Evidence for a genetic effect in altered cortical surface area but not in cortical thinning in siblings of patients with mesial temporal lobe epilepsy

Although studies have shown cortical and subcortical changes in first‐degree relatives of patients with familial forms of temporal lobe epilepsy, few studies have addressed extrahippocampal morphology changes in unaffected siblings of patients with sporadic mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS). Alhusaini et al described subtle reduced cortical volumes in the anteromedial temporal cortex of asymptomatic siblings of sporadic MTLE‐HS patients, suggesting that such localized traits are possibly heritable. In this issue of Epilepsia, Yaakub et al replicated these findings in first‐ degree asymptomatic relatives of patients with MTLE‐ HS. A positive history of simple febrile convulsions before the age of 4 years was present in two relatives in this study. Both these relatives had values above the median of the relative group for the reduced surface area in the anteromedial temporal cortex, further strengthening the possibility that these subtle morphological changes are inherited. Limitations of this study include the small number of subjects studied and that they side‐flipped the images to increase power to detect differences, thus treating both hemispheres as if they were equal, which is not the case, as shown recently by Kong et al. The study by Alhusaini et al showed that the alterations of cortical morphology found in anteromedial regions of unaffected siblings of subjects with left MTLE‐HS (more in the left entorhinal cortex and parahippocampal gyrus) differed from those found in unaffected siblings of subjects with right MTLE‐HS (more in the right entorhinal cortex and temporal pole). It is of relevance that both studies used FreeSurfer (http://surfer.nmr.mgh.harvard.edu), which measures cortical volume as a product of two distinct aspects of the cortical architecture: cortical thickness and surface area. Cortical thickness and surface area measurements appear to represent different early neurodevelopmental events with distinct genetic influences, as shown by Panizzon et al in a magnetic resonance imaging study of twins. They found that, although cortical thickness and surface area are both highly heritable (>0.80), they are mostly unrelated genetically (genetic correlation = 0.08). These results suggest some independence of these two surface‐based measures, and potentially, their asymmetry patterns. A recent study that mapped cortical brain asymmetry in 17 141 healthy individuals showed regions with different asymmetrical patterns in cortical thickness and surface area and a significant heritability of these asymmetry characteristics. Effect sizes of cortical thickness and surface area were independent, and the asymmetry was generally more prominent for surface area compared with that of cortical thickness. Most regions showed significant asymmetry in surface area, although with no clear directional pattern affecting neighboring regions, or along the anterior‐posterior axis, as they observed for cortical thickness. Widespread cerebral cortical thinning has been identified in patients with MTLE as compared to healthy DOI: 10.1111/epi.14636