Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults

Carolina Ferreira-Atuesta; Jane de Tisi; Andrew W McEvoy; Anna Miserocchi; Jean Khoury; Ruta Yardi; Deborah T Vegh; James Butler; Hamin J Lee; Victoria Deli-Peri; Yi Yao; Feng-Peng Wang; Xiao-Bin Zhang; Lubna Shakhatreh; Pakeeran Siriratnam; Andrew Neal; Arjune Sen; Maggie Tristram; Elizabeth Varghese; Wendy Biney; William P Gray; Ana Rita Peralta; Alexandre Rainha-Campos; António J C Gonçalves-Ferreira; José Pimentel; Juan Fernando Arias; Samuel Terman; Robert Terziev; Herm J Lamberink; Kees P J Braun; Willem M Otte; Fergus J Rugg-Gunn; Walter Gonzalez; Carla Bentes; Khalid Hamandi; Terence J O'Brien; Piero Perucca; Chen Yao; Richard J Burman; Lara Jehi; John S Duncan; Josemir W Sander; Matthias Koepp; Marian Galovic

doi:10.1093/brain/awac437

Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults

Carolina Ferreira-Atuesta, Jane de Tisi, Andrew W McEvoy, Anna Miserocchi, Jean Khoury, Ruta Yardi, Deborah T Vegh, James Butler, Hamin J Lee, Victoria Deli-Peri, Yi Yao, Feng-Peng Wang, Xiao-Bin Zhang, Lubna Shakhatreh, Pakeeran Siriratnam, Andrew Neal, Arjune Sen, Maggie Tristram, Elizabeth Varghese, Wendy BineyWilliam P Gray, Ana Rita Peralta, Alexandre Rainha-Campos, António J C Gonçalves-Ferreira, José Pimentel, Juan Fernando Arias, Samuel Terman, Robert Terziev, Herm J Lamberink, Kees P J Braun, Willem M Otte, Fergus J Rugg-Gunn, Walter Gonzalez, Carla Bentes, Khalid Hamandi, Terence J O'Brien, Piero Perucca, Chen Yao, Richard J Burman, Lara Jehi, John S Duncan, Josemir W Sander, Matthias Koepp, Marian Galovic^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 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.

Original language	English
Pages (from-to)	2389-2398
Number of pages	10
Journal	Brain : a journal of neurology
Volume	146
Issue number	6
Early online date	23 Nov 2022
DOIs	https://doi.org/10.1093/brain/awac437
Publication status	Published - 1 Jun 2023

Keywords

antiseizure medication
epilepsy
epilepsy surgery
prognosis
withdrawal

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10.1093/brain/awac437

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Ferreira-Atuesta, C., de Tisi, J., McEvoy, A. W., Miserocchi, A., Khoury, J., Yardi, R., Vegh, D. T., Butler, J., Lee, H. J., Deli-Peri, V., Yao, Y., Wang, F.-P., Zhang, X.-B., Shakhatreh, L., Siriratnam, P., Neal, A., Sen, A., Tristram, M., Varghese, E., ... Galovic, M. (2023). Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults. Brain : a journal of neurology, 146(6), 2389-2398. https://doi.org/10.1093/brain/awac437

@article{eca1c9cb3fb048faaafd0e646450bcd0,

title = "Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults",

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 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.",

keywords = "antiseizure medication, epilepsy, epilepsy surgery, prognosis, withdrawal",

author = "Carolina Ferreira-Atuesta and {de Tisi}, Jane and McEvoy, {Andrew W} and Anna Miserocchi and Jean Khoury and Ruta Yardi and Vegh, {Deborah T} and James Butler and Lee, {Hamin J} and Victoria Deli-Peri and Yi Yao and Feng-Peng Wang and Xiao-Bin Zhang and Lubna Shakhatreh and Pakeeran Siriratnam and Andrew Neal and Arjune Sen and Maggie Tristram and Elizabeth Varghese and Wendy Biney and Gray, {William P} and Peralta, {Ana Rita} and Alexandre Rainha-Campos and Gon{\c c}alves-Ferreira, {Ant{\'o}nio J C} and Jos{\'e} Pimentel and Arias, {Juan Fernando} and Samuel Terman and Robert Terziev and Lamberink, {Herm J} and Braun, {Kees P J} and Otte, {Willem M} and Rugg-Gunn, {Fergus J} and Walter Gonzalez and Carla Bentes and Khalid Hamandi and O'Brien, {Terence J} and Piero Perucca and Chen Yao and Burman, {Richard J} and Lara Jehi and Duncan, {John S} and Sander, {Josemir W} and Matthias Koepp and Marian Galovic",

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 Nestl{\'e} 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{\textquoteright}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: {\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.",

year = "2023",

month = jun,

day = "1",

doi = "10.1093/brain/awac437",

language = "English",

volume = "146",

pages = "2389--2398",

journal = "Brain : a journal of neurology",

issn = "0006-8950",

publisher = "Oxford University Press",

number = "6",

}

Ferreira-Atuesta, C, de Tisi, J, McEvoy, AW, Miserocchi, A, Khoury, J, Yardi, R, Vegh, DT, Butler, J, Lee, HJ, Deli-Peri, V, Yao, Y, Wang, F-P, Zhang, X-B, Shakhatreh, L, Siriratnam, P, Neal, A, Sen, A, Tristram, M, Varghese, E, Biney, W, Gray, WP, Peralta, AR, Rainha-Campos, A, Gonçalves-Ferreira, AJC, Pimentel, J, Arias, JF, Terman, S, Terziev, R, Lamberink, HJ, Braun, KPJ , Otte, WM, Rugg-Gunn, FJ, Gonzalez, W, Bentes, C, Hamandi, K, O'Brien, TJ, Perucca, P, Yao, C, Burman, RJ, Jehi, L, Duncan, JS, Sander, JW, Koepp, M & Galovic, M 2023, 'Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults', Brain : a journal of neurology, vol. 146, no. 6, pp. 2389-2398. https://doi.org/10.1093/brain/awac437

TY - JOUR

T1 - Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults

AU - Ferreira-Atuesta, Carolina

AU - de Tisi, Jane

AU - McEvoy, Andrew W

AU - Miserocchi, Anna

AU - Khoury, Jean

AU - Yardi, Ruta

AU - Vegh, Deborah T

AU - Butler, James

AU - Lee, Hamin J

AU - Deli-Peri, Victoria

AU - Yao, Yi

AU - Wang, Feng-Peng

AU - Zhang, Xiao-Bin

AU - Shakhatreh, Lubna

AU - Siriratnam, Pakeeran

AU - Neal, Andrew

AU - Sen, Arjune

AU - Tristram, Maggie

AU - Varghese, Elizabeth

AU - Biney, Wendy

AU - Gray, William P

AU - Peralta, Ana Rita

AU - Rainha-Campos, Alexandre

AU - Gonçalves-Ferreira, António J C

AU - Pimentel, José

AU - Arias, Juan Fernando

AU - Terman, Samuel

AU - Terziev, Robert

AU - Lamberink, Herm J

AU - Braun, Kees P J

AU - Otte, Willem M

AU - Rugg-Gunn, Fergus J

AU - Gonzalez, Walter

AU - Bentes, Carla

AU - Hamandi, Khalid

AU - O'Brien, Terence J

AU - Perucca, Piero

AU - Yao, Chen

AU - Burman, Richard J

AU - Jehi, Lara

AU - Duncan, John S

AU - Sander, Josemir W

AU - Koepp, Matthias

AU - Galovic, Marian

N1 - 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.

PY - 2023/6/1

Y1 - 2023/6/1

N2 - 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 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.

AB - 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 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.

KW - antiseizure medication

KW - epilepsy

KW - epilepsy surgery

KW - prognosis

KW - withdrawal

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U2 - 10.1093/brain/awac437

DO - 10.1093/brain/awac437

M3 - Article

C2 - 36415957

SN - 0006-8950

VL - 146

SP - 2389

EP - 2398

JO - Brain : a journal of neurology

JF - Brain : a journal of neurology

IS - 6

ER -

Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults

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