These grants were made in 2006 by the Epilepsy Research Foundation.

Memory decline in patients with temporal lobe epilepsy - could it be stopped?

Despite years of research into the causes of epilepsy and the treatment of seizures, little attention has been paid to the causes of memory loss and depression in patients with temporal lobe epilepsy (TLE), the commonest drug resistant form of epilepsy in adults. Patients with TLE often show progressing memory loss over a period of years.

We know that growing new brain cells in the hippocampus (the part of the brain most concerned with memory) is important to maintaining memory function, particularly spatial memory. Normally this process, called neurogenesis, continues throughout life. However in brains affected by epilepsy, neurogenesis does not happen, or only happens at a reduced rate.

This study will test the theory that reduced growth of new brain cells is the cause of reduced memory in TLE. Professor William Gray and colleagues at the University of Southampton, who have been awarded £60,515 over three years, will investigate the relationship between memory decline and reduced rate of neurogenesis, and how this is affected by the presence of epilepsy. The study, entitled "Does restoration of neurogenesis in chronic TLE improve spatial learning?" will also investigate whether this process can be reversed: whether administering a drug that increases neurogenesis can improve spatial memory function.

If this drug intervention is possible, this would be the first exciting step towards a new treatment for a debilitating aspect of chronic epilepsy for many patients.

Ion channels in the hippocampus and the development of epilepsy

It is thought that epilepsy develops after the occurrence of damage to the brain. This could be through events such as traumatic head injury or stroke. There is often a delay between the occurrence of this damage and the onset of chronic seizures. This period is called the latent period. An important question is whether treatment given during this period could prevent the onset of epilepsy.

The excitability of certain neurones in one section of the hippocampus called the entorhinal cortex has been found to be significantly increased during the latent period. This is due at least partly to a change in the nature of certain ion channels in the membranes of these cells. These, called h-channels, are opened or closed by the size of the difference in electrical charge between the neurone and the surrounding fluid. During the latent period, the number of h-channels decreases significantly, which means these neurones are more excitable, and therefore more prone to seizure activity.

This study will use lamotrigine, a commonly-prescribed anti-epileptic drug, to attempt to prevent the decrease in the number of h-channels from occurring, and to find out if this prevention can delay the beginning of chronic epilepsy. It will also look at whether preventing seizures using a drug such as valproate also alters the number of these channels present. This study will be carried out by Dr Mala Shah and Dr Matthew Walker at University College London, who have been awarded £60,000 over one year to investigate "The role of Ih in the entorhinal cortex during the latent period". This work will clarify the role of h-channels during the development of epilepsy and could identify a new approach for treatment.

Investing in an epilepsy DNA biobank

The effects of our genes in causing epilepsy are only just beginning to be explored by scientists. To investigate genes, a DNA sample is needed and this is normally taken from a blood sample given by people with epilepsy at a hospital or a specialised epilepsy centre.

This grant will allow the collection of a 'library' of DNA samples from 25,000 people with epilepsy in Wales over the next five years. These samples need to be frozen to remain useable, and this grant will buy the freezers needed to do this. Professor Mark Rees and colleagues at the University of Wales in Swansea have been awarded £9,660 to set up "Storage capacity for a DNA biobank for epilepsy".

This very large DNA database will include samples from patients with every type of epilepsy. It is very important to collect a very large number of samples, as many of the genes or gene combinations that lie behind epilepsy are very rare, and so will only occur a few times in every thousand people. This large database will therefore allow investigation of, for example, the genetic differences between people with or without epilepsy; which genes are associated with specific types of epilepsy; and which genes are associated with not responding to anti-epileptic drugs.

Electrical activity in the brain just before a seizure starts

The area of the brain in which seizures start is called the seizure focus. In this area, the normal electrical signalling of the brain is not always totally controlled. If the excitability gets out of control, a seizure arises. The seizure focus therefore often has different electrical properties to those of the normal surrounding tissue. The area's response to stimulation with a magnet has also been found to change in the run-up to a seizure.

This project will look at how these electrical and magnetic features are related. Dr Mark Richardson at the Institute of Psychiatry, London has been awarded £59,991.74 over one year to conduct "Electrical and magnetic brain stimulation studies of the epileptogenic zone in man". This will include whether stimulating the focus with a magnet produces a measurable electrical response, and whether the electrical properties of the focus change in the run-up to a seizure, in parallel to the magnetic changes. If these properties are related it may be possible to develop the use of EEG to forecast when a patient's next seizure will happen, a completely non-invasive, cheap, easy and safe investigation. If an imminent seizure could be reliably predicted, in theory a new therapy could be developed for administration at this point. At the very least these investigations should tell us more about the electrical and magnetic properties of epileptic brain tissue immediately before a seizure, which should tell us more about how seizures start.