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The largest neuroimaging study of people with epilepsy, which involved almost 4,000 people across Europe, North and South America, Asia and Australia, has revealed that epilepsy involves more widespread physical differences than previously assumed.

These structural changes were even noted among people with idiopathic generalised epilepsies, a type of epilepsy characterised by a lack of any noticeable changes in the brain, such that typically an experienced neuroradiologist would not be able to see anything unusual in their brain scans.

This study was carried out by researchers at RCSI in partnership with UCL and the Keck School of Medicine of USC, indicating an association between epilepsy and the thickness and volume differences in the grey matter of several brain regions. Structural brain measures were extracted from MRI brain scans of 2,149 people with epilepsy and then compared with 1,727 healthy controls.

Reduced grey matter thickness in parts of the brain’s outer layer (cortex) and reduced volume in subcortical brain regions in all epilepsy groups were noted in comparison with the control group. Reduced volume and thickness were associated with longer duration of epilepsy and people with epilepsy exhibited lower volume in the right thalamus – a region which relays sensory and motor signals, and has previously only been associated with certain epilepsies – and reduced thickness in the motor cortex, which controls the body’s movement.

The study’s first author, Dr Christopher Whelan, RCSI, commented: “Our study shows that although epilepsy is a highly heterogeneous disorder with dozens of different causes, presentations and treatments, multiple common forms of epilepsy do share similarities”.

Prof Sanjay Sisodiya (University College London), stated: “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”.

The authors have warned that more research is warranted to determine whether the patterns identified here are themselves responsible for epilepsy or a by-product of the disease; longitudinal and genetic studies could clarify some causes of the structural differences.

Dr Whelan explained: “Some of the differences we found were so subtle they could only be detected due to the large sample size that provided us with very robust, detailed data. We cannot currently disentangle cause from effect, but the study indicates which brain regions are important for further investigation”.

Prof Norman Delanty, Honorary Associate Professor at the RCSI Department of Molecular and Cellular Therapeutics and Consultant Neurologist at Beaumont Hospital, said: “This worldwide multi-centre initiative underscores the fact that epilepsy is more than just seizures, and also intuitively suggest that optimum seizure control, preferably complete seizure freedom, should be the goal for all patients”.

With over 100 clinicians, neuroscientists and bioinformaticians on five continents actively involved in the ENIGMA Epilepsy initiative, the researchers are optimistic about what the future may hold.

“Our hope is that the study has laid a foundation for meaningful new discoveries”, said Dr Whelan, “and has helped build lasting relationships that will allow us to combine our resources and address scientific questions with greater power than we could have done before”.

The research is published today in Brain.