Leukoencephalopathy in Patients Treated with Amphotericin B Methyl Ester

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Abstract
Clinical and autopsy studies of 14 patients treated with amphotericin B methyl ester (AME) for focal, disseminated, and nervous system mycotic infections revealed a high incidence of progressive neurologic dysfunction (dementia, akinesia, mutism, hyperreflexia, and tremor) and diffuse white matter degeneration. All of seven patients who received >9.8 g of AME intravenously developed severe neurologic and neuropathologic changes. Two of three patients given 5–732 g of AME developed less severe neurologic symptoms; all three had mild diffuse white matter gliosis. Four patients given <1.5 g of AME had no brain abnormalities except those related to coccidioidal meningitis. Thirty-one control patients who died of untreated or amphotericin B—treated coccidioidal meningitis showed no diffuse white matter abnormalities. These findings indicate that prolonged administration of AME and/or other contaminating polyenes injures human White matter. Long-term animal studies, with particular attention to nervous system histology, must precede human use of other polyene derivatives.