Optimizing antiepileptic drug treatment in tumoral epilepsy
Optimizing antiepileptic drug treatment in tumoral epilepsy
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DOI：
10.1111/epi.12452
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发表时间：
2013-12-01
期刊：
影响因子：
5.6
通讯作者：
Perucca, Emilio
中科院分区：
文献类型：
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作者：
Perucca, Emilio
30%至50%的脑肿瘤患者首先出现癫痫发作，随后会有多达30%的癫痫发作。因此，这些患者的最佳管理需要一个合理的方法来使用抗癫痫药物。根据目前的证据，在未出现癫痫发作的脑肿瘤患者中预防性开具长期抗癫痫药物（AED）是不合理的。然而，由于复发的高风险，在被认为是由于肿瘤引起的单次癫痫发作后，应强烈考虑AED治疗。由于缺乏良好对照的随机试验，AED在个体患者中提供最佳风险效益比的决定主要基于医生的判断，而不是合理的科学证据。在可能需要化疗的患者中，首选非酶诱导AED进行初始治疗，以最大限度地降低对抗癌化疗结果产生不利影响的药物相互作用风险。在接受化疗的胶质母细胞瘤癫痫患者中进行的几项回顾性研究提供了使用丙戊酸可中度改善生存率的证据，可能是由于抑制组蛋白脱乙酰酶。然而，丙戊酸可能通过抑制药物代谢而增加药物的血液学毒性，并可能独立损害止血，这是需要手术干预的患者的一些问题。在新一代AED中，左乙拉西坦具有许多有利的特征，包括胃肠外制剂的可用性，但也可以考虑其他药物，如加巴喷丁、拉莫三嗪、奥卡西平、托吡酯和唑尼沙胺。正在研究针对癫痫发生和发作的特定机制的潜在更有效的治疗方法。肿瘤切除、放疗或化疗可使难治性癫痫发作得到控制或延长无癫痫发作的持续时间，这种作用似乎与肿瘤块的切除或缩小不一定相关。对于肿瘤治疗成功且长期生存总体预后良好的患者，可考虑逐渐停用AED。
Between 30% and 50% of patients with brain tumors first present with a seizure, and up to 30% more will develop seizures later. Therefore, optimal management of these patients requires a rational approach to the use of antiseizure medications. Based on current evidence, prophylactic prescription of long-term antiepileptic drugs (AEDs) in patients with brain tumors in patients who did not present with seizures is not justified. Because of the high risk of recurrence, however, AED treatment should be strongly considered after a single seizure considered to be due to a tumor. Because of the lack of well-controlled randomized trials, the decision on which AED provides the best risk-benefit ratio in the individual patient is based mostly on physician's judgment rather than sound scientific evidence. In patients who may require chemotherapy, a non-enzyme-inducing AED is preferred for initial treatment to minimize the risk of drug interactions that impact adversely on the outcome of anticancer chemotherapy. Several retrospective studies in seizure patients with glioblastoma treated with chemotherapy have provided evidence for a moderately improved survival with the use of valproic acid, possibly due to inhibition of histone deacetylase. However, valproic acid may also increase the hematologic toxicity of antineoplastic drugs, presumably by inhibiting their metabolism, and may independently impair hemostasis, which is of some concern for patients who require surgical intervention. Among newer generation AEDs, levetiracetam has a number of advantageous features, including availability of a parenteral formulation, but other agents such as gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide may also be considered. Potentially more effective treatments targeting specific mechanisms of epileptogenesis and ictogenesis are being investigated. Resection of the tumor, radiation therapy, or chemotherapy can bring refractory seizures under control or prolong the duration of seizure freedom, an effect that does not appear to be necessarily related to removal or shrinkage of the tumor mass. In patients with a successfully treated tumor and an overall good prognosis for long-term survival, gradual discontinuation of AEDs may be considered.