TO THE EDITOR: We read with great interest the work by Beaudreault and colleagues1on the safety of concomitant vagus nerve stimulation (VNS) and responsive neurostimulation (RNS) in pediatric patients with multifocal, generalized onset epilepsy (Beaudreault CP, Spirollari E, Naftchi AF, et al. Safety of vagus nerve stimulation and responsive neurostimulation used in combination for multifocal and generalized onset epilepsy in pediatric patients.J Neurosurg Pediatr. 2023;31[6]:565-573). This team of authors performed an in-depth and robust evaluation of 7 pediatric patients who underwent implantation of both RNS and VNS systems between 2015 and 2021 with at least 1 month of overlapping therapy. The authors observed no adverse events due to interactions between these therapies and further indicated that RNS could augment the therapeutic effects of VNS in some patients.
RNS and VNS have both been approved in the United States for the management of drug-resistant epilepsy (DRE) since 2013.2,3The first study to assess the efficacy and safety of concomitant VNS and RNS was only recently published in April 2022 by Brown et al.4However, the study by Beaudreault and team is the first study to report outcomes of concomitant therapy in the pediatric population and the only study to provide granular primary data for each study participant.
Further investigation, ideally in the form of randomized controlled trials or long-term prospective studies, is certainly warranted. However, the significant heterogeneity in patient characteristics and responses noted by Beaudreault et al. introduces a critical question for neurosurgeons, neurologists, and relevant service providers and researchers: how can practitioners standardize reporting of neuromodulatory interventions to optimize the identification of causal relationships, despite studies being limited by critically low sample sizes? With increased access to real-time and real-world data, this is an emerging area of interest within the clinical neurosciences, with significant implications for the wider medical community.5
Central to the goal of clinical standardization is the identification and development of core outcome measures and novel metrics for quantifying posttreatment outcomes. In this study, several candidate outcome measures are reported, including patient-reported seizure severity, VNS swipe counts, and recorded electroclinical seizures. These provide insight into specific aspects of a patient’s response to neuromodulation but are difficult to critique quantitatively due to significant variability between patients. Consensus between researchers, providers, regulators, payers, and patients is urgently needed to identify clear and common best practices for data collection, assessment, and transparency. Only in this way can this study of 7 patients expand across national and international centers, increasing its power, and moving it from an evaluation of safety, and potential efficacy, to a study of the cause and effect of synergistic neuromodulation in individual DRE patients.
Disclosures
The authors report no conflict of interest.
References
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1 ↑
BeaudreaultCP,SpirollariE,NaftchiAF,et al.Safety of vagus nerve stimulation and responsive neurostimulation used in combination for multifocal and generalized onset epilepsy in pediatric patients.J Neurosurg Pediatr.2023;31(6):565–573.
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2 ↑
KrahlSE.Vagus nerve stimulation for epilepsy: a review of the peripheral mechanisms.Surg Neurol Int.2012;3(Suppl 1):S47–S52.
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3 ↑
HartshornA,JobstB.Responsive brain stimulation in epilepsy.Ther Adv Chronic Dis.2018;9(7):135–142.
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4 ↑
BrownMG,SillauS,McDermottD,et al.Concurrent brain-responsive and vagus nerve stimulation for treatment of drug-resistant focal epilepsy.Epilepsy Behav.2022;129:108653.
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5 ↑
ZhangJ,SymonsJ,AgapowP,et al.Best practices in the real-world data life cycle.PLOS Digit Health.2022;1(1):e0000003.
