The Saul R. Korey Department of Neurology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, U.S.A.
Epilepsia. 2013 Nov;54 Suppl 8(0 8):6-13. doi: 10.1111/epi.12417.
The application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike-wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype.
代谢成像和基因分析的应用，以及现在适当动物模型的发展，为癫痫性脑病的发病机制提供了关键的见解。在本文中，我们提出了一些想法，旨在从与癫痫性脑病相关的病变转向理解这些病变对大脑功能的影响，特别是对皮质的影响。我们认为，皮质和皮质下结构之间的相互作用可能会放大局灶性病变的影响，而皮质下唤醒中心在生命早期对大脑的调节失常可能会导致影响认知发育关键期的皮质内突触的改变。通过遗传病变的作用，全局神经元功能的中断同样会导致广泛的皮质功能障碍，表现在脑电图 (EEG) 上出现更多的 δ 慢波，并在临床上表现为发育迟缓或停滞。最后，睡眠期间持续的局灶性癫痫活动（如在慢波睡眠中持续棘慢波综合征或 CSWSS 中发生的那样）可能会干扰癫痫灶部位的局部慢波活动，从而损害与学习和其他认知功能相关的神经过程和可能的局部可塑性变化。癫痫发作肯定会加重这些病变过程，但它们可能不是认知病理学发展的必要条件。然而，尽管癫痫发作可能是潜在病变的结果或症状，但它们的有效治疗可以改善预后，这既可以通过临床研究也可以通过实验研究来证实。了解其发病机制可能会为癫痫性脑病表型的各个方面带来新的、有效的治疗方法。
