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Título

IPHOSPHAMIDE-INDUCED ENCEPHALOPATHY TREATED WITH METHYLENE BLUE: A PEDIATRIC CASE REPORT

Apresentação do caso

This is a 12-year-old female patient hospitalized for chemotherapy due to Acute Lymphoblastic Leukemia. She was on the fifth day of treatment, receiving iphosphamide, dexamethasone and daunorubicin. Suddenly, she developed hyporesponsiveness and focal seizure, which improved after Midazolam. A few hours later, there was another generalized seizure and she presented irritability afterwards. She was referred for pediatric ICU monitoring, admitted sleepy and hyperreactive. Methylene Blue at 1 mg/kg dose was started due to suspected neuro-intoxication by iphosphamide, maintained for 3 days total. Brain MRI showed multiple lesions with cortical and subcortical involvement. The patient showed clinical improvement after 24 hours of symptoms` onset. There was no neurological sequel afterwards. Control MRI after two months had no parenchymal lesions. Due to clinical and radiological improvement, the diagnosis of iphosphamide encephalopathy was maintained.

Discussão

Iphosphamide is an alkylating chemotherapy drug used in treatment of different tumors such as ovarian and testicular cancer, lymphomas and sarcomas. The neurotoxicity side effect of iphosphamide can affect 10 to 15% of patients, which may occur within 12 hours to 6 days after starting treatment and usually improves within 48 to 72 hours after discontinuation of the drug. Predisposing factors for iphosphamide encephalopathy include higher doses, poor initial treatment response, association with cisplatin, renal or liver failure and hypoalbuminemia.

The mechanisms involved at iphosphamide-induced encephalopathy are still unknown. However, it is known that precipitation of chloroacetaldehyde, its toxic metabolite, in the central nervous system (CNS) is the main cause of its neurotoxicity. Patient's symptoms can range from drowsiness, confusion, hallucinations, seizures to status epilepticus and coma. In addition, several patterns of electroencephalogram have been described.

To date, there is no specific treatment for reversing the iphosphamide's encephalopathy, however, Methylene Blue and Thiamine have been used, with variable efficacy.

Comentários finais

Iphosphamide-induced encephalopathy is a severe complication of some chemotherapy in children. All of its neurotoxicity mechanisms are still unclear and it is necessary to study and describe more cases to establish an effective and rapid treatment in order to minimize short and long-term neurological outcomes.

Referências (se houver)

Aaron MG, Rachna M, Xi C. J Clin Neurophysiol. 2019 March ; 36(2): 150–154.
Park IS, Lee HJ, Lee YS, Hwang JS, Lee MS. Ifosfamide - induced encephalopathy with or without using methylene blue. Int J Gynecol Cancer 2005;15: 807–810.
Amanda LB et al. Risk Factors for Ifosfamide-Related Encephalopathy in Adult Cancer Patients: An Integrative ReviewJ Adv Pract Oncol 2020;11(4): 368–380
Daoud AM et al. Reversible Encepahlopathy Induced by Ifosfamide with Brain Imaging. Global Pediatric Health volume 8: 1–5; 2021.

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