Autonomic Dysfunction May Play a Role in Gulf War Syndrome

Laurie Barclay, MD

September 30, 2004

Sept. 30, 2004 — Some symptoms of Gulf War syndrome may be related to subtle autonomic dysfunction, according to the results of a matched cohort study published in the Oct. 1 issue of the American Journal of Medicine.

"While the cause of the illness remains controversial, evidence of chronic central nervous system damage from exposure to low-level sarin nerve gas has emerged," write Robert W. Haley, MD, from the University of Texas Southwestern Medical Center in Dallas, and colleagues. "The symptoms of autonomic dysfunction without orthostatic hypotension or other signs of sympathetic neural failure led us to hypothesize a subtle abnormality of the autonomic nervous system similar to that found in very early diabetic neuropathy."

Investigators blinded to group status compared 22 ill Gulf War veterans and 19 control veterans matched for age, sex, and education. Measurements included circadian rhythm of heart rate variability on 24-hour electrocardiography, ambulatory blood pressure recording, Valsalva ratio testing, sympathetic skin response evaluation, sweat imprint testing, and polysomnography.

Control subjects had a normal increase in high-frequency spectral power of heart rate variability by 2.2-fold during sleep, whereas this increase was only 1.2-fold in ill veterans ( P < .0001). Compared with control subjects, ill veterans had lower heart rate variability at night ( P = .0006), higher during the morning ( P = .007), and no different during the rest of the day ( P = .80).

In the Gulf War group, mean heart rate decreased less at night ( P = .0002), and corrected QT intervals tended to be longer over the full 24 hours ( P = .07), especially at night ( P = .03). Polysomnography ( P = .03) and 24-hour automatic ambulatory blood pressure monitoring ( P = .05) confirmed the blunting of nocturnal heart rate dip in ill veterans. These differences remained significant after adjustment for potential confounding factors. Both groups were similar in measures of sympathetic adrenergic and sudomotor function, sleep architecture, respiratory function, and circadian variation in blood pressure and body temperature.

"Our findings document an abnormality of the neuroregulation of high-frequency heart rate variability, most likely indicative of parasympathetic nervous system activity, in members of a Naval Reserve construction battalion who became chronically ill during or shortly after service in the 1991 Gulf War," the authors write. "Our findings, although unable to attribute specific symptoms of Gulf War veterans directly to early autonomic dysfunction, suggest possible links to be explored in future research."

The U.S. Army Medical Research and Materiel Command cooperative agreement, the U.S. Public Health Service, and the Perot Foundation supported this study.

Am J Med. 2004;117:469-478

Reviewed by Gary D. Vogin, MD

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