Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease.

Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha-interferon (alpha-IFN). In seven of these patients, a progressive vegetative state developed during treatment. The patients became unresponsive to verbal commands but opened their eyes with auditory or tactile stimulation. It took an average of 3 weeks for these patients to become verbally responsive after treatment was discontinued. Electroencephalographic findings showed evidence of irritative involvement of the deep midline nuclei in 80% of patients. Periventricular white matter changes developed during treatment in three of six patients who underwent computed tomographic scans. All patients with this severe neurotoxicity received whole-brain irradiation before treatment. Possible mechanisms for the development of this neurotoxic syndrome are discussed. The neurotoxicity of alpha-IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment.