Epilepsy, migraine and episodic ataxia: a new window on nerve excitability
First published on 21 July 2008
Updated on 28 July 2014
What did the project achieve?
“We have demonstrated that a completely new test helps when diagnosing certain genetic diseases of the nervous system,” says Professor Dimitri Kullmann of University College London Institute of Neurology.
“Our new test can speed up diagnosis,” continues Professor Kullmann. “It can also give people more specific information about exactly what’s wrong by discriminating between different genetic disorders that cause similar symptoms. These include epilepsy and certain other disorders that cause problems coordinating movement. The new test involves administering harmless electrical pulses to a nerve in the wrist and recording the response in the muscle at the base of the thumb.”
People with a rare, inherited condition called episodic ataxia – which causes attacks of poor coordination and balance, and difficulties with speech, for example – took part in this study, but the findings could eventually benefit people with more common conditions too, including epilepsy.
“Our work has improved understanding of how genetic changes can alter the way nerves function,” says Professor Kullmann. “This has enabled us to secure a major grant from the Medical Research Council to develop an experimental treatment for epilepsy, which we hope will benefit people who carry on having seizures despite trying existing medications.”
Around 30 per cent of people with epilepsy find existing medicines don’t work properly for them.1 A new medicine that stops these people from experiencing seizures could improve their lives considerably.
1. NHS Choices. Epilepsy. http://www.nhs.uk/conditions/Epilepsy/Pages/Introduction.aspx Website accessed 20 May 2014.
This research was completed on 31 December 2012
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?
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?
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|
|Location||UCL Institute of Neurology, London.|
|Grant awarded||18 July 2008|
|Start date||1 January 2009|
|End date||31 December 2012|
|Grant code||SP4339, GN1725|
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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.
- NICE epilepsy guidelines 2004.
- Goadsby PJ, Lipton RB, Ferrari M.D. Migraine — Current Understanding and Treatment. N Engl J Med 2002; 346:257-270.