In response: Vagus nerve stimulation for epilepsy treatment in children.

Abstract

To the Editors: We thank Dr. Hoppe and colleagues for their valuable comments on our paper. We do agree that our study remains a pure observational study; the study design was explicitly described in the article. It is very difficult, both clinically and ethically, to conduct a regular “placebo”-controlled long-term trial with vagus nerve stimulation (VNS). This is particularly true with respect to the majority of the population involved in our study: those with severe childhood epilepsies, often with multiple types of daily seizures. All experienced childhood epileptologists agree that often some of these seizure types (atypical absences, myoclonic seizures, and short tonic seizures) are of such a high frequency that they are difficult to count. Given the well-known and published shortcomings of patient/caregiver-reported seizure “counts,” we focused on the predominant seizure type, with the expectation that these are more reliably tracked and reported, leading to a better assessment of the therapy's overall clinical impact.2009, 2007 This is preferable to hoping that every single absence seizure or myoclonic jerk will be counted adequately, as is done in many short-term controlled trials for new drugs. This is a major difference with focal drug-resistant epilepsies of adulthood. We appreciate the authors’ affirmation of the value of the recently published results of the PuLsE study (in which these authors participated), which demonstrated outcomes for VNS therapy similar to those of our study.2014 The PuLsE trial confirms the added benefit of VNS in drug-resistant epilepsy. In addition, we believe that our results cannot be explained by the natural history of the disease. A sustained seizure reduction of 30–40% for 2 years is rarely seen in drug-resistant childhood epilepsy syndromes and, to our knowledge, has never been demonstrated in the peer-reviewed literature. We also agree that the data on the relationship between “total charge” and outcome remains preliminary and will benefit from further study, but it seems an important first step in finding out the proper “dosage” of VNS, and it was presented as such in our article. We agree that the rate of common side effects was lower than anticipated in this study. However, this was addressed to the best of our ability by also reporting safety data collected from the company's complaint database, as was explicitly described in the article. Magnetic resonance imaging (MRI), both 1.5 and 3.0 Tesla, can be performed safely in patients with VNS under specified conditions. It is a pity that the authors of this letter seem to express any doubt about the integrity of the collaborating authors and suggest that Cyberonics would have influenced the data processing and writing process. All analyses were done by the senior authors and approved by all other investigators. Nowadays, as everybody realizes, it is difficult to run such a large multicenter trial without the logistics support of a company. We also regret that the peer-review process of the respectable International League Against Epilepsy (ILAE) Journal Epilepsia is questioned. Overall, it seems that some people want to continue to deny the possible beneficial effects of add-on VNS in drug-resistant childhood epilepsies. A. Arzimanoglou received grant support and speaker honoraria from Cyberonics, UCB, GlaxoSmithKline, Eisai, and Viropharma. L. Lagae received grant support and speaker honoraria form Cyberonics, UCB, Viropharma, Brabant Pharma, and Eisai. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.