Brief Communication Cumulative effect of vagus nerve stimulators on intractable seizures observed over a period of 3 years Fouzia Siddiqui 1, ⁎, Nabeel A. Herial 1 , Imran I. Ali 2 Department of Neurology, University of Toledo College of Medicine, Toledo, OH 43614, USA abstract article info Article history: Received 7 March 2010 Received in revised form 3 April 2010 Accepted 7 April 2010 Available online 23 May 2010 Keywords: Vagus nerve stimulator Refractory epilepsy Long-term evaluation Objective: The objective of the study was to evaluate the efficacy of vagus nerve stimulator (VNS) therapy and identify factors associated with reduction of seizures. The VNS is an accepted therapeutic option for patients with refractory partial epilepsy. There are, however, limited data regarding efficacy in any specific group of patients with epilepsy. Methods: This is a retrospective review of patients with epilepsy on VNS therapy initiated between January 2000 and December 2007 at a university medical center. Information collected included demographics, epilepsy type and duration, antiepileptic drug usage, stimulation parameters, and seizure frequency at baseline, 3 months, 6 months, 1 year, 2 years, and 3 years after VNS therapy initiation. Seizure frequency at different follow-up intervals was compared with baseline frequency. Patients were stratified into three subsets based on VNS response. Relationships between VNS response and factors including demographics, location of seizure focus, type or duration of epilepsy, and VNS settings were examined as a whole as well as in subsets. Results: Fifty-four patients were implanted with VNSs over a period of 7 years. Four patients were excluded. A total of 50 patients (31 men, 19 women) with mean age 39 years and on VNS therapy were included in this study. Average duration of VNS therapy was 4.5 years. Baseline average frequency was 10 seizures per month. Significant decreases in median seizure frequency were noted at 3 months (P b 0.001), 6 months (P b 0.001), 1 year (P = 0.004), 2 years (P b 0.001), and 3 years (P b 0.0001). Seventy-two percent of the patients reported a decrease in seizure frequency within the first 3 months, which increased to 80% by the end of 3 years. Overall, the percentage reduction in seizure frequency was 64% at 3 months and increased to 86% at the end of 3 years. In the subset of patients who responded to VNSs, reduction in seizure frequency improved from 80 to 89% by the end of 3 years. There were no correlations between seizure frequency and specific VNS settings, epileptic focus, or duration or type of epilepsy, in the group as a whole or in its subsets. Data suggest a favorable VNS response in patients with higher baseline seizure frequency. Conclusions: Significant reductions in seizure frequency were noted with VNS therapy over a 3-year follow- up period with a possible cumulative effect. Lateralization or localization of epileptic focus or epilepsy subtype did not correlate with response to VNSs. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Vagus nerve stimulators (VNSs) have been widely used since 1997 after their approval by the U.S. Food and Drug Administration for refractory partial seizures. The precise mode of action of VNSs in controlling seizures is still unknown [1,2]. The efficacy of VNSs in controlling seizures can range from 31% reduction of seizures, as reported in a double-blind study [3], to 34% at 3 months and 45% at 12 months in open-label studies [4,5]. The results are variable and differ with the type of epilepsy and underlying neurological state. Apart from reduction of seizure frequency, use of VNSs is also associated with decreases in seizure intensity and duration in 40–60% of patients [6]. VNS utilization as an acute abortive measure either in conjunction with benzodiazepines or without is also documented. An open-label, compassionate-use trial (E04) reported seizure termination in 22% and seizure diminution in 31% of the patients using magnets [7]. The cumulative effect of VNSs over time has been observed only in animal studies [8]. Recent comparison of the VNS with corpus callosotomy suggests similar effectiveness [9]. This device is known to desynchronize electroencephalographic activity, which is hypothesized to have an ameliorating effect on seizure activity [3]. Despite the effectiveness of VNSs in small and large cohorts, data on long-term effects of VNSs on Epilepsy & Behavior 18 (2010) 299–302 ⁎ Corresponding author. Department of Neurology, University of Toledo Medical Center, Mail Stop 1195, 3000 Arlington Avenue, Toledo, OH 43614, USA. Fax: +1 19 383 3903. E-mail address: drfsid@yahoo.com (F. Siddiqui). 1 No disclosure. 2 Ali II:speaker bureau for Cyberonics, GSK, UCB. 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.04.008 Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh