Leukoencephalopathy in patients treated with amphotericin B methyl ester

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.