Abstract
Objective
To examine the shared familial contribution to hippocampal and extrahippocampal morphological abnormalities in patients with sporadic temporal lobe epilepsy (TLE) and their unaffected siblings.
Methods
We collected clinical, electrophysiological, and T1‐weighted magnetic resonance imaging (MRI) data of 18 sporadic patients with TLE without lesions other than hippocampal sclerosis (12 right, 6 left), their 18 unaffected full siblings, and 18 matched healthy volunteers. We compared between‐group differences in cortical thickness and volumes of five subcortical areas (hippocampus, amygdala, thalamus, putamen, and pallidum). We determined the subregional extent of hippocampal abnormalities using surface shape analysis. All our imaging results were corrected for multiple comparisons using random field theory.
Results
We detected smaller hippocampal volumes in patients (right TLE: median right hippocampus 1.92 mL, interquartile range [IQR] 1.39‐2.62, P < .001; left TLE: left hippocampus 2.05 mL, IQR 1.99‐2.33, P = .01) and their unaffected siblings (right hippocampus 2.65 mL, IQR 2.32‐2.80, P < .001; left hippocampus 2.39 mL, IQR 2.18‐2.53, P < .001) compared to healthy controls (right hippocampus 2.94 mL, IQR 2.77‐3.24; left hippocampus 2.71 mL, IQR 2.37‐2.89). Surface shape analysis showed that patients with TLE had bilateral subregional atrophy in both hippocampi (right > left). Similar but less‐pronounced subregional atrophy was detected in the right hippocampus of unaffected siblings. Patients with TLE had reduced cortical thickness in bilateral premotor/prefrontal cortices and the right precentral gyrus. Siblings did not show abnormalities in cortical or subcortical areas other than the hippocampus.
Significance
Our results demonstrate a shared vulnerability of the hippocampus in both patients with TLE and their unaffected siblings, pointing to a contribution of familial factors to hippocampal atrophy. This neuroimaging trait could represent an endophenotype of TLE, which might precede the onset of epilepsy in some individuals.
MAR