Ictal neural oscillatory alterations precede sudden unexpected death in epilepsy.
Ictal neural oscillatory alterations precede sudden unexpected death in epilepsy.
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DOI：
10.1093/braincomms/fcac073
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发表时间：
2022
影响因子：
4.8
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中科院分区：
文献类型：
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癫痫的突然意外死亡是癫痫最灾难性的后果。每年，每1000名癫痫患者中就有多达1.65人死于此类死亡。目前，还没有预测或预防这一悲惨事件的方法，部分原因是对癫痫发作后导致死亡的病理级联缺乏了解。我们最近从遗传多样性的协作杂交小鼠群体中发现了四个近交系小鼠癫痫诱导的死亡率增加。这些癫痫小鼠猝死模型提供了一种独特的工具来系统地研究致命性癫痫发作期间的生理变化，这可以在受控环境中进行研究，并考虑到遗传复杂性。在这里，我们使用氟乙基诱发的自由活动小鼠癫痫模型，监测了非致命性和致命性癫痫发作之前、期间和之后的脑振荡和心功能。与在癫痫发作中幸存下来的小鼠相比，在致命癫痫发作的发作期，死亡者表现出脑干神经振荡的显著抑制，这种振荡与皮层癫痫活动和心动过速相一致。死亡者大脑皮质(0.5~4 HZ)/伽马(30~2 0 0 HZ)相位-幅度耦合受到抑制，而脑干未见。连接性分析显示，与非致命性癫痫发作相比，致命性癫痫发作期间大脑皮质和脑干三角区振荡的同步性增强。致命性癫痫发作的动态发作、振荡和连通性特征为癫痫的突然意外死亡提供了洞察力，并可能提示生物标记物和最终的治疗靶点。本文的科学评论见Gonzalez-Sulser(https://doi.org/10.1093/braincomms/fcac097))。利用协作性跨鼠癫痫猝死模型，Gu等人。报告脑电功率、相位-幅度耦合以及皮层和脑干连接性的电生理学改变，以区分致命性和非致命性癫痫发作。这项研究揭示了癫痫猝死的潜在病理生理学，并提供了干预的靶点。
Sudden unexpected death in epilepsy is the most catastrophic outcome of epilepsy. Each year there are as many as 1.65 cases of such death for every 1000 individuals with epilepsy. Currently, there are no methods to predict or prevent this tragic event, due in part to a poor understanding of the pathologic cascade that leads to death following seizures. We recently identified enhanced seizure-induced mortality in four inbred strains from the genetically diverse Collaborative Cross mouse population. These mouse models of sudden unexpected death in epilepsy provide a unique tool to systematically examine the physiological alterations during fatal seizures, which can be studied in a controlled environment and with consideration of genetic complexity. Here, we monitored the brain oscillations and heart functions before, during, and after non-fatal and fatal seizures using a flurothyl-induced seizure model in freely moving mice. Compared with mice that survived seizures, non-survivors exhibited significant suppression of brainstem neural oscillations that coincided with cortical epileptic activities and tachycardia during the ictal phase of a fatal seizure. Non-survivors also exhibited suppressed delta (0.5–4 Hz)/gamma (30–200 Hz) phase-amplitude coupling in cortex but not in brainstem. A connectivity analysis revealed elevated synchronization of cortex and brainstem oscillations in the delta band during fatal seizures compared with non-fatal seizures. The dynamic ictal oscillatory and connectivity features of fatal seizures provide insights into sudden unexpected death in epilepsy and may suggest biomarkers and eventual therapeutic targets. See Gonzalez-Sulser (https://doi.org/10.1093/braincomms/fcac097) for a scientific commentary on this article. Utilizing Collaborative Cross mouse models of sudden unexpected death in epilepsy, Gu et al. report electrophysiological alterations in EEG power, phase-amplitude coupling, and connectivity in cortex and brainstem that distinguish fatal from nonfatal seizure. This study reveals potential pathophysiology of sudden unexpected death in epilepsy and provides targets for intervention.
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影响因子：
3.4
作者：
Hofmeijer, Jeannette;van Kaam, C. R.;van Putten, Michel J. A. M.
通讯作者：
van Putten, Michel J. A. M.
影响因子：
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羟色胺神经元具有抗惊厥作用，可降低癫痫发作引起的死亡率
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4.8
作者：
Grigorovsky V;Jacobs D;Breton VL;Tufa U;Lucasius C;del Campo JM;Chinvarun Y;Carlen PL;Wennberg R;Bardakjian BL
通讯作者：
Bardakjian BL
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作者：
Einarsdottir, Anna B.;Sveinsson, Olafur;Olafsson, Elias
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