Di Genova Lorenza, Perruccio Katia, Celani Maria Grazia, Mastrodicasa Elena, Cantisani Teresa Anna, Esposito Susanna, Caniglia Maurizio
Pediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, Italy.
Pediatric Oncohematology Unit, Santa Maria della Misericordia Hospital, Perugia, Italy.
Front Pharmacol. 2019 Sep 2;10:963. doi: 10.3389/fphar.2019.00963. eCollection 2019.
Osteosarcoma is the most frequent primary cancer of the bones, and a combination of primary chemotherapy, surgery, and adjuvant chemotherapy is its current treatment. In adults, some authors have reported problems with memory and concentration following chemotherapy, but in children, severe neurologic dysfunction has been rarely reported. This report describes a 13-year-old patient with primary high-grade nonmetastatic osteosarcoma of the tibia who developed encephalopathy with super-refractory status epilepticus related to chemotherapy. He received methotrexate (MTX) and cisplatin (CDDP)-containing polychemotherapy, and after the first course of drug administration, he developed fever, confusion, a state of psychomotor agitation, and super-refractory status epilepticus with normal laboratory and imaging findings. The causal relationship between the administration of the first polychemotherapy course and his neurological manifestations may be supported by the evaluation and exclusion of other causes. The administration of antiepileptic drugs and off-label atypical antipsychotics was necessary to treat his neurological complications and behavioral changes. This patient represents the first known example of super-refractory status epilepticus in a child treated with MTX and CDDP-containing chemotherapy. Physicians should be aware that encephalopathy and seizures are possible consequences of CDDP therapy when administered alone or in combination with other chemotherapeutic agents. Further studies are needed to better define this relationship in children.
骨肉瘤是最常见的原发性骨癌,目前其治疗方法是综合运用新辅助化疗、手术和辅助化疗。在成人中,一些作者报告了化疗后出现记忆和注意力不集中的问题,但在儿童中,严重神经功能障碍的报道很少。本报告描述了一名13岁的原发性高分级非转移性胫骨骨肉瘤患者,其在化疗后出现了伴有超级难治性癫痫持续状态的脑病。他接受了含有甲氨蝶呤(MTX)和顺铂(CDDP)的多药化疗,在第一个疗程给药后,他出现了发热、意识模糊、精神运动性激越状态以及超级难治性癫痫持续状态,实验室检查和影像学检查结果均正常。通过对其他病因的评估和排除,可支持首个多药化疗疗程与他的神经学表现之间存在因果关系。为治疗其神经并发症和行为改变,有必要使用抗癫痫药物和超说明书使用的非典型抗精神病药物。该患者是已知首例在接受含MTX和CDDP化疗的儿童中出现超级难治性癫痫持续状态的病例。医生应意识到,单独使用CDDP或与其他化疗药物联合使用时,脑病和癫痫发作可能是CDDP治疗的后果。需要进一步研究以更好地明确儿童中的这种关系。