Sex-specific disease modifiers in juvenile myoclonic epilepsy
Document Type
Article
Publication Date
2-21-2022
Abstract
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.
Keywords
Cortical Excitability, Seizure Precipitants, Photic-stimulation, Ovarian Hormones
Divisions
fac_med,Science
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
Publication Title
Scientific Reports
Volume
12
Issue
1
Publisher
Nature Portfolio
Publisher Location
HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY