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 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.
Insights
Amphotericin B methyl ester (AME) treatment for fungal infections can cause progressive neurological damage and white matter degeneration in patients. Higher AME doses correlate with more severe neuropathologic changes, necessitating caution with polyene derivatives.
Area of Science:
- Neuroscience
- Mycology
- Toxicology
Background:
- Fungal infections pose significant health risks, particularly in immunocompromised individuals.
- Amphotericin B methyl ester (AME) is used to treat various mycotic infections.
- Neurological complications associated with antifungal therapies require thorough investigation.
Purpose of the Study:
- To investigate the neurological and neuropathological effects of amphotericin B methyl ester (AME) in patients with mycotic infections.
- To determine the dose-dependent relationship between AME administration and white matter injury.
- To evaluate the safety of AME and other polyene derivatives for human use.
Main Methods:
- Clinical and autopsy studies were conducted on 14 patients treated with AME.
- Patients received varying cumulative doses of AME intravenously.
- Neurological examinations and neuropathological assessments of brain tissue were performed.
- Control groups included patients with coccidioidal meningitis.
Main Results:
- Progressive neurologic dysfunction (dementia, akinesia, mutism, hyperreflexia, tremor) and diffuse white matter degeneration were observed in AME-treated patients.
- Seven patients receiving >9.8 g AME showed severe neurologic and neuropathologic changes.
- Three patients receiving 5-7.2 g AME exhibited less severe symptoms and mild white matter gliosis.
- Four patients receiving <1.5 g AME had no brain abnormalities beyond their underlying meningitis.
- Control patients showed no diffuse white matter abnormalities.
Conclusions:
- Prolonged administration of amphotericin B methyl ester (AME) injures human white matter.
- The observed white matter damage appears to be dose-dependent.
- Further long-term animal studies focusing on nervous system histology are crucial before introducing new polyene derivatives into human clinical practice.