Supplementary Material for: Neuron-Specific Enolase as a Biomarker in Ifosfamide-Induced Encephalopathy: A Case Report

Introduction Ifosfamide, an alkylating agent is used in treatment of various malignancies and may cause encephalopathies. The pathophysiology of this treatment adverse event is well-documented, complex and multifactorial, and involves the production of drug-related metabolites interfering with the normal functionality of neuronal synapses. Risk factors associated with the development of ifosfamide-induced encephalopathy have been identified including concurrent cisplatin administration and female gender. The clinical symptoms vary, ranging from simple confusion to seizure or coma. To date, no biomarkers have been evaluated in ifosfamide-induced encephalopathy. Neuron-specific enolase (NSE) elevation has already been correlated with in toxic or metabolic encephalopathies regardless of the underling etiology. Case Presentation We report the case of a 56-year-old woman who received adjuvant chemotherapy for high-grade osteosarcoma including cisplatin, doxorubicin and ifosfamide. The patient experienced ifosfamide-induced encephalopathy the day after completion of the ifosfamide infusion protocol. Treatment with methylene blue was initiated as soon as confusion developed. The patient presented behavioral problems, cognitive impairment, agitation and aphasia, which resolved within few days, with persistent fatigue. NSE levels were assessed after every electroencephalogram (EEG). The kinetics of NSE levels from 20.41 to 7.69 µg/L and EEG toxic pattern improving from grade 2 to normal, were consistent with recovery from clinical encephalopathy in this patient. Conclusion Although increased levels of NSE in peripheral blood have been correlated with other etiologies of encephalopathy, its use as a companion biomarker for ifosfamide-induced encephalopathy warrants further investigation.