Epilepsy, migraine and episodic ataxia: a new window on nerve excitability

Published on 18 October 2008

Some people with epilepsy, migraine and a disorder called episodic ataxia have inherited abnormalities in proteins called ion channels, which control the flow of messages along nerves. For the first time ever, researchers are studying how these abnormalities change the way messages travel along intact nerves in living people, rather than in the laboratory. Their groundbreaking approach could boost understanding and lead to better diagnosis and treatment.

What's the problem and who does it affect?
What is the project trying to achieve?
What are the researchers' credentials?
Who stands to benefit from this research and how?
References

What's the problem and who does it affect?

Problem proteins

Special proteins, called ion channels, control the flow of messages along nerves. Some people with a disorder called episodic ataxia, and certain rare forms of epilepsy and migraine, have inherited changes – or mutations – in the genes for these proteins. Laboratory studies show these changes cause ion channels to malfunction.

The people who are taking part in this study have episodic ataxia. They suffer attacks of profound uncoordination, which cause slurred speech and difficulties with walking and using their hands. Other symptoms include headaches, double vision, muscle spasms, twitching and involuntary head shaking.

There is no cure for episodic ataxia, though treatment can relieve symptoms in some people. Sadly, sufferers are sometimes thought to be clumsy or drunk, which compounds their social and professional isolation.

Episodic ataxia is relatively rare, but it is widely speculated that changes in ion channels may also be linked to much more widespread disorders, such as migraine and common forms of epilepsy – it is estimated that around 450,000 people in the UK have epilepsy.1

What is the project trying to achieve?

Abnormal impulses

Researchers are studying, for the first time ever, how genetic changes in ion channels affect the way electrical signals – or impulses – travel along intact nerves in living people, and how this may lead to different symptoms, such as muscle spasms, muscle weakness or problems with coordination.

The researchers are using nerve excitability tests. These involve administering harmless electrical pulses to a nerve in the wrist and recording the response in the muscle at the base of the thumb. They are using innovative equipment developed specially for this purpose within their own laboratory.

Around 50 people with episodic ataxia are taking part in the study. Some already know they have an abnormality in a gene for an ion channel. Others are having blood samples taken so their genes can be tested. Parallel studies in healthy volunteers, and in a laboratory model, are providing further insight to the results.

What are the researchers' credentials?

Project Leader	Professor D M Kullmann DPhil FRCP FMedSci
Project team	Professor Hugh Bostock MA DPhil Professor Mike G Hanna BSc FRCP
Location	UCL Institute of Neurology, London.
Duration	Two years
Grant awarded	18 July 2008
Start date	1 January 2009
End date	31 August 2012
Grant amount	£152,934.00
Grant code	SP4339, GN1725

This project brings together three expert investigators. All three are at the top of their speciality worldwide.

The project leader, Professor Kullmann, leads a world-class research team, studying the fundamental processes that underlie electrical signalling by nerve cells. He has collaborated for over 10 years with Professor Hanna to investigate how signalling is disturbed by changes in ion channels.

Professor Hanna, a Consultant Neurologist, treats people from all over the country at a national referral centre. More patients with episodic ataxia have been identified at this centre than at any other centre in the world.

The third member of the team, Professor Bostock, has pioneered the radically new approach that is being used in this study to measure how ion channels work in the intact nerves of affected and unaffected volunteers.

Close collaboration and complementary expertise mean this expert project team is uniquely placed to succeed.

Who stands to benefit from this research and how?

A cutting-edge approach to diagnosis

The radical technique that’s being used in this research could prove useful as a completely new and non-invasive diagnostic tool. Researchers envisage it would work by matching distinct patterns of nerve excitability to specific changes in ion channels.

A new diagnostic tool could be particularly beneficial for people whose symptoms are too ambiguous to allow a definitive diagnosis. It could, in principle, also help when assessing someone’s response to treatment.

Researchers hope their work will also boost understanding of how changes in ion channels cause disease. This may ultimately help in the development of badly needed new treatments.

The immediate impact of the research project is restricted to people with episodic ataxia who have mutations in genes for ion channels. However, this study could have important implications for many more people with much more common disorders of the nervous system, such as epilepsy, which is estimated to affect 0.5-1% of the population, or migraine, which affects 15%.1,2 The potential impact of this research could be far reaching indeed.