Multifocal inflammatory leukoencephalopathy associated with levamisole and 5-fluorouracil: case report

Levamisole and 5-fluorouracil have now become the standard chemotherapeutic regimen for patients with Stage III colon carcinoma. A case of multifocal inflammatory leukoencephalopathy secondary to levamisole alone or combination of levamisole and 5-fluorouracil is reported. Magnetic resonance imaging with gadolinium demonstrated multifocal contrast-enhancing frontal, parietal, occipital, and periventricular white matter lesions. A stereotactic biopsy revealed reactive gliosis and macrophage infiltration, without evidence of metastatic tumor. Despite continuation of 5-fluorouracil, resolution of contrast-enhancing lesions on magnetic resonance imaging without further neurological sequelae occurred when levamisole was stopped. The patient died with evidence of systemic metastasis 6 months later. Autopsy examination of the brain revealed multifocal demyelinating lesions, with no evidence of metastatic tumor. Immunoperoxidase studies of demyelinated lesions demonstrated infiltrating macrophages strongly positive for Class II antigens, interleukin-6, and interleukin-1 alpha. Surrounding astrocytes were positive for granulocyte macrophage colony-stimulating factor. Small numbers of perivascular T cells were present. This patient represents the first autopsy documented case of levamisole associated multifocal inflammatory leukoencephalopathy.