Structural Brain Alterations Seen In Global Epilepsy Study

Epilepsy is associated with thickness and volume differences in the grey matter of several brain regions, according to new research led by UCL and the Keck School of Medicine of USC. The brain abnormalities the researchers identified were subtle, and have not yet been implicated in any loss of function.

The largest-ever neuroimaging study of people with epilepsy 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.

“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,”

said the study’s lead author, Professor Sanjay Sisodiya.

Reduced Grey Matter

The study was conducted by the global ENIGMA-Epilepsy consortium, part of ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) which is headquartered at the Keck School of Medicine of USC, and pooled data from 24 research centres across Europe, North and South America, Asia and Australia.

Structural brain measures were extracted 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. 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.

epilepsy Cortical thickness findings

Cortical thickness findings
Cohen’s d effect size estimates for case-control differences in cortical thickness, across the (A) all-epilepsies,
(B) mesial temporal lobe epilepsies with left hippocampal sclerosis (MTLE-L),
(C) mesial temporal lobe epilepsies with right hippocampal sclerosis (MTLE-R),
(D) idiopathic generalized epilepsies (IGE), and
(E) all-other-epilepsies groups. Cohen’s d effect sizes were extracted using multiple linear regressions, and pooled across research centres using random-effects meta-analysis.
Cortical structures with P-values < 1.49 × 10−4 are shown in heatmap colours; strength of heat map is determined by the size of the Cohen’s d (d < 0 = blue, d > 0 = yellow/red).
Credit: Christopher D Whelan, et al. CC-BY

These patterns were even present 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.

“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,”

said the study’s first author, Dr Christopher Whelan, of the Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC & Royal College of Surgeons in Ireland.

Common Neuroanatomical Signature

The researchers also identified differences between the subgroups, which they say must reflect differences in underlying biology, as suggested by recent genetic studies.

“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,”

Dr Whelan said.

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

“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,”

said Professor Sisodiya.

Christopher D Whelan, et al
Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study
Brain, awx341, https://doi.org/10.1093/brain/awx341

Image: Wellcome Images