The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures.
All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy.
The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years ( p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained ( p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%).
The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures.
(1) Neuromodulation, Editorial Board, 2013-present (2) Epileptology- Facts and Controversies, Editorial Board, 2013-present
(1)Application of a responsive neurostimulator for treatment of psychiatric disease. (2)Refillable reservoir lead systems (3) Drug-eluting lead systems (4) Method for determining stimulation parameters for treatment of epileptic seizures
Scientific Advisory Board, Neonatal seizure treatment with medication off patient (NEMO trial), sponsorded by European Union, based in Unitied Kingdom (2009-2014)
Lippincott, Williams & Wilkens Publishers, Philadelphia, PA; McGraw-Hill Publishers, New York, NY; UpToDate, Wolters Kluwers Health, Waltham, MA.
Neuropace, Inc. Responsive neurostimulator (RNS) system long-term treatment clinical investigation. Site, PI. (2008-2014).
Department of Defense, USA. Grant number W81XWH-08-2- 0148. Mission Connect mild TBI translational research consortium: neurophysiology core. Core, PI.(2008-2014).
Editorial Board Epilepsy Currents 2011 to now Editiorial Board Epilepsia 2013 to now
(1) Neuropace, Inc. (2) Lundbeck, Inc. (3) Pfizer, Inc. (4) Upsher- Smith, Inc.
(1)Home-based Self Management and Cognitive Training Changes Lives for patients with Epilepsy. CDC 3U48DP001935-04S3, PI, 2012-2014. (2) Mechanisms of cognitive impairment in temporal lobe epilepsy.NIH 5R01NS074450-02. Co-I. 2011-2015.
1. Stereotactic and Functional Neurosurgery 2. World Neurosurgery 3. Neurosurgery 4. PLoS One
1. Medtronic 2. Boston Scientific 3. St. Jude Medical Corp 4. Visualase 5. Neuropace 6. Medtronic/Lilly 7. Deep Brain Innovation 8. Duke University/International Stem Cell Organization 9. Genegrafts 10. University of Alabama
Emory Clinic, Implantation of responsive neurostimulator, 0.5%, 2008 - 2014
1. SanBio 2. Visualase 3. Neuropace 4. Medtronic 5. Integra 6. Schering
Role: PI (Multi-PI mechanism); Wei, L (PI); Shan, Y (PI) Source: National Institutes of Health (NINDS) Award Type: R01 NS085568 Title: Application of optogenetics in iPS cell transplantation therapy for ischemic stroke Amount: $1,375,000 (direct) Years: 10/1/14 ? 9/30/19 (Pending; 6%ile) Role: PI Source: National Institutes of Health (NINDS) Award Type: R01 NS079268 Title: Autonomous Optogenetic Inhibition of Epileptic Activity Using a Bioluminescent Light Source Amount: $800,000 (direct) Years: 4/1/12 ? 3/31/16 Role: Co-investigator/Site PI Source: Department of Defense; Subcontract from Univ. of Pennsylvania (Michael Kahana, PhD, Overall PI) Award Type: DARPA-BAA-14-08 Broad Agency Announcement Restore Active Memory (RAM) Title: Memory Enhancement with Modeling, Electrophysiology, and Stimulation (MEMES) Amount: $661,774 (Emory site) Years: 2014 ? 2018 (awarded; pending subcontract) Role: Subcontract PI (PI: Warren Grill, PhD, Duke University) Source: National Institutes of Health Award Type: R01NS079312 Title: Recording Evoked Potentials for Closed-Loop DBS Amount: $109,863 Years: 9/1/12 ? 8/31/15 Role: Subcontract PI (PI: Steve M. Potter, PhD, Georgia Tech) Source: National Institutes of Health Award Type: RO1 NS079757 Title: Optogenetic Population Clamp to Study Long-term Plasticity in Vitro Amount: $1,800,000 Years: 07/01/2012 - 06/30/2017 Role: PI Source: National Institutes of Health (NINDS) Award Type: R21 NS054809 Title: Distributed microstimulation for epilepsy Amount: $275,000 (Direct costs) Years: 9/2008 ? 8/2010 Role: PI Source: National Institutes of Health, NINDS Award Type: K08 NS46322 Title: Axon guidance molecules in nigrostriatal regeneration Amount $772,750 (direct costs) Years 6/1/04 ? 3/31/09 Role: Co-investigator (PI: Ling Wei, PhD) Award Type: R21 NS075338 Title: Promoting axonal growth and tissue repair in stem cell therapy after stroke Source: National institute of Health Amount: $275,000 Years: 07/01/2011-06/30/2013 Role: Subcontract PI (PI: Warren M. Grill, PhD, Duke University) Source: National Institutes of Health Award Type: R01 NS040894-06A1 Title: Temporal Patterns of Deep Brain Stimulation Amount: $322,423 (Year 1 direct) Years: 1/15/09-12/31/13
1. Woodruff Foundation 2. Stanley Foundation 3. Coulter Foundation 4. American Epilepsy Society 5. Epilepsy Foundation of America 6. Citizens United for Research in Epilepsy 7. Dana Foundation
Indiana University Site PI for the NIH ROSE ( Radiosurgery vs Open Surgery for Epilepsy trial,the Medtronic SANTE trial, and the Neuro-Pace trial. Indiana University receives research grants from NIH, Medtronic, and Neuro-Pace
Indiana University Site PI for the Neuro-Pace, ROSE and Medtronic trials. Indiana University receives grant support from NIH, Neuro-Pace and Medtronic
Filed patent: Microscale Electrophysiology for mapping epileptogenic brain and predicting seizures
NIH R01 NS 63039-1, PI: Worrell 04/01/2009 ? 03/31/2014 European Union Agreement FP 00066387 Co-I: Worrell 11/01/2011-12/31/2015 NeuroPace, Inc 15682PI: Worrell 11/01/2007 -?10/31/2014; National Natural Science Foundation of China 81271447 and 81271448: Liankun Ren 01/01/2013-12/31/2016
(1) Eisai Pharma- Scientific Advisory Board (2) UCB Pharma- Scientific Advisory Board
Journal of Child Neurology, Associate Editor, 1997-2013 Epilepsia, Associate Editor, 2006-2013 Faculty of 100 Medicine, Section Editor, 2004-present Pediatric Neurology, Editor, 1997-2013 Epileptic Disorders, Editor/Assoc. Editor, 1998-present Epilepsy Research and Treatment, Editor, 2009-present
Intractable Focal Epilepsy, WB Saunders, 2000 Pediatric Epilepsy, McGraw-Hill, 2013
Neuropace, 2009-2010 Novartis, 2009-2010 King Pharmaceuticals,2010
Department of Defense, USAMRAA Grant No. 05098002; Contract No. XWH-06-1-0663, 2007-present
Neurology, Patient Page Editor, including past 2 years EMedicine, Chief Editor, Since 2010 Journal of Behavior and Brain Science, Associate Editor 2011 Neurology Now, Professional Advisory Board, including past 2 years
(1) NeuroPace, Inc. Local PI for study (2) Upsher-Smith Labs. Local PI for study Stock/Stock Options, Medical Equipment & Materials: Small amount (<$2000) in Stem Cells, Inc
1. Institute of Neurology and Neurosurgery at Saint Barnabas, prescribing and managing the Responsive Neurostimulator, 1-2% effort, 2014.
Neuropace Inc., participant in the Long-Term Treatment Trial of Responsive Neurostimulation for Epilepsy
Automated Home Medication Dispenser (4 issued and 2 pending patents). Assigned to University of Rochester, licensed to PharmAdva, LLC. Unrelated to current study.
Participated as site PI or SubI in research studies sponsored by: Neuropace, Eisai, Sunovion, Pfizer, Lundbeck
US Food and Drug Administration, HHSF223201110112A, Co- Principal Investigator 2011-current. Study: Equivalence Among Generic AEDs.
Is is possible that RNS would increase the volume of cases in my clinical practice, though my income is almost all a flat salary and any bonus for clinical productivity is tiny going forward for the next 4 years.
(1) UCB research support for epilepsy drug trials (2) NeuroPace research support for a device trial (3) Upsher Smith research support for an epilepsy drug trial
100% effort as epileptologist at the University of Virginia Comprehensive Epilepsy Program
The University of Virginia received grants with Dr. Fountain as PI from UCB, SK Life Sciences, Sunovion, Medtronic, NeuroPace
NIH study of gamma knife for epilepsy, R01 NS 058634- 01A2m site PI, 2010-2014. Non-financial disclosures: Board of Directors, National Association of Epilepsy Centers and chair of the Epilepsy Foundation Professional Advisory Board
I am the medical safety monitor for a DARPA study on brain stimulation and memory (not involving the company or product of the current study)
Honoraria from Neuropace for speaking in Webinars for neurologists new to responsive neurostimulation.
Journal of Clinical Neurophysiology: Editorial Board member, 2008-now. Epilepsy Currents: Contributing Editor, 2008-now
1. For authoring chapters for UpToDate-Neurology (2008+) 2. For co-authoring the book ?Atlas of EEG in Critical Care?, by Hirsch and Brenner (2010+), Wiley-Blackwell.
Responsive neurostimulation programming is a billable service that is occasionally performed at our epilepsy center (Yale Comprehensive Epilepsy Center). This procedure accounts for under 1% of the center's effort or revenue, and under 5% of each physician's effort or generated revenue.
UCB-Pharma and Lundbeck for the Antiepileptic Drug Database project. Upsher-Smith, for a study on seizure clusters.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by NeuroPace.
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