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

Brain. 2023 Jun 1;146(6):2389-2398. doi: 10.1093/brain/awac437.

Authors

Carolina Ferreira-Atuesta^{1

2

3}, Jane de Tisi^{1

2}, Andrew W McEvoy^{1

2}, Anna Miserocchi^{1

2}, Jean Khoury⁴, Ruta Yardi⁴, Deborah T Vegh⁴, James Butler⁵, Hamin J Lee⁵, Victoria Deli-Peri⁵, Yi Yao^{6

7}, Feng-Peng Wang⁷, Xiao-Bin Zhang⁷, Lubna Shakhatreh^{8

9

10}, Pakeeran Siriratnam¹⁰, Andrew Neal^{8

9

10}, Arjune Sen^{11

12}, Maggie Tristram^{11

12}, Elizabeth Varghese¹³, Wendy Biney¹³, William P Gray¹⁴, Ana Rita Peralta^{15

16}, Alexandre Rainha-Campos^{15

16}, António J C Gonçalves-Ferreira^{15

16}, José Pimentel^{15

16}, Juan Fernando Arias¹⁷, Samuel Terman¹⁸, Robert Terziev¹⁹, Herm J Lamberink^{20

21}, Kees P J Braun²², Willem M Otte²², Fergus J Rugg-Gunn^{1

2}, Walter Gonzalez¹⁷, Carla Bentes^{15

16}, Khalid Hamandi¹⁴, Terence J O'Brien^{8

9}, Piero Perucca^{8

9

10

22

23}, Chen Yao^{24

25}, Richard J Burman^{5

11

12}, Lara Jehi⁴, John S Duncan^{1

2}, Josemir W Sander^{1

2

26

27}, Matthias Koepp^{1

2}, Marian Galovic^{1

2

19}

Affiliations

¹ Department of Clinical and Experimental Epilepsy (DCEE), NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
² Chalfont Centre for Epilepsy, Chalfont St Peter, Bucks SL9 0RJ, UK.
³ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁴ Cleveland Clinic Epilepsy Center, Cleveland, OH 44195, USA.
⁵ Constantiaberg Mediclinic Hospital, Division of Neurology, Neuroscience Institute, University of Cape Town, Cape Town 7800, South Africa.
⁶ Department of Epilepsy Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong 518048, China.
⁷ Department of Functional Neurosurgery, Xiamen Humanity Hospital, Xiamen, FuJian 361016, China.
⁸ Department of Neuroscience, Central Clinical School, Alfred Health, Monash University, Level 6, Melbourne, Victoria 3000, Australia.
⁹ Departments of Medicine and Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia.
¹⁰ Department of Neurology, Alfred Health, Melbourne, Victoria 3000, Australia.
¹¹ Oxford Epilepsy Research Group, NIHR Biomedical Research Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 7BN, UK.
¹² Department of Neurology, 3rd Floor, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, UK.
¹³ Department of Neurology, University Hospital of Wales, Cardiff CF14 4XW, UK.
¹⁴ The Wales Epilepsy Unit, Department of Neurology, University Hospital of Wales, Cardiff CF14 4XW, UK.
¹⁵ Division of Psychological Medicine and Clinical Neurosciences Cardiff, Cardiff University, Cardiff CF14 4XW, UK.
¹⁶ Centro de Referência para Epilepsias Refratárias (member of EpiCare), Hospital de Santa Maria-Centro Hospitalar Universitário Lisboa Norte, Centro de Estudos Egas Moniz, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
¹⁷ Epilepsy Center, Instituto Roosevelt, Bogotá 472, Colombia.
¹⁸ University of Michigan Department of Neurology, Ann Arbor, MI 48109, USA.
¹⁹ Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, CH-8006 Zurich, Switzerland.
²⁰ Department of Neurology, Haaglanden Medical Center, The Hague 2512 VA, The Netherlands.
²¹ Department of Child Neurology, University Medical Center Utrecht, Utrecht 3508 GA, The Netherlands.
²² Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria 3084, Australia.
²³ Comprehensive Epilepsy Program, Austin Health, Heidelberg, Victoria 3084, Australia.
²⁴ Department of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong 518037, China.
²⁵ Shenzhen Epilepsy Center (Shenzhen Children's Hospital and Shenzhen Second People's Hospital), Shenzhen 518037, China.
²⁶ Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China.
²⁷ Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede 2103SW, The Netherlands.

PMID: 36415957
DOI: 10.1093/brain/awac437

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.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anticonvulsants / adverse effects
Epilepsies, Partial*
Epilepsy* / drug therapy
Epilepsy* / surgery
Epilepsy, Generalized* / drug therapy
Humans
Neoplasm Recurrence, Local / drug therapy
Seizures / drug therapy

Substances

Anticonvulsants