Immune and autonomic nervous system interactions in multiple sclerosis: clinical implications

  • Mario HabekEmail author
Review Article


Multiple sclerosis is characterized by a wide spectrum of clinical manifestations, among which dysfunction of the autonomic nervous system represents an important cause of multiple sclerosis-related disability. The aim of this review is to provide an overview of autonomic dysfunction in people with multiple sclerosis, and to discuss the interactions between the immune and autonomic nervous systems and the effects of these interactions on various aspects of multiple sclerosis. Autonomic dysfunction in people with multiple sclerosis can be demonstrated clinically and on a molecular level. Clinically, it can be demonstrated by measuring autonomic symptoms with the Composite Autonomic Symptom Score (COMPASS-31), and neurophysiologically, with different autonomic nervous system tests. Both symptomatic and objectively determined autonomic dysfunction can be associated with increased risk of multiple sclerosis disease activity. Further supporting these clinical observations are molecular changes in immune cells. Changes in the sympathetic autonomic system, such as different expression of dopaminergic and adrenergic receptors on immune cells, or modulation of the cholinergic anti-inflammatory pathway over different subunits of the nicotinic acetylcholine receptor in the peripheral immune system, may mediate different effects on multiple sclerosis disease activity.


Multiple sclerosis Autonomic nervous system Cardiovascular autonomic reflexes Sudomotor function 


Author contributions

MH: Study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and administrative, technical, and material support.


None received for the preparation of this manuscript.

Compliance with ethical standards

Conflict of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, and royalties. No writing assistance was utilized in the production of this manuscript.


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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, Referral Center for Autonomic Nervous System DisordersUniversity Hospital Center ZagrebZagrebCroatia
  2. 2.School of MedicineUniversity of ZagrebZagrebCroatia

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