Development of a clinical model to predict vagus nerve stimulation response in pediatric patients with drug-resistant epilepsy

Abstract

OBJECTIVE Epilepsy impacts 470,000 children in the United States. For patients with drug-resistant epilepsy (DRE) and unresectable seizure foci, vagus nerve stimulation (VNS) is a treatment option. Predicting response to VNS has been historically challenging. The objective of this study was to create a clinical VNS prediction tool for use in an outpatient setting. METHODS The authors performed an 11-year retrospective cohort analysis with 1-year follow-up. Patients < 21 years of age with DRE who underwent VNS (n = 365) were included. Logistic regressions were performed to assess clinical factors associated with VNS response (≥ 50% seizure frequency reduction after 1 year); 70% and 30% of the sample were used to train and validate the multivariable model, respectively. A prediction score was subsequently developed. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS Variables associated with VNS response were < 4-year epilepsy duration before VNS (p = 0.008) and focal motor seizures (p = 0.037). The variables included in the clinical prediction score were epilepsy duration before VNS, age at seizure onset, number of pre-VNS antiseizure medications, if VNS was the patient’s first therapeutic epilepsy surgery, and predominant seizure semiology. The final AUCs were 0.7013 for the "fitted" sample and 0.6159 for the "validation" sample. CONCLUSIONS The authors developed a clinical model to predict VNS response in a large sample of pediatric patients treated with VNS. Despite the large sample size, clinical variables alone were not able to accurately predict VNS response. This score may be useful after further validation, although its predictive ability underscores the need for more robust biomarkers to predict treatment response.

Effect of vagus nerve stimulation against generalized seizure and status epilepticus recurrence

“…Patients with generalized seizures achieving a > 50% reduction in seizure frequency 1 and 2 years after VNS implantation were 46 and 49%, respectively. On the other hands, focal seizures are more likely to respond to VNS than generalized seizure ( 24 ). Although it is still controversial which type of seizure VNS is effective for, involvement of the thalamus in seizure onset suggests a mechanism for the effect of VNS on generalized seizure.…”

Analysis of factors influencing the efficacy of vagus nerve stimulation for the treatment of drug-resistant epilepsy in children and prediction model for efficacy evaluation

“…However, there is limited research on the prognostic factors of VNS in children, and the selection of surgical methods mainly relies on the clinical experience of doctors, lacking clear surgical indicators. Nallammai Muthiah found that < 4-year epilepsy duration before VNS and focal motor seizures were factors associated with VNS response ( 9 ), yet no correlation was found between epilepsy duration and VNS response in J Janszky's research ( 10 ). Due to sample heterogeneity, there is no uniform conclusion on predictors of VNS efficacy, and there is still a lack of simple predictive models to predict VNS efficacy in the clinic.…”

“…Years of clinical trials have confirmed its safety, and it has been approved for use in the treatment of DRE in children since 1997 (7). Studies have shown that VNS can reduce seizures to a certain degree in epileptic children, and improve cognition, memory, emotion, and other functions (8). However, there is limited research on the prognostic factors of VNS in children, and the selection of surgical methods mainly relies on the clinical experience of doctors, lacking clear surgical indicators.…”