Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy.
Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy.
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DOI：
10.1002/ana.26053
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发表时间：
2021-05
影响因子：
11.2
通讯作者：
Patel MK
中科院分区：
文献类型：
--
作者：
Wenker IC;Teran FA;Wengert ER;Wagley PK;Panchal PS;Blizzard EA;Saraf P;Wagnon JL;Goodkin HP;Meisler MH;Richerson GB;Patel MK
癫痫猝死（SUDEP）是癫痫的一种不可预测和毁灭性的合并症，被认为是由于全身性惊厥发作后立即出现心肺功能衰竭。我们对癫痫致死亡的小鼠进行了心肺监测，这些小鼠携带p.a arg1872trp或p.a asn1768asp等位基因突变，这些突变来自于死于sudap的患者和戊四唑治疗的野生型小鼠的癫痫致死亡。所有小鼠癫痫性死亡的主要原因是呼吸暂停，因为(1)呼吸暂停在癫痫发作期间开始并持续数十分钟直到终末无搏停止，(2)机械通气可防止死亡。致命的癫痫发作总是包括与呼吸暂停相一致的强直期。这种强直性阶段呼吸暂停并不足以导致死亡，因为它也发生在许多非致命性癫痫发作中；然而，所有致命的癫痫发作都有强直期呼吸暂停。我们还观察到，在强直期呼吸暂停期间，持续的强直膈肌收缩发生，这可能通过阻止呼气而导致呼吸暂停，只有在强直期结束后呼吸没有恢复时才会致命。最后，一名发育性癫痫脑病患者的癫痫发作记录显示，其SCN8A可能的致病变异（p.l u257val）与小鼠相似，即延长的紧张期伴随着呼吸暂停。我们得出结论，在Scn8a突变小鼠中，与癫痫发作紧张期相一致的呼吸暂停以及随后无法恢复呼吸是导致癫痫诱发死亡的决定性事件。
Sudden unexpected death in epilepsy (SUDEP) is an unpredictable and devastating comorbidity of epilepsy that is believed to be due to cardiorespiratory failure immediately after generalized convulsive seizures. We performed cardiorespiratory monitoring of seizure-induced death in mice carrying either a p.Arg1872Trp or p.Asn1768Asp mutation in a single Scn8a allele—mutations identified from patients who died from SUDEP—and of seizure-induced death in pentylenetetrazole-treated wild-type mice. The primary cause of seizure-induced death for all mice was apnea, as (1) apnea began during a seizure and continued for tens of minutes until terminal asystole, and (2) death was prevented by mechanical ventilation. Fatal seizures always included a tonic phase that was coincident with apnea. This tonic phase apnea was not sufficient to produce death, as it also occurred during many nonfatal seizures; however, all seizures that were fatal had tonic phase apnea. We also made the novel observation that continuous tonic diaphragm contraction occurred during tonic phase apnea, which likely contributes to apnea by preventing exhalation, and this was only fatal when breathing did not resume after the tonic phase ended. Finally, recorded seizures from a patient with developmental epileptic encephalopathy with a previously undocumented SCN8A likely pathogenic variant (p.Leu257Val) revealed similarities to those of the mice, namely, an extended tonic phase that was accompanied by apnea. We conclude that apnea coincident with the tonic phase of a seizure, and subsequent failure to resume breathing, are the determining events that cause seizure-induced death in Scn8a mutant mice.
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影响因子：
5.3
作者：
DeVos, Sarah L.;Goncharoff, Dustin K.;Miller, Timothy M.
通讯作者：
Miller, Timothy M.
影响因子：
2.2
作者：
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通讯作者：
Kommajosyula, Srinivasa P.
影响因子：
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作者：
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通讯作者：
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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
影响因子：
5.5
作者：
Buchanan, Gordon F.;Murray, Nicholas M.;Richerson, George B.
通讯作者：
Richerson, George B.
影响因子：
15.9
作者：
Kim, YuJaung;Bravo, Eduardo;Richerson, George B.
通讯作者：
Richerson, George B.