Brain Networks in Focal Epilepsy
Research type
Research Study
Full title
Brain networks in focal epilepsy: endophenotypes and generative models
IRAS ID
143971
Contact name
Mark Richardson
Contact email
Sponsor organisation
King's College London
Research summary
Epilepsy is the commonest serious brain disease, affecting 750,000 people in the UK. It causes catastrophic seizures, resulting in at least 1000 deaths per year in the UK. It is the commonest cause of repeated admission to hospital. About 1 in 3 of all people with epilepsy do not respond to any medication, and continue to have uncontrolled seizures. The personal, social and economic costs of epilepsy are very high. It is not yet known how epileptic seizures start. There are clues from experiments in animals and genetic studies in people which suggest that epilepsy can be caused by a wide range of disturbances in brain cell function. Furthermore, there are different patterns of epileptic seizure, which occur in different combinations in different people, and associated with other specific findings in clinical tests. This has given rise to the view that epilepsy is at least 20 different diseases (or types of epilepsy), and that each type of epilepsy might have a different cause.
However, this does not explain some well-recognised aspects of epilepsy:
Firstly, although there may appear to be many causes, there are only small number of types of epileptic seizure; and an individual with epilepsy may suffer from several different types of seizure.
Secondly, epilepsy may sometimes be inherited within a family; if epilepsy were a set of entirely different diseases, it might be expected that within one family all affected members would have the same type of epilepsy. On the contrary, it is known that within some families there are affected individuals who have completely different types of epilepsy. Thirdly, drugs for the treatment of epilepsy have broadly similar therapeutic effects across all types of seizure and epilepsy, with very few exceptions.These observations suggest that there must be important mechanisms in common between different seizure types, and between different types of epilepsy.
It is increasingly recognised that functions of the brain are properties of complex networks of brain cells. We have worked for several years on new methods to identify whether brain networks in people with epilepsy have abnormal properties, and whether these properties allow seizures to occur. Using MRI brain scans, we have shown abnormalities of specific brain regions and their connections. Using electrical recordings of brain waves (EEG) we have shown that brain networks differ between people with epilepsy and people who do not have epilepsy; and that unaffected relatives of people with epilepsy may have similar brain networks to their affected relatives. Using computer models of how EEG activity is produced, we have shown that these inherited networks have an abnormal ability to suddenly switch to seizure activity.
In this study we build on this background, to examine three questions:
(1) Are brain networks which have an abnormal ability to generate seizures found across a range of common types of epilepsy?
(2) Are these network abnormalities inherited?
(3) Does successful surgical treatment act by altering the properties of these brain networks?
In the first part of this project, we will collect MRI brain scans and EEGs from more than 50 people with one particular type of focal-onset epilepsy (temporal lobe epilepsy), in addition to 25 of their close family relatives, and a “control“ group of 35 people who have no personal or family connection with epilepsy. We will develop new methods to identify the relevant brain networks from MRI and EEG, and examine how these networks differ between people with epilepsy, their relatives and controls. We anticipate that this will provide information about the network basis of epilepsy, and its heritability.
In the second part of this project, we will make use of existing EEG data from our Epilepsy Surgery programme. These data will be anonymised for use in research. We will identify the networks responsible for generating seizures, and using novel analysis methods attempt to find predictive markers of outcome following surgery.
REC name
London - Bromley Research Ethics Committee
REC reference
14/LO/0193
Date of REC Opinion
26 Feb 2014
REC opinion
Favourable Opinion