Ifosfamide-induced Encephalopathy With Rapid Response to Thiamine: A Pediatric Case

Abstract

Ifosfamide is an important chemotherapeutic agent used in the therapeutic protocols of many malignant tumors. Central nervous system toxicity of ifosfamide manifests with encephalopathy in 10% to 30% of patients treated with ifosfamide. Thiamine and methylene blue have been reported beneficial in the treatment and prevention of ifosfamide-induced encephalopathy (IIE). We describe an episode of encephalopathy developed at the third cycle of ifosfamide treatment in a child with Ewing sarcoma. With the administration of thiamin, the encephalopathy resolved and no episode was noted during subsequent courses of ifosfamide. Previous use of cisplatin, concomitant use of opioids, low levels of serum albumin and hemoglobin, and elevated levels of serum creatinine are potential risk factors for IIE. The current case illustrates the possibility of IIE even in the absence of such additional risk factors, treated successfully with thiamin and draws attention to the need for close neurological monitorization of patients treated with ifosfamide.

Rare Delayed Ifosfamide Encephalopathy: A Case Report of Chemotherapeutic Neurotoxicity

“…Aside from hydration, thiamine [12][13][14], and discontinuation of the offending agent, methylene blue is the antidote for ifosfamide toxicity, often with complete resolution of symptoms [1,3,15]. As the neurotoxins inhibit mitochondrial oxidative phosphorylation, methylene blue is hypothesized to work by acting as an alternative electron acceptor, allowing the mitochondrial respiratory chain to function as previously [3].…”

Ifosfamide-Induced Encephalopathy Successfully Prevented by Methylene Blue: A Pediatric Case Report and Review of the Literature

“…No treatment is necessary if the patient with IIE recovers spontaneously; however, some cases require anticonvulsants, and there are reports that methylene blue and thiamine are effective as treatment options for the acute phase of the disease [ 1 , 15 ]. Although there is no established strategy for subsequent chemotherapy, including the re-administration of ifosfamide in patients with developing IIE, methylene blue has been reported to be effective in preventing the development of IIE.…”