Leukoencephalopathy in patients treated with amphotericin B methyl ester.
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 greater than 9.8 g of AME intravenously developed severe neurologic and neuropathologic changes. Two of three patients given 5-7.2 g of AME developed less severe neurologic symptoms; all three had mild diffuse white matter gliosis. Four patients given less than 1.5 g of AME had no bran abnormalities except those related to coccidioidal meningitis. Thirty-one control patients who died on 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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D001228:Aspergillosis / Q000188:drug therapy; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000139:chemically induced* / Q000473:pathology; D002648:Child; D003047:Coccidioidomycosis / Q000188:drug therapy; D003711:Demyelinating Diseases / Q000139:chemically induced; D005911:Gliosis / Q000139:chemically induced; D006801:Humans; D008172:Lung Diseases, Fungal / Q000188:drug therapy; D008875:Middle Aged; D009186:Myelin Sheath / Q000473:pathology
C017501:methylamphotericin B; D000666:Amphotericin B