Cortical excitability in refractory focal epilepsy treated with novel gene therapy and conventional resective surgery

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Epilepsy is one of the most common neurological conditions, and affects around 50 million people worldwide. It is caused by increased excitability of the brain. Patients with epilepsy have recurrent seizures. Unfortunately about a third of patients have ongoing seizures despite taking the many anti-epileptic medications available. Seizures have risks that commonly include injuries but also rarely can result in fatality due to effects of the seizures on breathing and heart rate (known as Sudden Unexpected Death in Epilepsy). In some of these patients, an operation to remove the part of the brain that is causing the seizures, can help to cure seizures. However, there are risks of surgery, especially if the seizures start in or near parts of the brain that are vital for important functions, for example, movement, language or memory function. Another exciting possible new treatment is gene therapy, where a gene is introduced into the brain using a virus as a carrier. In our research institution at UCL, we have developed a gene therapy that works well to control seizures in rats with epilepsy. The next step is to test if this treatment also works in humans. There is a plan to start a clinical trial using a trial of gene therapy as a novel therapy for our patients who would normally be considered for epilepsy surgery. Transcranial magnetic stimulation is useful and safe tool that uses a magnet held over the head to stimulate nerves in the brain and the response can be measured using recording electrodes on the muscles of the hand or by measuring brainwaves on the scalp. It is ideal for studying brain activity in patients with epilepsy, as it can directly probe the workings of brain circuits and give us measures of brain excitability. In this study we plan to use transcranial magnetic stimulation to measure brain activity in patients with focal epilepsy, who are still having seizures, even though they are taking regular anti-epileptic medications. These patients will be treated with either the new gene therapy or the already established treatment of epilepsy surgery. We will take brain excitability measures before and after these treatments. This will help to improve our understanding of this type of epilepsy, and how brain excitability changes in these patients, compared to healthy people. In addition it will also help us understand how both these treatments affect brain excitability. In particular this will give us an insight into the effects of the new gene therapy treatment on the brain. The information we get from this study, will help us understand why some people may become seizure free with either of these treatments whereas others might not. In turn we envisage that, in future, this will help us to predict which patients will benefit most from either treatment. This will allow us to choose the best treatment for patients and improve their seizures and thereby their quality of life.