Abstracts

Rationale: Hippocampal and extrahippocampal structural abnormalities are frequently observed in temporal lobe epilepsy (TLE). The pathological mechanisms of these neuroimaging findings are not well understood. We aimed to define the genetic contribution to these neuroimaging traits by identifying shared morphological abnormalities in TLE patients and their asymptomatic siblings. Methods: We collected clinical, electrophysiological, and high-resolution structural neuroimaging data of 18 sporadic non-lesional TLE patients (12 right TLE, 6 left TLE), their 18 unaffected full siblings, and 18 matched healthy volunteers. We compared overall hippocampal volumes between groups and determined the subregional extent of hippocampal abnormalities using shape analysis, and whole-brain differences in cortical thickness and folding complexity. We corrected analyses for age, sex, level of education, and results of neuropsychological testing. Results: We detected significant (p<0.01) differences of hippocampal volumes in both groups, patients (left TLE: median volume ipsilateral hippocampus 2.23ml; interquartile range (IQR) 2.11-2.28; right TLE: ipsilateral hippocampus 1.92ml, IQR: 1.57-2.59) and their unaffected siblings (left hippocampus 2.47, IQR: 2.29-2.65; right hippocampus 2.65, 2.32-2.76) compared to healthy controls (left 2.82, 2.56-2.98; right 2.94, 2.77-3.24). Shape analysis demonstrated significant (p<0.05, corrected for multiple comparisons) subregional atrophy of both hippocampi (right>left) in TLE patients compared to healthy controls. The right lateral body and anterior head of the hippocampus were predominantly affected, corresponding to the right CA1 subfield and subiculum. Similarly, significant subregional atrophy was detected in siblings vs. controls, affecting the right lateral body and anterior head of the hippocampus, mainly involving the right CA1 subfield. Reduced cortical thickness in TLE patients was observed in the pericentral, frontal, and temporal areas, whereas cortical thinning was restricted to the right postcentral gyrus in unaffected siblings (p<0.05). Both TLE patients and asymptomatic siblings showed increased cortical folding complexity but in a diverging spatial distribution (predominant frontal in patients; predominant parieto-occipital in siblings; p<0.05). Conclusions: We detected shared hippocampal and cortical morphological abnormalities in TLE patients and their unaffected siblings. Our results suggest a shared genetic vulnerability that could represent a neuroimaging endophenotype of TLE, which might precede the onset of epilepsy in these individuals. Funding: National Natural Science Foundation of China (NSFC:81671300), Research Project of the Ministry of Science and Technology of China (2016YFC0904400), Xiangya Hospital Clinical Project (No. 2016L08)