The neuromyopathy of vincristine in man. Clinical, electrophysiological and pathological studies

This report details the neuromyopathy caused by vincristine in a group of patients receiving the drug for the treatment of malignant intracranial gliomata. Weekly intravenous injections of the drug (0.05 mg/kg body weight) were given for up to 20 months to 37 patients, 23 adults and 14 children. All adults receiving vincristine for more than 2 months developed a mixed sensorimotor peripheral neuropathy of varying severity. The subjective complaints were mainly sensory, while the objective deficit was mainly motor. In 3 patients the neuropathy was painful; 3 developed external ophthalmoplegia, and 2 vocal cord paralysis. Proximal muscle pain with weakness and wasting developed in many adults. Children appeared less sensitive to the toxic effects of vincristine. Motor and sensory nerve conduction velocities were measured at intervals during the treatment of 2 adults and 3 children with vincristine for periods of up to 10 months. The distal sensory and motor latency increased during treatment, and complete conduction block developed in several of the nerves studied. Apart from this conduction block, significant slowing of motor nerve conduction in the main nerve trunks did not occur. Biopsies from proximal limb muscles were obtained from 3 patients at the time of the myalgia. A few areas of segmental necrosis and phagocytosis were seen with the light microscope. Under the electron microscope many fibres showed myofibrillary disruption, with the accumulation of occasional fibrillary subsarcolemmal masses. A sural nerve biopsy from a patient with a sensorimotor neuropathy contained both myelinated and non-myelinated fibres undergoing axonal degeneration, with phagocytosis of myelin debris. In addition to the changes seen in the biopsies, autopsy material from 5 of these patients showed denervation atrophy of the distal muscles. There was no abnormality of dorsal root ganglia, or of the spinal cord or brain attributable to the vincristine, though the ultrastructure of these regions was not studied. The significance and mechanism of the toxic damage produced in nerve and muscle by vincristine is discussed.