Sex-specific disease modifiers in juvenile myoclonic epilepsy

Shakeshaft, Amy and Panjwani, Naim and Collingwood, Amber and Crudgington, Holly and Hall, Anna and Andrade, Danielle M. and Beier, Christoph P. and Fong, Choong Yi and Gardella, Elena and Gesche, Joanna and Greenberg, David A. and Hamandi, Khalid and Koht, Jeanette and Lim, Kheng Seang and Moller, Rikke S. and Ng, Ching Ching and Orsini, Alessandro and Rees, Mark and Rubboli, Guido and Selmer, Kaja K. and Striano, Pasquale and Syvertsen, Marte and Thomas, Rhys H. and Zarubova, Jana and Richardson, Mark P. and Strug, Lisa J. and Pal, Deb K. (2022) Sex-specific disease modifiers in juvenile myoclonic epilepsy. Scientific Reports, 12 (1). ISSN 2045-2322, DOI

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Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.

Item Type: Article
Funders: Canadian Institutes of Health Research (CIHR) [Grant No: 201809FDN-407295 & 201503MOP-342469], UK Research & Innovation (UKRI) Medical Research Council UK (MRC) [Grant No: MR/N026063/1 & MR/K013998/1], NIHR Specialist Biomedical Research Centre for Mental Health of South London and Maudsley National Health Service Foundation Trust, UK Engineering and Physical Sciences Research Council, Centre for Predictive Modelling in Healthcare [Grant No: EP/N014391/1], DINOGMI Department of Excellence of MIUR 2018-2022, Wales BRAIN Unit, Welsh Government through Health and Care Research Wales, Biomarin srl, ENECTA srl, GW Pharmaceuticals, Kolfarma srl., Eisai Co Ltd, South-Eastern Regional Health Authority, Norway [Grant No: 2016129], Research Council of Norway [Grant No: 299266], Epilepsy Research UK, Health & Care Research Wales, Wales Gene Park, Abertawe Bro Morgannwg University NHS RD, UCB Pharma SA, Ohio State University, Odense University Hospital, University of Southern Denmark [Grant No: ]17/18517
Uncontrolled Keywords: Cortical Excitability; Seizure Precipitants; Photic-stimulation; Ovarian Hormones
Subjects: Q Science > Q Science (General)
T Technology > T Technology (General)
Divisions: Faculty of Medicine
Faculty of Science
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 04 Aug 2022 03:05
Last Modified: 04 Aug 2022 03:05

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