Sex-related structural alterations across common epilepsies: a worldwide ENIGMA study.
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Wen Huantao, Wan Bin, Gholipour Taha, Xie Ke, Chen Judy, Serio Bianca, Hettwer Meike D, Alvim Marina K M, Arienzo Donatello, João Rafael Batista, Bauer Tobias, Bernasconi Andrea, Bernasconi Neda, Bonanni Paolo, Caligiuri Maria Eugenia, Cendes Fernando, Christin Raphaël, Concha Luis, Dascal Arielle, Boyd Edward Davoodi, Devinsky Orrin, Focke Niels K N, Fortunato Francesco, Galovic Marian, Gambardella Antonio, Guerrini Renzo, Hatton Sean N, Iliza Mirana, Inati Sara, Ives-Deliperi Victoria, Juster Robert-Paul, Kleen Jonathan K, Koubeissi Mohamad Z, Labate Angelo, Larivière Sara, Law Meng, Lenge Matteo, Meletti Stefano, Moloney Patrick B, Naish Marlo, Ngo Alexander, O'Brien Terence J, Pana Raluca, Panzeri Sofia, Pardoe Heath, Rauf Erik H U, Riva Antonella, Rodríguez-Cruces Raúl, Royer Jessica, Rüber Theodor, Sahlas Ella, Scárdua-Silva Lucas, Schubert Kai Michael, Sepeta Leigh N, Severino Mariasavina, Sinclair Benjamin, Soltanian-Zadeh Hamid, Stoub Travis, Striano Pasquale, Thomopoulos Sophia I, Valientes Nina V, Vaudano Anna Elisabetta, Vivash Lucy, Yasuda Clarissa L, Thompson Paul M, Sisodiya Sanjay M, McDonald Carrie R, Bernhardt Boris C, Valk Sofie L
Аннотация
Epilepsy is characterized by widespread structural brain alterations extending beyond the epileptic zone, involving both cortical and subcortical regions. Importantly, the clinical manifestation of epilepsy, including seizure types, psychiatric comorbidities, and treatment responses, has been shown to differ between sexes. However, sex differences in structural alterations in epilepsy have been seldomly reported in neuroimaging studies, partly due to limited sample sizes and single-center designs. Here, we systematically investigated sex differences in common epilepsies and their related clinical variables using structural neuroimaging biomarkers in an international multi-center cohort of 1,253 epilepsy patients and 1,077 healthy controls. We studied cortical thickness and subcortical volume in two types of epilepsy: temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). Both male and female patients with TLE showed widespread cortical and subcortical thinning compared with controls. In GGE, when compared separately to controls, male patients showed only subtle structural alterations, whereas female patients exhibited more widespread structural alterations. Sex-stratified analyses revealed some variation in the extent and distribution of cortical thickness and subcortical volume alterations between male and female patients in both epilepsy cohorts. Yet, we did not find significant sex-by-diagnosis interaction effects in TLE and GGE. Similarly, no significant interaction effects were observed between sex and age of onset or disease duration in either patient group. Overall, although we observed some differences in regional cortical thickness and subcortical volume between male and female patients with epilepsy, we did not find significant sex-by-diagnosis interactions. Our findings indicate that sex differences in behavioral and clinical outcomes of epilepsy may involve biological or functional processes that require further investigation.