Holmes G L
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, USA.
Epilepsia. 1997 Jan;38(1):12-30. doi: 10.1111/j.1528-1157.1997.tb01074.x.
Children with epilepsy present unique challenges to the clinician. In addition to having differences in clinical and EEG phenomena, children differ from adults in regard to etiological factors, response to antiepileptic drugs (AEDs), and outcome. It is now recognized that the immature brain also differs from the mature brain in the basic mechanisms of epileptogenesis and propagation of seizures. The immature brain is more prone to seizures due to an imbalance between excitation and inhibition. gamma-Aminobutyric acid (GABA), the major CNS inhibitory neurotransmitter in the mature brain, can lead to depolarization in the hippocampal CA3 region in very young rats. There are also age-related differences in response to GABA agonists and antagonists in the substantia nigra, a structure important in the propagation of seizures. These age-related differences in response to GABAergic agents provide further evidence that the pathophysiology of seizures in the immature brain differs from that in the mature brain. Although prolonged seizures can cause brain damage at any age, the extent of brain damage after prolonged seizures is highly age dependent. Far less histological damage and fewer disturbances in cognition result from prolonged seizures in the immature brain than from seizures of similar duration and intensity in mature animals. However, detrimental effects of AEDs may be greater in the immature brain, than in the mature brain. These lessons from the animal laboratory raise questions about the appropriateness of current therapeutic approaches to childhood seizure disorders.
癫痫患儿给临床医生带来了独特的挑战。除了在临床和脑电图现象上存在差异外，儿童在病因、对抗癫痫药物（AEDs）的反应以及预后方面也与成人不同。现在人们认识到，未成熟脑在癫痫发生和癫痫发作传播的基本机制方面也与成熟脑不同。由于兴奋和抑制之间的失衡，未成熟脑更容易发生癫痫发作。γ-氨基丁酸（GABA）是成熟脑中主要的中枢神经系统抑制性神经递质，在非常年幼的大鼠海马CA3区可导致去极化。在黑质中，对GABA激动剂和拮抗剂的反应也存在年龄相关差异，黑质是癫痫发作传播中一个重要的结构。这些对GABA能药物反应的年龄相关差异进一步证明，未成熟脑癫痫发作的病理生理学与成熟脑不同。虽然长时间癫痫发作在任何年龄都可导致脑损伤，但长时间癫痫发作后脑损伤的程度高度依赖于年龄。与成熟动物中类似持续时间和强度的癫痫发作相比，未成熟脑长时间癫痫发作导致的组织学损伤和认知障碍要少得多。然而，AEDs对未成熟脑的有害影响可能比对成熟脑更大。动物实验室的这些经验教训引发了关于当前儿童癫痫疾病治疗方法是否恰当的问题。
