Symptom Clustering

The study was the first to cluster symptoms into new syndromes by applying factor analysis. Through standardized symptom questionnaires and two-stage factor analysis, the investigators defined what they considered to be either six syndromes or six variants of a single syndrome, which they labeled impaired cognition, confusion-ataxia, arthromyoneuropathy, phobia-apraxia, fever-adenopathy, and weakness-incontinence. One-fourth of the veterans in this uncontrolled study (n = 63) were classified as having one of the six syndromes. The first three syndromes had the strongest factor clustering of symptoms.

In a followup study of the same cohort, Haley and colleagues (1997a) used a case-control design to examine neurologic function. They chose as cases the 23 veterans who had scored highest on the three syndromes with the strongest factor clustering. Controls consisted of two small groups of healthy veterans, of which one (n = 10) was deployed to the Gulf War and the other (n = 10) was not. The results of extensive neurologic and neurobehavioral testing demonstrated that cases had significantly greater evidence of neurologic dysfunction compared with controls. Investigators concluded that the three syndromes, derived from factor analysis of symptoms, might signify variant forms of expression of a generalized injury to the nervous system.10 In a later study, cases with one of the three syndromes were more likely than healthy controls to exhibit vestibular dysfunction (Roland et al. 2000). Related research on the same subset of veterans found evidence of basal ganglia and brainstem neuronal loss through magnetic resonance spectroscopy (Haley et al. 2000b). Those studies are discussed further in Chapter 5.

Exposure-Symptom Relationships

The three syndromes identified by Haley and colleagues (1997a) were the focus of another case-control study that examined their relationship to self-reported exposures to neurotoxicants. The study tested the hypothesis that exposure to organophosphates and related chemicals that inhibit cholinesterase are responsible for the three nervous system-based syndromes (Haley and Kurt 1997). Each of the syndromes was associated with a distinct set of risk factors. The “impaired-cognition syndrome” was found, through multiple logistic regression, to be associated with jobs in security and the wearing of flea-and-tick collars. The “confusion-ataxia syndrome” was associated with self-reports of having been involved in a chemical-weapons attack and of having advanced adverse effects of PB. Finally, “arthromyoneuropathy” was associated with higher scores on the scale of advanced adverse effects of PB and with an index created by the investigators to enable veterans to self-report the amount and frequency of their use of government-issued insect repellent. The authors concluded that some Gulf War veterans had delayed chronic nervous system syndromes as a result of exposure to combinations of neurotoxic chemicals (Haley and Kurt 1997).

Another study by Haley and collaborators (1999) examined whether genetic susceptibility could play a role in placing some veterans at risk for neurologic damage by organophosphate chemicals. They hypothesized that neurologic symptoms in ill veterans might be explained by their having genetic polymorphisms (variations) in metabolizing enzymes. One set of polymorphisms could impair their ability to quickly detoxify organophosphorus compounds,


Neuropsychologic or neurologic impairments have been the focus of several smaller studies as well. Some found subtle changes in nerve-conduction velocity and cold sensation (Jamal et al. 1996) and in some tests of finger dexterity and executive functioning (Axelrod and Milner 1997); others found no significant differences in measures of nerve conduction and neuromuscular functioning (Amato et al. 1997) or neuropsychologic performance (Goldstein et al. 1996).

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