Abstract：
Encephalopathy following Ifosfamide treatment is a well-described phenomenon that is typically treated with Methylene Blue (MB). Chloroacetaldehyde, a potentially neurotoxic metabolite of Ifosfamide is hypothesized to cause this encephalopathy. Current guidelines for treatment is to stop Ifosfamide and provide supportive care. MB acts to inhibit Chloroacetaldehyde formation and has been described as a therapy and prophylaxis for Ifosfamide-encephalopathy. MB is effective within 30 min and lasts up to 3 days. Prolonged encephalopathy and MB therapy has not been described in the literature as lasting longer than 30 days following treatment.
We present the case of an 11-year-old female with autistic spectrum disorder and recurrent episodes of severe somnolence for 7 months following Ifosfamide therapy for her Non-Germinomatous Germ Cell Tumor (GCT). Periods of somnolence occurred prior to receiving cranial RT. Administration of MB gave immediate but limited response, with resolution of somnolence lasting 1-2 days between administrations. The somnolence could not be explained by neuroimaging or laboratory evaluation, but EEG indicated persistent encephalopathy.
A literature review determines that neurotoxicity is a side effect of Ifosfamide, but this effect has not been described persisting longer than 30 days. Our case continued to require treatment with MB for 7 months following cessation of therapy. We report these novel clinical findings, and hypothesize that there could be a genetic/metabolic component linking this reaction to Ifosfamide with the case patient\'s pre-existing autism. This possible association may also correlate to the already-established link between autism and the development of GCTs. This hypothesis leads to further discussion on the suitable usage of Ifosfamide in children with co-morbidities and the necessity of screening prior to its usage.
We present the case of an 11-year-old female with autistic spectrum disorder and recurrent episodes of severe somnolence for 7 months following Ifosfamide therapy for her Non-Germinomatous Germ Cell Tumor (GCT). Periods of somnolence occurred prior to receiving cranial RT. Administration of MB gave immediate but limited response, with resolution of somnolence lasting 1-2 days between administrations. The somnolence could not be explained by neuroimaging or laboratory evaluation, but EEG indicated persistent encephalopathy.
A literature review determines that neurotoxicity is a side effect of Ifosfamide, but this effect has not been described persisting longer than 30 days. Our case continued to require treatment with MB for 7 months following cessation of therapy. We report these novel clinical findings, and hypothesize that there could be a genetic/metabolic component linking this reaction to Ifosfamide with the case patient\'s pre-existing autism. This possible association may also correlate to the already-established link between autism and the development of GCTs. This hypothesis leads to further discussion on the suitable usage of Ifosfamide in children with co-morbidities and the necessity of screening prior to its usage.
摘要：
异环磷酰胺治疗后的脑病是一种描述良好的现象，通常用亚甲基蓝（MB）治疗。氯乙醛,据推测,一种具有潜在神经毒性的异环磷酰胺代谢物会导致这种脑病.目前的治疗指南是停止异环磷酰胺并提供支持性护理。MB具有抑制氯乙醛形成的作用，并已被描述为异环磷酰胺脑病的治疗和预防。MB在30分钟内有效，持续3天。在文献中没有描述长期脑病和MB治疗在治疗后持续超过30天。
我们介绍了一名11岁女性，患有自闭症谱系障碍，并在异环磷酰胺治疗她的非生殖细胞生殖细胞肿瘤（GCT）后7个月反复出现严重嗜睡的情况。在接受头颅RT之前发生了嗜睡期。甲基溴的管理给予了立即但有限的回应，两次给药之间持续1-2天的嗜睡消退。神经影像学或实验室评估不能解释嗜睡，但脑电图提示持续性脑病.
文献综述确定神经毒性是异环磷酰胺的副作用，但是这种效果并没有被描述为持续超过30天。我们的病例在停止治疗后继续需要用MB治疗7个月。我们报告了这些新的临床发现，并假设可能存在遗传/代谢成分将这种反应与异环磷酰胺与患者先前存在的自闭症联系起来。这种可能的关联也可能与自闭症和GCT发展之间已经建立的联系有关。这一假设导致进一步讨论异环磷酰胺在合并症儿童中的合适用法以及在使用前进行筛查的必要性。
我们介绍了一名11岁女性，患有自闭症谱系障碍，并在异环磷酰胺治疗她的非生殖细胞生殖细胞肿瘤（GCT）后7个月反复出现严重嗜睡的情况。在接受头颅RT之前发生了嗜睡期。甲基溴的管理给予了立即但有限的回应，两次给药之间持续1-2天的嗜睡消退。神经影像学或实验室评估不能解释嗜睡，但脑电图提示持续性脑病.
文献综述确定神经毒性是异环磷酰胺的副作用，但是这种效果并没有被描述为持续超过30天。我们的病例在停止治疗后继续需要用MB治疗7个月。我们报告了这些新的临床发现，并假设可能存在遗传/代谢成分将这种反应与异环磷酰胺与患者先前存在的自闭症联系起来。这种可能的关联也可能与自闭症和GCT发展之间已经建立的联系有关。这一假设导致进一步讨论异环磷酰胺在合并症儿童中的合适用法以及在使用前进行筛查的必要性。
