ENIGMA study finds limited sex-specific structural brain differences in common epilepsies

An international multicenter ENIGMA study published in Epilepsia examined whether epilepsy-related brain structural alterations differ by clinician-assigned biological sex. Researchers analyzed cortical thickness and subcortical volumes in 1,253 patients with temporal lobe epilepsy (TLE) or genetic generalized epilepsy (GGE) and 1,077 healthy controls. They also assessed whether associations between structural measures and age at onset or disease duration varied by sex.

Sex-stratified analyses showed widespread cortical and subcortical alterations in both male and female patients with TLE. In GGE, alterations appeared more extensive in female patients and subtle in male patients. However, formal sex-by-diagnosis interactions were not significant in either epilepsy group after false-discovery-rate correction. Interactions between sex and age at onset or disease duration were also nonsignificant; all corrected p values exceeded .05.

These findings suggest that macroscale structural MRI measures do not strongly capture previously reported sex differences in epilepsy manifestations and outcomes. Differences observed in separate sex-stratified analyses should therefore not be interpreted as established differences between sexes. The authors propose hormonal, neurochemical, or functional-network mechanisms as possible explanations, but these were not established by the reported analyses. Only the abstract was available for assessment.