Rethinking cortical hypertrophy in temporal lobe epilepsy

Abstract

Epilepsy is one of the most common chronic neurological disorders, and temporal lobe epilepsy (TLE) is its most prevalent form in adults. Although TLE is classified as a focal epilepsy, it has traditionally been defined by hippocampal and extra-hippocampal atrophy. However, several studies also report regions of increased cortical thickness, or cortical hypertrophy, in TLE, challenging the notion that structural change in epilepsy is unidirectional. In this narrative review, we synthesize evidence for cortical hypertrophy in TLE and place these findings in a broader neurobiological context. We provide an overview of cortical thickness and MRI approaches used to measure it, highlighting differences between surface-based, volume-based, and voxel-based methods. We then review MRI studies reporting cortical hypertrophy in TLE, noting variability in affected regions, patient populations, and analytical techniques. We discuss potential mechanisms that may underlie cortical hypertrophy, including seizure-related structural remodeling, glial or inflammatory processes, compensatory neuroplasticity, network effects, and methodological limitations. Finally, we outline key gaps and controversies regarding the biological validity, temporal dynamics, and clinical relevance of cortical hypertrophy in TLE. We conclude that consideration of both cortical atrophy and hypertrophy may improve broader understanding of TLE as a disorder involving brain remodeling rather than isolated regional atrophy.