The study, published in the journal Brain, 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.
The brain abnormalities researchers identified were subtle and have not yet been implicated in any loss of function.
"We found differences in brain matter even in common epilepsies that are often considered to be comparatively benign," said Sanjay Sisodiya professor at University College London in the UK.
Epilepsy is a neurological disorder that affects 0.6-1.5 per cent of the global population, comprising many different syndromes and conditions, and defined by a tendency for seizures.
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The study 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 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.
"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 Christopher Whelan from University of Southern California in the US.
The researchers also identified differences between the subgroups, which they say must reflect differences in underlying biology, as suggested by recent genetic studies.