New York: Researchers have identified a gene associated with sudden death in epilepsy.
Usually, it is believed that the patient had a seizure that killed them. But seizures happen in the cortex, the top of the brain and life-sustaining processes like breathing are controlled somewhere else entirely -- the brainstem, the very bottom part of the brain that connects to the spinal cord.
In a study, published in the scientific journal 'eLife', the researchers from the University of Connecticut tried to figure out if there was a genetic basis for sudden unexpected death in epilepsy (SUDEP). They tried to understand if the same genetic mutation that causes the seizures also disrupts the cells in the brainstem that control breathing.
For the study, researchers raised mice with the human mutation for a severe form of epilepsy called Dravet syndrome, which is caused by mutations in a gene that shapes the channels through which sodium moves in and out of cells in the brain. If the sodium channels don't function properly, cells can get overexcited. One cell's over-excitement can travel through the brain like hysteria through a crowded stadium, stampeding into a seizure.
The gene mutated in the Dravet syndrome is called the sodium channel gene 1a or 'Scn1a'. It's considered a super-culprit for epilepsy, with more than 1,200 different Scn1a mutations identified.
The severity of epilepsy caused by Scn1a depends on whether the mutation causes partial or complete loss of the sodium channel's function.
People with Dravet syndrome tend to have dramatic seizures, exacerbated by hot weather and the syndrome is very hard to control with anti-epileptic medications.
The study's findings showed that Scn1a mutation makes the sodium channels less active. Instead of making cells overactive, it makes them underactive.
This mutation mostly affects inhibitory cells or cells in charge of calming the brain down.
To understand how this might lead to the patients' sudden death, the researchers tested whether the mice with the Dravet syndrome mutation show breathing problems and die prematurely of SUDEP and also, whether the cells in the part of the mice's brainstem that controls breathing were normal or were somehow perturbed by the mutation.
The researchers observed the mice with Dravet syndrome had bad seizures that became more severe when the mice got hot, exactly like humans with Dravet syndrome.
They also found that mice with Dravet Syndrome had a breathing disorder. They tended to hyperventilate (breathe too little) for no apparent reason sometimes. Other times they would have long apneas or pauses between breaths. And these mice didn't breathe more in response to high carbon dioxide levels in the air, the way humans and normal mice do.
"We felt really good that our model was reflecting the human condition," noted Dan Mulkey, a neuroscientist from the University of Connecticut.