Department of Neuro-oncology Mazarin, GH Pitie-Salpetriere, Paris, France.
Department of Neurophysiology, Pitie-Salpetriere Hospital, UPMC, Sorbonne Universites, Paris, France.
Curr Pharm Des. 2017;23(42):6464-6487. doi: 10.2174/1381612823666171027130003.
In cancer, epilepsy can be the manifestation of a primary brain tumour, metastatic disease, vascular or surgical complications, opportunistic infection or secondary to anti-tumour therapy. Seizures are frequently the first symptom of a brain tumour. The epilepsy is related to elevated extracellular glutamate stimulating NMDAand AMPA-receptors and to the formation of D-2HG which resembles glutamate in IDH1 mutated gliomas. Epilepsy as presenting sign is associated with a longer survival in low- and high- grade gliomas, particularly with the IDH1 mutation. Anti-tumour treatment by surgery, radiotherapy or chemotherapy strongly contributes to seizure control. Symptomatic management of brain tumour-related epilepsy (BTE) by evidenced-based anti-epileptic drugs (AEDs) as indicated for focal epilepsy depends on individual patient factors including age, sex, weight, co-morbidity and cotherapy. Levetiracetam followed by lacosamide or valproic acid are the agents of choice. Both can be combined with levetiracetam in case monotherapy is inactive or produces side-effects. Lamotrigine, perampanel, zonisamide or clobazam are other good choices. On seizure prophylaxis, there is some evidence for its application in the peri-operative period. The most prevalent side-effects of AEDs in neuro-oncology are cognitive dysfunction, bone marrow toxicity and skin hypersensitivity. Combining anti-epileptic drugs with chemotherapy, tyrosinekinase inhibitors or steroids increases the risks of drug-drug interactions. Plasma monitoring of AEDs for detecting drug insufficiency, interactions or toxicity helps in choosing the proper dose regimen. For practical use, tables on drug interactions between AEDs and cancer therapy are added together with a guideline on the medical management of seizure control including dose regimens.
在癌症中,癫痫可能是原发性脑肿瘤、转移性疾病、血管或手术并发症、机会性感染或抗肿瘤治疗的结果。癫痫发作通常是脑肿瘤的首发症状。癫痫与细胞外谷氨酸升高有关,谷氨酸可刺激 NMDA 和 AMPA 受体,并形成类似于 IDH1 突变型神经胶质瘤中谷氨酸的 D-2HG。作为首发症状的癫痫与低级别和高级别神经胶质瘤的生存时间延长有关,尤其是与 IDH1 突变有关。手术、放疗或化疗等抗肿瘤治疗对控制癫痫发作有很大帮助。根据个体患者因素(包括年龄、性别、体重、合并症和共病治疗),针对局灶性癫痫,采用基于证据的抗癫痫药物(AEDs)对脑肿瘤相关癫痫(BTE)进行对症治疗。左乙拉西坦随后用拉科酰胺或丙戊酸是首选药物。如果单药治疗无效或产生副作用,可以将这两种药物与左乙拉西坦联合使用。拉莫三嗪、培美曲塞、佐米曲坦或氯巴占也是不错的选择。关于癫痫预防性治疗,有一些证据表明在围手术期应用它。神经肿瘤学中 AED 最常见的副作用是认知功能障碍、骨髓毒性和皮肤过敏反应。将抗癫痫药物与化疗、酪氨酸激酶抑制剂或类固醇联合使用会增加药物相互作用的风险。监测 AED 的血浆浓度以检测药物不足、相互作用或毒性有助于选择适当的剂量方案。为了实际应用,添加了关于 AED 与癌症治疗之间药物相互作用的表格,并附有关于控制癫痫发作的医疗管理的指南,包括剂量方案。