Supplementary Material for: Rare Delayed Ifosfamide Encephalopathy: A Case Report of Chemotherapeutic Neurotoxicity

<b><i>Introduction:</i></b> Neurotoxicity is a well-documented side effect of ifosfamide chemotherapy. The presentation includes hallucinations, seizures, disorientation, coma, and death. Treatment with methylene blue can shorten the duration and severity of symptoms. Ifosfamide neurotoxicity almost always happens during or shortly after drug infusion and so is usually immediately recognized. Here, we describe a case of ifosfamide neurotoxicity with onset 14 days after treatment started. <b><i>Case Presentation:</i></b> A 25-year-old woman with round cell sarcoma of the jaw presented to the emergency department with 2 days of encephalopathy and bizarre behavior. Antipsychotic medications and benzodiazepines produced no benefit. After consultation, oncology recommended methylene blue, hypothesizing that her symptoms could be a rare presentation of delayed ifosfamide-induced neurotoxicity, 14 days after first administration. After 4 days of methylene blue infusion, her functioning returned to baseline. <b><i>Conclusion:</i></b> Delayed ifosfamide-related neurotoxicity is a rare side effect of this chemotherapeutic agent and should be considered in the workup of altered mental status, even if symptoms occur after the previously accepted 5-day standard. In such patients, delayed symptomology may require extended use of methylene blue as treatment.

**引言：** 神经毒性（Neurotoxicity）是异环磷酰胺（ifosfamide）化疗中已被充分证实的不良反应。其临床表现包括幻觉、癫痫发作、定向障碍、昏迷甚至死亡。亚甲蓝（methylene blue）治疗可缩短症状持续时间并减轻症状严重程度。异环磷酰胺相关神经毒性几乎均发生于药物输注期间或输注后不久，因此通常可被及时识别。本文报道1例于治疗开始后14天发病的异环磷酰胺神经毒性病例。

**病例介绍：** 1例25岁女性患者，因罹患颌骨圆形细胞肉瘤，因出现2天的脑病及怪异行为就诊于急诊科。抗精神病药物与苯二氮䓬类药物治疗均无获益。经会诊后，肿瘤学科建议使用亚甲蓝，推测其症状为首次给药14天后出现的罕见迟发性异环磷酰胺诱导性神经毒性表现。经4天亚甲蓝静脉输注后，患者的神经功能恢复至基线水平。

**结论：** 迟发性异环磷酰胺相关性神经毒性是该化疗药物的罕见不良反应，即使症状出现于既往公认的5天窗口期之后，也应将其纳入精神状态改变的鉴别诊断流程。此类患者的迟发性症状可能需要延长亚甲蓝的使用疗程以作为治疗手段。