Abstract

Little is known about the interplay between the autonomic nervous system and disease activity in multiple sclerosis (MS). We examined the relationship between heart rate variability (HRV), a reliable measure of vagal nerve function, and disease characteristics in a prospective MS cohort. Standard deviation of each normal-to-normal inter-beat interval (SDNN) and root mean square of successive differences (RMSSD), global indices of HRV, were measured in 114 MS patients, which included four predefined subgroups, and 30 age and sex-matched healthy controls (HC). We assessed group differences at baseline, HRV reproducibility at month 3, and used logistic regression modeling to relate baseline HRV with relapse occurrence. No significant HRV differences were found between MS and HC and between MS subgroups. In MS patients, both HRV indices correlated with age (r = −0.278, p = 0.018 and r = −0.319, p < 0.001, respectively) and with month 3 assessments (r = 0.695 and r = 0.760, p < 0.001). Higher SDNN and RMSSD at baseline were associated with self-reported relapses at month 3 (OR = 1.053, 95% CI (1.013–1.095), p = 0.009 and OR = 1.065, 95% CI (1.016–1.117), p = 0.009), and SDNN at baseline with relapses at month 12 (OR = 1.034, 95% CI (1.009–1.059), p = 0.008; ROC, AUC = 0.733, p = 0.002). There were no baseline HRV differences between MS and HC or between subgroups. Post-hoc analysis showed an association with an increased relapse risk.

Highlights

  • Multiple sclerosis (MS) a complex, chronic disease of the central nervous system (CNS), is known for its wide clinical, radiological, and pathological heterogeneity including a varying degree of inflammation and neurodegeneration [1]

  • Higher Standard deviation of each normal-to-normal inter-beat interval (SDNN) and root mean square of successive differences (RMSSD) at baseline were associated with self-reported relapses at month 3 (OR = 1.053, 95% CI (1.013–1.095), p = 0.009 and OR = 1.065, 95% CI (1.016–1.117), p =

  • We focused on the standard deviation of each normal-to-normal inter-beat interval (SDNN) and the root mean square of successive differences (RMSSD), measures of parasympathetic function and global heart rate variability (HRV) [18,19], as most relevant HRV

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Summary

Introduction

Multiple sclerosis (MS) a complex, chronic disease of the central nervous system (CNS), is known for its wide clinical, radiological, and pathological heterogeneity including a varying degree of inflammation and neurodegeneration [1]. Most patients start with a relapsing-remitting course, which may be followed by a secondary progressive phase. A minority of subjects present with an insidious progression of disability from onset, or primary progressive [2]. Autonomic symptoms are prevalent in MS [3,4,5]. Based on the immunoregulatory functions of the autonomic nervous system (ANS) [6], ANS dysfunction might play a role in the pathogenesis and progression of MS. The vagal nerve, responsible for the main parasympathetic output, directly communicates with the brain and can reduce peripheral inflammation in experimental conditions [7]

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