Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies.

Oliver Findling,Paulus S. Rommer,Walter Struhal,Larissa Hauer,Thomas Pezawas,Johann Sellner

doi:10.3390/jcm9020335

Abstract

Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case–control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing–remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.

Highlights

The autonomic nervous system maintains homeostasis of heart rate (HR), blood pressure (BP), respiration, and bowel and bladder control, amongst others
Studies in the 1990s found lower HR variability (HRV) in multiple sclerosis (MS) patients, caused by a significant increase in sympathetic cardiovascular tone [35,36]
An Australian study investigating spontaneous changes in BP and HR showed diminished baroreceptor sensitivity in 23 MS patients compared with 23 age- and sex-matched controls (p < 0.05), with the authors suggesting that this provides valuable information on the interaction of sympathetic and parasympathetic activity in assessing the overall autonomic function [4]

Summary

Introduction

The autonomic nervous system maintains homeostasis of heart rate (HR), blood pressure (BP), respiration, and bowel and bladder control, amongst others. Autonomic dysfunction can lead to a wide range of symptoms, including HR and BP dysregulation, as well as pulmonary symptoms and bowel or bladder dysfunction. Sympathetic activity may be increased significantly during the early stages of MS, while later disease stages may lead to progressive noradrenergic failure and adrenergic receptor dysfunction [3]. It has been assumed that with increasing impairment of the autonomic nervous system during MS, sympathetic or parasympathetic modulation alters immune responses, causing a vicious neuroinflammatory cycle. It is unclear whether those alterations are associated with the structural damage to the CNS in MS or an epiphenomenon of disturbed autonomic feedback cycles. MS activity has been linked with changes in the expression of different receptors responsible for the communication between immune cells and the sympathetic autonomic system—for example, in the expression of dopaminergic and adrenergic receptors or of different subunits of the nicotinic acetylcholine receptor in the peripheral nervous system [6]

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