Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1aR1407X/+ Mice

Frida A Teran; YuJaung Kim; Megan S Crotts; Eduardo Bravo; Katlynn J Emaus; George B Richerson

doi:10.3389/fneur.2019.00278

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Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1aR1407X/+ Mice

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Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1aR1407X/+ Mice

Frida A Teran, YuJaung Kim, Megan S Crotts, Eduardo Bravo, Katlynn J Emaus and George B Richerson

Frontiers in neurology, Vol.10, 278

03/29/2019

DOI: 10.3389/fneur.2019.00278

PMCID: PMC6449461

PMID: 30984098

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Abstract

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.

Epilepsy

Neurology

sleep

circadian

seizure

SUDEP

ketogenic diet

breathing

Details

Title: Subtitle: Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1aR1407X/+ Mice
Creators: Frida A Teran - Department of Neurology, University of Iowa
YuJaung Kim - Department of Neurology, University of Iowa
Megan S Crotts - Department of Neurology, University of Iowa
Eduardo Bravo - Department of Neurology, University of Iowa
Katlynn J Emaus - Department of Neurology, University of Iowa
George B Richerson - Department of Neurology, University of Iowa
Resource Type: Journal article
Publication Details: Frontiers in neurology, Vol.10, 278
DOI: 10.3389/fneur.2019.00278
PMID: 30984098
PMCID: PMC6449461
NLM abbreviation: Front Neurol
ISSN: 1664-2295
eISSN: 1664-2295
Publisher: Frontiers Media S.A
Grant note: F31 NS110333; U01 NS090414 / National Institute of Neurological Disorders and Stroke
Language: English
Date published: 03/29/2019
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984070885602771

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