Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: A single-center experience Dilek Yalnizoglu a, ⁎ ,1 , Didem Ardicli a,b,1 , Burcak Bilginer c , Bahadir Konuskan a,d , Kader Karli Oguz e , Nejat Akalan c,f , Güzide Turanli a,g , Serap Saygi h , Meral Topcu a,g a Hacettepe University Faculty of Medicine, Department of Pediatric Neurology b currently at Health Sciences University Ankara Kecioren Research and Training Hospital c Hacettepe University Faculty of Medicine, Department of Neurosurgery d currently at Mardin State Hospital e Hacettepe University Faculty of Medicine, Department of Neuroradiology f currently at Medipol University Department of Neurosurgery g currently retired from Hacettepe University, Department of Pediatric Neurology h Hacettepe University Faculty of Medicine, Department of Neurology abstract article info Article history: Received 19 February 2020 Accepted 25 April 2020 Available online 27 June 2020 Introduction: Vagus nerve stimulation (VNS) has been used as an adjunctive therapy for both children and adults with refractory epilepsy, over the last two decades. In this study, we aimed to evaluate the long-term effects and tolerability of VNS in the pediatric drug-resistant epilepsy (DRE) and to identify the predictive factors for respon- siveness to VNS. Methods: We retrospectively reviewed the medical records of pediatric patients who underwent VNS implanta- tion between 1997 and 2018. Patients with ≥ 50% reduction of seizure frequency compared with the baseline were defined as “responders”. The clinical characteristics of responders and nonresponders were compared. Results: A total of 58 children (male/female: 40/18) with a mean follow-up duration of 5.7 years (3 months to 20 years) were included. The mean age at implantation was 12.4 years (4.5 to 18.5 years). Approximately half (45%) of our patients were responders, including 3 patients (5.8%) who achieved seizure freedom during follow-up. The age of seizure-onset, duration of epilepsy, age at implantation, and etiologies of epilepsy showed no significant difference between responders and nonresponders. Responders were more likely to have focal or multifocal epileptiform discharges (63%) on interictal electroencephalogram (EEG), when compared to nonre- sponders (36%) (p = .07). Vocal disturbances and paresthesias were the most common side effects, and in two patients, VNS was removed because of local reaction. Conclusion: Our series had a diverse etiological profile and patients with transition to adult care. Long-term fol- low-up showed that VNS is an effective and well-tolerated treatment modality for refractory childhood onset ep- ilepsy. Age at implantation, duration of epilepsy and underlying etiology are not found to be predictors of responsiveness to VNS. Higher response rates were observed for a subset of patients with focal epileptiform discharges. © 2020 Elsevier Inc. All rights reserved. Keywords: Vagus nerve stimulation Drug-resistant epilepsy Pediatric 1. Introduction Effective treatment of epilepsy is critical in pediatric patients, as un- controlled seizures may have unfavorable impact on neurodevelopment and quality of life [1,2]. About half of the children with epilepsy respond to the first or second appropriately chosen antiepileptic drug (AED) [3]. About one-third of patients with epilepsy who do not respond to AEDs are considered to have drug-resistant epilepsy (DRE), and only 20– 40% of them are suitable candidates for epilepsy surgery [3,4]. Over the past two decades, vagus nerve stimulation (VNS, Cyberonics®) has become an accepted treatment modality with a predictable and benign side-effect profile for both pediatric and adult patients with DRE, who are not suitable candidates for epilepsy surgery or have failed surgery [5]. Since 1997, VNS has been approved by the United States Food and Drug Administration (FDA) for N 12 years children and adults with intrac- table seizures [6]. Since 2000, the efficacy and safety of VNS in the treatment of DRE have been reported in many studies from different centers. In a meta- analysis of 74 studies, the mean reduction of seizure frequency was Epilepsy & Behavior 110 (2020) 107147 ⁎ Corresponding author at: Hacettepe University Faculty of Medicine, Department of Pediatric Neurology, 06100 Ankara, Turkey. E-mail address: dileky@hacettepe.edu.tr (D. Yalnizoglu). 1 These authors jointly share first authorship. https://doi.org/10.1016/j.yebeh.2020.107147 1525-5050/© 2020 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh