title: Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.
abstract: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin.
  
  
  
  Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset.
  
  
  
  There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices.
  
  
  
  Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.
authors.affiliation: Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, U.S.A.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Jobst
authors.affiliation: NeuroPace, Inc., Mountain View, California, U.S.A.
authors.forename: Ritu
authors.initials: R
authors.lastname: Kapur
authors.affiliation: Henry Ford Hospital, Detroit, Michigan, U.S.A.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Barkley
authors.affiliation: Columbia University Medical Center, New York, New York, U.S.A.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Bazil
authors.affiliation: University of Rochester Medical Center, Rochester, New York, U.S.A.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Berg
authors.affiliation: Johns Hopkins Medicine, Baltimore, Maryland, U.S.A.
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Bergey
authors.affiliation: Wake Forest University Health Sciences, Winston-Salem, North Carolina, U.S.A.
authors.forename: Jane G
authors.initials: JG
authors.lastname: Boggs
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, U.S.A.
authors.forename: Sydney S
authors.initials: SS
authors.lastname: Cash
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, U.S.A.
authors.forename: Andrew J
authors.identifier: 0000-0002-0828-826X
authors.initials: AJ
authors.lastname: Cole
authors.affiliation: Miami Children's Hospital / Nicklaus Children's Hospital, Miami, Florida, U.S.A.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Duchowny
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Duckrow
authors.affiliation: Medical University of South Carolina, Charleston, South Carolina, U.S.A.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Edwards
authors.affiliation: University of Florida, Gainesville, Florida, U.S.A.
authors.forename: Stephan
authors.initials: S
authors.lastname: Eisenschenk
authors.affiliation: University of Rochester Medical Center, Rochester, New York, U.S.A.
authors.forename: A James
authors.initials: AJ
authors.lastname: Fessler
authors.affiliation: University of Virginia School of Medicine, Charlottesville, Virginia, U.S.A.
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Fountain
authors.affiliation: Institute of Neurology and Neurosurgery at Saint Barnabas, Livingston, New Jersey, U.S.A.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Geller
authors.affiliation: Baylor College of Medicine, Houston, Texas, U.S.A.
authors.forename: Alica M
authors.initials: AM
authors.lastname: Goldman
authors.affiliation: Saint Luke's Hospital, New York, New York, U.S.A.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Goodman
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia, U.S.A.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gross
authors.affiliation: Swedish Neuroscience Institute, Seattle, Washington, U.S.A.
authors.forename: Ryder P
authors.initials: RP
authors.lastname: Gwinn
authors.affiliation: Keck School of Medicine of USC, Los Angeles, California, U.S.A.
authors.forename: Christianne
authors.initials: C
authors.lastname: Heck
authors.affiliation: Via Christi Epilepsy Center, Wichita, Kansas, U.S.A.
authors.forename: Aamr A
authors.initials: AA
authors.lastname: Herekar
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Hirsch
authors.affiliation: California Pacific Medical Center, San Francisco, California, U.S.A.
authors.forename: David
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authors.lastname: King-Stephens
authors.affiliation: Weill Cornell Medical College, New York, New York, U.S.A.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Labar
authors.affiliation: Mayo Clinic Minnesota, Rochester, Minnesota, U.S.A.
authors.forename: W R
authors.initials: WR
authors.lastname: Marsh
authors.affiliation: Stanford University, Stanford, California, U.S.A.
authors.forename: Kimford J
authors.initials: KJ
authors.lastname: Meador
authors.affiliation: Miami Children's Hospital / Nicklaus Children's Hospital, Miami, Florida, U.S.A.
authors.forename: Ian
authors.initials: I
authors.lastname: Miller
authors.affiliation: Baylor College of Medicine, Houston, Texas, U.S.A.
authors.forename: Eli M
authors.initials: EM
authors.lastname: Mizrahi
authors.affiliation: Augusta University, Augusta, Georgia, U.S.A.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Murro
authors.affiliation: Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.
authors.forename: Dileep R
authors.initials: DR
authors.lastname: Nair
authors.affiliation: Mayo Clinic Arizona, Scottsdale, Arizona, U.S.A.
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Noe
authors.affiliation: Louisiana State University, New Orleans, Louisiana, U.S.A.
authors.forename: Piotr W
authors.initials: PW
authors.lastname: Olejniczak
authors.affiliation: Augusta University, Augusta, Georgia, U.S.A.
authors.forename: Yong D
authors.initials: YD
authors.lastname: Park
authors.affiliation: University of Wisconsin Hospital and Clinics, Madison, Wisconsin, U.S.A.
authors.forename: Paul
authors.initials: P
authors.lastname: Rutecki
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
authors.forename: Vicenta
authors.initials: V
authors.lastname: Salanova
authors.affiliation: Nemours Foundation, Jacksonville, Florida, U.S.A.
authors.forename: Raj D
authors.initials: RD
authors.lastname: Sheth
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
authors.forename: Christopher
authors.initials: C
authors.lastname: Skidmore
authors.affiliation: Rush University Medical Center, Chicago, Illinois, U.S.A.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Smith
authors.affiliation: Oregon Health & Science University, Portland, Oregon, U.S.A.
authors.forename: David C
authors.initials: DC
authors.lastname: Spencer
authors.affiliation: Columbia University Medical Center, New York, New York, U.S.A.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Mayo Clinic's Campus in Florida, Jacksonville, Florida, U.S.A.
authors.forename: William
authors.initials: W
authors.lastname: Tatum
authors.affiliation: Baylor College of Medicine, Houston, Texas, U.S.A.
authors.forename: Paul
authors.initials: P
authors.lastname: Van Ness
authors.affiliation: Valley Neuroscience Institute, Renton, Washington, U.S.A.
authors.forename: David G
authors.initials: DG
authors.lastname: Vossler
authors.affiliation: Mayo Clinic's Campus in Florida, Jacksonville, Florida, U.S.A.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Wharen
authors.affiliation: Mayo Clinic Minnesota, Rochester, Minnesota, U.S.A.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Worrell
authors.affiliation: Baylor College of Medicine, Houston, Texas, U.S.A.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yoshor
authors.affiliation: Mayo Clinic Arizona, Scottsdale, Arizona, U.S.A.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Zimmerman
authors.affiliation: NeuroPace, Inc., Mountain View, California, U.S.A.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Skarpaas
authors.affiliation: NeuroPace, Inc., Mountain View, California, U.S.A.|Stanford University, Stanford, California, U.S.A.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Morrell
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D046690:Deep Brain Stimulation / Q000295:instrumentation / Q000379:methods*; D000069279:Drug Resistant Epilepsy / Q000503:physiopathology* / Q000628:therapy*; D004599:Electric Stimulation Therapy / Q000295:instrumentation / Q000379:methods*; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000503:physiopathology / Q000628:therapy; D017029:Epilepsy, Complex Partial / Q000503:physiopathology / Q000628:therapy; D020938:Epilepsy, Partial, Motor / Q000503:physiopathology / Q000628:therapy; D004830:Epilepsy, Tonic-Clonic / Q000503:physiopathology / Q000628:therapy; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000503:physiopathology*; D055815:Young Adult
keywords: Brain stimulation; Closed-loop; Eloquent cortex; Neuromodulation; Partial seizures