Distinct Medial Temporal Volumetric Signatures in Extra-medial Temporal Lobe Lesional Epilepsy
Yonatan Serlin1, Bijal Patel2, Elena Hayday3, Alexandrea Kilgore-Gomez4, Tianxia Wu1, Shareena Rahman5, William Theodore1, Sara Inati1
1NIH, 2Bijal Patel, 3University of Minnesota, 4University of Nevada, Reno School of Medicine, 5University of Alabama at Birmingham
Objective:

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.

Background:

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.

Design/Methods:
Retrospective cross-sectional study of 298 participants evaluated at the NIH Clinical Center (2004-2023), including 252 patients with focal DRE and 46 healthy volunteers. Of the DRE cohort, 63 had lateralized EMTL (48 left, 15 right). High-resolution brain MRIs were segmented and analyzed to obtain normalized amygdala and hippocampal volumes. An asymmetry index (AI) assessed directionality, and absolute AI measured magnitude. Atrophy and hypertrophy were defined relative to healthy medians using robust dispersion thresholds. Group comparisons incorporated correction for multiple testing.
Results:

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%.

Conclusions:

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.

10.1212/WNL.0000000000215205
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