CORTICOSTERONE LEVEL IS A RISK-FACTOR FOR SUDDEN UNEXPECTED DEATH IN EPILEPSY

Dravet syndrome is associated with a particularly high risk of Sudden Unexpected Death in Epilepsy (SUDEP). The underlying pathological mechanisms of SUDEP remain unclear, and predictive or preventive strategies are currently lacking. We aimed to investigate whether corticosterone, the rodent equivalent of cortisol, contributes to SUDEP susceptibility.
We developed an innovative approach combining microdialysis with Liquid Chromatography-Mass Spectrometry (LC-MS) to continuously monitor corticosterone in the subcutaneous interstitial fluid of freely moving mice, minimizing stress-induced artifacts. Two Scn1a-mutated mouse models of Dravet syndrome were studied to evaluate the effects of repeated seizures and experimental modulation of corticosterone levels.
Repeated seizures were associated with significant reductions in corticosterone levels. Furthermore, complete suppression of corticosterone production via bilateral adrenalectomy directly decreased survival probabilities in mutant mice and supplementation via slow-release pellets drastically increased survival. These results are establishing a causal relationship between corticosterone levels and SUDEP risk.
These findings identify reduced corticosterone levels as a novel risk factor for SUDEP, highlighting a potential target for intervention in Dravet syndrome.
Funding: Neurosense project (European Commission Pathfinder program).