基于脑连接组学的具有PGES表征癫痫猝死高危人群的脑源性机制研究

The overall rate of sudden unexpected death in people with epilepsy (SUDEP) is more than 20 times higher than in the general population, which has been a serious public health issue. However, breakthrough progress has not been made in the risk prediction of the SUDEP due to its elusive physiopathological mechanism. From a traditional point of view, cardiorespiratory failure may constitute the most likely potential mechanism of SUDEP. Based on the electrophysiological observation of postictal generalized electroencephalographic suppression (PGES), scholars have postulated that cardiorespiratory failure, which directly leads to SUDEP, is actually secondary to cerebral inhibition. It guided our reasoning that the future investigations on SUDEP mechanisms should focus on the cerebral origin. The key scientific problem to be solved is how PGES can lead to SUDEP by affecting the cardiorespiratory function. We have successfully introduced the neuroimaging methods in research on the mechanisms of SUDEP in our previous study, which provided an innovative and effective way to investigate this issue. In view of the chief role of PGES and the important value of neuroimaging technology in the cerebral mechanism research of SUDEP, the project aims to introduce modern brain connectome method to describe the intensity and causality of connectivity between the PGES-related inhibitory neural networks and cardiorespiratory neural networks. We hope the result can find the mislink among the PGES, cardiorespiratory dysfunction and the SUDEP, which may provide promising neuroimaging biomarker for risk prediction of SUDEP and give new clues to the phathophysilogical mechanism of SUDEP.

癫痫患者发生猝死的风险是健康人群的20倍以上，已成为重大的公共卫生问题。近年来，通过对发作后全面脑电抑制（PGES）的研究逐步揭开了癫痫猝死脑源性机制研究的序幕，并有望在癫痫猝死的最终病理生理机制及风险预警方面取得突破。目前，亟待解决的关键科学问题是PGES如何通过影响呼吸循环功能而最终导致癫痫猝死。本次项目在课题组前期基于神经影像学技术对癫痫猝死脑源性机制研究的基础上，以具有PGES表征癫痫猝死高危人群为研究对象，引入脑连接组学的前沿分析方法，纵向研究PGES相关抑制性神经网络与呼吸循环神经网络之间的联接强度及因果关系，力求揭示PGES-呼吸循环功能障碍-癫痫猝死之间的深层次联接基础，为癫痫猝死的脑源性机制研究提供新的线索。同时，通过明确这些神经网络间联接的关键节点及信息传递模式，构建具有PGES表征癫痫猝死高危人群的动态影像学模型，以期为癫痫猝死高危人群的风险预警提供客观的影像学标志。

癫痫患者发生猝死的风险是健康人群的20倍以上，已成为重大的公共卫生问题。近年来，通过对发作后全面脑电抑制(PGES)的研究逐步揭开了癫痫猝死脑源性机制研究的序幕，本次项目在课题组前期基于神经影像学技术对癫痫猝死脑源性机制研究的基础上，以具有PGES表征的癫痫猝死高危人群为研究对象，不仅对其围发作期的临床电生理特征进行了详细阐述，发现PGES的发生及持续时长与年龄、发病年龄、GCS发作症状学分型、强直相时长相关，具有PGES表征的患者更易出现发作后无反应和无活动，更为重要的是，无论何种形式的发作后干预动作均有助于PGES的阻断，这为我们更好的识别、干预PGES，阻断其可能的不良后果有重要的参考价值。同时，我们运用多模态影像学技术对入组被试的高分辨率结构MRI数据进行了基于顶点的全脑皮层厚度分析，发现具有PGES表征的癫痫人群存在颞顶区部分皮层厚度的降低，且呈现出与SUDEP人群和SUDEP高危人群相同的的右侧半球优势性分布，而在与健康对照组的对比当中，具有PGES表征的癫痫人群皮层厚度的降低反而更局限，提示我们或许从另一个角度来说PGES对痫性发作造成的脑微结构进行性损伤有一定的保护作用，本研究结果不仅证实PGES确有其对应的异常神经网络基础存在，还为PGES与SUDEP之间神经网络的相关关系研究及两者的脑源性机制研究打开了新的思路。