Response: “The importance of methodological context in pediatric VNS outcome reporting”

To the Editors: We thank Dr. Dinger and colleagues for their thoughtful commentary on our article, “Transforming Pediatric Epilepsy Care: Real-World Insights From a Leading Single-Center Study on Vagus Nerve Treatment Outcomes.” Their observations highlight important methodological considerations that warrant clarification.1, 2 The primary objective of our study was to share real-world experience from a high-volume pediatric epilepsy center over nearly 2 decades. We fully acknowledge the inherent limitations of retrospective analyses and agree that prospective, multicenter studies represent the gold standard. However, such data remain limited in pediatric populations. In this context, we believe our findings provide meaningful insights into long-term clinical practice and outcomes that are otherwise difficult to capture. Regarding seizure burden, categorization into multiple daily, daily, weekly, monthly, and sporadic frequencies was intentionally designed to reflect the heterogeneity of seizure patterns and multiple seizure types within individual patients. Placement in the “sporadic” category often reflected a low frequency of one seizure type, whereas other seizure types could persist at higher frequencies in the same patient. Clinical response was assessed using standard practice by comparing cumulative baseline seizure frequency with follow-up frequency across all seizure types, graded using a validated seizure reduction scale. Although seizure type-specific outcomes were not presented due to volume and complexity, this approach mirrors real-world clinical workflows and longitudinal decision-making. We acknowledge reliance on caregiver-reported seizure outcomes as an inherent limitation of retrospective studies. These data were extracted from provider-validated clinical documentation, ensuring consistency with routine care practices. For patients achieving seizure freedom, electroencephalographic confirmation was incorporated when available and explicitly addressed in the Results section. Similarly, quality of life (QoL) improvements were based on caregiver narratives, which we identified as a limitation. Prior studies have also relied on subjective QoL measures,3 and given the well-established association between seizure reduction and QoL,4 the higher responder rates observed in our cohort likely contributed to perceived improvements. We appreciate the emphasis on statistical rigor. Several associations did not retain statistical significance following Bonferroni correction; however, effect size measures (Cramér V) indicate small-to-moderate relationships that may hold clinical relevance despite limited statistical power. Our observation of higher response rates at higher output currents may reflect the combined influence of earlier implantation, more aggressive titration, higher duty cycling—including ultrarapid duty cycling—and longer duration of follow-up. These factors differ from prior population-level analyses and are summarized longitudinally in Figure 4 in Bansal et al.2, 5 Medication adjustments and other cointerventions were summarized in the Results section and supplementary materials, although detailed modeling was not feasible within the retrospective framework. Durations of sustained seizure freedom for subsets of patients are provided in Table S4 in Bansal et al.2 Although breakthrough seizures related to device inactivation are clinically relevant, systematic evaluation was beyond the scope of the present study. In conclusion, we agree that careful methodological context is essential when interpreting outcomes. Our study was designed to complement—not replace—prospective evidence by providing long-term, real-world insights that may inform clinical decision-making in pediatric vagal nerve stimulation therapy. We appreciate the opportunity to clarify these points and welcome continued dialogue to advance the field of pediatric epilepsy care. None. The authors declare no conflicts of interest. A.A. receives honoraria for serving on the LivaNova speaker bureau. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. This article is linked to Bansal et al.2 To view this article, visit https://doi.org/10.1111/epi.70002. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.