Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy

CNS Neurosci Ther. 2019 Jan;25(1):14-20. doi: 10.1111/cns.12869. Epub 2018 Jun 22.


Background: The purposes of this study were three-fold: (i) to determine the contribution of known genes to the causation of a broad-spectrum of pediatric drug-resistant epilepsy (DRE), (ii) to compare the diagnostic yield and cost among different next-generation sequencing (NGS) approaches, and especially (iii) to assess how NGS approaches can benefit patients by improving diagnosis and treatment efficiency.

Methods: This study enrolled 273 pediatric DRE patients with no obvious acquired etiology. Seventy-four patients underwent whole-exome sequencing (WES), 141 patients had epilepsy-related gene panel testing, and another 58 patients had clinical WES gene panel testing. We obtained these patients' seizure and hospitalization frequency by periodic follow-up phone calls and outpatient visits.

Results: Genetic diagnosis was achieved in 86 patients (31.5%) and involved 93 likely disease-causing mutations in 33 genes. In this study, the detection rates of the epilepsy-related gene panel, the clinical WES gene panel, and WES were 32.6% (46/141), 44.8% (26/58), and 17.3% (13/74), respectively. Moreover, 34 patients accepted corrective therapy according to their mutant genes, after which 52.9% (18/34) became seizure-free and 38.2% (13/34) achieved seizure reduction. In the end, patients with either positive or negative genetic results had significantly fewer hospitalization incidents (times/half year) than before (positive genetic results group 0.58 ± 1.14 vs 0.10 ± 0.26; negative genetic results group 0.72 ± 1.65 vs 0.12 ± 0.33).

Conclusions: These results offer further proof that NGS approaches represent powerful tools for establishing a definitive diagnosis. Moreover, this study indicated how NGS can improve treatment efficacy and reduce hospitalization in children with DRE.

Keywords: drug-resistant epilepsy; hospitalization frequency; next-generation sequencing; treatment efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Drug Resistant Epilepsy / diagnosis
  • Drug Resistant Epilepsy / genetics*
  • Drug Resistant Epilepsy / therapy*
  • Female
  • Genetic Testing*
  • High-Throughput Nucleotide Sequencing*
  • Hospitalization*
  • Humans
  • Infant
  • Male
  • Mutation
  • Pilot Projects
  • Treatment Outcome
  • Whole Exome Sequencing