Atypical Diffusion-Restricted Lesion in 5-Fluorouracil Encephalopathy

Discussion

5-FU encephalopathy usually develops within 7 days from the beginning of the chemotherapy cycle. After 5-FU is discontinued, most patients improve within a few days.³ Lesions of 5-FU encephalopathy are most commonly seen in the deep white matter and corpus callosum.^2,3 This present case had clinical characteristics similar to those in previous reports. However, the MR imaging findings disclosed high signal intensities in unusual locations; diffusion- and T2-weighted-images showed involvement of the bilateral basal ganglia and thalami. Although some studies have reported that symmetric lesions of deep gray matter nuclei are also seen in uremic encephalopathy,⁴ our case showed the following differences: 1) our patient had undergone regular hemodialysis; 2) his serum BUN and creatinine levels remained unchanged with respect to initial data; and 3) the period from symptom onset to recovery was brief.

The disease mechanism of 5-FU encephalopathy is unclear. The toxicity of 5-FU is strongly influenced by the dosage used and the rate and duration of drug administration. Our patient received a small dose according to routine usage. Another possible cause of 5-FU toxicity is a deficit of DPD. More than 80% of administered 5-FU is eliminated by DPD, which suggests that enzyme deficiency would result in highly toxic effects such as severe mucositis, myelosuppression/neutropenia, and severe diarrhea.⁵ DPD deficiency in our patient is unlikely, given that he did not manifest any of the other severe toxic effects.

Hyperammonemic encephalopathy has also been reported to be a significant cause of neurologic deterioration after chemotherapy.⁶ The serum ammonia level and PT/INR of our patient were initially increased and became normalized during 3 days, as the patient improved. The association between hyperammonemia and 5-FU encephalopathy may be a clue in determining the mechanism involved.⁷ We postulate that transient hepatic dysfunction might play an important role in the pathogenesis of reversible 5-FU encephalopathy.

In conclusion, we have reported a case of 5-FU encephalopathy with manifestations of hyperammonemia, prolonged PT/INR, and unique brain MR imaging findings. Additional research is needed to clarify the pathophysiologic mechanism for 5-FU encephalopathy.