We report instances of fatal leukoencephalopathy associated with the intravenous administration of the antifungal agent amphotericin B (AmB) to a 16-year-old girl treated for acute lymphoblastic leukemia and a 22-year-old man who underwent bone marrow transplantation for a myelodysplastic syndrome. Both received AmB in association with cranial irradiation and developed a subacutely evolving neurologic disorder characterized by personality change and confusion rapidly progressing to akinetic mutism. Neuroimaging studies disclosed diffuse nonenhancing abnormalities of the cerebral, particularly frontal, white matter that included hypodensity on CT and increased signal on T2-weighted MRI. Postmortem examinations demonstrated a diffuse, noninflammatory leukoencephalopathy with florid astrogliosis, demyelination, and infiltration of the hemispheric white matter by foamy macrophages. In neither case was there evidence of opportunistic infection or neoplastic infiltration of the nervous system. We review the evidence that polyene macrolide antibiotics such as AmB are potential leukotoxins.
