Bauer J
Department of Epileptology, University of Bonn, Germany.
Acta Neurol Scand. 1996 Dec;94(6):367-77. doi: 10.1111/j.1600-0404.1996.tb00047.x.
Seizure-inducing effects can be observed in the treatment of epileptic patients with antiepileptic drugs (AED). This may be a paradoxical reaction (for example the increase of complex focal seizures due to carbamazepine, vigabatrin or phenytoin treatment) or a result of AED-induced encephalopathy (commonly induced by valproate in patients with complex focal seizures). A seizure increase during intoxication with AED is a rare phenomenon, thus, it is not directly related to this condition. An incorrect choice of drugs in the treatment of an epileptic syndrome or seizure type may provoke seizures (as for example the provocation of absences due to carbamazepine or phenytoin). The possible seizure-inducing effect of AEDs has to be differentiated from seizure occurrence due to the natural course of epilepsy. This may be especially difficult in patients suffering from West syndrome or Lennox-Gastaut syndrome, in whom seizure frequency may vary even without medication. However, especially in these patients, drug-induced worsening of seizure manifestation is often observed. In general, a seizure-inducing effect of antiepileptic drugs has to be considered when a seizure increase is observed soon after the initiation of therapy, when a stepwise increase of the dosage is followed by a further increase of seizures, a decrease of seizures is seen with tapering of the dosage and a renewed increase of seizures can be observed after this therapy has been reestablished. Finally, one knows that the clinical condition of encephalopathy due to valproate or carbamazepine is accompanied by seizure increase. In spite of these clinical aspects, the underlying mechanisms of seizure increase mostly remain unclear. From animal experiments it is obvious that especially carbamazepine and phenytoin may provoke generalized seizures as absences or myoclonic seizures. A seizure increase during vigabatrin therapy has been attributed to the increase of the cerebral amount of gamma-amino butyric acid, which is known to possibly exhibit inhibitory or excitatory neuronal effects. The occurrence of tonic seizures in patients with Lennox-Gastaut syndrome has been attributed to the sedative effect of the drugs; however, this conclusion is controversial. From a clinical point of view, one should consider young age of the patient, mental retardation, antiepileptic polytherapy, high frequency of seizures or prominent epileptic activity in the electroencephalogram previous to medication as risk factors for a possible seizure-inducing effect of antiepileptic drugs.
在使用抗癫痫药物（AED）治疗癫痫患者时可观察到诱发性癫痫发作的效应。这可能是一种矛盾反应（例如卡马西平、氨己烯酸或苯妥英治疗导致复杂局灶性癫痫发作增加），或者是AED诱发的脑病的结果（通常由丙戊酸盐在复杂局灶性癫痫发作患者中诱发）。AED中毒期间癫痫发作增加是一种罕见现象，因此，它与这种情况没有直接关系。在治疗癫痫综合征或癫痫发作类型时药物选择不当可能会诱发癫痫发作（例如卡马西平或苯妥英诱发失神发作）。AED可能的诱发性癫痫发作效应必须与癫痫自然病程导致的癫痫发作相区分。这在患有韦斯特综合征或伦诺克斯 - 加斯托综合征的患者中可能尤其困难，在这些患者中，即使不使用药物，癫痫发作频率也可能变化。然而，尤其是在这些患者中，经常观察到药物导致癫痫发作表现恶化。一般来说，当在治疗开始后不久观察到癫痫发作增加、剂量逐步增加后癫痫发作进一步增加、剂量逐渐减少时癫痫发作减少而在重新开始治疗后又观察到癫痫发作再次增加时，必须考虑抗癫痫药物的诱发性癫痫发作效应。最后，人们知道丙戊酸盐或卡马西平导致的脑病临床状况伴有癫痫发作增加。尽管有这些临床情况，但癫痫发作增加的潜在机制大多仍不清楚。从动物实验中可以明显看出，尤其是卡马西平和苯妥英可能诱发全身性癫痫发作，如失神发作或肌阵挛发作。氨己烯酸治疗期间癫痫发作增加归因于脑中γ-氨基丁酸量的增加，已知γ-氨基丁酸可能表现出抑制或兴奋神经元的作用。伦诺克斯 - 加斯托综合征患者中强直发作的发生归因于药物的镇静作用；然而，这一结论存在争议。从临床角度来看，应将患者年龄小、智力低下、抗癫痫药物联合治疗、癫痫发作频率高或用药前脑电图中癫痫活动明显等因素视为抗癫痫药物可能产生诱发性癫痫发作效应的危险因素。
