Our research focuses on how metabolic and pharmacological therapies influence seizures and longevity in animal models of epilepsy.
The lifetime incidence of epilepsy is 1:26 and approximately 30% of people with epilepsy are refractory to current anti-seizure drugs.
We have found that a high fat, low carbohydrate diet (the ketogenic diet) is able to stabilize previously hyperexcitable neuronal networks in the brain thereby reducing seizures.
Using electroencephalography and electromyography we are able to record seizures, assess changes in severity and frequency, and analyze sleep architecture throughout life in animal models of epilepsy. This figure depicts the fast fourier transform time frequency analyses and its corresponding raw EEG trace during a severe seizure representative of Kv1.1 knockout mice.
Collectively, in all of our studies combined, we have found that the ketogenic diet reduces seizures of Kv1.1 knockout mice by more than 25% in 20% of subjects and by more than 75% in 80% of subjects.
Sudden unexpected death in epilepsy (SUDEP) occurs in at least 1:1000 people with epilepsy each year, a risk that increases to ~1:150 per year for individuals with poorly controlled and severe seizures.
We have been studying comorbid sleep disorders that are associated with epilepsy. We recently found that there is a substantial build up of sleep deficiency prior to sudden death in Kv1.1 knockout mice, a model of SUDEP.
Using a novel retrospective method of analyses developed in the laboratory, we found that sleep deficiency increases immediately prior to death.
We have found that treatment with the ketogenic diet increases lifespan in an animal model of SUDEP.
The figure on the right depicts the probability of mortality (y axis) as a function of age (x axis). The mortality of epileptic mice used in the study (red) and the entire animal colony (black) were compared to epileptic mice treated with the ketogenic diet (green). Lifespan increased by more than 40% in mice treated with the ketogenic diet.
We currently aim to determine whether or not there are physiological changes that can be temporal indicators of the moving probability of death. Hopefully by understanding these better, it will offer a window of opportunity to intervene.
KA Simeone has published under KA Dorenbos and KA Fenoglio.
New collaborations! We are excited to continue to push the boundaries of SUDEP research with our new collaborators Drs. Gordon Buchanan and Edward Glasscock. American Epilepsy Society 2017.
Tim and Kristina with friend and mentor Dr. Jong Rho. American Epilepsy Society Meeting 2017.