The effects of genetic make-up on cognition in juvenile myoclonic epilepsy

青少年肌阵挛性癫痫（juvenile myoclonic epilepsy，JME）是一种常见的癫痫综合征。有一个高度的遗传易感性与JME和参与的几个基因已被讨论。在过去的几年里，一些临床研究引起了微妙的认知缺陷的JME患者，主要影响额叶脑功能，如视觉工作记忆和执行功能，即规划。先进的成像研究表明，微妙的结构和功能异常，主要涉及额叶的特定区域，以及更深的大脑结构（丘脑）。考虑到遗传易感性，这强烈支持年龄相关和遗传决定的脑网络功能障碍的概念，表现为癫痫发作和认知缺陷。到目前为止，一些研究可以确定微妙的认知缺陷，在其他健康的JME同胞。在即将到来的研究中，我们计划调查的影响，遗传组成对认知缺陷的JME使用功能性磁共振成像（fMRI）。功能磁共振成像将帮助我们识别在特定记忆任务中激活的大脑区域。我们将调查JME患者，他们的健康兄弟姐妹和健康对照使用功能磁共振成像和神经心理测试。我们假设，与健康对照相比，患者和兄弟姐妹在fMRI上会表现出不同的认知激活模式。神经病学研究所先前对工作记忆的功能磁共振成像研究显示，JME患者大脑运动区（运动皮层）存在显著的异常共激活。在接受抗癫痫药丙戊酸盐（VPA）治疗的患者中，该协同作用与VPA剂量呈负相关。假设这些发现是特定的JME和遗传决定，我们还假设一个类似的共激活运动皮层在JME兄弟姐妹。

Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome. There is a high genetic predisposition associated with JME and an involvement of several genes has been discussed.Within the last years, several clinical studies elicited subtle cognitive deficits in JME-patients, mainly affecting frontal brain functions, such as visual working memory and executive functions, i.e. planning. Advanced imaging studies suggest subtle structural and functional abnormalities, mainly involving specific areas of the frontal brain, as well as deeper brain structures (thalami). Taking the genetic predisposition into account, this strongly supports the concept of an age-related and genetically determined brain-network-dysfunction presenting with both seizures and cognitive deficits. So far, some studies could identify subtle cognitive deficits in otherwise healthy JME siblings.In the forthcoming study, we plan to investigate the influence of genetic make-up on cognitive deficits in JME using functional MRI imaging (fMRI). FMRI will help us to identify the brain areas which are activated during specific memory tasks. We will investigate JME patients, their healthy siblings and healthy controls using fMRI and neuropsychological testing. We hypothesize that patients and siblings will show different cognitive activation patterns in comparison to healthy controls on fMRI. A previous fMRI study on working memory of the Institute of Neurology could show a significant abnormal coactivation of the movement area of the brain, the motor cortex, in JME patients. In patients treated with the antiepileptic agent valproate (VPA) this coactiviation correlated negatively with VPA dosage. Assuming that these findings are specific for JME and genetically determinate, we also hypothesize a similar coactivation of motor cortex in JME siblings.