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Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a(R1407X/+) Mice
Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in patients with drug-resistant epilepsy. Most SUDEP cases occur in bed at night and are preceded by a generalized tonic-clonic seizure (GTCS). Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly caused by mutat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449461/ https://www.ncbi.nlm.nih.gov/pubmed/30984098 http://dx.doi.org/10.3389/fneur.2019.00278 |
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author | Teran, Frida A. Kim, YuJaung Crotts, Megan S. Bravo, Eduardo Emaus, Katlynn J. Richerson, George B. |
author_facet | Teran, Frida A. Kim, YuJaung Crotts, Megan S. Bravo, Eduardo Emaus, Katlynn J. Richerson, George B. |
author_sort | Teran, Frida A. |
collection | PubMed |
description | Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in patients with drug-resistant epilepsy. Most SUDEP cases occur in bed at night and are preceded by a generalized tonic-clonic seizure (GTCS). Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly caused by mutations in the SCN1A gene. Affected individuals suffer from refractory seizures and an increased risk of SUDEP. Here, we demonstrate that mice with the Scn1a(R1407X/+) loss-of-function mutation (DS) experience more spontaneous seizures and SUDEP during the early night. We also evaluate effects of long-term ketogenic diet (KD) treatment on mortality and seizure frequency. DS mice showed high premature mortality (44% survival by P60) that was associated with increased spontaneous GTCSs 1–2 days prior to SUDEP. KD treated mice had a significant reduction in mortality (86% survival by P60) compared to mice fed a control diet. Interestingly, increased survival was not associated with a decrease in seizure frequency. Further studies are needed to determine how KD confers protection from SUDEP. Moreover, our findings implicate time of day as a factor influencing the occurrence of seizures and SUDEP. DS mice, though nocturnal, are more likely to have SUDEP at night, suggesting that the increased incidence of SUDEP at night in may not be solely due to sleep. |
format | Online Article Text |
id | pubmed-6449461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64494612019-04-12 Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a(R1407X/+) Mice Teran, Frida A. Kim, YuJaung Crotts, Megan S. Bravo, Eduardo Emaus, Katlynn J. Richerson, George B. Front Neurol Neurology Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in patients with drug-resistant epilepsy. Most SUDEP cases occur in bed at night and are preceded by a generalized tonic-clonic seizure (GTCS). Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly caused by mutations in the SCN1A gene. Affected individuals suffer from refractory seizures and an increased risk of SUDEP. Here, we demonstrate that mice with the Scn1a(R1407X/+) loss-of-function mutation (DS) experience more spontaneous seizures and SUDEP during the early night. We also evaluate effects of long-term ketogenic diet (KD) treatment on mortality and seizure frequency. DS mice showed high premature mortality (44% survival by P60) that was associated with increased spontaneous GTCSs 1–2 days prior to SUDEP. KD treated mice had a significant reduction in mortality (86% survival by P60) compared to mice fed a control diet. Interestingly, increased survival was not associated with a decrease in seizure frequency. Further studies are needed to determine how KD confers protection from SUDEP. Moreover, our findings implicate time of day as a factor influencing the occurrence of seizures and SUDEP. DS mice, though nocturnal, are more likely to have SUDEP at night, suggesting that the increased incidence of SUDEP at night in may not be solely due to sleep. Frontiers Media S.A. 2019-03-29 /pmc/articles/PMC6449461/ /pubmed/30984098 http://dx.doi.org/10.3389/fneur.2019.00278 Text en Copyright © 2019 Teran, Kim, Crotts, Bravo, Emaus and Richerson. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Teran, Frida A. Kim, YuJaung Crotts, Megan S. Bravo, Eduardo Emaus, Katlynn J. Richerson, George B. Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a(R1407X/+) Mice |
title | Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a(R1407X/+) Mice |
title_full | Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a(R1407X/+) Mice |
title_fullStr | Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a(R1407X/+) Mice |
title_full_unstemmed | Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a(R1407X/+) Mice |
title_short | Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a(R1407X/+) Mice |
title_sort | time of day and a ketogenic diet influence susceptibility to sudep in scn1a(r1407x/+) mice |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449461/ https://www.ncbi.nlm.nih.gov/pubmed/30984098 http://dx.doi.org/10.3389/fneur.2019.00278 |
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