Elsevier

Epilepsy & Behavior

Volume 110, September 2020, 107147
Epilepsy & Behavior

Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: A single-center experience

https://doi.org/10.1016/j.yebeh.2020.107147Get rights and content

Highlights

  • We have demonstrated the efficacy and safety of VNS in a large group of pediatric patients with a long-term follow-up.

  • Improvement in the quality of life was observed in more than half of our patients, even in the non-responder group.

  • Transition to adult care is critical for patients with drug-resistant epilepsy and VNS who require long-term follow-up.

  • VNS appears to be effective for different types of epilepsy regardless of the underlying etiology.

  • Higher response rates were observed for a subset of patients who have focal or multifocal epileptiform discharges.

Abstract

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 responsiveness to VNS.

Methods

We retrospectively reviewed the medical records of pediatric patients who underwent VNS implantation 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 nonresponders (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 follow-up showed that VNS is an effective and well-tolerated treatment modality for refractory childhood onset epilepsy. 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.

Introduction

Effective treatment of epilepsy is critical in pediatric patients, as uncontrolled 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 > 12 years children and adults with intractable 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 higher in the pediatric age group (55.3%) as compared to adults (49.5%) [7]. In the largest pediatric VNS cohort of 347 children, the response rates at 12 and 24 months of therapy were 38% and 44%, respectively [2]. Improvement in cognitive functions, verbal communication, memory, attention and concentration has also been reported in many studies [2,[8], [9], [10]]. There are limited numbers of studies with long-term outcomes especially more than 10 years follow-up period of VNS therapy in the pediatric age group [8,11,12].

Predictive factors for responsiveness to VNS therapy have also been evaluated in previous studies [4,7,[13], [14], [15]]. Clinical characteristics such as duration of epilepsy, age at implantation, seizure type, etiology, and prior epilepsy surgery have been analyzed as the potential predictive factors.

In this study, we aimed to evaluate the long-term effects and the tolerability of VNS therapy in pediatric patients followed in our center and to compare the clinical characteristics between responders and nonresponders.

Section snippets

Methods

To analyze the long-term outcomes of VNS therapy in children, we performed a retrospective single-center study including the patients with DRE followed at Hacettepe University Hospitals between June 1997 and December 2018. Patients with a minimum follow-up period of three months were included. The indications for VNS implantation included patients with DRE according to the International League Against Epilepsy (ILAE) criteria and who are not appropriate candidates for epilepsy surgery. A total

Study population

A total of 58 children (40 male, 18 female) with a mean age of 12.4 ± 3.4 years (range 4.5–19 years) at the time of VNS implantation were included. The mean age of the patients at the time of last visit was 22.13 ± 7.41 years (9–39 years). The mean age at seizure-onset and duration of epilepsy were 3.6 ± 3.1 years (1 month to 11 years) and 8.8 ± 3.4 years (2.1–16 years), respectively. The VNS implantation was performed in 24 patients (41%) < 12 years of age and in 34 (59%) ≥ 12 years of age. The

Discussion

Vagus nerve stimulation is a well-tolerated, adjunctive neuromodulatory treatment for DRE with long-term favorable effects both in pediatric and adult population. Our results confirm the efficacy and safety of VNS for pediatric DRE in the long-term follow-up (mean = 5.7 years). Almost half (45.1%) of our patients had more than 50% seizure reduction at the last follow-up, including three (5.8%) patients who reached seizure freedom. Response rates ranged between 35.2–71.3% in the earlier

Conclusion

The results of the current study are consistent with the earlier reports that seizure reduction showed time dependence. Age at seizure onset, age at implantation, and duration of epilepsy are not found to be predictors of seizure reduction outcome after VNS implantation. Our patients had a diverse etiological profile, and seizure outcome was not related to the underlying etiology. Vagus nerve stimulation appears to be effective for different types of epilepsy regardless of the underlying

Declaration of competing interest

The authors have declared that no conflict of interest exits.

Acknowledgments

We thank referring physicians, pediatric and adult neurologists/epileptologists, neurosurgeons who took care of our patients at Hacettepe University Hospitals and outside hospitals.

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