Oncoscience

Silent toxicity: A rare case of 5-fluorouracil-induced hyperammonemic encephalopathy

Areti Kalfoutzou1, Cleopatra Rapti2, Eleftheria Bagiokou3, Vasileios Kolintzikis4 and Vasileios Ramfidis2

1 Second Propaedeutic Department of Internal Medicine, Attikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece

2 Department of Medical Oncology, 251 Air Force General Hospital, Athens, Greece

3 Oncology Unit, 3rd Department of Internal Medicine, Athens General Hospital of Thoracic Diseases “Sotiria”, National and Kapodistrian University of Athens, Athens, Greece

4 Second Department of Medical Oncology, Agios Savvas Cancer Hospital, Athens, Greece

Correspondence to:

Areti Kalfoutzou, email: [email protected]

Keywords: hyperammonemia; encephalopathy; fluorouracil; neurotoxicity

Received: July 22, 2025     Accepted: December 12, 2025     Published: December 23, 2025

ABSTRACT

Hyperammonemic encephalopathy (HE) is a rare but serious neurological condition characterized by an acute alteration in mental status due to elevated serum ammonia levels, occurring in the absence of known liver disease. The build-up of ammonia, a by-product of protein metabolism, in the bloodstream leads to its crossing of the blood-brain barrier, where it acts as a neurotoxin, causing potentially reversible brain damage. Chemotherapeutic agents such as 5-fluorouracil (5-FU) are known to cause drug-induced HE. Our case reports a 63-year-old woman who presented with several episodes of reduced consciousness shortly after 5-FU administration, highlighting the necessity of monitoring serum ammonia levels in patients treated with 5-FU who develop neurological symptoms, and the need for expert consultation in attempting a 5-FU rechallenge.


PII: 638