Review Sex differences in human epilepsy Ivanka Savic ⁎ Karolinska Institute, Department of Women's, Children's Health, Neurology Clinic Karolinska Hospital, Q2:07, SE-171 76 Stockholm, Sweden abstract article info Article history: Received 26 November 2013 Revised 5 April 2014 Accepted 9 April 2014 Available online xxxx Keywords: Brain Epilepsy MTLE Sex difference MRI In the majority of neuropsychiatric conditions, marked gender-based differences have been found in the epide- miology, clinical manifestations, and therapy of disease. Emerging data suggest that gender differences exist also in the epidemiology, and pathophysiology of epilepsy. The present review summarizes the current information regarding gender and epilepsy. These differences are regarded from the perspective of innate sex differences in cerebral morphology, structural and functional connections, and assuming that these differences may render men and women differently vulnerable to epileptogenicity. © 2014 Published by Elsevier Inc. Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Sex differences in the epidemiology of epilepsies in humans. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Cerebral sex differences in the healthy brain and the tentative mechanisms underlying these differences . . . . . . . . . . . . . . . . . . . . . . . 0 Possible implications of cerebral sex dimorphism for genetic generalized epilepsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Childhood absence epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Juvenile myoclonic epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Possible implications of cerebral sexual dimorphism for temporal lobe epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Sex differences in the amygdala connections — can they affect the ictal and interictal behaviors in patients with MTLE? . . . . . . . . . . . . . . 0 Psychiatric comorbidities with epilepsy — impact of gender . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Introduction Epileptic seizures are generated by specific cerebral networks. De- pending on the networks involved the semiology of seizures, as well as the interictal behavioral, cognitive, and emotional changes may vary. Dif- ferent regions in the brain seem to have a different propensity to gener- ate and sustain seizure activity in humans (Engel, 2013). During the last decade there has been a rapid increase of reports on sex differences in cerebral structure and function (Giedd et al., 2006; Savic, 2010). These new data highlight the possibility that in epilepsy, similarly to other neu- ropsychiatric conditions, epidemiological and phenomenological sex may exist, and that some of these differences may be explained by inher- ent sex differences in cerebral structure, connectivity, and function. Such differences are important to identify, as they may potentially offer valu- able information when trying to understand the mechanisms of epileptogenesis, and develop new treatment strategies. The present review discusses possible sex differences in epilepsy in humans addressing four different issues. First of all, is the general sensi- tivity to develop epileptic seizures different in women compared to men? Secondly, is there a sex difference in the epidemiology of various epilepsy syndromes? Third, given the described sex differences in Experimental Neurology xxx (2014) xxx–xxx ⁎ Fax: +46 8 517 773 49. E-mail address: ivanka.savic-berglund@ki.se. YEXNR-11700; No. of pages: 6; 4C: http://dx.doi.org/10.1016/j.expneurol.2014.04.009 0014-4886/© 2014 Published by Elsevier Inc. Contents lists available at ScienceDirect Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr Please cite this article as: Savic, I., Sex differences in human epilepsy, Exp. Neurol. (2014), http://dx.doi.org/10.1016/j.expneurol.2014.04.009