Vagus nerve stimulation: Analysis of device parameters in 154 patients during the long-term XE5 study

Purpose: To determine the effect of changes in device settings and duty cyc le (on and off times) on the efficacy of vagus nerve stimulation (VNS) for refractory epilepsy. In the long-term XE5 study of VNS for intractable epil epsy, the median reduction in seizure frequency improved significantly afte r 1 year of follow-up, A central question is whether device changes improve efficacy. We analyzed the effects of device parameter changes on seizure f requency in 154 subjects who completed the study and who had complete data for analysis. Methods: Retrospective analysis of device changes during the XE5 long-term study of VNS. During the XE5 long-term follow-up study, the subject's devic e settings were modified within a Food and Drug Administration (FDA)-approv ed range of output current. pulse duration, frequency, on time, and off tim e. Significant changes in device settings occurred after 3 months. We inves tigated the relationship between percentage reduction in seizures and chang es in device parameters between the 3- and 12-month visits. Within-group co mparisons were performed for those who continued on standard on/off cycle o f 30 s on and 5 min off, and those with the most common off times of 3, 1.8 , and < 1.1 min. Results: Output current, pulse duration, frequency, and off time changed si gnificantly between the 3- and 12-month longterm follow-ups. For the group as a whole. changes in device settings were not correlated with an improvem ent in efficacy. However, a significant improvement in efficacy occurred in a subgroup whose off time was reduced to less than or equal to1.1 min. In this group, the median reduction in seizures improved from 21% before the c hange in off time, to 39% after the change in off time (Wilcoxon Signed-Ran k, p = 0.011), The responder rate (> 50% reduction in seizures) also signif icantly improved from 19 to 35% (McNemar's test, p = 0.046). Conclusions: The data from this retrospective analysis indicate that device changes were not the primary determinant of increased efficacy at 12 month s of long-term follow-up. In general, patients who remained on the original settings of 30 s on and 5 min off continued to respond or improve in their response over the 1-year period. However, some patients may benefit from r eductions in off time (increases in duty cycle). In a subgroup initially re sistant to VNS. a change in off time to less than or equal to1.1 min off di d result in significant improvements in efficacy.