To quantify amygdala and hippocampal volumetric asymmetries in patients with drug-resistant epilepsy (DRE) and extra-medial temporal lesions (EMTLs), and to assess the prevalence of structural alterations relative to drug resistant temporal lobe epilepsy (TLE), extratemporal lobe epilepsy (ETLE), and healthy individuals.

Mesial temporal sclerosis is the canonical pathological substrate of TLE. EMTLs may secondarily alter amygdala and hippocampal volumes. Quantitative MRI asymmetry metrics can potentially improve lateralization and prognosis, yet the prevalence, directionality, and relevance of these changes in patients with EMTLs remain undefined.

Dual pathology with mesial temporal sclerosis was radiologically identified in 20.6% of EMTL cases, predominantly ipsilateral. Adjusted amygdala and hippocampal volumes did not differ significantly across groups and consistent amygdala atrophy was not observed. Left EMTL showed increased hippocampal asymmetry magnitude and a 39.6% prevalence of ipsilateral hippocampal atrophy, comparable to left TLE (34%). Right EMTL showed loss of the physiologic left-smaller-than-right hippocampal pattern, with hypertrophy in the right amygdala (40%), left amygdala (46.7%), and contralateral hippocampus (40%), as well as ipsilateral hippocampal atrophy in 26.7%.

We found mesial temporal volumetric changes in a significant proportion of EMTL patients. Directional, magnitude, and outlier-based analyses help disentangle coexisting atrophy and hypertrophy, revealing potential compensatory network-level changes in EMTL-associated DRE not previously identified.