Study shows link between epilepsy and structural differences in grey matter

Largest-ever neuroimaging study of people with epilepsy shows that the condition involves more widespread physical differences than previously assumed

Research carried out by researchers at RCSI in partnership with UCL and the Keck School of Medicine of USC has revealed an association between epilepsy and the thickness and volume differences in the grey matter of several brain regions. The research is published today in Brain.

The largest-ever neuroimaging study of people with epilepsy, involving almost 4,000 people across Europe, North and South America, Asia and Australia, shows that epilepsy involves more widespread physical differences than previously assumed, even in types of epilepsy that are typically considered to be more benign if seizures are under control.

Conducted by the global ENIGMA-Epilepsy consortium, the study extracted structural brain measures MRI brain scans of 2,149 people with epilepsy, and compared with 1,727 healthy controls.

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. Reduced volume and thickness were associated with longer duration of epilepsy. Notably, 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.

“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,” said the study’s first author, Dr Christopher Whelan, RCSI.

These structural changes were even present among people with idiopathic generalized epilepsies, a type of epilepsy characterized 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.

According to the study’s senior author, Prof Sanjay Sisodiya (University College London):

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 realize, and now we need to do more research to understand the causes of these differences.

The authors caution that more research is needed 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 that:

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-center 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.”

RCSI is ranked among the top 250 (top 2%) of universities worldwide in the Times Higher Education World University Rankings (2018) and its research is ranked first in Ireland for citations. It is an international not-for-profit health sciences institution, with its headquarters in Dublin, focused on education and research to drive improvements in human health worldwide. RCSI is a signatory of the Athena SWAN Charter.