Abstract Temporal lobe epilepsy (TLE) is associated with progressive neocortical thinning that may be prevented by resective surgery, but little knowledge exists on dynamic changes in the hippocampus. Here, we assessed progressive morphological changes of the hippocampus before and after TLE surgery. In this longitudinal case-control neuroimaging study, we included patients with unilateral drug-resistant TLE before (main cohort n=23; replication cohort n=81) or after (n=54) anterior temporal lobe resection and healthy volunteers (n=120) matched for age and sex. We compared hippocampal volumes and surface shape morphology on paired scans between groups using linear mixed effects models. We did not find accelerated atrophy of the ipsilateral hippocampus in chronic presurgical TLE (-2.1 µl/year) compared to normal aging (-3.6 µl/year, p=0.78). In contrast, there was progressive hypertrophy of the contralateral hippocampus before epilepsy surgery (+1.4 µl/year) compared to normal aging (-4.1 µl/year), which was further accelerated after surgery (+4.0 µl/year, p=0.01). We validated these findings in the replication cohort (n=81). Factors contributing to contralateral hippocampal hypertrophy included left-sided epilepsy lateralisation, ipsilateral hippocampal sclerosis, and visual memory encoding deficits before or after surgery. Conversely, a history of focal to bilateral tonic clonic seizures was associated with accelerated pre- and postsurgical atrophy of the contralateral hippocampus. Refractory TLE is associated with progressive hypertrophy of the contralateral hippocampus before and after resective surgery. These contralateral changes may represent compensatory plasticity that is related to pre- and postoperative disturbances in cognition, mainly affecting visual memory. In contrast to progressive cortical thinning, the ipsilateral hippocampus does not show additional atrophy in chronic TLE.
Buecheler et al. (2025) studied this question.