Sudden unexpected death in epilepsy (SUDEP) poses a significant risk to life expectancy for individuals with epilepsy. Mechanistic insight, while incomplete, has advanced through clinical observational studies and animal models. Yet we lack preventative therapies, which will depend on understanding SUDEP mechanisms. Recurrent convulsive seizures are the major SUDEP risk factor. Cardiorespiratory dysfunction precedes SUDEP, but whether cardiac arrhythmias are major proximate culprits for SUDEP remains to be determined. Here, we highlight recent data from mouse models and clinical studies that provide increasing support for respiratory depression and decreasing evidence for tachyarrhythmia-induced SUDEP. Further, we review data from genetic and chemoconvulsant mouse models that have enabled a deeper understanding for how seizures initiated in the central nervous system propagate to the autonomic nervous system and drive seizure-induced respiratory depression and subsequent SUDEP, rather than supporting a proximate cardiac arrhythmia cause. Ongoing research will continue to identify predictive SUDEP biomarkers, improve animal models, and translate basic research into precision medicine approaches. Identifying and understanding the brainstem circuits vulnerable in seizure-induced apnoea will enable therapeutic interventions to enhance the quality of life and life expectancy for individuals with epilepsy.

中文翻译：

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癫痫猝死：呼吸 vs. 心脏


癫痫猝死 （SUDEP） 对癫痫患者的预期寿命构成重大风险。机制洞察力虽然不完整，但已经通过临床观察研究和动物模型取得了进展。然而，我们缺乏预防性疗法，这将取决于对 SUDEP 机制的理解。复发性惊厥性癫痫发作是 SUDEP 的主要危险因素。心跳功能障碍先于 SUDEP 发生，但心律失常是否是 SUDEP 的主要近端罪魁祸首仍有待确定。在这里，我们重点介绍了来自小鼠模型和临床研究的最新数据，这些数据为呼吸抑制提供了越来越多的支持，并为快速性心律失常诱导的 SUDEP 提供了越来越多的证据。此外，我们回顾了来自遗传和化疗惊厥小鼠模型的数据，这些数据使我们能够更深入地了解从中枢神经系统开始的癫痫发作如何传播到自主神经系统并驱动癫痫发作引起的呼吸抑制和随后的 SUDEP，而不是支持近端的心律失常原因。正在进行的研究将继续确定预测性 SUDEP 生物标志物，改进动物模型，并将基础研究转化为精准医学方法。识别和了解在癫痫发作引起的呼吸暂停中易受伤害的脑干回路将使治疗干预能够提高癫痫患者的生活质量和预期寿命。