Abstract
BACKGROUND: Mesial temporal lobe epilepsy (mTLE) is the most common form of focal epilepsy, often associated with hippocampal sclerosis. Increasing evidence suggests the pivotal role of neuroinflammation in mTLE onset and progression. METHODS: We used morphometric similarity network (MSN) analysis and the Allen Human Brain Atlas (AHBA) database to investigate structural changes between mTLE and healthy controls, as well as correlation with inflammation-related gene expression. RESULTS: We identified widespread alterations across the frontal and parietal lobes and cingulate cortex linked to neuroinflammatory genes such as PRR5, SMAD3, and IRF3. This correlation was even more pronounced in mTLE patients with hippocampal sclerosis compared to those without. Enrichment analysis highlighted pathways related to neurodevelopment and neurodegeneration, supporting a bidirectional link between mTLE and neurodegenerative diseases. CONCLUSIONS: These findings suggest that brain-wide macroscopic morphometric alternations in mTLE are correlated to the neuroinflammation process. It provides circumstantial evidence from a new perspective to support the bidirectional link between mTLE and neurodegenerative diseases.