Researchers aim to understand and prevent sudden unexpected death in epilepsy

SUDEPWhile many people with epilepsy live a full life, some die abruptly without warning or other clear medical cause due to a devastating phenomenon called sudden unexpected death in epilepsy (SUDEP). SUDEP is the most common cause of death in those with severe forms of epilepsy where seizures cannot be controlled with treatment, but what causes this tragic event remains unclear.

Franck Kalume, PhD, and other researchers at Seattle Children’s Research Institute are working to change this.

“Having a family member unexpectedly pass away from this – without any explantation as to why – is extremely devastating,” said Kalume, who lost his nephew to SUDEP. “Even though this condition has been around since the dawn of time, it is only in the recent decades that there’s been a substantial increased interest in SUDEP research and in raising awareness about its risk. I hope that we will be able to make a life changing impact by furthering our knowledge of the physiological mechanisms of SUDEP and finding ways to prevent it.”

The heart plays a role in SUDEP

Kalume has focused his research on one of the most severe forms of epilepsy; one that has a higher incidence of sudden death called Dravet syndrome (DS). DS is a drug-resistant and life-threatening form of epilepsy that begins in infancy (6 to 9 months of age). In a study published last year in The Journal of Clinical Investigation, Kalume used mouse models to examine this usually unpredictable event and made a major discovery as to what takes place in SUDEP. He found that sudden death occurs when a tonic-clonic seizure (the most severe type of convulsive seizures) causes the vagus nerve (part of the parasympathetic nervous system that slows the heart) to become hyperactive. This then leads to electrical dysfunction of the ventricles and a lethal slowing of the heart rate.

Understanding that the heart may hold the clue as to why some seizures become deadly has important implications for how doctors can one day prevent this tragedy.

“While more research needs to be done, our findings indicate that for those that are at high risk for SUDEP, we may be able to prevent premature death by implanting a pacemaker that would help people survive these fatal seizures by regulating their heartbeat,” Kalume said.

Kalume and his team will now use electrodes to follow the path of the abnormal electrical impulses that travel from the brain after a seizure, through the vagus nerve and down to the heart. They suspect that these impulses may also affect a person’s ability to breathe, which may contribute to sudden death. Their goal is to understand this pathway even more so they can find a way to cut the path short and stop them from reaching the heart altogether. This can possibly be done by using a modified vagus nerve stimulator that could be referred to as vagus nerve suppressor, a small implantable device that will help prevent the electrical bursts from seizures in the brain from reaching the heart.

“I think we are getting close to the answer and it may be a combination of technologies, like the vagus nerve suppressor and a pacemaker, that are key to preventing SUDEP,” Kalume said. “It would be a major accomplishment to find a solution for this disease and a great honor to be able to save the lives of the thousands who are affected each year.”