Journal article
Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy
Annals of neurology, Vol.89(5), pp.1023-1035
05/2021
DOI: 10.1002/ana.26053
PMCID: PMC8411945
PMID: 33604927
Abstract
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. ANN NEUROL 2021;89:1023-1035.
Details
- Title: Subtitle
- Postictal Death Is Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy
- Creators
- Ian C Wenker - Department of Anesthesiology, University of Virginia Health System, Charlottesville, VAFrida A Teran - Iowa Neuroscience Institute, University of Iowa, Iowa City, IAEric R Wengert - Neuroscience Graduate Program, University of Virginia, Charlottesville, VAPravin K Wagley - Department of Neurology, University of Virginia Health System, Charlottesville, VAPayal S Panchal - Department of Anesthesiology, University of Virginia Health System, Charlottesville, VAElizabeth A Blizzard - Department of Anesthesiology, University of Virginia Health System, Charlottesville, VAPriyanka Saraf - Department of Anesthesiology, University of Virginia Health System, Charlottesville, VAJacy L Wagnon - Department of Human Genetics, University of Michigan, Ann Arbor, MIHoward P Goodkin - Department of Neurology, University of Virginia Health System, Charlottesville, VAMiriam H Meisler - Department of Human Genetics, University of Michigan, Ann Arbor, MIGeorge B Richerson - Veterans Affairs Medical Center, Iowa City, IAManoj K Patel - Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.89(5), pp.1023-1035
- DOI
- 10.1002/ana.26053
- PMID
- 33604927
- PMCID
- PMC8411945
- NLM abbreviation
- Ann Neurol
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Publisher
- United States
- Grant note
- NS103090 / NINDS NIH HHS Citizens United for Research in Epilepsy T32 GM007337 / NIGMS NIH HHS Wishes for Elliot NS090414 / NINDS NIH HHS NS034509 / NINDS NIH HHS NS110333 / NINDS NIH HHS
- Language
- English
- Date published
- 05/2021
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984070674602771
Metrics
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