the absence of any toxicant exposure but all may be triggered by aspects of the environment, including toxicant exposure.

Disorders of the PNS are generally referred to as neuropathies. Neuropathies may be purely motor and affect only movement or purely sensory; most often, however, both motor and sensory fibers are affected. Neuropathies usually are symmetric and start with symptoms related to dysfunction of fibers that travel the greatest distance to their target organ. For that reason, symptoms of neuropathy generally start in the digits and travel toward the torso. Most neuropathies also affect autonomic fibers and thus can result in changes in blood pressure and heart rate and in symptoms related to the control of digestion. Toxicant exposure can induce immediate damage to peripheral nerves, and previous updates have found limited or suggestive evidence that dioxin exposure caused such short-term effects. Evidence related to rapid onset of these conditions is presented in Appendix B, which deals with short-term adverse health effects. Previously undistilled information concerning persistence of symptoms after early effects is also evaluated in Appendix B. The overall focus of this chapter is delayed adverse effects on the PNS and the CNS.

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: Health Effects of Herbicides Used in Vietnam report, hereafter referred to as VAO (IOM, 1994), attention was deliberately focused on persistent neurobehavioral disorders. That focus was maintained in Update 1996 (IOM, 1996), Update 1998 (IOM, 1999), Update 2000 (IOM, 2001), and Update 2002 (IOM, 2003). A slight change in emphasis toward chronic neurodegenerative disorders was reflected in the change in the name of this chapter to “Neurologic Disorders” in Update 2004 (IOM, 2005), which was carried forward in Update 2006 (IOM, 2007) and Update 2008 (IOM, 2009). The present chapter reviews data pertinent to persistent neurologic disorders of all types.

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. However, identifiable neurologic disorders always result in objective abnormalities that are reflected in anatomic or functional tests or discovered via clinical examination.

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), picloram (4-amino-3,5,6-trichloropicolinic acid), and cacodylic acid (dimethyl arsenic acid)—and a contaminant of 2,4,5-T, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Thus,



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