title: A prospective long-term study of external trigeminal nerve stimulation for drug-resistant epilepsy.
abstract: BACKGROUND
  External trigeminal nerve stimulation (eTNS) is an emerging noninvasive therapy for drug-resistant epilepsy (DRE). We report the long-term safety and efficacy of eTNS after completion of a phase II randomized controlled clinical trial for drug-resistant epilepsy.
  
  
  METHODS
  This was a prospective open-label long-term study. Subjects who completed the phase II randomized controlled trial of eTNS for DRE were offered long-term follow-up for 1year. Subjects who were originally randomized to control settings were crossed over to effective device parameters (30s on, 30s off, pulse duration of 250s, frequency of 120Hz). Efficacy was assessed using last observation carried forward or parametric imputation methods for missing data points. Outcomes included change in median seizure frequency, RRATIO, and 50% responder rate.
  
  
  RESULTS
  Thirty-five of 50 subjects from the acute double-blind randomized controlled study continued in the long-term study. External trigeminal nerve stimulation was well tolerated. No serious device-related adverse events occurred through 12months of long-term treatment. At six and twelve months, the median seizure frequency for the original treatment group decreased by -2.39 seizures per month at 6 months (-27.4%) and -3.03 seizures per month at 12 months (-34.8%), respectively, from the initial baseline (p<0.05, signed-rank test). The 50% responder rates at three, six, and twelve months were 36.8% for the treatment group and 30.6% for all subjects.
  
  
  CONCLUSIONS
  The results provide long-term evidence that external trigeminal nerve stimulation is a safe and promising long-term treatment for drug-resistant epilepsy.
authors.affiliation: Olive View/UCLA Medical Center, UCLA Department of Neurology, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Soss
authors.affiliation: USC Department of Neurology, USA.
authors.forename: Christi
authors.initials: C
authors.lastname: Heck
authors.affiliation: Olive View/UCLA Medical Center, UCLA Department of Neurology, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Murray
authors.affiliation: UCLA Department of Biomathematics, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Markovic
authors.affiliation: USC Department of Neurology, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Oviedo
authors.affiliation: USC Department of Neurology, USA.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Corrale-Leyva
authors.affiliation: Olive View/UCLA Medical Center, UCLA Department of Neurology, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Gordon
authors.affiliation: NeuroSigma, Inc., USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Kealey
authors.affiliation: Olive View/UCLA Medical Center, UCLA Department of Neurology, USA; NeuroSigma, Inc., USA. Electronic address: cmd@ucla.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: DeGiorgio
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004351:Drug Resistance; D004599:Electric Stimulation Therapy / Q000379:methods*; D004827:Epilepsy / Q000628:therapy*; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014276:Trigeminal Nerve / Q000502:physiology*; D055815:Young Adult
keywords: Drug-resistant epilepsy; Seizures; Trigeminal nerve stimulation