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Epileptic Disorders - Editor's Choice

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December, 2014

Time to relapse after epilepsy surgery in children: AED withdrawal policies are a contributing factor.

Epileptic Disorders September 2014

Boshuisen et al.
Epileptic Disorders. 2014 Sep;16(3):305-11

Commentary by Pr. Michael Duchowny, Associate Editor
Director, Neurology Training and the Comprehensive Epilepsy Center
Miami Children's Hospital, Professor of Neurology and Pediatrics, University of Miami Miller School of Medicine
Florida, USA

Can the time course of seizure recurrence after epilepsy surgery in childhood be explained by operative or post-operative factors? This question has practical relevance as many children with intractable focal epilepsy who fail to become seizure-free after an excisional procedure return for further surgical consideration. Early postoperative seizure recurrence (generally regarded as occurring within the first six months) is traditionally believed to indicate a failure to fully excise the entire epileptogenic zone and structural lesion if found on MR imaging. Re-emergence of a postoperative seizure semiology that resembles the pre-operative pattern is believed to further implicate residual epileptic tissue in seizure persistence rather than a new independent seizure focus.

Until now there has been little interest in the specific role of post-operative AED withdrawal in promoting seizure recurrence. Indeed, studies of post-operative medical treatment have mainly focused on how long to continue treatment rather than examining any cause and effect relationship on seizure recurrence. Boshuisen and colleagues (1) set out to examine this issue in the Paediatric Epilepsy Surgery cohort of 95 patients from the “Time to Stop” study (2). Using multivariate analyses, they found that a shorter interval to AED reduction was the only independent predictor of a shorter time to relapse, revealing more rapidly whether surgery had the intended curative effect, independently of the other factors involved. It was also noted that univariate analysis identified incompleteness of resection of the epileptogenic zone was also associated with a shorter time to recurrence.

These observations extend the traditional view of surgical failure and in doing so raise many interesting questions. Does medication withdrawal “promote epileptogenesis after surgery and if so, how does this situation differ from the contribution of AED withdrawal in medical epilepsy patients? Should postoperative AED treatment be prolonged for a longer period of time, and are these findings unique to the pediatric patient? Further studies are clearly in order to address the questions raised by this important and provocative study.

Importantly, surgery was finally offered in more than 3/4 of the most complicated cases (25/32), with results that remained very good (64% of Engel class I). Even patients whose pathology finally proved normal or inconclusive - a finding, which remains challenging in the field of epilepsy surgery - could do well after surgery, although the rate of seizure freedom proved much less satisfactory (36% of Engel class I).

Overall, the merit of this study is to exist, and to serve as a reference in the field of invasive evaluation in children older than 2 years of age. The advent of 3D multimodality imaging methods should help in the future to better target the regions suspected to be epileptogenic, in order to avoid a second SEEG investigation (which represented almost 10% of the cases) and improve surgical results (17% of the children were classified as Engel class IV after surgery).

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References:

1) Boshuisen K, Schmidt D, Uiterwaal CS, Arzimanoglou A, Braun KP, TimeToStop Study Group. Time to relapse after epilepsy surgery in children: AED withdrawal policies are a contributing factor. Epileptic Disord. 2014 Sep;16(3):305-11.

(2) Boshuisen K, Arzimanoglou A, Cross JH, Uiterwaal CS, Polster T, van Nieuwenhuizen O, Braun KP; TimeToStop study group. Timing of antiepileptic drug withdrawal and long-term seizure outcome after paediatric epilepsy surgery (TimeToStop): a retrospective observational study. Lancet Neurol. 2012
Sep;11(9):784-91.

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