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Neurotoxicity of intraventricularly administered alpha‐interferon for leptomeningeal disease

Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha‐interferon (α‐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 α‐IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment.