Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults
Ferreira-Atuesta, Carolina; de Tisi, Jane; McEvoy, Andrew W; Miserocchi, Anna; Khoury, Jean; Yardi, Ruta; Vegh, Deborah T; Butler, James; Lee, Hamin J; Deli-Peri, Victoria; Yao, Yi; Wang, Feng-Peng; Zhang, Xiao-Bin; Shakhatreh, Lubna; Siriratnam, Pakeeran; Neal, Andrew; Sen, Arjune; Tristram, Maggie; Varghese, Elizabeth; Biney, Wendy; Gray, William P; Peralta, Ana Rita; Rainha-Campos, Alexandre; Gonçalves-Ferreira, António J C; Pimentel, José; Arias, Juan Fernando; Terman, Samuel; Terziev, Robert; Lamberink, Herm J; Braun, Kees P J; Otte, Willem M; Rugg-Gunn, Fergus J; Gonzalez, Walter; Bentes, Carla; Hamandi, Khalid; O'Brien, Terence J; Perucca, Piero; Yao, Chen; Burman, Richard J; Jehi, Lara; Duncan, John S; Sander, Josemir W; Koepp, Matthias; Galovic, Marian
(2023) Brain : a journal of neurology, volume 146, issue 6, pp. 2389 - 2398
(Article)
Abstract
More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in
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nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.
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Keywords: antiseizure medication, epilepsy, epilepsy surgery, prognosis, withdrawal, Clinical Neurology, Journal Article
ISSN: 0006-8950
Publisher: Oxford University Press
Note: Funding Information: C.F.A. and M.G. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This work was carried out at University College London Hospitals Comprehensive Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health's National Institute for Health Research centres funding scheme. A.S. is supported by the NIHR Oxford Biomedical Research Centre. The RACP Foundation Margorie Hooper Scholarship supports A.K. J.W.S. receives support from the Dr Marvin Weil Epilepsy Research Fund, UK Epilepsy Society, Christelijke Vereniging voor de Verplegingvan Lijders aan Epilepsie (Netherlands). Special thanks to Harry Marr BSc (Senior Director of Software Engineering at GitHub) for his technical assistance in creating the website. No compensation was provided, and permission granted to include his name. Funding Information: M.G. reports fees and travel support from Bial pharmaceutical and Nestlé Health Science outside the submitted work. P.P. has received speaker honoraria or consultancy fees to his institution from Chiesi, Eisai, LivaNova, Novartis, Sun Pharma, Supernus and UCB Pharma, outside the submitted work. He is an Associate Editor for Epilepsia Open. J.S.D. is on the Editorial Board of Annals of Neurology. J.W.S. has received speaker honoraria or consultancy fees from Eisai, UCB Pharma, Arvelle and Zogenix Pharma; grants from Eisai, UCB Pharma outside the submitted work and is on the Editorial Board of the Lancet Neurology, S.T. is supported by the Susan S. Spencer Clinical Research Training Scholarship and the Michigan Institute for Clinical and Health Research J Award no. UL1TR002240. Funding Information: C.F.A. and M.G. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This work was carried out at University College London Hospitals Comprehensive Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health’s National Institute for Health Research centres funding scheme. A.S. is supported by the NIHR Oxford Biomedical Research Centre. The RACP Foundation Margorie Hooper Scholarship supports A.K. J.W.S. receives support from the Dr Marvin Weil Epilepsy Research Fund, UK Epilepsy Society, Christelijke Vereniging voor de Verplegingvan Lijders aan Epilepsie (Netherlands). Special thanks to Harry Marr BSc (Senior Director of Software Engineering at GitHub) for his technical assistance in creating the website. No compensation was provided, and permission granted to include his name. Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
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