Neurotoxicity of vincristine on the medial olivocochlear bundle

Abstract

Vincristine is a well known neurotoxic chemotherapeutic agent. Dose dependent and cumulative peripheral neuropathy is the main dose limiting side effect of chemotherapy with vincristine. The mechanisms responsible for the neurotoxic effects of vincristine have not yet been fully understood. This prospective study was directed at determining whether vincristine treatment interferes with the function of the medial olivocochlear bundle. Fifteen children suffering from leukemia were subjected to tympanogram, stapedial muscle reflex, pure tone audiometry and transient evoked otoacoustic emissions (TEOAEs) in the absence and presence of contralateral white noise on day 1 and on day 22 of treatment with vincristine. The function of the medial olivocochlear bundle was assessed by the phenomenon of suppression of otoacoustic emissions by contralateral application of white noise. The study revealed a statistically significant decrease of contralateral suppression amplitudes in all cases after three sessions of chemotherapy with vincristine. On the contrary no alterations were observed in pure tone audiometry thresholds. A non-significant decrease of the mean TEOAEs' amplitudes was also noted. When analyzed by frequency, however, this decrease reached the level of statistical significance at two frequencies. Vincristine treatment seems to exert a neurotoxic effect on the efferent olivocochlear system, which takes place early in the course of chemotherapy. This is a new aspect to be added to the possible mechanisms underlying the toxicity of vincristine in the auditory periphery. Whether changes in efferent function might contribute to understanding the mechanisms of neurotoxicity caused by vincristine, or find any clinical application as a predictor or early detector of neurological side effects of vincristine still remains to be seen.