Increased facial asymmetry in focal epilepsies associated with unilateral lesions

The epilepsies are now conceptualized as network disruptions: focal epilepsies are considered to have network alterations in the hemisphere of seizure onset, whilst generalized epilepsies are considered to have bi-hemispheric network changes. Increasingly, many epilepsies are also considered to be neurodevelopmental disorders, with early changes in the brain underpinning seizure biology. The development of the structure of the face is influenced by complex molecular interactions between surface ectoderm and underlying developing forebrain and neural crest cells. This influence is likely to continue postnatally, given the evidence of facial growth changes over time in humans until at least 18 years of age. In this case-control study, we hypothesized that people with lateralized focal epilepsies (i.e. unilateral network changes) have an increased degree of facial asymmetry, compared with people with generalized epilepsies or controls without epilepsy. We applied three-dimensional stereophotogrammetry and dense surface models to evaluate facial asymmetry in people with epilepsy, aiming to generate new tools to explore pathophysiological mechanisms in epilepsy. We analysed neuroimaging data to explore the correlation between face and brain asymmetry. We consecutively recruited 859 people with epilepsy attending the epilepsy clinics at a tertiary referral centre. We used dense surface modelling of the full face and signature analyses of three-dimensional facial photographs to analyse facial differences between 378 cases and 205 healthy controls. Neuroimaging around the time of the facial photograph was available for 234 cases. We computed the brain asymmetry index between contralateral regions. Cases with focal symptomatic epilepsy associated with unilateral lesions showed greater facial asymmetry compared to controls (P = 0.0001, two-sample t-test). This finding was confirmed by linear regression analysis after controlling for age and gender. We also found a significant correlation between duration of illness and the brain asymmetry index of total average cortical thickness (r = -0.19, P = 0.0075) but not for total average surface area (r = 0.06, P = 0.3968). There was no significant correlation between facial asymmetry and asymmetry of regional cortical thickness or surface area. We propose that the greater facial asymmetry in cases with focal epilepsy caused by unilateral abnormality might be explained by early unilateral network disruption, and that this is independent of underlying brain asymmetry. Three-dimensional stereophotogrammetry and dense surface modelling are a novel powerful phenotyping tool in epilepsy that may permit greater understanding of pathophysiology in epilepsy, and generate further insights into the development of cerebral networks underlying epilepsy, and the genetics of facial and neural development.