Fluorouracil-induced neurotoxicity

OBJECTIVE: To report a case of acute neurologic adverse effects related to fluorouracil administration and to review the neurotoxicity of this agent. CASE SUMMARY: A 73-year-old white man with a history of esophageal carcinom a was treated with fluorouracil 1500 mg iv daily for four days. After compl eting treatment, he presented with sudden onset of confusion, cognitive dis turbances, a cerebellar syndrome, and repeated seizures, A magnetic resonan ce image of the brain showed no structural abnormalities, and cerebrospinal fluid examination was normal; none of the other laboratory tests provided an explanation for his symptoms. The patient was treated with anticonvulsan ts, and the cognitive changes resolved in 72 hours. The cerebellar signs. h owever, did not resolve completely and persisted when the patient was exami ned two weeks after discharge. DISCUSSION: Fluorouracil can cause both acute and delayed neurotoxicity. Ac ute neurotoxicity manifests as encephalopathy or as cerebellar syndrome; se izures, as seen in our patient, have rarely been reported. Acute neurotoxic ity due to fluorouracil is dose related and generally self-limiting. Variou s mechanisms for such toxicity have been postulated, and treatment with thi amine has been recommended, Delayed neurotoxicity has been reported when fl uorouracil was given in combination with levamisole; this form of subacute multifocal leukoencephalopathy is immune mediated and responds to treatment with corticosteroids. CONCLUSIONS: Clinicians should be aware of the adverse neurologic effects o f fluorouracil and should include them in the differential diagnosis when p atients receiving the drug present with neurologic problems.