• Exposure-free period for reversible neurologic effects. To be relevant to Gulf War veterans, the study had to examine long-term rather than short-term effects. Some neurologic outcomes can be determined only after an exposure-free period of weeks or months before evaluation of study subjects. The committee required an exposure-free period period specifically for effects that might be reversible (such as headache, light-headedness, poor coordination, and difficulty in concentrating), but not for irreversible effects (such as neurologic disease and peripheral neuropathy). The rationale for this criterion is described below.

The committee evaluated long-term effects because they are most relevant to the veterans’ situation: exposure to fuels and combustion products during the Gulf War but symptoms that persist for years after the exposure. Long-term or very high exposure to fuels produce well-known short-term effects, including headache, light-headedness, poor coordination, difficulty in concentrating, tremors, myoclonus, and seizures (ATSDR 1995). The short-term effects are reversible and do not persist beyond hours or days after cessation of exposure. Long-term effects are often less well studied than short-term effects.

Occupational or other epidemiologic studies of neurologic effects often do not permit distinction between short-term effects (hours or weeks) and long-term effects (months or years), because many studies examine workers who have both past and current exposure. Consequently, if a study finds a neurologic effect (for instance, headache or fatigue), it is difficult to determine whether the effect will persist after cessation of the exposure unless an exposure-free period of weeks or months has passed before the effect is measured. Many of the available studies were not designed to determine whether an effect was a long-term or a short-term effect.

The challenge of distinguishing long-term and short-term effects is greater in the case of neurobehavioral effects than neurologic diseases for reasons related to onset, reversibility, and availability of objective testing. Neurobehavioral effects (such as symptoms of memory loss and fatigue) can be short-term effects, long-term effects, or both; they can appear within hours of exposure or later; and they can persist or disappear after cessation of exposure. Neurobehavioral effects cannot usually be verified with pathologic or biochemical tests, although objective and validated neurobehavioral tests of memory, attention, and other functions can be used in addition to symptom reporting (IOM 2003). Conversely, neurologic diseases are generally believed to be irreversible after a confirmed diagnosis and are associated with abnormal results of pathology or biochemistry tests. Thus, in evaluating the body of evidence, the committee required that there had been an exposure-free period of weeks or months before testing for a potentially reversible effect. For studies of peripheral neuropathy and neurologic diseases, the committee did not require an exposure-free period, because these effects are almost always long-lasting (although some degree of recovery or lack of progression is possible).

Fuels

This section covers fuel exposure and two neurologic effects: peripheral neuropathy and neurobehavioral effects. Some studies of neurologic effects, whether of those particular outcomes or others, were excluded by the committee for lack of methodologic rigor, nonspecific outcomes (Christie et al. 1987; Dagg et al. 1992; Hanis et al. 1985; Miller et al. 1986; Tsai et al. 1992; Wen et al. 1984), or lack of an exposure-free period in the case of reversible outcomes (Hakkola et al. 1997; Kilburn and Warshaw 1995; Kumar et al. 1988; Odkvist et al. 1987; Struwe et al. 1983).



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