利用VBM技术联合功能核磁共振及脑磁图研究岛叶癫痫的致痫网络机制

With the development of the research on the pathogenesis of epilepsy, epileptogenic network has been proposed to play an important role in this process. In the concept of epileptogenic network, focal epilepsy is considered as a result of abnormalities in a focal or lateral part of the brain. Insular epilepsy is a special type of drug-resistant focal epilepsy, accounting for a nonnegligible proportion of drug-resistant focal epilepsy, which needs to be surgically resected for most of the time. However, because of the following reasons, such as the complex clinical manifestations, mimic some other types of epilepsies, and lack of remarkable MRI lesions in some patients, the decision of surgery can be very difficult. So far, the characteristic of epileptogenic network in insular epilepsy is still unclear. This project is aimed at describing the characteristic of epileptogenic network in insular epilepsy by using non-invasive neuroimaging techniques including voxel-based morphometric (VBM) MRI postprocessing, functional MRI and magnetoencephalography (MEG), based on voxel-based MRI morphometric analysis program (MAP) and graph theory. Meanwhile, we will use surgical intervention to verify the epileptogenic network features and analyze the prognosis and postoperative pathology results to further explore the different effects of surgery on the different parts of the epileptogenic network. This project is intended to finally reveal the pathogenesis of the epileptogenic network in insular epilepsy, and try to provide new imaging indicators for further invasive examination, preoperative evaluation and postoperative prognosis.

随着对癫痫发病机制研究的不断深入，致痫网络在癫痫发病中所起的作用日益受到重视，局灶性癫痫被认为是由于一侧或局部脑网络异常所引起。岛叶癫痫是局灶性耐药性癫痫的一种特殊类型，往往需要手术治疗。然而，由于岛叶癫痫临床表现复杂、难以与其他类型癫痫相区别，且有相当一部分患者在结构像MRI上无病灶，为进一步癫痫手术治疗带来极大困难。目前对于岛叶癫痫致痫网络特点仍然不甚清楚。本研究利用非侵入性影像学技术，将基于体素的形态学测量（VBM）技术与功能核磁共振、脑磁图相结合，利用形态测量分析技术（MAP）和图论分析方法，从结构及功能网络两个方面，多角度对岛叶癫痫致痫网络机制进行深入探索。并通过手术干预，结合手术预后、术后病理等指标，对致痫网络的特点进行验证，发现手术对致痫网络不同部位所产生的不同影响，揭示岛叶癫痫的致痫网络机制，力图为进一步侵入性检查及术前评估、手术预后提供新的影像学指标。

对于药物难治性癫痫，手术切除致痫灶是一种有效的治疗方法。致痫灶的识别和病灶范围的确定对于手术的成功与否至关重要。不论是儿童还是成人癫痫患者，核磁共振（MRI）上缺少结构性病灶对于手术的实施均有巨大挑战。MRI阴性（无病灶）癫痫患者可能需要更加昂贵且有创伤的颅内电极来协助病灶定位，且往往手术效果欠佳。岛叶癫痫是局灶性耐药性癫痫的一种特殊类型，在局灶性药物难治性癫痫中占有不小的比例。由于岛叶癫痫临床表现复杂、难以与其他类型癫痫相区别，且有相当一部分患者在结构像MRI上无病灶，为进一步手术治疗带来极大困难。目前对于岛叶癫痫致痫网络特点仍然不甚清楚。本研究利用非侵入性影像学技术，将基于体素的形态学测量（VBM）技术与功能核磁共振、脑磁图相结合，从结构及功能两个方面对MRI阴性的药物难治性癫痫，特别是岛叶癫痫致痫灶定位和特点进行探索。本研究利用形态测量分析技术（MAP）对无病灶的药物难治性癫痫进行分析，试图寻找到潜在的致痫灶，并通过手术干预，结合手术预后、术后病理等指标，对致痫灶的特点进行验证。在研究结果方面，本研究发现在MRI阴性的儿童药物难治性癫痫患者中，MAP阳性率可达56%；相较于MAP阳性病灶未切除或部分切除的患者，MAP阳性病灶完全切除与术后癫痫无发作呈正相关（P < 0.001）。另外，MAP阳性率在3-5岁、5-10岁、10-15岁和15-21岁年龄组分别为100%、77%、63%和40%。MAP阳性率在颞叶切除癫痫患者为45%，而在颞叶外切除癫痫患者为63%，完全切除MAP阳性病灶在颞叶外切除的癫痫患者中与手术预后呈正相关（P = 0.001），而在颞叶切除的患者中未发现此相关性（P = 0.070）。同时，MAP在MRI阴性的岛叶/岛盖癫痫患者的病灶识别中也起到重要作用，结合MEG结果，完全切除MAP及MEG阳性病灶与患者手术预后呈正相关。本研究提示非侵入性影像学技术，如VBM和MEG在MRI阴性药物难治性癫痫，特别是岛叶/岛盖癫痫的致痫灶识别中有重要作用，可能为进一步侵入性检查、下一步手术以及手术预后起到提示作用。