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

Author:

Muthiah Nallammai1,Mallela Arka N.1,Vodovotz Lena1,Sharma Nikhil1,Akwayena Emefa1,Pan Evelyn1,Welch William2,Ibrahim George M.3,Abel Taylor J.14

Affiliation:

1. Department of Neurological Surgery, University of Pittsburgh;

2. Department of Pediatrics, Division of Child Neurology, University of Pittsburgh, Pennsylvania;

3. Department of Surgery, Division of Neurosurgery, The Hospital for Sick Children, University of Toronto, Ontario, Canada; and

4. Department of Bioengineering, University of Pittsburgh, Pennsylvania

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.

Publisher

Journal of Neurosurgery Publishing Group (JNSPG)

Subject

General Medicine

Reference28 articles.

1. National and state estimates of the numbers of adults and children with active epilepsy—United States, 2015;Zack MM,2017

2. The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis;Kalilani L,2018

3. Trends in the use of vagus nerve stimulation for epilepsy: analysis of a nationwide database;Baaj AA,2008

4. Responsive vagus nerve stimulation for drug resistant epilepsy: a review of new features and practical guidance for advanced practice providers;Fisher B,2021

5. Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures;Ben-Menachem E,1994

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