Building Momentum: Autoimmune associated epilepsy

In this Research Blog, we catch up with Professor Sarosh Irani and Professor Arjune Sen from the University of Oxford. Thanks to funding from Epilepsy Research UK, the research group, led by Professor Bethan Lang, helped provide evidence for a link between autoimmunity and specific types of epilepsy with implications for new, targeted treatment options. Here, Professor Irani and Professor Sen explain how the group helped build research momentum in this area.

Professor Lang said “when we first suggested that autoimmunity could have a role in epilepsy, we were told that it was unlikely and we were roundly dismissed. But through the foresight of Epilepsy Research UK’s funding in 2008 and 2012, we have been able to show that autoimmune antibodies (autoantibodies) do play an important role in some forms of epilepsy.”

The International League Against Epilepsy now recognise ‘immune’ causes of seizures in the most recent classifications of epilepsy. Studies in patients with very frequent seizure syndromes – often diagnosed with autoimmune encephalitis (brain swelling) – have shown that treatments with medications that modulate the immune system are highly effectively used to treat some forms of seizures. The aim of this study was to ask how frequently this occurred in unselected people first presenting with epilepsy.

But how exactly is the immune system linked to epilepsy?

The immune system normally protects a person from invading infections and viruses. Amongst other protective factors, it produces antibodies that recognise infections as foreign and neutralises them. This is part of how we acquire immunity to infections and viruses, such as COVID-19.

Sometimes the immune system becomes over-excited and, in error, antibodies are made against a target in our own tissues, rather than against the infection. If this “autoimmune” reaction is against targets in the brain, the autoantibodies can lead to seizures.

Through a study funded by Epilepsy Research UK, we were able to show that autoantibodies against certain brain proteins were present in several people with epilepsy. We did this by enrolling over 200 people with different epilepsies and collated their clinical histories, routine test results and antibody status. Our analysis found evidence of seizure causing autoantibodies in around 10% of our cohort.

We found that these 10% with new-onset focal epilepsies who had detectable autoantibodies presented with similar, but milder, clinical features to individuals with encephalitis. Due to this, we believe that people with these clinical features and autoantibodies may have a mild form of encephalitis.

What does this mean for people living with epilepsy?

Importantly, we found that people with seizure causing autoantibodies often responded well to medications that suppress the immune system, such as steroids, rather than traditional antiseizure medication. Furthermore, if autoantibodies are found to be the underlying cause of some epilepsies, drugs that target these antibodies can potentially be developed, and these are likely to also prove more effective in controlling seizures than antiseizure medication. If successful, this could help to avoid the unnecessary long-term use of antiseizure medication which can associate with significant side effects.

Thanks to the foresight of ERUK, this research has already led to significant change in clinical practice, in that we are able to use tests for specific autoantibodies linked to epilepsy, so we can ensure the correct and appropriate treatment is administered as soon as possible. In addition, these autoantibodies are often considered the causative agents, hence allowing people with epilepsy to understand the actual underlying cause of their condition.

What’s next?

We are now investigating how far these findings extend to people with other forms of seizures. This would help clinicians identify who might benefit from immunomodulatory therapy and focus their treatments on the seizure causing autoantibodies.

-Professor Arjune Sen & Professor Sarosh Irani