Degeneration and Necrosis of Neurones in Eighth Cranial Nuclei Caused by Streptomycin

Abstract

Toxic effects of streptomycin on the eighth noted, cranial nerve apparatus have been frequently 1 , 8 but the pathogenesis of these dis turbances has not yet been established. 1 , 2 , 4 , 8

This preliminary report is based on the neuropathological findings in 5 human beings who became partially or completely deaf while receiving large amounts of streptomycin, and on the study of the eighth cranial nerve nuclei in 3 dogs given the drug experimentally.

Table I provides a summary of the findings in the 5 clinical cases. It is noteworthy that all of the patients died with tuberculosis and all manifested varying degrees of tuberculous involvement of the central nervous system, though there was no clinical evidence that the function of any of the cranial nerves except the eighth had been disturbed in any of the cases. In one case (patient No. 4) there was softening of a part of the basis of the pons immediately below the ventral cochlear nucleus, this change being unilateral whereas the degeneration and necrosis of neurones presumably due to streptomycin was bilateral.

To learn whether neuronal changes similar to those encountered in the 5 patients could be produced experimentally, 3 medium sized, adult, mongrel dogs were given 170 mg of-highly purified streptomycin per kg of body weight during 12 hours each day in 4 equal doses intramuscularly, this being roughly equivalent to a 12 g dose for an adult human being. 10 All 3 dogs developed marked ataxia, weaving of the head, tail-chasing, and weakness following administration of the drug, the symptoms being markedly accentuated following the final dose each evening. An accurate appraisal of auditory acuity could not be made, but none of the animals became manifestly deaf. One of the dogs died on the 9th day with advanced, bilateral, necrotizing renal arteriolitis and glomerulitis; the