Grant: Project Grant

Epilepsy has a tremendous impact on quality of life. Patients not only suffer from recurrent seizures but also many other issues such as depression, anxiety and poor memory. Brain-only genetic changes are a recently recognized cause of epilepsy that may explain a significant proportion of epilepsy. These genetic changes are not inherited but occur during fetal brain development and are, therefore, not present in other body cells. Hence, they can only be found in brain tissue. Epilepsy surgery can be done if patients do not become seizure free with anti-seizure drugs. In some patients, a special recording with depth electrodes inside the brain is needed to find out if surgery is possible. After the recording is completed, the electrodes are removed. We have developed a technique to harvest the few brain cells sticking to these electrodes to identify brain-only genetic changes causing epilepsy. Previously, we could only examine brain tissue after a patient had epilepsy surgery. With our special technique we can now investigate patients who do not eventually undergo epilepsy surgery. This allows us to investigate patients with different types of epilepsy and clarify the relevance of brain-only genetic changes in epilepsy more broadly. We will determine genetic changes in the so-called coding part of the genes in 45 patients with epilepsy. This is where most genetic changes causing disease have so far been identified. However, disease-causing genetic changes in other parts of the genes (non-coding) are increasingly recognized as well. Hence, we will expand the analysis in 12 patients to analyse the complete genetic information. Subsequently, we will carefully review the type of epilepsy in patients with identified genetic changes. Our study will broaden our understanding of brain-only genetic changes in epilepsy and pave the way to the development of novel treatments, ultimately resulting in better quality of life and reduced mortality for people with epilepsy.