TY - JOUR

T1 - Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy

T2 - a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications

AU - Rubboli, Guido

AU - Beier, Christoph P.

AU - Selmer, Kaja K.

AU - Syvertsen, Marte

AU - Shakeshaft, Amy

AU - Collingwood, Amber

AU - Hall, Anna

AU - Andrade, Danielle M.

AU - Fong, Choong Yi

AU - Gesche, Joanna

AU - Greenberg, David A.

AU - Hamandi, Khalid

AU - Lim, Kheng Seang

AU - Ng, Ching Ching

AU - Orsini, Alessandro

AU - Strug, Lisa

AU - Panjwani, Naim

AU - Lin, Fan

AU - Zarubova, Jana

AU - Šobíšková, Zuzana

AU - Cechovaz, null

AU - Pracoviste, null

AU - Kajsova, Michaela

AU - Rubboli, Guido

AU - Møller, Rikke S.

AU - Gardella, Elena

AU - Beier, Christoph P.

AU - Gesche, Joanna

AU - Miranda, Maria

AU - Talvik, Inga

AU - Striano, Pasquale

AU - Orsini, Alessandro

AU - Fong, Choong Yi

AU - Ng, Ching Ching

AU - Lim, Kheng Seang

AU - Selmer, Kaja K.

AU - Syvertsen, Marte

AU - Bala, Pronab

AU - Kitching, Amy

AU - Irwin, Kate

AU - Walding, Lorna

AU - Adams, Lynsey

AU - Jegathasan, Uma

AU - Swingler, Rachel

AU - Wane, Rachel

AU - Aram, Julia

AU - Sudarsan, Nikil

AU - Mullan, Dee

AU - Ramsay, Rebecca

AU - Khan, Muhammad

AU - BIOJUME Consortium

N1 - Funding Information: This work was supported by the Canadian Institutes of Health Research: Biology of Juvenile Myoclonic Epilepsy 201503MOP-342469 (D.K.P. and L.J.S.) and 201809FDN-407295 (L.J.S.); UK Medical Research Council, Centre for Neurodevelopmental Disorders MR/N026063/1 (D.K.P. and M.P.R.); UK Medical Research Council, Programme grant MR/K013998/1 (M.P.R.); PhD stipend from UK Medical Research Council and the Sackler Institute for Translational Neurodevelopment (A.S.); National Institute for Health and Care Research Specialist Biomedical Research Centre for Mental Health of South London and Maudsley National Health Service Foundation Trust (D.K.P. and M.P.R.); UK Engineering and Physical Sciences Research Council, Centre for Predictive Modelling in Healthcare (EP/N014391/1) (M.P.R.); Grant 21/17483 from Region Southern Denmark (J.G.); Ministero della Salute - Ricerca corrente 2022; and DINOGMI. Dipartimento di Eccellenza MIUR 2018–2022 (P.S.). Funding Information: This work was supported by the Canadian Institutes of Health Research: Biology of Juvenile Myoclonic Epilepsy 201503MOP-342469 (D.K.P. and L.J.S.) and 201809FDN-407295 (L.J.S.); UK Medical Research Council, Centre for Neurodevelopmental Disorders MR/N026063/1 (D.K.P. and M.P.R.); UK Medical Research Council, Programme grant MR/K013998/1 (M.P.R.); PhD stipend from UK Medical Research Council and the Sackler Institute for Translational Neurodevelopment (A.S.); National Institute for Health and Care Research Specialist Biomedical Research Centre for Mental Health of South London and Maudsley National Health Service Foundation Trust (D.K.P. and M.P.R.); UK Engineering and Physical Sciences Research Council, Centre for Predictive Modelling in Healthcare (EP/N014391/1) (M.P.R.); Grant 21/17483 from Region Southern Denmark (J.G.); Ministero della Salute - Ricerca corrente 2022; and DINOGMI. Dipartimento di Eccellenza MIUR 2018-2022 (P.S.). Publisher Copyright: © 2023 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.

PY - 2023

Y1 - 2023

N2 - Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.

AB - Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.

KW - classification

KW - definition

KW - drug resistance

KW - juvenile myoclonic epilepsy

KW - prognosis

U2 - 10.1093/braincomms/fcad182

DO - 10.1093/braincomms/fcad182

M3 - Review

C2 - 37361715

AN - SCOPUS:85164387918

VL - 5

JO - Brain Communications

JF - Brain Communications

SN - 2632-1297

IS - 3

M1 - fcad182

ER -