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A Blinded Case-Control Study

Robert W. Haley, MD; Jim Hom, PhD; Peter S. Roland, MD; Wilson W. Bryan, MD; Paul C. Van Ness, MD; Frederick J. Bonte, MD; Michael D. Devous, Sr, PhD; Dana Mathews, PhD, MD; James L. Fleckenstein, MD; Frank H. Wians, Jr, PhD; Gil I. Wolfe, MD; Thomas L. Kurt, MD, MPH

JAMA. 1997;277(3):223-230.

Abstract
Objective.
—To determine whether Gulf War-related illnesses are associated with central or peripheral nervous system dysfunction.

Design.
—Nested case-control study.

Participants.
—Twenty-three veterans with factor analysis-derived syndromes (the cases), 10 well veterans deployed to the Gulf War (the deployed controls), and 10 well veterans not deployed to the Gulf War (the nondeployed controls).

Method.
—With investigators blinded to group identities, participants underwent objective neurophysiological, audiovestibular, neuroradiological, neuropsychological, and blood tests.

Main Outcome Measures.
—Evidence of neurologic dysfunction.

Results.
—Compared with the 20 controls, the 23 cases had significantly more neuropsychological evidence of brain dysfunction on the Halstead Impairment Index (P=.01), greater interside asymmetry of the wave I to wave III interpeak latency of brain stem auditory evoked potentials (P=.02), greater interocular asymmetry of nystagmic velocity on rotational testing, increased asymmetry of saccadic velocity (P=.04), more prolonged interpeak latency of the lumbar-to-cerebral peaks on posterior tibial somatosensory evoked potentials (on right side, P=.03, and on the left side, P=.005), and diminished nystagmic velocity after caloric stimulation bilaterally (P values range from.02 to.04). Cases (n=5) with syndrome 1 ("impaired cognition") were the most impaired on brain stem auditory evoked potentials (P=.005); those (n=13) with syndrome 2 ("confusion-ataxia") were the most impaired on the Halstead Impairment Index (P=.006), rotational testing (P=.01), asymmetry of saccadic velocity (P=.03), and somatosensory evoked potentials (P.01); and those (n=5) with syndrome 3 ("arthro-myo-neuropathy") were the most impaired on caloric stimulation (P.01).

Conclusions.
—The 3 factor-derived syndromes identified among Gulf War veterans appear to represent variants of a generalized injury to the nervous system.

Author Affiliations
From the Departments of Internal Medicine (Drs Haley and Kurt), Otolaryngology (Dr Roland), Neurology (Drs Bryan, Hom, Van Ness, and Wolfe), Radiology (Drs Bonte, Devous, Fleckenstein, and Mathews), and Pathology (Dr Wians), University of Texas Southwestern Medical Center at Dallas; and The Neuropsychology Center, Dallas, Tex (Dr Hom).

Footnotes
Corresponding author: Robert W. Haley, MD, Epidemiology Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-8874.

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