title: Timing of antiepileptic drug withdrawal and long-term seizure outcome after paediatric epilepsy surgery (TimeToStop): a retrospective observational study.
abstract: BACKGROUND
  Postoperative antiepileptic drug (AED) withdrawal practices remain debatable and little is known about the optimum timing. We hypothesised that early AED withdrawal does not affect long-term seizure outcome but allows identification of incomplete surgical success earlier than late withdrawal. We aimed to assess the relation between timing of AED withdrawal and subsequent seizure recurrence and long-term seizure outcome.
  
  
  METHODS
  TimeToStop included patients aged under 18 years from 15 centres in Europe who underwent surgery between Jan 1, 2000, and Oct 1, 2008, had at least 1 year of postoperative follow-up, and who started AED reduction after having reached postoperative seizure freedom. Time intervals from surgery to start of AED reduction (TTR) and complete discontinuation (TTD) were studied in relation to seizure recurrence during or after AED withdrawal, seizure freedom for at least 1 year, and cure (defined as being seizure free and off AEDs for at least 1 year) at latest follow-up. Cox proportional hazards regression models were adjusted for identified predictors of timing intervals.
  
  
  RESULTS
  TimeToStop included 766 children. Median TTR and TTD were 12·5 months (95% CI 11·9-13·2) and 28·8 months (27·4-30·2), respectively. 95 children had seizure recurrence during or after AED withdrawal. Shorter time intervals predicted seizure recurrence (hazard ratio [HR] 0·94, 95% CI 0·89-1·00, p=0·05 for TTR; and 0·90, 0·83-0·98, p=0·02 for TTD). After a mean postoperative follow-up of 61·6 months (SD 29·7), 728 patients were seizure free for at least 1 year. TTR and TTD were not related to regain of seizure freedom after restart of drug treatment (HR 0·98, 95% CI 0·92-1·05, p=0·62; and 0·93, 0·83-1·05, p=0·26, respectively), or to seizure freedom (0·97, 0·89-1·07, p=0·55; and 1·03, 0·93-1·14, p=0·55, respectively) or cure (0·97, 0·97-1·03, p=0·84; and 0·98, 0·94-1·02, p=0·31, respectively) at final follow-up.
  
  
  CONCLUSIONS
  Early AED withdrawal does not affect long-term seizure outcome or cure. It might unmask incomplete surgical success sooner, identifying children who need continuous drug treatment and preventing unnecessary continuation of AEDs in others. A prospective randomised trial is needed to study the possible cognitive effects and confirm the safety of early AED withdrawal after epilepsy surgery in children.
  
  
  BACKGROUND
  Dutch National Epilepsy Fund.
authors: Department of Child Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands.
authors: Kim
authors: K
authors: Boshuisen
authors: Alexis
authors: A
authors: Arzimanoglou
authors: J Helen
authors: JH
authors: Cross
authors: Cuno S P M
authors: CS
authors: Uiterwaal
authors: Tilman
authors: T
authors: Polster
authors: Onno
authors: O
authors: van Nieuwenhuizen
authors: Kees P J
authors: KP
authors: Braun
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy* / Q000601:surgery*; D005060:Europe / Q000453:epidemiology; D005260:Female; D038421:Hemispherectomy / Q000379:methods*; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000927:Anticonvulsants