Progressive Hippocampal Volume Reduction Beyond Normal Aging in Temporal Lobe Epilepsy: A Longitudinal MRI Study

Recent neuroimaging studies have suggested that epilepsy may show progressive brain structural changes over time. However, longitudinal hippocampal volume changes in temporal lobe epilepsy (TLE) have not been adequately compared with those observed in normal aging. In this study, we enrolled 46 patients with unilateral TLE and 25 healthy controls with longitudinal structural MRI scans using the same scanner. Hippocampal volumes were quantified using the Hipposeg software, and the annual percentage volume reduction relative to baseline (%Reduction/year) was calculated for each hippocampus. Compared to healthy hippocampi (median -0.37% per year, IQR = 3.97), both ipsilateral (median -1.04% per year, IQR = 3.65) and contralateral (median -1.08% per year, IQR = 3.17) hippocampi in TLE showed significantly greater volume reduction over time (both p < 0.05). Furthermore, annual ipsilateral hippocampal volume reduction was significantly correlated with disease duration (Spearman's rs = 0.366, FDR-corrected p = 0.036), suggesting that hippocampal atrophy progresses more rapidly during the early stage after epilepsy onset. These findings indicate that hippocampal volume loss in TLE exceeds that expected from normal aging and provide further evidence supporting progressive structural alterations during the course of the disease. PLAIN LANGUAGE SUMMARY: Temporal lobe epilepsy may cause progressive changes in the brain beyond those expected from normal aging. Using repeated MRI scans, we found that the hippocampus showed greater volume loss over time in people with temporal lobe epilepsy than in healthy individuals. This volume loss occurred bilaterally and appeared to be greater during the earlier stages of the disease. These results provide further evidence supporting progressive structural brain changes in TLE and contribute to a better understanding of disease progression and abnormal brain aging in epilepsy.