Autoimmune epilepsy: Current research in Oxford
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A number of antibodies against different cell proteins have been detected in people with epilepsy but that does not automatically mean that these antibodies cause epilepsy. There are important questions to ask:
- Can the antibodies cause seizures themselves or are there other factors involved?
- Is the appearance of antibodies in the patient’s blood linked to the onset of the seizures, or do they appear later, perhaps as a response to the disease process or to treatment?
Bethan Lang and the Autoimmune Neurology Group, at the University of Oxford, have been trying to answer these questions, so that useful clinical tests for epilepsy-causing antibodies can be developed. In 2012, they were awarded an Epilepsy Research UK grant of £149,916 to progress their work. ERUK monies funded a study in which 232 adults with newly diagnosed focal-onset epilepsy provided blood samples that were tested for a large range of antibodies. Important details about each person’s seizures and medical history were also recorded to look for patterns associated with any particular antibodies that were identified.
The study is now complete and twenty people were found to have antibodies that are thought to play a role in epilepsy. Antibodies to brain proteins such as LGI1, CASPR2, NMDA receptors and GABA receptors were detected. These proteins are involved in maintaining the balance between excitation and inhibition of neurons in the brain, and it is known that too much excitation or too little inhibition can lead to epilepsy. Additionally, four other people had antibodies for which the target has not yet been identified. These results indicate that around 10% of people with epilepsy may benefit from immunotherapy rather than standard antiepileptic drug treatment.
Are there any visible/measurable characteristics that can help doctors identify people with autoimmune epilepsy?
Answering this question was another major aim of this study, and to do this the Oxford team collected detailed medical and social information from all the subjects. They also asked them to undergo cognitive assessments. Dr Ronan McGinty, Epilepsy Research Fellow, has now joined the team to analyse all of these data; to compare the results from the 24 antibody-positive cases with those of the remaining 208, to discover whether the presence of epilepsy-causing antibodies associates with particular clinical features. If so, this will enable doctors to identify early on the people for whom antibody testing may be most appropriate.
What is the significance of this study?
This work, which builds on previous efforts by both this group and others, is crucial because it further reinforces the validity of autoimmunity as a cause of epilepsy. The findings have already changed practice in Oxford where specific testing for antibodies to LGI1 and CASPR2 have become routine and this will no doubt be applied further afield. The study also revealed antibodies to unknown protein targets, which are being further investigated.
The clinical work (finding out if measurable characteristics are linked to the presence of epilepsy-causing antibodies) is particularly exciting, as the results could impact on clinical decision-making and improve the management of people with autoimmune epilepsy in the future.
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