Volumetric Analysis of Thalamic Nuclei in Epilepsy Patients: A Sex-Based Comparative Study

Background/Objectives: Epilepsy is a long-term condition marked by recurring seizures that greatly affect daily life. The thalamus, with its extensive connections to the cortex, plays a vital role in epileptic processes. Changes in the volume of the thalamic nuclei are believed to occur in epilepsy. Our study aimed to examine the volumetric characteristics of thalamic nuclei in individuals diagnosed with generalized epilepsy and to explore the potential role of changes in these nuclei in the process of epileptogenesis. Methods: In this retrospective study, a total of 232 participants were included in the study. 1.5T MRI images of epilepsy patients and age- and sex-matched healthy individuals were analyzed. Thalamus nucleus volumes were measured using the VolBrain automatic segmentation system. Right-left volumetric comparisons of homologous thalamic nuclei were performed within each study group to evaluate hemispheric lateralization patterns. Groups were compared based on sex. FDR correction and ANCOVA adjustment for ICV and age were applied; significance threshold was p < 0.05 after correction. Results: After applying false discovery rate (FDR) correction, significant differences were observed in multiple thalamic nuclei in the epilepsy group compared to controls. In women, volume increases were confirmed in the right VAN, bilateral VPLN, and left MGN, while bilateral MTN volumes were significantly reduced and right ISN volume was lower in the epilepsy group. In men, only bilateral MTN volumes remained significant after FDR correction; no nucleus survived after additional ANCOVA adjustment for intracranial volume and age. Right-left comparisons revealed consistent lateralization patterns, with AVN showing right-sided predominance and VAN showing left-sided predominance across both sexes after FDR correction. Conclusions: After correction for multiple comparisons and adjustment for intracranial volume and age, only a limited number of thalamic nuclei remained significantly altered, predominantly in female patients. These findings suggest that thalamic involvement in generalized epilepsy may be selective rather than widespread and may vary according to sex.