Sudden unexpected death in epilepsy (SUDEP) occurs more frequently during early evening and is significantly prevented by prolonged use of the ketogenic diet, research in a mouse model of Dravet syndrome (DS) suggests.
The reasons why this happens are unclear, and should be examined in more depth by future studies, but these findings may be useful to understand why most SUDEP episodes happen at night and how certain diets can benefit epileptics, especially those with Dravet syndrome, researchers say.
Their study, “Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1aR1407X/+ Mice,” was published in the journal Frontiers in Neurology.
Studies estimate that about 1 in 1,000 people with epilepsy experience SUDEP each year. For patients with Dravet syndrome, their risk of SUDEP is estimated to be 15 times higher than for people with other types of childhood-onset epilepsy. Premature death occurs in 21% of Dravet patients, with SUDEP accounting for nearly half of these deaths.
Most SUDEP cases occur during or immediately after a seizure, but the exact cause is unknown. Breathing problems (apnea) or airway obstructions, dangerous heart rhythms, or a combination of both may contribute to SUDEP.
Although the circumstances surrounding SUDEP remain unclear, most cases occur in bed at night and are preceded by generalized tonic-clonic seizures (seizures that start in both sides of the brain).
Because studying SUDEP in patients is extremely difficult, many researchers rely on mouse models to investigate the phenomena. These models have proven to be effective research tools “as they recapitulate many aspects of the clinical condition: they have heat-induced seizures, spontaneous seizures and a high incidence of premature mortality due to SUDEP,” the researchers said.
Using an established mouse model of Dravet syndrome, the researchers investigated if the time of the day influences the chances of sudden death. They also sought to determine if a ketogenic diet — a high-fat, low-carbohydrate (low-sugar) diet which helps to control seizures in some epileptic patients — can change the frequency of seizures and the rate of mortality.
Mice were continuously recorded on video to monitor for spontaneous seizures and sudden deaths. The recordings showed that SUDEP and spontaneous seizures happened more often during the early evening.
In the one to two days before death, most mice had few or no spontaneous seizures, then seizures began to increase and spiked in the 24 hours prior to death.
To test the effect of the ketogenic diet, mice were separated into two groups, each fed either a ketogenic or regular diet.
The control mice had a high number of premature deaths (44% survival rate by day 60), accompanied by greater spontaneous generalized tonic-clonic seizures, shortly prior to death. But mice on the ketogenic diet had a significant reduction in mortality (86% survival rate by day 60). Researchers noted that the improvement in survival was not associated with fewer seizures.
The fact that a ketogenic diet prevented death without affecting the frequency of seizures “challenges the notion that uncontrolled [generalized tonic-clonic seizures] are the strongest risk factor for SUDEP,” they said.
A possible explanation is that this type of diet stabilizes seizure-induced breathing changes, thereby preventing fatal apnea.
More studies are necessary to investigate why dietary changes can prevent sudden deaths and how the time of the day influences the incidence of seizures and SUDEP, the scientists said.
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