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Organophosphate polyneuropathy

Pathogenesis and prevention

From the Departments of Medicine (Drs. Becker and Lotti) and Neurology (Dr. Aminoff), and the Northern California Occupational Health Center (Drs. Becker and Lotti), University of California, San Francisco, CA. Marcello Lotti was on sabbatical leave from Istituto di Medicina del Lavoro dell' Universita di Padova (Italy).

Organophosphorus-induced delayed polyneuropathy (OPIDP) is initiated by the phosphorylation of a protein neurotoxic esterase (NTE) in the nervous system. A second step, the "aging" of the phosphoryl-enzyme complex, is required to produce the toxic effect. The experimental evidence for this molecular target and the importance of the aging process are reviewed. The catalytic activity of NTE has been used to develop an in vitro screening test that may distinguish the organophosphorus compounds (OPs) that cause neuropathy from those that do not, thereby providing a means for prevention of OPIDP. Moreover, a biochemical screening test, the determination of NTE activity in blood lymphocytes, may predict the development of OPIDP after acute or chronic exposure to OPs, and requires evaluation by carefully designed studies of occupational exposure to OPs.

Address correspondence and reprint requests to Dr. Lotti, Universita di Padova, Istituto di Medicina del Lavoro, Via Facciolati 51, 35100 Padova, Italy.

Accepted for publication September 9, 1983.

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