptine) and stimulatory (metoclopramide) tests were performed in a subsample (n = 39) to gain functional information. We found no correlation of baseline values with disease course or activity. Nevertheless in the regression analysis of stimulatory test results, 14% of the variance was attributable to disease activity. In conclusion PRL does not seem to be relevant as an activity marker in the whole MS population.