CURE Epilepsy Discovery: Identification of Environmental Contributors to SUDEP 

Key Points: 

  • CURE Epilepsy awardee Dr. Franck Kalume and colleagues at the Seattle Children’s Research Institute and New York University sought to identify simple environmental factors that may increase the risk of SUDEP. 

  • The team examined the effects of increased temperature and moderate exercise on several basal involuntary bodily functions of an established mouse model of Dravet syndrome (DS), a severe form of epilepsy with an increased incidence of SUDEP. 

  • When compared to normal mice, DS mice showed diminished regulation of core body temperature as well as cardiac and respiratory function.  

  • Understanding the mechanisms behind these impairments might help develop effective approaches to reduce the risk of and perhaps even prevent SUDEP.   

Deep Dive: 

Sudden unexpected death in epilepsy (SUDEP) is a devastating event that occurs in approximately 1 in 1,000 people with epilepsy [1,2]. It appears to be related to seizure-induced dysfunction of the autonomic nervous system (ANS) [3]. The ANS controls body functions essential for survival and is responsive to environmental changes. Some of these functions include maintenance of core body temperature as well as tight regulation of heart and breathing rates. Previous research has revealed that disruptions in ANS function related to a seizure event are marked by diminished control of these three body processes, but the precise nature and mechanisms of these weakened responses are not clear.  

Dr. Franck Kalume, a recipient of CURE Epilepsy’s Sleep and Epilepsy Award, generously funded by the BAND Foundation, explored this important area of research by utilizing his mouse model of Dravet syndrome (DS). [4] DS is a treatment-resistant form of epilepsy with a high risk
of SUDEP, and an increased prevalence of ANS dysfunction. This particular mouse model was developed by deleting the gene linked to most cases of DS in humans (known as SCN1A), which is also one of the many genes responsible for propagating electrical signals in the brain.  

The first set of experiments involved assessing the ability of DS mice to regulate 1) core body temperature, 2) heart rate, and 3) breathing rate in response to an increase in surrounding temperature, i.e., to 86-90°F. Responses from the DS mice and control mice were subsequently compared [5].
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