一种新型异环磷酰胺脑病伴亚甲蓝长期治疗病例报告及文献复习。
A novel case of prolonged Ifosfamide encephalopathy and long-term treatment with methylene blue: a case report and review of literature.
机构信息
Department of Pediatrics, The Children's Hospital at Saint Peter's University Hospital, 254 Easton Avenue, New Brunswick, NJ, 08901, USA.
Division of Pediatric Hematology/Oncology, The Children's Hospital at Saint Peter's University Hospital, New Brunswick, NJ, 08901, USA.
出版信息
BMC Pediatr. 2022 Feb 2;22(1):76. doi: 10.1186/s12887-022-03144-1.
BACKGROUND
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.
CASE PRESENTATION
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.
CONCLUSION
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.
背景
异环磷酰胺治疗后脑病是一种已被充分描述的现象，通常用亚甲蓝（MB）治疗。氯乙醛是异环磷酰胺的一种潜在神经毒性代谢物，据推测会导致这种脑病。目前的治疗指南是停止异环磷酰胺并提供支持性治疗。MB 可抑制氯乙醛的形成，已被描述为异环磷酰胺脑病的治疗和预防药物。MB 在 30 分钟内有效，持续时间长达 3 天。在文献中，没有描述治疗后超过 30 天的持续时间更长的延长性脑病和 MB 治疗。
病例介绍
我们报告了一例 11 岁女性病例，患有自闭症谱系障碍，在接受异环磷酰胺治疗非生殖细胞瘤生殖细胞肿瘤（GCT）后 7 个月出现反复发作的严重嗜睡。嗜睡发生在接受颅放射治疗之前。MB 的给药立即但有限地产生反应，每次给药之间嗜睡缓解持续 1-2 天。嗜睡不能通过神经影像学或实验室评估来解释，但脑电图表明存在持续性脑病。
结论
文献综述确定神经毒性是异环磷酰胺的副作用，但这种作用未被描述持续超过 30 天。我们的病例在停止治疗后仍需继续使用 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/代谢因素将这种反应与病例患者的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与 GCT 发展之间已经建立的联系相关。这一假设导致了关于异环磷酰胺在合并症儿童中的适当使用以及在使用前进行筛查的必要性的进一步讨论。
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