Macro-structural brainstem volumetry in generalized epilepsy: assessment of subcortical network involvement

Traditionally, Generalized Epilepsy (GE) is viewed as a thalamocortical network disorder; however, recent evidence highlights subcortical network involvement. This study aims to investigate volumetric changes in brainstem substructures (midbrain, pons, medulla oblongata) between GE patients and healthy controls using a multi-atlas-based segmentation method (MRICloud).

Twenty patients with chronic GE and 20 age- and sex-matched healthy controls were included. High-resolution 3T T1-weighted 3D MPRAGE MRI scans were analyzed using the MRICloud platform. The brainstem was segmented into the midbrain, pons, and medulla oblongata. Data were analyzed using Analysis of Covariance (ANCOVA) models, with Age, Sex, and Total Intracranial Volume (ICV) entered as covariates.

Significant volume reduction was observed in all brainstem structures in the GE group, even after adjusting for ICV and age (p < 0.001). Compared to controls, patients exhibited highly significant lower mean total volumes in the midbrain (8889 ± 216 vs. 9907 ± 248 mm³), pons (17087 ± 199 vs. 18323 ± 287 mm³), and medulla oblongata (5425 ± 104 vs. 5999 ± 144 mm³).

The anatomical basis of GE may involve a structural process encompassing the brainstem and affecting deep brain structures. The detected volume reduction in the medulla oblongata could be associated with a potential disruption in cardiorespiratory regulation. Further prospective studies are needed to elucidate the link between this condition and Sudden Unexpected Death in Epilepsy (SUDEP) mechanisms.