Engel J, Bandler R, Griffith N C, Caldecott-Hazard S
Department of Neurology, UCLA School of Medicine 90024.
Adv Neurol. 1991;55:97-111.
It is not in the best interest of persons with epilepsy to deny the possibility that seizures could cause enduring behavioral disturbances. Rather, it is essential to pursue clinical and animal investigations in order to identify any such changes that might occur and to elucidate their mechanisms. Many testable hypotheses can be developed from existing evidence. Antiepileptic medication may produce interictal behavioral disturbances in patients with epilepsy by indirect mechanisms. Some aberrant behaviors could be due to medication-induced systemic disorders, neuroendocrine dysfunction, or REM deficit, whereas depression following successful treatment with drugs, as well as with surgery, may be related more specifically to cessation of seizures. The underlying neuropathological process also induces neurological and mental deficits, but it is not always possible to differentiate those behavioral disturbances due to destructive effects of the lesion from those due to recurrent epileptic seizures. Behavioral disturbances are associated more frequently with epileptogenic lesions in limbic structures than with those elsewhere in the brain, but a relationship between hemispheric lateralization of the epileptogenic lesion and specific interictal behavioral symptoms remains controversial. When considering the effects of seizures per se on interictal behavior, it is important to realize that some "interictal" behavioral disturbances may actually be ictal events. Prolonged affective, autonomic, and psychic disturbances can occur in clear consciousness with unilateral limbic seizures that are not associated with scalp EEG changes. When epilepsy is acquired as a result of cerebral damage, the epileptogenic process takes time to develop before spontaneous seizures appear. It is more reasonable to assume that this progressive process continues than to postulate that it stops completely at the time the first seizure occurs. Epilepsy-induced protective homeostatic mechanisms that act to terminate ictal events, prevent ictal spread, and maintain the interictal state may also disrupt interictal function. Furthermore, seizures could indirectly influence interictal behavior as a result of their effects on neuroendocrine function and sleep. Because of confounding biological factors, it is difficult to document the association of any epilepsy disorder, by itself, with progressive behavioral disturbances in humans. Secondary epileptogenesis, protective homeostatic mechanisms, and epilepsy-induced disturbances in development can be readily demonstrated, however, in experimental animal models. In experimental animals, endogenous opoids are released during seizures and mediate some postictal behaviors. A physiological dependency on high levels of endogenous opioids released during seizures could produce depression as a withdrawal symptom interictally or when seizures no longer occur as a result of successful therapy. Experimental animal models of depression exist to test hypotheses concerning pro- and antidepressant effects of epileptogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
否认癫痫发作可能导致持久行为障碍的可能性，这不符合癫痫患者的最大利益。相反，开展临床和动物研究以确定可能发生的此类变化并阐明其机制至关重要。从现有证据中可以得出许多可检验的假设。抗癫痫药物可能通过间接机制在癫痫患者中产生发作间期行为障碍。一些异常行为可能归因于药物引起的全身性疾病、神经内分泌功能障碍或快速眼动睡眠不足，而药物治疗以及手术成功治疗后的抑郁可能更具体地与癫痫发作停止有关。潜在的神经病理过程也会导致神经和精神缺陷，但往往无法区分由病变的破坏作用引起的行为障碍和由反复癫痫发作引起的行为障碍。行为障碍与边缘系统结构中的致痫性病变的关联比与大脑其他部位的病变更为频繁，但致痫性病变的半球侧化与特定的发作间期行为症状之间的关系仍存在争议。在考虑癫痫发作本身对发作间期行为的影响时，重要的是要认识到一些“发作间期”行为障碍实际上可能是发作期事件。在清醒状态下，单侧边缘系统癫痫发作可出现持续的情感、自主神经和精神障碍，且与头皮脑电图变化无关。当癫痫是由脑损伤引起时，致痫过程在自发癫痫发作出现之前需要时间来发展。假设这个渐进过程会持续下去比假设它在首次发作时完全停止更合理。癫痫诱导的保护性稳态机制，其作用是终止发作期事件、防止发作期扩散并维持发作间期状态，也可能扰乱发作间期功能。此外，癫痫发作因其对神经内分泌功能和睡眠的影响，可能间接影响发作间期行为。由于存在混杂的生物学因素，很难证明任何一种癫痫疾病本身与人类进行性行为障碍之间的关联。然而，在实验动物模型中，可以很容易地证明继发性癫痫发生、保护性稳态机制以及癫痫诱导的发育障碍。在实验动物中，内源性阿片类物质在癫痫发作期间释放，并介导一些发作后行为。对癫痫发作期间释放的高水平内源性阿片类物质产生生理依赖，可能会在发作间期或由于成功治疗癫痫发作不再发生时产生抑郁作为戒断症状。存在抑郁症的实验动物模型来检验关于癫痫发生的促抑郁和抗抑郁作用的假设。（摘要截断于400字）
