Screening for Neurotoxic Disease in Humans

Abstract

Detection of neurotoxic disease is a formidable task requiring clinical, epidemiologic and detective skills.(l) Rarely does neurotoxic insult occur in isolation, and rarely are precise details of the putatiive exposure known. False positive and false negative diagnoses of neurotoxicity are common because of the similarity of the major signs and symptoms with those associated with metabolic, traumatic, or age-related diseases. No single test or sign is pathognomonic for neurotoxic disease; routine clinical laboratory results and imaging procedures are generally of little value. Exposure to a specific toxin can result in a vastly (different clinical profile depending on the magnitude and route of exposure. For example, acute high level exposure to acrylamide causes a toxic encephalopathy with convulsions and hallucinations; prolonged low level exposure causes distal sensory loss. Since metabolites are often the toxic moiety, it is rarely possible to predict neurotoxicity by examining the chemical formula of agents. Thus, the neurotoxic properties of n-hexane and methyl-n-butylketone are attributable to a common gamma-diketone metabolite (2,5-HD), whereas chemically related compounds (i.e., heptane, pentane) have failed to produce experimental neuropathy. Nontoxins also can enhance toxic situations,, Symptoms may intensify for months after exposure is stopped (coasting), and, conversely, dysfunction may not appear until years of low level exposure. Preexisting subclinical nervous system dysfunction (i.e., carpal tunnel syndrome) may first become mainifest after toxic exposure (unmasking phenomena). The onset of symptoms, particularly negative symptoms, can be insidious and may continue undetected by patient and physician. It is suggested that neurotoxic damage in early life can enhance late life central nervous system dysfunction, such as Parkinson's disease.T from one patient acutely exposed to a known single neurotoxicant to an entire population exposed for years to a combination of known and suspected toxins (i.e., workplace assessment, ~~ _ _ _ _ _ _~

Self-reported post-exertional fatigue in Gulf War veterans: roles of autonomic testing

“…Fourteen participants in Ill group and 11 Controls received NCS of at least one hand examining for carpal tunnel syndrome (CTS) and ulnar neuropathy. We performed QST for thermal and vibration threshold on index fingers and big toes of all 28 participants as an additional approach comparing the group differences regarding small or large nerve fiber function (Arezzo and Schaumburg, 1989 ). We used the procedure of “Method of Limits” to determine the thermal and vibration threshold (Arezzo, 1988 ).…”

Workshop on human health impacts of halogenated biphenyls and related compounds.

“…Vibration testing can assess large fiber function, and thermal testing can be used for small fiber assessment. Results from these and other recently developed techniques can be combined to provide an accurate assessment ofthe presence or absence of neurological deficits as well as diagnostic information about the type of effect and the possible site of action (48). Such studies could be valuable in assessing PHB toxicity as well as possibly indicating that exposure at toxicologically significant levels has occurred.…”

Hazardous Waste and Neurobehavioral Effects: A Developmental Perspective

“…In this situation, analysis of population central tendencies (means, modes, and medians) is useful. The statistical power of field studies may uncover a significant dysfunction below values usually accepted as clinically abnormal in office evaluations (Arrezzo and Schaumburg, 1989). Alternatively, the majority of the population may show no effect, while a small number of subjects may demonstrate significant toxic neuropathies or the differences in neurophysiological measurements may be important for them.…”

“…Thus, while most laboratory data are considered normal if the results fall within 2 SD of the mean, the test results of each measurement in our assessment are recorded along a scale of MRVs, providing a way to identify possible subclinical cases or borderline states. This procedure recognizes limitations of measuring the speed of conduction along many different sizes of nerve fibers using maximal electrical stimulus strength and not limiting to the threshold measurements of a maximum stimulation (Arrezzo and Schaumburg, 1989). In this situation, analysis of the pattern of variance within the population is critical.…”