An international team of scientists together with the University of Bonn Hospital have taken a new path in the research into causes of epilepsy: The researchers determined the networks of the active genes and, like a dragnet, looked for the "main perpetrators" using a computer model, reports Science Newsline. In doing so, they discovered the molecule sestrin-3 as a central switch. In animal models, the scientists were able to demonstrate that inhibition of sestrin-3 leads to a reduction in seizures.
During an epileptic seizure, many nerve cells lose their regular rhythm and switch into a rapid rhythm. This results in seizures to the point of a loss of consciousness. The temporal lobes in the brain are most frequently the region in which such synchronous discharges occur. "Drugs have the desired effect in only about two-thirds of patients with temporal lobe epilepsy," says Prof Albert Becker from the Institute of Neuropathology of the University of Bonn Hospital. If no drug therapy helps, the seizure focus with the out-of-rhythm nerve cells are surgically removed as last therapy option.
The brain tissue removed during these procedures gives science the unique opportunity to learn more about the causes and new treatment options for temporal lobe epilepsy. "Without tissue samples of this type, we would not have been able to conduct our large-scale investigation on the networks of genes and signal chains at all," says Becker. Together with their colleagues from the UK, US, Australia, Finland and Belgium, the scientists examined surgically removed tissue samples from the temporal lobes of a total of 129 epilepsy patients.
The researchers determined which genes were active in the diseased nerve cells and other supporting brain cells. The scientists working with lead author Dr Enrico Petretto from Imperial College London (England) entered these "suspects" into a computer model. As in the case of a dragnet, this allows connections between the conning tower and the signal chains thus set in motion to be sought. Just as the culprit is ultimately caught in the police's net due to certain manhunt connections, the scientists very similarly encountered an important switch during their analyses: Sestrin-3.
It is known that the molecule has an activating function in brain cells, among others, and also in immune cells. "Our data show: Sestrin-3 is centrally involved in the development and progression of temporal lobe epilepsy," explains Dr Katharina Pernhorst. The scientists proved this in mice and zebra fish whose brains demonstrate changes as in the case of human epilepsy. If "sestrin-3" is silenced, the severity and frequency of epileptic seizures is also reduced.
The scientists see a platform in their novel method for further investigations. "This method broadens the view of individual gene/effect relationships to a systematic examination of the entire network," says Becker. In this way, the key positions in the interaction of signal chains and genes as well as with the immune system can be better detected. Moreover, the results show promising starting points for novel therapies. Conventional epilepsy drugs intervene in a regulatory way in the ion channels of the diseased nerve cells.
New research shows that stomach sleepers with epilepsy may be at higher risk of sudden unexpected death, drawing parallels to sudden infant death syndrome in babies, reports Science Codex. "Sudden unexpected death is the main cause of death in uncontrolled epilepsy and usually occurs unwitnessed during sleep," said study author Dr James Tao, with the University of Chicago. People with tonic clonic seizures (formerly known as grand mal seizures) that affect the entire brain are more likely to die suddenly than people with partial seizures that affect an area of the brain.
For the study, researchers reviewed 25 studies that included 253 sudden unexpected death cases where body position was recorded. The study found that 73% of the cases died in the stomach sleep position, whereas 27% died in other sleep positions. Looking at a sub-group of 88 people, researchers found that people younger than 40 were four times more likely to be found on their stomachs at the time of sudden death than people over 40. A total of 86% of those under 40 were sleeping on their stomachs, compared to 60% for those over the age of 40.
"We're not sure why this was more common in younger people," Tao said. "It may be that they are more likely to be single and not have anyone with them during a seizure while sleeping." He noted that a person sleeping with someone who has a generalised tonic clonic seizure while on their stomach should help them turn over or on the side during or after the seizure.
A total of 11 cases of sudden death have occurred while the people were being monitored with video EEG and their sleeping position was recorded. In all of those cases, all the people were died in a prone position, and most of these people were sleeping on their stomachs before the terminal seizures.
[link url="http://www.sciencenewsline.com/articles/2015012316090017.html"]Full Science Newsline report[/link]
[link url="http://www.nature.com/ncomms/2015/150123/ncomms7031/full/ncomms7031.html"]Nature Communications abstract[/link]
[link url="http://www.sciencecodex.com/sleeping_on_stomach_may_increase_risk_of_sudden_death_in_epilepsy-149309"]Full Science Codex report[/link]
[link url="http://www.neurology.org/content/early/2015/01/21/WNL.0000000000001260.short?sid=1a15ed49-c17c-4314-a654-fd40c39affe8"]Neurology abstract[/link]