Cerebellar degeneration caused by high‐dose cytosine arabinoside: A clinicopathological study

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Abstract
Twenty-four patients with leukemia or lymphoma refractory to conventional chemotherapy were given a course of systemic, high-dose cytosine arabinoside (3 gm/m2 every 12 hours for twelve doses). Four patients developed cerebellar degeneration during treatment. Ataxia of gait and limb movements, dysarthria, and nystagmus appeared five to seven days after the first dose, worsened over the next two to three days, and then remained stable for two to six days. Incomplete improvement occurred over the following one to two weeks. Postmortem examination disclosed loss of Purkinje cells in the depths of cortical sulci with relative preservation of those at the crests of folia and those in the most posterior inferior portions of the cerebellum. Other patients developed a mild, reversible cerebellar syndrome over the same time course as that of the irreversible disorder. Manifestations ranged from nystagmus alone to dysarthria and unsteadiness of gait without limb ataxia. We conclude that cytosine arabinoside at this dosage causes a cerebellar degeneration with characteristic clinical and pathological features. Among the present patients with refractory hematological malignancies, such degeneration occurred with an incidence of 16.7%, more than twice that reported in previous series.