Migraine: A Chronic Sympathetic Nervous System Disorder

Stephen J. Peroutka

Disclosures

Headache. 2004;44(1) 

In This Article

Physiological

Orthostatic Blood Pressure Changes. Orthostatic hypotension has been defined as a systolic BP decrease of greater than 20 mm Hg or a diastolic BP decrease of at least 10 mm Hg within 3 minutes of standing.[1] The most commonly recognized clinical sign of sympathetic failure is orthostatic hypotension, yet much more subtle clinical signs and symptoms are present with mild SNS dysfunction. Moderately severe SNS failure may cause symptoms of presyncope or syncope resulting from decreased cerebral perfusion due to hypotension, but with little change in heart rate. Moderate SNS failure results in both tachycardia and mild orthostatic hypotension. An even milder orthostatic dysfunction of the SNS results in a relative tachycardia with little change in BP.

In Individuals with Pure Autonomic Failure and Multiple System Atrophy. One of the pathognomonic clinical signs in patients with either PAF or MSA is orthostatic hypotension.[2,3] Consistent with the inability of these patients to increase their plasma NE levels following an orthostatic change, there is a significant decrease in both their systolic and diastolic BP when arising from a supine position.

In Migraineurs. Migraine has been associated with orthostatic hypotension and occasionally with syncope.[15,16] Orthostatic hypotension was found to be significantly greater (P< .0002) in migraineurs than in controls.[7] Both systolic and diastolic BPs decrease more in migraineurs than in controls immediately after tilting.[9,17] The BP response to standing is also blunted in migraineurs.[18,19,20] In all of these studies, however, the drop in BP rarely met the technical definition of orthostatic hypotension.

The Valsalva maneuver is a simple test of vasomotor function that consists of forced expiration for as long as 10 to 15 seconds, during which BP and heart rate are monitored. The resulting increase in intrathoracic pressure decreases venous return to the heart and secondarily lowers cardiac output. The normal response is an increase in the heart rate, because of a reduction in vagal activity and an increase in sympathetic activity, followed by a reflex bradycardia mediated by vagal activation. The Valsalva ratio is the ratio of the fastest heart rate that occurs immediately at the end of the forced expiration to the slowest heart rate.

In Individuals with Pure Autonomic Failure and Multiple System Atrophy. In individuals with both PAF and MSA, the Valsalva maneuver results in a continuous fall in BP. Following release, there is no BP overshoot and, therefore, no secondary bradycardia.[3]

In Migraineurs. The BP response that results from the Valsalva maneuver is significantly decreased (P< .003) in both migraineurs with and without aura compared to controls.[7] These results have been confirmed by some investigators,[8,17] but not by others.[21]

The sustained handgrip test represents a simple noninvasive method that measures cardiovascular reflexes. It is considered to reflect most clearly the activity of the peripheral SNS since the efferent fibers to the heart mediate the induced rise in BP and heart rate. In one isometric test paradigm, the subject exerts 30% of the maximal voluntary contraction with the dominant hand for 2 to 4 minutes using a hand dynamometer. The subject is told to breathe normally and relax all other muscles not involved in the handgrip contraction during the testing period. Blood pressure is recorded in the non-exercising arm at rest and at 1-minute intervals during the test. The average R-R interval during the 15 seconds preceding the test is divided by the minimal R-R interval during the contraction period and the resulting value is called the handgrip ratio.

Effects on Blood Pressure in Individuals With Pure Autonomic Failure and Multiple System Atrophy. In individuals with both PAF and MSA, the BP and heat rate responses to isometric exercise are decreased or absent.[3]

Effects on Blood Pressure in Migraineurs. Migraineurs display clear and consistent differences in isometric exercise results compared to controls, as documented by various investigators. For example, the mean diastolic BP increase in migraineurs during the handgrip test was significantly lower than in controls.[8,17,19,22] The impairment was greater in migraineurs with aura than without aura, in females than males, and in migraineurs with frequent attacks compared to migraineurs with infrequent attacks.[22] Significant impairment of both systolic and diastolic BP increases induced by isometric exercise has also been noted by an independent group of investigators.[9,18] In another study, the heart rate increase during sustained handgrip was significantly (P< .05) reduced in migraineurs compared to controls.[23] These data suggest that the handgrip test may be an extremely sensitive measure of peripheral SNS hypofunction in individuals with migraine, especially if the test is conducted for at least 3 to 4 minutes.[22]

The cold pressor test (CPT) is another physiological stress test that allows for examination of the SNS. A peripheral cold stimulus excites pain and temperature fibers that traverse the spinothalamic tracts to the reticular formation. The descending SNS is then activated in response to the stimulus, as evidenced by an increase in NE, dopamine β-hydroxylase, and neuropeptide Y levels. In most CPTs, BP and heart rate changes are measured after immersion of the hand or face in cold water (1° to 5°C) for 1 to 5 minutes. Heart rate increases maximally during the first 30 seconds of the CPT and returns to normal during the second minute.

In Individuals With Pure Autonomic Failure and Multiple System Atrophy. In individuals with both PAF and MSA, the BP and heat rate responses to the CPT are decreased or absent.[3]

In Migraineurs. In migraineurs, the CPT-induced increase in NE levels is significantly less than in controls.[10] These data suggest a sympathetic hypofunction in the SNS in those with migraine.

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