PROPHYLAXIS AND REVERSAL OF IFOSFAMIDE ENCEPHALOPATHY WITH METHYLENE-BLUE

The antineoplastic ifosfamide produces dose-dependent signs of neuroto xicity. After ifosfamide overdose in a patient, we found excessive uri nary excretion of glutaric acid and sarcosine, which is compatible wit h glutaric aciduria type II, a defect in mitochondrial fatty acid oxid ation that results from defective electron transfer to flavoproteins. We therefore used the electron-accepting drug methylene-blue as an ant idote for ifosfamide encephalopathy. In one patient, ifosfamide neurot oxicity was rapidly reversed by methylene-blue 50 mg intravenously. In another patient with previous episodes of ifosfamide encephalopathy, methylene-blue was administered orally prophylactically. No symptoms o f neurotoxicity were noted.