Portal de Periódicos da CAPES

Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications

2023; Oxford University Press; Volume: 5; Issue: 3 Linguagem: Inglês

10.1093/braincomms/fcad182

2632-1297

Guido Rubboli, Christoph P. Beier, Kaja Kristine Selmer, Marte Syvertsen, Amy Shakeshaft, Amber Collingwood, Anna Hall, Danielle M. Andrade, Choong Yi Fong, Joanna Gesche, David A. Greenberg, Khalid Hamandi, Kheng Seang Lim, Ching Ching Ng, Alessandro Orsini, Lisa J. Strug, Naim Panjwani, Fan Lin, Danielle M. Andrade, Jana Zárubová, Zuzana Šobíšková, Cechovaz, Pracoviste, Michaela Kajšová, Guido Rubboli, Rikke S. Møller, Elena Gardella, Christoph P. Beier, Joanna Gesche, M Miranda, Inga Talvik, Pasquale Striano, Alessandro Orsini, Choong Yi Fong, Ching Ching Ng, Kheng Seang Lim, Kaja Kristine Selmer, Marte Syvertsen, Pronab Bala, Amy Kitching, Kate Irwin, Lorna Walding, Lynsey Adams, Uma Jegathasan, Rachel Swingler, Rachel Wane, Julia Aram, Nikil Sudarsan, Dee Mullan, Rebecca Ramsay, Vivien Richmond, M. Sargent, Paul Frattaroli, Matthew D. Taylor, Marie Home, Sal Uka, Susan Kilroy, Tonicha Nortcliffe, Kheng Seang Lim, Kelly Holroyd, Khalid Hamandi, Alison McQueen, Dympna Mcaleer, Dina Jayachandran, Dawn Egginton, Bridget MacDonald, Michael Chang, David Deekollu, Alok Gaurav, Caroline Hamilton, Jaya Natarajan Inyan Takon, Janet Cotta, Nick Moran, Jeremy D.P. Bland, Rosemary Belderbos, Heather Collier, Joanne Henry, Matthew J. Milner, Sam White, Michalis Koutroumanidis, William Stern, Mark P. Richardson, Jennifer M. Quirk, Javier Peña‐Ceballos, Anastasia, Papathanasiou, Ioannis Stavropoulos, Dora A. Lozsádi, Andrew Swain, Charlotte Quamina, Jennifer Crooks, Tahir Majeed, Sonia Raj, Shakeelah Patel, Michael C. Young, Melissa Maguire, Munni Ray, Caroline Peacey, Linetty Makawa, Asyah Chhibda, Eve Sacre, Shanaz Begum, Martin O’Malley, Lap Yeung, Claire Holliday, Louise Woodhead, Karen Helton Rhodes, Rhys H. Thomas, Shan Ellawela, Joanne Glenton, Verity Calder, John M. Davis, Paul McAlinden, Sarah Francis, Lisa Robson, Karen Lanyon, Graham A. Mackay, Elma Stephen, Coleen Thow, Margaret Connon, Martin Kirkpatrick, Susan MacFarlane, Anne Scott MacLeod, Debbie Rice, Siva Kumar, Carolyn Campbell, Vicky Collins, William Whitehouse, Christina Giavasi, Boyanka Petrova, Thomas D. Brown, Catie Picton, Michael O’Donoghue, Charlotte West, Helen Navarra, Sean Slaght, Catherine Edwards, Andrew Gribbin, Liz Nelson, Stephen Warriner, Heather Angus‐Leppan, Loveth Ehiorobo, Bintou Camara, T Samakomva, Rajiv Mohanraj, Victoria A. Parker, Rajesh K. Pandey, Lisa Charles, Catherine Cotter, Archana Desurkar, Alison Hyde, Rachel Harrison, Markus Reuber, R. T. Clegg, J Sidebottom, Mayeth Recto, Patrick Easton, Charlotte Waite, Alice Howell, Jacqueline Smith, R. T. Clegg, Shyam Mariguddi, Zena Haslam, Elizabeth Caruana Galizia, Hannah R. Cock, Mark Mencias, Samantha Truscott, Déirdre Daly, Hilda Mhandu, Nooria Said, Mark I. Rees, Seo‐Kyung Chung, William Owen Pickrell, Beata Fonferko‐Shadrach, Mark D. Baker, Amy B. Heagle, Louise Swain, Kirsty O’Brien, Fraser Scott, Naveed Ghaus, Gail Castle, Jacqui Bartholomew, Ann Needle, Julie Ball, Andrea Clough, Shashikiran Sastry, Charlotte Busby Amit Agrawal, Debbie Dickerson, Almu Duran, Muhammad Shamim Khan, Laura Thrasyvoulou, Eve Irvine, Sarah Tittensor, Jacqueline Daglish, Sumant Kumar, Claire Backhouse, Claire Mewies, Julia Aram, Nikil Sudarsan, Dee Mullan, Rebecca Ramsay, Vivien Richmond, Denise Skinner, M. Sargent, Rahul Bharat, Sarah-Jane Sharman, Arun Saraswatula, Helen Cockerill, David A. Greenberg, Pasquale Striano, Rhys H. Thomas, Jana Zarubova, Mark P. Richardson, Lisa J. Strug, Deb K. Pal,

Genetics and Neurodevelopmental Disorders

Abstract 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.