Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1a R1407X /+ Mice.

Autor:	Teran FA; Department of Neurology, University of Iowa, Iowa City, IA, United States.; Medical Scientist Training Program, University of Iowa, Iowa City, IA, United States.; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, United States., Kim Y; Department of Neurology, University of Iowa, Iowa City, IA, United States.; Department of Biomedical Engineering, University of Iowa, Iowa City, IA, United States., Crotts MS; Department of Neurology, University of Iowa, Iowa City, IA, United States., Bravo E; Department of Neurology, University of Iowa, Iowa City, IA, United States.; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, United States., Emaus KJ; Department of Neurology, University of Iowa, Iowa City, IA, United States., Richerson GB; Department of Neurology, University of Iowa, Iowa City, IA, United States.; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, United States.; Department of Molecular Physiology & Biophysics, University of Iowa, Iowa City, IA, United States.; Neurology, Veterans Affairs Medical Center, Iowa City, IA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in neurology [Front Neurol] 2019 Mar 29; Vol. 10, pp. 278. Date of Electronic Publication: 2019 Mar 29 (Print Publication: 2019).
DOI:	10.3389/fneur.2019.00278
Abstrakt:	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.
Databáze:	MEDLINE
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