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Title: Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.
Austin Authors: 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
Affiliation: Department of Clinical and Experimental Epilepsy (DCEE), NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London, WC1N 3BGUK.
Cleveland Clinic Epilepsy Center, Cleveland, USA.
Constantiaberg Mediclinic Hospital, Division of Neurology, Neuroscience Institute, University of Cape Town, South Africa.
General Medicine
Department of Epilepsy Surgery, Shenzhen Children's Hospital, Shenzhen, Guangdong, China.
Department of Functional Neurosurgery, Xiamen Humanity Hospital, Xiamen, FuJian, China.
Department of Neuroscience, Central Clinical School, Alfred Health, Monash University, Level 6, Melbourne VIC 3000, Australia.
Neurology Department, Alfred Health, Melbourne, VIC 3000, Australia.
Oxford Epilepsy Research Group, NIHR Biomedical Research Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, UK.
Department of Neurology, University Hospital of Wales, Cardiff, CF144XW, UK.
The Wales Epilepsy Unit, Department of Neurology, University Hospital of Wales and Division of Psychological Medicine and Clinical Neurosciences Cardiff, Cardiff University, Cardiff, CF144XW, UK.
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, Lisboa, Portugal.
Epilepsy Center, Instituto Roosevelt, Bogota, Colombia.
University of Michigan Department of Neurology, Ann Arbor, MI 48109, USA.
Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands.
Department of Child Neurology, University Medical Center Utrecht, Utrecht, The Netherlands.
The Wales Epilepsy Unit, Department of Neurology, University Hospital of Wales and Division of Psychological Medicine and Clinical Neurosciences Cardiff, Cardiff University, Cardiff, CF144XW, UK.
Department of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China.
Issue Date: 1-Jun-2023
Date: 2022
Publication information: Brain: a Journal of Neurology 2023; 146(6)
Abstract: More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications (ASMs). We aimed to identify predictors of seizure recurrence after starting postoperative ASM 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 ASM withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting ASM 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 ASM withdrawal were focal non motor-aware seizures after surgery and before withdrawal (adjusted hazards 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 ASM withdrawal (aHR 0.9, 95% CI 0.8-0.9), and number of ASMs 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 (, can provide probabilities of seizure outcomes after starting postoperative ASMs withdrawal. These multicentre-validated models may assist clinicians when discussing ASM withdrawal after surgery with their patients.
DOI: 10.1093/brain/awac437
ORCID: 0000-0001-7595-8887
Journal: Brain
PubMed URL: 36415957
ISSN: 1460-2156
Type: Journal Article
Subjects: antiseizure medication
epilepsy surgery
Appears in Collections:Journal articles

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