Multifocal inflammatory leukoencephalopathy with 5-fluorouracil and levamisole

Area of Science:

• Neuro-oncology
• Neuropathology
• Clinical Neurology

Background:

• Adjuvant therapy with 5-fluorouracil and levamisole is standard for colon adenocarcinoma.
• Neurological side effects are rare but can be severe.
• The specific mechanism of neurotoxicity in this combination therapy is not fully understood.

Purpose of the Study:

• To report and characterize a novel inflammatory leukoencephalopathy in patients receiving 5-fluorouracil and levamisole.
• To investigate the potential link between this neurological syndrome and the administered chemotherapy.
• To describe the clinical, radiological, and pathological findings of this adverse event.

Main Methods:

• Case series of 3 patients with colon adenocarcinoma treated with 5-fluorouracil and levamisole.
• Clinical evaluation, magnetic resonance imaging (MRI) with gadolinium, and stereotactic cerebral biopsy.
• Histopathological and electron microscopic examination of brain tissue.

Main Results:

• All 3 patients developed subacute neurological decline (altered mental status, ataxia, loss of consciousness) 15-19 weeks into chemotherapy.
• MRI revealed multifocal enhancing white matter lesions.
• Biopsies showed active demyelinating disease with macrophages, axonal sparing, and perivascular inflammation.

Conclusions:

• This study describes the first reported cases of inflammatory leukoencephalopathy associated with 5-fluorouracil and levamisole chemotherapy.
• The syndrome may represent a pathological basis for 5-fluorouracil neurotoxicity.
• Cessation of chemotherapy and corticosteroid therapy led to clinical improvement in all patients.