5-Fluorouracil-induced acute leukoencephalopathy in the absence of dihydropyrimidine dehydrogenase deficiency: A case report

Introduction5-Fluorouracil (5-FU) is a chemotherapeutic agent used in various malignancies. 5-FU-induced leukoencephalopathy is a rare but reversible neurotoxic effect occurring within days of administration. Symptoms include confusion, agitation, and cognitive disturbances, with severe cases potentially causing coma. Diagnosis is supported by magnetic resonance imaging (MRI) showing characteristic brain changes. Treatment involves discontinuing 5-FU and initiating supportive care. Most patients recover within one week, but relapse may occur with repeated exposure, making early recognition critical.Case reportA 42-year-old male with recurrent Stage IV gastric adenocarcinoma and chronic kidney disease developed progressive 5-FU-related leukoencephalopathy after repeated exposure. MRI findings and symptoms of confusion, disorientation, and memory deficits were consistent with 5-FU leukoencephalopathy. Initial work-up was inconclusive, therefore, treatment was continued. Neurologic symptoms worsened after further cycles, leading to chemotherapy discontinuation and surgical resection. Disease recurrence led to reinitiation of modified 5-FU therapy, triggering acute neurotoxicity confirmed by MRI.Management and outcomeThe patient was managed by discontinuing 5-FU, beginning high-dose intravenous thiamine and methylprednisolone, and providing supportive care. Neurologic symptoms including confusion, facial diplegia, and unsteady gait gradually resolved. By Day 9, he returned to baseline mental status without deficits.DiscussionEarly recognition and intervention in 5-FU-induced leukoencephalopathy is crucial, especially in patients with renal dysfunction or repeated exposures. Dihydropyrimidine dehydrogenase (DPD) deficiency has not been directly implicated in this condition. Metabolic disruption and thiamine depletion contribute to pathogenesis. Prompt 5-FU discontinuation and initiation of supportive care can hasten recovery. Clinical vigilance is imperative in patients with known risk factors.