Epilepsy discovery reveals why some seizures show lethal

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Epilepsy discovery reveals why some seizures prove deadly

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New research from the University of Virginia Medical School has shed light on the leading cause of epilepsy death and provided a long-awaited answer to why some patients die unexpectedly after an epileptic seizure.

The researchers found that a certain type of seizure was associated with sudden death in a mouse model of epilepsy, and that death only occurred if the seizure caused airway failure.

The new understanding will help scientists in their efforts to develop ways to prevent Sudden Unexpected Death in Epilepsy (SUDEP). Based on their research, the UVA team has already identified possible approaches to stimulate the mice's breathing and prevent death after an attack. The team believes this new approach could one day help save lives.

"SUDEP is a major concern for patients with epilepsy and their loved ones," said Manoj Patel, Ph.D., of the UVA's Department of Anaesthesiology. "Our study has identified a sequence of events that occur and progress during a seizure and can lead to death. In addition, we show that intervention during a seizure can save the deaths of mice with epilepsy – and we are excited to have it with you to share with the scientific community. "

Sudden unexpected death in epilepsy

Many people were unfamiliar with the sudden unexpected death from epilepsy when young Disney Channel star Cameron Boyce died in 2019. He was only 20 years old. However, SUDEP is the leading cause of epilepsy-related death. It is estimated to be responsible for 8% to 17% of all epilepsy deaths, increasing to 50% in patients whose seizures are unresponsive to treatment.

Scientists have suggested a variety of possible causes of SUDEP, but UVA researchers have shed light on why some seizures lead to death, others do not, and how we can potentially prevent death from progressing.

The researchers found that breathing disorders known as apnea began during seizures as the muscles began to stiffen. This stiffening involved a contraction of the diaphragm, the main breathing muscle, preventing exhalation and stopping the normal breathing process.

Not all cases of this seizure apnea have been fatal; Only when breathing did not recover immediately after the attack did the mice die, the researchers found. The UVA team argued that artificial stimulation of breathing would help prevent sudden death after a seizure. In a mouse model for epilepsy, they found that direct ventilation of the mouse could prevent death.

While working on laboratory mice, they confirmed their results by monitoring the respiratory rate and patterns in a human patient with epilepsy. They found that seizures caused breathing disorders or apneas that were very similar to those of their mice.

"These results imply respiratory arrest as a major factor in SUDEP and give us targets for future research on the intervention," said researcher Ian Wenker, Ph.D.

Using their innovative new SUDEP model, UVA researchers have identified possible ways to prevent SUDEP. One could be to target "adrenergic" receptors, which regulate the body's response to adrenaline and other neurotransmitters. Scientists believe that these receptors are vital to resuming breathing after a seizure and preventing death.

"By identifying some of the receptors involved in stimulating respiratory regeneration after a seizure, we believe our results will advance other approaches to reducing the risk of death in epilepsy patients," said PhD student Eric Wenger, a PhD student. "We look forward to seeing other researchers use our new model to expand our understanding and ability to prevent SUDEP."

Scientists pinpoint a region of the brain that no longer breathes in pediatric epilepsy

More information:
Ian C. Wenker et al., Postictal Death Associated with Tonic Phase Apnea in a Mouse Model of Sudden Unexpected Death in Epilepsy, Annals of Neurology (2021). DOI: 10.1002 / ana.26053

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University of Virginia

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