Neurotoxicology of vincristine in the cat

Abstract

Vincristine is a vinca alkaloid widely utilized in cancer chemotherapy. Its major clinical limitation is due to a drug induced sensory-motor neuropathy, the pathogenesis of which is poorly understood. This communication describes the morphological basis of a vincristine neuropathy in cats. Major pathological lesions were focal axonal swellings (giant axon formations) due to malaligned accumulations of neurofilaments and secondary demyelination of the paranodal type. These were primarily confined to the proximal portions of the peripheral nerves. The distal portions of the peripheral nerves contained only a few giant axon formations. Wallerian degeneration was noted to involve a small number of nerve fibers in the distal regions.

Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons in vincristine-induced painful peripheral neuropathy in the rat

“…In approximately 30% of the large sensory neurons of vincristine‐treated rats, there was swelling of neuronal cell bodies, as well as a build up of neurofilaments in the cell body and proximal axon, as had been observed in a previous study of the neurotoxic effects of systemic vincristine in the cat (Cho et al, 1983). Some of the morphologic alterations were similar to those observed in the classic chromatolytic reaction that occurs secondary to peripheral axotomy.…”

Motor nervous system impairment persists in long‐term survivors of childhood acute lymphoblastic leukemia

“…6 Vincristine-induced neuropathy is a widely known side effect of ALL treatment 5 and the results of the current study point to long-lasting sequelae in the motor pathway that are concentrated primarily in the proximal nerve tracts in both the hands and the legs. According to Cho et al, 18 there are giant axonal swellings with neurofibrillary material in the proximal parts of the axons in cats after the administration of intravenous vincristine, and this may explain the concentration of the conduction delay in those segments in our human cases as well. Hence, we assume that intravenous vincristine mainly is responsible for the results reported herein.…”

Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: A study with motor evoked potentials*

“…According to neuropathological and neurophysiological studies the vincristine neuropathy is mainly axonal, but secondary demyelination has also been described [10,13,35]. The major pathologic lesions found experimentally have been focal axonal swellings and secondary demyelination of the paranodal type [38]. The inverse correlation between the conduction delay within the peripheral nerve and the post-therapeutic interval after vincristine indicates remyelination after treatment.…”