Changes in Hippocampal Volume after Traumatic Brain Injury (TBI).

Objective: To investigate hippocampal volume changes in moderate to severe traumatic brain injury (TBI) patients compared to healthy controls and assess their association with post-traumatic epilepsy (PTE), focusing on age-related effects.

Methods: Imaging and demographic data for TBI patients were obtained from the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) database; healthy controls matched by age and sex were sourced from Alzheimer's Disease Neuroimaging Initiative (ADNI), the National Institute of Mental Health (NIMH) Intramural Healthy Volunteer Dataset, the Parkinson's Progression Markers Initiative (PPMI), and the Autism Brain Imaging Data Exchange (ABIDE). MRI images for TBI subjects were obtained within 14-32 days post-injury. MRI data were preprocessed and segmented using FreeSurfer's recon-all pipeline and the hippocampal subfield segmentation module.

Results: TBI patients showed significantly smaller average hippocampal volumes than controls (β = -191.0, p = 8.33e-04, FDR p = 1.47e-03, Cohen's d = -0.36), notably in the right and left CA1 head regions. No significant hippocampal volume differences were found between TBI⁺ and TBI⁻ patients overall. In patients aged 60+, TBI⁺ patients had significantly larger volumes in the right CA1 head than TBI⁻ patients (β = 57.43, p = 0.0300, FDR p = 0.040; Cohen's d = 1.06).

Conclusion: Hippocampal atrophy is evident in TBI patients but not directly linked to PTE development in most age groups. In patients over 60, hypertrophy in the right CA1 head may be associated with PTE, suggesting age and regional hippocampal changes influence epilepsy risk post-TBI. These findings highlight the complexity of hippocampal involvement in PTE and suggest potential shared mechanisms with neurodegenerative disorders such as Alzheimer's disease.