PDF(Pubmed)
Abstract：
The progressive myoclonic epilepsies (PMEs) are a group of rare neurodegenerative diseases characterized by myoclonus, epileptic seizures, and progressive neurological deterioration with cerebellar involvement. They include storage diseases like Gaucher disease, Lafora disease, and forms of neuronal ceroid lipofuscinosis (NCL). To date, 13 NCLs have been reported (CLN1-CLN8, CLN10-CLN14), associated with mutations in different genes. These forms, which affect both children and adults, are characterized by seizures, cognitive and motor impairments, and in most cases visual loss. In NCLs, as in other PMEs, central nervous system (CNS) neurodegeneration is widespread and involves different subpopulations of neurons. One of the most affected regions is the cerebellar cortex, where motor and non-motor information is processed and transmitted to deep cerebellar nuclei through the axons of Purkinje cells (PCs). PCs, being GABAergic, have an inhibitory effect on their target neurons, and provide the only inhibitory output of the cerebellum. Degeneration of PCs has been linked to motor impairments and epileptic seizures. Seizures occur when some insult upsets the normal balance in the CNS between excitatory and inhibitory impulses, causing hyperexcitability. Here we review the role of PCs in epilepsy onset and progression following their PME-related loss. In particular, we focus on the involvement of PCs in seizure phenotype in NCLs, highlighting findings from case reports and studies of animal models in which epilepsy can be linked to PC loss.
摘要：
进行性肌阵挛性癫痫（PME）是一组罕见的神经退行性疾病，其特征是肌阵挛症，癫痫发作,和小脑受累的进行性神经系统恶化。它们包括像戈谢病这样的贮积病，Lafora病,和形式的神经元类脂褐菌病（NCL）。迄今为止,已报告13个NCL（CLN1-CLN8，CLN10-CLN14），与不同基因的突变有关。这些形式,影响儿童和成人，以癫痫发作为特征，认知和运动障碍，在大多数情况下，视力丧失。在NCL中，与其他PME一样，中枢神经系统（CNS）神经变性是广泛的，涉及不同的神经元亚群。受影响最大的区域之一是小脑皮层，其中运动和非运动信息被处理并通过浦肯野细胞（PC）的轴突传输到小脑深部核。PC,是GABA,对它们的目标神经元有抑制作用，并提供小脑的唯一抑制性输出。PC的退化与运动障碍和癫痫发作有关。癫痫发作发生时，一些侮辱破坏了中枢神经系统中兴奋性和抑制性冲动之间的正常平衡，导致过度兴奋。在这里，我们回顾了PC在PME相关损失后癫痫发作和进展中的作用。特别是,我们专注于PC参与NCLs的癫痫发作表型，强调病例报告和动物模型研究的发现，其中癫痫可能与PC丢失有关。
