Introduction: In unilateral mesial temporal lobe epilepsy (TLE) the relation of ipsi- and contralateral amygdala and hippocampus volumes remains unclear. Here we used 3T MRI-volumetry to identify systematic differences between ipsi- and contralateral amygdala and hippocampus volumes with interictal and ictal intracerebral Stereo-EEG (sEEG) findings.

Methods: In 64 patients who underwent epilepsy surgery of unilateral TLE including resection of the amygdala and hippocampus between 07/2015 and 03/2023, presurgical amygdala and hippocampal volumes were reconstructed from 3T T1-weighted images. We created z-scores based on normative data from a scanner-specific sample of 781 healthy controls using a generalized additive model. Z-scores of the amygdala and the hippocampus ipsi- and contralateral to the epileptic focus were validated by postsurgical histopathology. sEEG was evaluated if available.

Results: Fifty-five out of 64 patients had histopathologically proven hippocampal sclerosis (HS). Nine patients out of 64 had no mesial temporal lesion except hippocampal gliosis (HG) and gliosis of the amygdala. A mixed-effect model showed a significant interaction of groups (HG vs. HS) by side (ipsi- vs. contralateral) in terms of increased ipsilateral amygdala and hippocampus volumes in patients with HG and decreased ipsilateral amygdala and hippocampus volume in patients with HS. Volume increases were more pronounced in the amygdala whereas the volume decrease was more pronounced in the hippocampus. There were no significant deviations from the normal reference data in the contralateral amygdala or hippocampus.

In 16 patients (8/9 patients with HG), sEEG was recorded. All 16 patients had an ipsilateral mesial temporal seizure onset. The ipsilateral amygdala was part of the irritative zone (IZ) involved in the seizure onset zone (SOZ) or early seizure propagation (<2s) in all patients, but the ipsilateral amygdala was only enlarged in patients with HG.

Conclusion: An increase in ipsilateral mesial temporal volume, particularly pronounced at the amygdala, typically occurs in patients with HG. Ipsilateral volume reduction in HS, notably pronounced at the hippocampus, also involves the amygdala to a lesser extent. sEEG evidence supports the notion that an enlarged amygdala signifies its involvement in the SOZ or early seizure propagation in patients with HG.