Klinkenberg et al. reply

Abstract

SIR-Klinkenberg et al.1 are to be congratulated for publishing the first prospective randomized controlled trial on vagal nerve stimulation in children. The design was similar to that of the initial adult studies in which a 'high' (normal) stimulus regime was compared to 'low' stimulus. Like the adult studies, a number of participants appeared to respond to the low stimulus, a result which could be a real effect or one possibly due to chance particularly with the fluctuating nature of their conditions. This result might also be more likely to have arisen with the relatively short time (20wks) of the treatment phase. This, and the underpowered nature of the study -some 100 participants would be needed in each group given their assumptions as to relative efficacy -go some way to explaining the similar results obtained in both groups.A further confounding factor which is not discussed was changes in concomitant antiepileptic drug dosage. Clearly this would have to be held constant during the baseline and treatment periods. It would be reassuring to know that this was in fact the case.The study found a decrease in seizure severity overall. Was this effect irrespective of a decrease in seizure frequency, i.e. seen in both non-responders as well as in responders?The difficulties in carrying out a trial such as this should not be underestimated. Clearly further work needs to be done in order to establish the place for vagal nerve stimulation in children with difficult-to-treat epilepsy. Professor Robinson makes a valid remark by pointing out the possible confounding effect of changing the concomitant antiepileptic drug dosage during the study. For this reason neither the type of drug nor the dosage were altered during the complete study in all participating children. Furthermore, there was the question of whether the effects on seizure severity were dependent on the effects on seizure frequency reduction. This was not the case: vagus nerve stimulation significantly decreased seizure severity in both responders and non-responders.We agree that the positive effects in patients receiving lowoutput stimulation might be due to the fluctuating nature of the disease and the short follow-up. However, we based our study design on the previously published randomized controlled trials in adults, which led to US Food and Drug Administration approval for vagus nerve stimulation for intractable epilepsy. Our treatment phase was at least 1 month longer than the trial of both the VNS study group and Handforth et al.

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