We present the case of a 59-year-old man with persistent cerebellar atrophy and ataxia following treatment with 5-fluorouracil. Our patient has a history of chronic alcohol use and pancreatic cancer, and had previously been treated with 5-fluorouracil (5-FU), leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) therapy. He first noted worsening coordination and stability over the past several months shortly after the first cycle of FOLFIRINOX therapy. Neurological exam was most notable for significant cerebellar findings, such as scanning speech, abnormal rebound in the upper extremities, and frank bilateral dysmetria. Further diagnostic workup revealed chronic cerebellar atrophy on MRI of the brain, and CSF studies returned positive for Varicella Zoster Virus (VZV). Our patient was then started on antiviral therapy. Given the lack of improvement on neurological exam following antiviral therapy and lack of headache and other typical meningeal symptoms, it is unlikely that the cerebellar findings were due to VZV cerebellitis. Our patient’s cerebellar deficits were noticed in correlation to the 5-FU treatment. 5-FU toxicity, though rare, should be considered in patients who have undergone a chemotherapeutic regimen containing 5-FU and present with symptoms of ataxia, dysmetria, dysarthria, and nystagmus.

5-fluorouracil (5-FU) is an antimetabolic chemotherapeutic agent with activity against many solid tumors. Common side effects include diarrhea, photosensitivity, and myelosuppression. In very rare cases, 5-FU can cause an acute cerebellar syndrome, including ataxia, lack of coordination, and nystagmus. It is important for neurologists to be aware of the neurological complications of malignancy and chemotherapeutic regimens in order to develop a robust differential in cases concerning for CNS injury.

Here, we report an important and possibly irreversible manifestation of 5-FU toxicity. Thorough cerebellar examination during administration of 5-FU is of critical importance, as cerebellar findings may prove to be persistent and debilitating with ongoing therapy.