title: Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial.
abstract: OBJECTIVE
  To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.
  
  
  METHODS
  Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up.
  
  
  RESULTS
  All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood.
  
  
  CONCLUSIONS
  Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures.
authors.affiliation: Neurology, University of Southern California, Los Angeles, California, U.S.A.
authors.forename: Christianne N
authors.initials: CN
authors.lastname: Heck
authors.forename: David
authors.initials: D
authors.lastname: King-Stephens
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Massey
authors.forename: Dileep R
authors.initials: DR
authors.lastname: Nair
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Jobst
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Barkley
authors.forename: Vicenta
authors.initials: V
authors.lastname: Salanova
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cole
authors.forename: Michael C
authors.initials: MC
authors.lastname: Smith
authors.forename: Ryder P
authors.initials: RP
authors.lastname: Gwinn
authors.forename: Christopher
authors.initials: C
authors.lastname: Skidmore
authors.forename: Paul C
authors.initials: PC
authors.lastname: Van Ness
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Bergey
authors.forename: Yong D
authors.initials: YD
authors.lastname: Park
authors.forename: Ian
authors.initials: I
authors.lastname: Miller
authors.forename: Eric
authors.initials: E
authors.lastname: Geller
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rutecki
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmerman
authors.forename: David C
authors.initials: DC
authors.lastname: Spencer
authors.forename: Alica
authors.initials: A
authors.lastname: Goldman
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Edwards
authors.forename: James W
authors.initials: JW
authors.lastname: Leiphart
authors.forename: Robert E
authors.initials: RE
authors.lastname: Wharen
authors.forename: James
authors.initials: J
authors.lastname: Fessler
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Fountain
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Worrell
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gross
authors.forename: Stephan
authors.initials: S
authors.lastname: Eisenschenk
authors.forename: Robert B
authors.initials: RB
authors.lastname: Duckrow
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Hirsch
authors.forename: Carl
authors.initials: C
authors.lastname: Bazil
authors.forename: Cormac A
authors.initials: CA
authors.lastname: O'Donovan
authors.forename: Felice T
authors.initials: FT
authors.lastname: Sun
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Courtney
authors.forename: Cairn G
authors.initials: CG
authors.lastname: Seale
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Morrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004599:Electric Stimulation Therapy / Q000295:instrumentation / Q000379:methods / Q000639:trends*; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D058542:Implantable Neurostimulators / Q000639:trends*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life / Q000523:psychology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
keywords: Cortical stimulation; Focal seizures; Neurostimulator; Partial seizures; Responsive stimulation