Epilepsy – when the brain fires to much

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Eric Mangen
In our brain 100 billion (1011) of neurons form connections and communicate with one another. Usually, the brain’s activity is in balance. If two brain regions however activate each other continuously, thereby becoming hypersynchronized, people experience seizures. Depending on the brain regions affected, seizures can vary widely in form. People with epilepsy experience unprovoked seizures, although everybody could be affected by seizures caused for instance by long periods without sleep or severe dehydration. Treatment with medications can control seizures but has side effects as they affect brain function in general. In addition, not all people with epilepsy respond to medication; for some surgery is an option.

Gene hunters at work

At the LCSB, we investigate the genetic origin of epilepsy, particularly of those types that are resistant to current therapy or that are common. Collaborating with scientists and clinicians worldwide, our scientists perform genetic analysis, also called ‘DNA sequencing’, of affected families or groups of patients.Understanding which genes are affected allows to divide patients in subgroups that go beyond mere clinical differences and to subsequently develop new specific therapies. Since 2009, LCSB scientists have been involved in the discovery of more than 20 new epilepsy genes.
Studying the course of epilepsy

To develop new therapies, our researchers develop epilepsy models that can be used to screen for new medication. One such model are the larvae of zebrafish. This small fish, originating in the Ganges river in India, has 60% of its gene are similar to those in humans making it a good model to study genetic effects. As the larvae is transparent, we can observe epileptic seizures with special dyes under a microscope and at the same time record their brain activity using an EEG. This allows us to study in immense detail how the seizure starts, spreads through the brain and ends again. Using this methodology, our researchers were able to show that in a zebrafish model of Dravet Syndrome – a rare genetic epileptic encephalopathy - a specific type of inhibitory nerve cells is lost during development. This causes a hyperactivation in the brain, resulting in epileptic seizures.When it comes to epilepsy research also our computer scientists come into play. They are developing machine learning algorithms that can automatically identify when a seizure happens in an EEG recording and that can help to classify different types of seizures.
The ultimate goal is to use such computational tools to identify early warning signals that predict when a seizure is going to happen.
In sum, LCSB’s researchers investigate epilepsy on different levels: from the genetic analysis to the dysfunctional molecule and to the cellular problems that causes nerve cells to fire abnormally. This gives a unique opportunity to unravel the causes of epilepsies and develop future therapies that tackle them right at their core.