Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: A single-center experience
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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These authors jointly share first authorship.