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19 January 2018

Epilepsy linked to subtle changes in brain volume and thickness


Latest research is throwing new light on how epilepsy affects the structure of the brain. And scientists hope that the findings could lead to a greater understanding of the condition.

Map of the world, projecte on to the human brain, shows centres around the world that took part in the research.
Brain map shows centres around the world that took part in the research.

Volume and thickness

The study, led by Epilepsy Society's director of genomics, Professor Sanjay Sisodiya, shows, in the largest study of its kind, that epilepsy affects the volume and thickness of certain regions of the brain.

The structural changes are very subtle and were even seen in people with idiopathic generalised epilepsies, a type of epilepsy characterised by a lack of any visible changes in the brain. Typically, an experienced neuroradiologist would not be able to see anything unusual in their brain scans.

No loss of function

The brain abnormalities have yet to be associated with any loss of function and Professor Sisodiya was quick to stress that they cannot be compared with the loss of brain tissue and shrinkage seen in degenerative diseases such as Alzheimer's and other dementias.

It is only by looking at the brain scans of a large group of people with epilepsy, compared to a group without the condition, that scientists have been able to identify common patterns and gain new insights.

Professor Sisodiya said: “We found differences in brain matter even in common epilepsies that are often considered to be comparatively benign. While we haven’t yet assessed the impact of these differences, our findings suggest there’s more to epilepsy than we realise, and now we need to do more research to understand the causes of these differences.”

Global research

The research has been led by University College London and University of South California and is the largest neuroimaging study of people with epilepsy. The results are published in Brain today (22 January 2018).

The study was conducted by the global ENIGMA-Epilepsy consortium, and pooled data from 24 research centres across Europe, North and South America, Asia and Australia.

Common patterns

Structural brain measures were taken from MRI brain scans of 2,149 people with epilepsy, and compared with 1,727 healthy controls. The epilepsy group was analysed together for common patterns, and divided into four subgroups to identify differences.

The team found reduced grey matter thickness in parts of the brain’s outer layer (cortex) and reduced volume in subcortical brain regions in all epilepsy groups when compared to the control group. The researchers also identified differences between subgroups, which they say must reflect differences in underlying biology, as suggested by recent genetic studies.

Cause of changes?

“From our study, we cannot tell whether the structural brain differences are caused by seizures, or perhaps an initial insult to the brain, or other consequences of seizures – nor do we know how this might progress over time. But by identifying these patterns, we are developing a neuroanatomical map showing which brain measures are key for further studies that could improve our understanding and treatment of the epilepsies,” continued Professor Sisodiya.

The study’s first author, Dr Christopher Whelan (USC & Royal College of Surgeons in Ireland), added: “We have identified a common neuroanatomical signature of epilepsy, across multiple epilepsy types. We found that structural changes are present in multiple brain regions, which informs our understanding of epilepsy as a network disorder.”

The authors say their findings need to be followed up by longitudinal and genetic studies which could clarify the cause of the structural differences.

Q&A with Professor Sanjay Sisodiya, lead author of the research paper and director of genomics at Epilepsy Society

Professor Sanjay Sisodiya is wearing a striped, white shirt and metallic rimmed glasses. He is slightly sideways on to the camera.

What are the causes of the structural changes that you have identified in the brain?

At the moment we don't know and this is why further longitudinal studies, over a number of years, are so important. This study is a snapshot of what is happening in the brains of those people who are part of the research.

We don't know whether the structural changes were pre-existing and perhaps predisposed the person to seizures; or if they were as a result of an injury to the brain or perhaps an inflammation of the brain; or if they have occurred as a result of ongoing epilepsy and seizures. We need to look at more brain tissue samples to try to understand what is happening.

We also need to find out which brain cells are involved in the changes.

Where will you get further brain tissue samples from?

We are currently looking at tissue samples from the Epilepsy Society Brain and Tissue Bank. Many people with epilepsy - and those without the condition - very generously donate their brains to us when they die, to enable us to carry out this sort of research.

Are you able to look at brain tissue donated by people who have undergone surgery for their epilepsy?

Yes, this is important, and we do, but this tells us only what is happening in one particular region of the brain.

Once you understand what is happening, will you be able to reverse the changes in the brain

If we find that the changes pre-date the epilepsy and that the person was born with structural differences in the brain, we will not be able to change that. Similarly, if the abnormalities are as a result of a brain injury or inflammation at the start of the epilepsy, we will probably not be able  to reverse the changes.

However, if we can see that the structural changes are happening slowly as part on ongoing epilepsy, this is where we may be able to affect with what is happening. And that is our next challenge, to work out how we can make a difference.

More information

Find out more about our research.

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