Sun, Feb 19, 2017 | updated 07:44 PM IST

Here`s how leaky calcium puts epileptics at heart risk

Updated: Aug 02, 2016 13:26 IST

Washington D.C, Aug 2 (ANI): Sudden unexpected death in epilepsy (SUDEP) has long bedeviled doctors and now, a team of researchers may have found the cause of it.

In a paper, researchers from Baylor College of Medicine reported how a mutation in a gene involved in the regulation of calcium inside brain cells can help trigger blackouts of the brainstem, the center that controls heartbeat and breathing, and increase the risk of sudden unexpected death.

"SUDEP turns out to be the most common cause of premature death in people with epilepsy. It's not accidents or suicide, it's just this unexplained mortality," said senior author Dr Jeffrey L. Noebels.

He added, "Most people with epilepsy live long lives and do not seem to have an increased risk of SUDEP. But there is a subset of people at additional risk. We have been looking for genes that cause epilepsy to see if any of them might give us a clue as to who might be at risk. Specifically, we have been looking at genes that might explain what appears to be a collapse of the cardiac and respiratory system after a seizure."

In their years-long quest to understand the cellular and genetic mechanisms that may trigger SUDEP, Noebels and his colleagues studied the genes that are involved in the heart beat. Some of these genes are already well known to be related to sudden unexpected cardiac death.

"We wondered whether some of those same genes could also cause seizures if they were expressed in the brain, and, if so, whether those genes would also place people with epilepsy at risk, not only for having epilepsy, but an abnormal heart beat and risk of death," said Noebels. "In our first experiments we found several genes that actually filled that description: they are expressed in the brain and the heart, and mutations of those genes cause an abnormal heart beat and epilepsy in mouse models."

The researchers then found that these same genes carry an additional risk for a phenomenon called spreading depolarization, a slowly-progressing, temporary electrical blackout of a region in the brain. During a blackout, the brain cells in that area cease their activity until it is restored.

Noebels and colleagues studied another gene - RyR2 - which is also expressed in the heart and known to cause heart problems. They showed that RyR2, which is also expressed in the brain, also causes epilepsy in mice and sets up an electrical surge that makes a fatal blackout likely.

For Noebels and colleagues, the discovery of how the 'leaky' RyR2 increases the chances of SUDEP is a step forward toward a future in which neurologists could sit with a patient and their family and have a conversation about the possibility of offering an accurate prediction of the risks of SUDEP and effective interventions.

The study is published on the Proceedings of the National Academy of Sciences. (ANI)

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