Migraine: A Chronic Sympathetic Nervous System Disorder

Stephen J. Peroutka

Disclosures

Headache. 2004;44(1) 

In This Article

Abstract and Introduction

Abstract

Objective. To determine the degree of diagnostic and clinical similarity between chronic sympathetic nervous system disorders and migraine.
Background: Migraine is an episodic syndrome consisting of a variety of clinical features that result from dysfunction of the sympathetic nervous system. During headache-free periods, migraineurs have a reduction in sympathetic function compared to nonmigraineurs. Sympathetic nervous system dysfunction is also the major feature of rare neurological disorders such as pure autonomic failure and multiple system atrophy. There are no known reports in the medical literature, however, comparing sympathetic nervous system function in individuals with migraine, pure autonomic failure, and multiple system atrophy.
Methods: A detailed review of the literature was performed to compare the results of a wide variety of diagnostic tests and clinical signs that have been described in these 3 heretofore unrelated disorders.
Results: The data indicate that migraine shares significant diagnostic and clinical features with both pure autonomic failure and multiple system atrophy, yet represents a distinct subtype of chronic sympathetic dysfunction. Migraine is most similar to pure autonomic failure in terms of reduced supine plasma norepinephrine levels, peripheral adrenergic receptor supersensitivity, and clinical symptomatology directly related to sympathetic nervous system dysfunction. The peripheral sympathetic nervous system dysfunction is much more severe in pure autonomic failure than in migraine. Migraine differs from both pure autonomic failure and multiple system atrophy in that migraineurs retain the ability, although suboptimal, to increase plasma norepinephrine levels following physiological stressors.
Conclusions: The major finding of the present study is that migraine is a disorder of chronic sympathetic dysfunction, sharing many diagnostic and clinical characteristics with pure autonomic failure and multiple system atrophy. However, the sympathetic nervous system dysfunction in migraine differs from pure autonomic failure and multiple system atrophy in that occurs in an anatomically intact system. It is proposed that the sympathetic dysfunction in migraine relates to an imbalance of sympathetic co-transmitters. Specifically, it is suggested that a migraine attack is characterized by a relative depletion of sympathetic norepinephrine stores in conjunction with an increase in the release of other sympathetic cotransmitters such as dopamine, prostaglandins, adenosine triphosphate, and adenosine. An enhanced understanding of the sympathetic dysfunction in migraine may help to more effectively diagnose, prevent, and/or treat migraine and other types of headache.

A wide variety of clinical signs and diagnostic tests indicate that dysfunction of the sympathetic nervous system (SNS) exists in migraineurs. The SNS dysfunction is present both in the headache-free or interictal period, as well as during migraine attacks. Both functional tests of the SNS and clinical data consistently document a reduction in sympathetic function in migraineurs compared to nonmigraineurs, especially in norepinephrine-related functional tests.

Sympathetic nervous system dysfunction is also a major feature of rare neurological disorders such as pure autonomic failure (PAF) (formerly called idiopathic orthostatic hypotension) and multiple system atrophy (MSA) (also called Shy-Drager syndrome, striatonigral degeneration, and nonfamilial olivopontocerebellar atrophy).[1] A wide variety of clinical signs have been described in these disorders, and diagnostic tests have documented specific quantitative changes in SNS function in both PAF and MSA.[2,3,4,5] In general, PAF is considered to be a disorder of primarily peripheral sympathetic neurons, whereas MSA involves predominantly central SNS neurons.[2]

There are no known reports in the medical literature, however, comparing SNS function in individuals with PAF, MSA, and migraine. A recent PubMed search (performed on January 21, 2003) failed to detect any publication involving all 3 of these heretofore unrelated disorders. Therefore, in the present study, a detailed literature review was performed in an attempt to determine the degree of similarity between SNS function in migraine, PAF, and MSA. It should be noted that the articles reviewed were published between 1860 and 2003, using a wide variety of subject recruitment techniques, and involved a number of functional tests of SNS function that are influenced by ovarian steroids and multiple environmental factors.

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