or delayed onset; or on the basis of duration as transient or 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 or 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 neurological function and must be considered in the design and critique of epidemiologic studies. In the original Veterans and Agent Orange (VAO) report (IOM, 1994), attention was deliberately focused on persistent neurobehavioral disorders. Later reports—Veterans and Agent Orange: Update 1996 (hereafter, Update 1996 [IOM, 1996]), Veterans and Agent Orange: Update 1998 (hereafter, Update 1998 [IOM, 1999]), Veterans and Agent Orange: Update 2000 (hereafter, Update 2000 [IOM, 2001]) and Veterans and Agent Orange: Update 2002 (hereafter, Update 2002 [IOM, 2003])—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. Neurologic disorders are by their nature largely subjective; so there often is no objective evidence with which to confirm diagnosis.
Many studies have addressed the possible contribution of herbicides and pesticides to neurologic disorders. Studies relevant to this report investigated exposures from one of three general settings: in the workplace, from the environment, or during military service in Vietnam.
This chapter reviews the association between exposure to 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); 4-amino-3,5,6-trichloropicolinic acid (picloram); and cacodylic acid (dimethylarsenic acid or DMA) and neurobehavioral disorders, movement disorders, and peripheral neuropathy. The scientific evidence for biologic plausibility also is reviewed briefly. More complete discussions of the categories of association and this committee’s approach to categorizing health outcomes are presented in Chapters 1 and 2. A more thorough discussion of biologic plausibility is found in Chapter 3. For studies new to this update that report only a single neurological health outcome and that are not revisiting a previously studied population, their design information is summarized with their results; the design information for all other new studies can be found in Chapter 4.