Screening for neurotoxic disease in humans

J. C. Arezzo, H. H. Schaumburg

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Detection of neurotoxic disease is a formidable task requiring clinical, epidemiologic and detective skills. Rarely does neurotoxic insult occur in isolation, and rarely are precise details of the putative 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 manifest 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.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalJournal of the American College of Toxicology
Issue number1
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology


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