persistent. For example, global CNS dysfunction can lead to a general abnormality, such as an altered level of consciousness, whereas focal CNS dysfunction might lead to an isolated abnormality, such as difficulty with language function (aphasia). Early-onset disorders are seen within days or weeks of exposure; delayed onset may occur after months or years. Transient disorders are short-lived; persistent disorders produce lasting deficits. Timing is important in assessing the effects of chemical exposure on neurologic function and must be considered in the design and critique of epidemiologic studies. In the original Veterans and Agent Orange report, hereafter referred to as VAO (IOM, 1994), attention was deliberately focused on persistent neurobehavioral disorders. Veterans and Agent Orange: Update 1996, or Update 1996 (IOM, 1996); Veterans and Agent Orange: Update 1998, or Update 1998 (IOM, 1999); Veterans and Agent Orange: Update 2000, or Update 2000 (IOM, 2001); Veterans and Agent Orange: Update 2002, or Update 2002 (IOM, 2003); Veterans and Agent Orange: Update 2004, or Update 2004 (IOM, 2005); and this report review data pertinent to all neurologic disorders.
Case identification in neurologic disorders is often difficult because there are few disorders for which there are specific diagnostic tests. Many disorders involve cellular or molecular biochemical effects, so even the most advanced imaging techniques can miss an abnormality. Because the nervous system is not readily accessible for biopsy, pathologic confirmation usually is not feasible. Furthermore, neurologic disorders are by their nature largely subjective, so there often is no objective evidence with which to confirm a diagnosis.
Many studies have addressed the possible contribution of various chemical exposures to neurologic disorders, but the committee’s focus is on the health effects of a particular set of chemicals: four herbicides (2,4-dichlorophenoxyacetic acid [2,4-D], 2,4,5-trichlorophenoxyacetic acid [2,4,5-T], 4-amino-3,5,6-trichloropicolinic acid [picloram], and cacodylic acid [dimethyl arsinic acid or DMA]) and a contaminant of 2,4,5-T, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Thus, the specificity of exposure assessment is an important consideration in weighing evidence relevant to the committee’s charge, as described earlier (Chapters 2 and 5).
This chapter reviews the association between exposure to the compounds of interest and neurobehavioral disorders, movement disorders, and peripheral neuropathy. The scientific evidence supporting biologic plausibility also is reviewed briefly here; a more thorough discussion of updated toxicologic studies is in Chapter 3. More complete discussions of the categories of association and of this committee’s approach to categorizing health outcomes are presented in Chapters 1 and 2. If a study new to this update reports only a single neurologic outcome and is not revisiting a previously studied population, its design information is summarized with its results; design information on other new studies is in Chapter 4.