5-Fluorouracil-Induced Neurotoxicity Presenting as Acute Toxic Leukoencephalopathy in a Patient with Metastatic Carcinoma Rectum: A Case Report

Fluorouracil (5-FU), despite common use in management of colorectal cancer, shows a narrow therapeutic range, with neurological toxicity. A 75-year-old man with metastatic rectal cancer developed 10–12 episodes of persistent vomiting, followed by left-sided hemiparesis and dysarthria, two days after his third FOLFIRI cycle. Initial assessment and non-contrast CT suggested an acute ischemic stroke in the right middle cerebral artery territory. However, MRI subsequently demonstrated bilateral supratentorial hyperintensities with restricted diffusion, indicating acute toxic leukoencephalopathy related to chemotherapy. DPYD genotyping revealed a wild-type status, with no detectable dihydropyrimidine dehydrogenase deficiency. The patient was treated conservatively with intravenous fluids and supportive measures, resulting in significant neurological recovery and mRS score of 1 at discharge. This case demonstrates that 5-FU-associated neurotoxicity may occur despite the absence of DPYD mutations and highlights the potential importance of combining pharmacogenomic testing with phenotypic DPD assessment to improve fluoropyrimidine treatment safety.