Predictors of brain atrophy in focal epilepsy

Epilepsy as a progressive disease is a topic of dispute, with only limited evidence supportive of a neurodegenerative hypothesis across structural etiologies other than hippocampal sclerosis.

We performed cross-sectional brain volumetry on T1-weighted MRI scans in 59 people with drug-resistant focal epilepsy (PWFE), who had undergone extensive evaluation at a tertiary epilepsy center and were compared to three independent age-and sex-matched healthy control cohorts. 36 (61%) PWFE showed structural pathologies such as malformations of cortical development, low-grade epilepsy-associated neuroepithelial tumours and hippocampal sclerosis or encephaloceles, 23 (19%) PWFE were MRI-negative.

59 PWFE (female/male: 25/34, mean age 32.4 years, SD: 10.5) presenting with a median seizure frequency score (SFS) of 7 (range 1-10) and mean epilepsy duration of 14.3 years (SD: 9.9) were compared to 59 healthy control subjects (f/m: 33/26, mean age 33.7 years, SD 9.9). Adjusted for effects of age and gender, cortical gray matter volume in PWFE with a high SFS (≥ 7) was decreased by 30.1 ml (CI: -46.92 ml - -13.34 ml, p < 0.001). Similar results were observed for total deep gray matter volume, decreasing -4.35 ml (CI: -6.13 ml - -2.58 ml, p < 0.001) and white matter volume -40.65 ml (CI: -57.70 ml - -23.59 ml, p = 0.001) in patients suffering from a high seizure frequency. This effect was not significantly influenced by the structural etiology, seizure severity, nor lesion location.

Widespread brain volume loss, exceeding that of normal aging, shows correlation with a high seizure frequency irrespective of structural etiology in focal epilepsy.