Objective:

To report a rare case of capecitabine-induced toxic leukoencephalopathy presenting with atypical MRI and EEG findings, highlighting diagnostic challenges and management.

Background:

Capecitabine, an oral prodrug of 5-fluorouracil, is widely used in breast cancer treatment. Neurological adverse effects are uncommon, typically presenting with acute confusion, ataxia, and dysarthria. MRI often shows transient splenial lesions, and EEG is usually normal or shows nonspecific slowing.

Design/Methods:

NA

Results:

A 54-year-old woman with breast carcinoma presented with acute behavioral changes after starting capecitabine therapy two days prior. Family reported unresponsiveness and intermittent right leg stiffness. Examination revealed fluctuating mental status and generalized rigidity. Vital signs were stable; laboratory tests showed leukopenia (WBC 1.4 × 10⁹/L) and hypomagnesemia. Non-contrast cranial CT and CT angiography were unremarkable. MRI revealed confluent restricted diffusion in extensive deep supratentorial white matter—including periventricular areas, centrum semiovale, corpus callosum beyond the splenium, and posterior internal capsules—findings rarely reported in capecitabine-induced leukoencephalopathy. EEG demonstrated poorly lateralized frontal subclinical seizures characterized by bursts of fast frequencies evolving into Brief Ictal Rhythmic Discharges (BIRDs), which were distinct from semi-rhythmic delta activity observed separately. These EEG findings are atypical, as capecitabine toxicity usually presents with normal EEG or nonspecific slowing. After initiating brivaracetam, seizures resolved on EEG. Further investigations, including cerebrospinal fluid analysis and autoimmune panels, were unremarkable. The rapid onset after capecitabine initiation, unusual MRI findings, and atypical EEG patterns—including the presence of BIRDs—suggested medication-induced neurotoxicity. Capecitabine was discontinued, and the patient was maintained on anti-seizure medication with plans for outpatient tapering. Repeat MRI after one month showed significant resolution of white matter abnormalities.

Conclusions:

This case highlights a rare neurological complication of capecitabine with atypical MRI and EEG findings, including extensive deep white matter involvement and subclinical seizures with BIRDs. Awareness of these atypical presentations is crucial for timely diagnosis and management.