Large International Study Finds Sex-Related Differences in Brain Structure Among Epilepsy Patients
A worldwide neuroimaging study of over 2,300 individuals found some sex-related differences in brain structural alterations in temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE), but no statistically significant sex-by-diagnosis interactions. The ENIGMA consortium study used cortical thickness and subcortical volume measurements across multiple international centers to overcome the sample-size limitations of prior single-center research. The findings suggest that known sex differences in epilepsy's clinical outcomes likely stem from biological or functional processes not fully captured by structural brain imaging alone.
Researchers from the ENIGMA consortium analyzed structural MRI data from 1,253 epilepsy patients and 1,077 healthy controls across international sites to investigate whether brain structural changes in epilepsy differ by sex. In temporal lobe epilepsy, both male and female patients showed widespread cortical thinning and subcortical volume reductions compared to controls, with some variation in the regional distribution between sexes. In genetic generalized epilepsy, a more pronounced pattern emerged: female patients exhibited broader structural alterations relative to controls, while male patients showed only subtle changes. Despite these descriptive differences, formal statistical testing found no significant sex-by-diagnosis interaction effects in either epilepsy type, nor were significant interactions found between sex and age of onset or disease duration. The authors conclude that while structural neuroimaging reveals some sex-related variation, the well-documented sex differences in seizure types, psychiatric comorbidities, and treatment responses in epilepsy likely involve mechanisms—such as hormonal, genetic, or functional factors—that structural MRI does not capture. The study's large, multi-center design addresses a key limitation of prior work but also highlights the need for complementary approaches beyond morphometric analysis.
What's missing
The study does not report whether patients were on antiseizure medications or which medications, which could confound structural brain measurements differently across sexes. Additionally, hormonal status (e.g., menstrual cycle phase, use of hormonal contraceptives, or menopausal status in female patients) is not addressed, despite being a plausible mediator of sex differences in epilepsy. The cross-sectional design precludes causal inference about whether structural differences precede or follow epilepsy onset.
What different sources said
- bioRxivCenter
Sex-related structural alterations across common epilepsies: a worldwide ENIGMA study
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