Electrophysiological assessment of delayed neurotoxicity in sheep treated with haloxon [0,0 di-(2-chlorethyl) 0-(3-chloro-4-methylcoumarin-7-yl)phosphate]

Abstract

Delayed neurotoxicity has occurred in livestock treated for parasitism with haloxon. The condition, characterized by posterior ataxia, has been produced experimentally in sheep. The neurotoxic effect of haloxon is similar to other organophosphates that cause delayed neurotoxicity. The extent of neurological injury was partly determined in this study and electrophysiological measurements were made in an attempt to locate the part of the nervous system that was damaged. This information adds to the present store of knowledge about neurotoxic organophosphates. The study also provides information to the veterinary clinician about the nature of the injury. Haloxon caused delayed neurotoxicity in sheep given doses approximately 5-20 times higher than therapeutic levels. The sheep were dosed orally at 290, 370, 470, 550, and 600 mg/kg. Posterior ataxia and paresis developed approximately 20 days after treatment at all dose levels. Skin sensitivity to needle prick, pupillary light response, and patellar reflex were normal. For ataxic sheep were tested for abnormalities of peripheral nerve and skeletal muscle. Motor nerve and skeletal muscle function were found to be normal by measuring contractile strength of the gastrocnemius and extensor digitorum lateralis muscles in an acute experimental preparation. No abnormally slow conduction velocities were measure in tibial and fibular nerves of ataxic sheep. Somatosensory evoked responses (SER) were recorded in ataxic sheep and compared to the individual pre-treatment records. Post-treatment SER's of some sheep have very low amplitudes; others had prolonged wave component latencies. The SER results demonstrated injury in the central neural pathways for somesthesia. The electrophysiological evidence indicates that the lesions of haloxon delayed neurotoxicity were confined to the central neural pathways.