脑胶质瘤继发癫痫的发病机制及治疗

Pathogenesis of glioma-associated epilepsy and its therapy

脑胶质瘤是脑部肿瘤最常见的类型,30%~50%的脑胶质瘤患者可继发癫痫发作。部分脑胶质瘤患者在接受肿瘤切除术后依然有癫痫发作。因此,探讨脑胶质瘤继发癫痫的发病机制及治疗具有重要的临床意义。本文对脑胶质瘤继发癫痫的发病机制进行探讨,包括谷氨酸及其转运体的变化、脑胶质瘤细胞内Cl-浓度调节异常、γ-氨基丁酸(gamma-amino butyric acid,GABA)信号通路介导的抑制性作用的变化以及哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)信号通路异常等,并介绍了基于脑胶质瘤继发癫痫发病机制的治疗药物,包括胱氨酸-谷氨酸转运体(cystineglutamate transporter,x CT)阻断剂柳氮磺吡啶、Cl-浓度调节剂布美他尼以及m TOR抑制剂雷帕霉素等,以期为脑胶质瘤继发癫痫提供新的有效治疗药物。本文还对控制脑胶质瘤继发癫痫发作的传统抗癫痫药物(anti-epileptic drugs,AEDs)的使用方法进行了小结。

Epilepsy can be developed in 30%-50% of the patients with glioma, which is the most common form of brain tumors. The seizures induced by glioma are still remained after resection of glioma lesions, therefore it is essential and meaningful to explore the pathogenesis and the related treatment of glioma-associated epilepsy. This paper discusses the pathogenic mechanisms involved in the development of glioma-associated epilepsy, including the alteration of glutamate and its transporters, the dysregulation of intracellular chloride(Cl)–, the alteration of gamma-amino butyric acid(GABA) signal pathway-mediated inhibitory effect, and the abnormalities in mammalian target of rapamycin(m TOR) signal pathway. The related drugs based on the pathogenic mechanisms of glioma-associated epilepsy are summarized, such as sulfasalazine—the blocker of cystine-glutamate transporter(x CT), bumetanide—the regulator for Cl–, and rapamycin which is an inhibitorof m TOR, in order to provide effective treatment strategies for glioma-associated epilepsy. Finally, the guidance about the use of anti-epileptic drugs(AEDs) in controlling the gliomaassociated seizures is also summarized.