Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation

Final results of the RNS System Pivotal trial

Christianne N. Heck, David King-Stephens, Andrew D. Massey, Dileep R. Nair, Barbara C. Jobst, Gregory L. Barkley, Vicenta Salanova, Andrew J. Cole, Michael C. Smith, Ryder P. Gwinn, Christopher Skidmore, Paul C. Van Ness, Gregory K. Bergey, Yong D. Park, Ian Miller, Eric Geller, Paul A. Rutecki, Richard Zimmerman, David C. Spencer, Alica Goldman & 16 others Jonathan C. Edwards, James W. Leiphart, Robert E. Wharen, James Fessler, Nathan B. Fountain, Gregory A. Worrell, Robert E. Gross, Stephan Eisenschenk, Robert B. Duckrow, Lawrence J. Hirsch, Carl Bazil, Cormac A. O'Donovan, Felice T. Sun, Tracy A. Courtney, Cairn G. Seale, Martha J. Morrell

Research output: Contribution to journalArticle

221 Citations (Scopus)

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. Significance 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.

Original languageEnglish (US)
Pages (from-to)432-441
Number of pages10
JournalEpilepsia
Volume55
Issue number3
DOIs
StatePublished - 2014

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Partial Epilepsy
Seizures
Drug Resistant Epilepsy
Epilepsy
Therapeutics

Keywords

  • Cortical stimulation
  • Focal seizures
  • Neurostimulator
  • Partial seizures
  • Responsive stimulation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation : Final results of the RNS System Pivotal trial. / Heck, Christianne N.; King-Stephens, David; Massey, Andrew D.; Nair, Dileep R.; Jobst, Barbara C.; Barkley, Gregory L.; Salanova, Vicenta; Cole, Andrew J.; Smith, Michael C.; Gwinn, Ryder P.; Skidmore, Christopher; Van Ness, Paul C.; Bergey, Gregory K.; Park, Yong D.; Miller, Ian; Geller, Eric; Rutecki, Paul A.; Zimmerman, Richard; Spencer, David C.; Goldman, Alica; Edwards, Jonathan C.; Leiphart, James W.; Wharen, Robert E.; Fessler, James; Fountain, Nathan B.; Worrell, Gregory A.; Gross, Robert E.; Eisenschenk, Stephan; Duckrow, Robert B.; Hirsch, Lawrence J.; Bazil, Carl; O'Donovan, Cormac A.; Sun, Felice T.; Courtney, Tracy A.; Seale, Cairn G.; Morrell, Martha J.

In: Epilepsia, Vol. 55, No. 3, 2014, p. 432-441.

Research output: Contribution to journalArticle

Heck, CN, King-Stephens, D, Massey, AD, Nair, DR, Jobst, BC, Barkley, GL, Salanova, V, Cole, AJ, Smith, MC, Gwinn, RP, Skidmore, C, Van Ness, PC, Bergey, GK, Park, YD, Miller, I, Geller, E, Rutecki, PA, Zimmerman, R, Spencer, DC, Goldman, A, Edwards, JC, Leiphart, JW, Wharen, RE, Fessler, J, Fountain, NB, Worrell, GA, Gross, RE, Eisenschenk, S, Duckrow, RB, Hirsch, LJ, Bazil, C, O'Donovan, CA, Sun, FT, Courtney, TA, Seale, CG & Morrell, MJ 2014, 'Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial', Epilepsia, vol. 55, no. 3, pp. 432-441. https://doi.org/10.1111/epi.12534
Heck, Christianne N. ; King-Stephens, David ; Massey, Andrew D. ; Nair, Dileep R. ; Jobst, Barbara C. ; Barkley, Gregory L. ; Salanova, Vicenta ; Cole, Andrew J. ; Smith, Michael C. ; Gwinn, Ryder P. ; Skidmore, Christopher ; Van Ness, Paul C. ; Bergey, Gregory K. ; Park, Yong D. ; Miller, Ian ; Geller, Eric ; Rutecki, Paul A. ; Zimmerman, Richard ; Spencer, David C. ; Goldman, Alica ; Edwards, Jonathan C. ; Leiphart, James W. ; Wharen, Robert E. ; Fessler, James ; Fountain, Nathan B. ; Worrell, Gregory A. ; Gross, Robert E. ; Eisenschenk, Stephan ; Duckrow, Robert B. ; Hirsch, Lawrence J. ; Bazil, Carl ; O'Donovan, Cormac A. ; Sun, Felice T. ; Courtney, Tracy A. ; Seale, Cairn G. ; Morrell, Martha J. / Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation : Final results of the RNS System Pivotal trial. In: Epilepsia. 2014 ; Vol. 55, No. 3. pp. 432-441.
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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. Significance 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.",
keywords = "Cortical stimulation, Focal seizures, Neurostimulator, Partial seizures, Responsive stimulation",
author = "Heck, {Christianne N.} and David King-Stephens and Massey, {Andrew D.} and Nair, {Dileep R.} and Jobst, {Barbara C.} and Barkley, {Gregory L.} and Vicenta Salanova and Cole, {Andrew J.} and Smith, {Michael C.} and Gwinn, {Ryder P.} and Christopher Skidmore and {Van Ness}, {Paul C.} and Bergey, {Gregory K.} and Park, {Yong D.} and Ian Miller and Eric Geller and Rutecki, {Paul A.} and Richard Zimmerman and Spencer, {David C.} and Alica Goldman and Edwards, {Jonathan C.} and Leiphart, {James W.} and Wharen, {Robert E.} and James Fessler and Fountain, {Nathan B.} and Worrell, {Gregory A.} and Gross, {Robert E.} and Stephan Eisenschenk and Duckrow, {Robert B.} and Hirsch, {Lawrence J.} and Carl Bazil and O'Donovan, {Cormac A.} and Sun, {Felice T.} and Courtney, {Tracy A.} and Seale, {Cairn G.} and Morrell, {Martha J.}",
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TY - JOUR

T1 - Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation

T2 - Final results of the RNS System Pivotal trial

AU - Heck, Christianne N.

AU - King-Stephens, David

AU - Massey, Andrew D.

AU - Nair, Dileep R.

AU - Jobst, Barbara C.

AU - Barkley, Gregory L.

AU - Salanova, Vicenta

AU - Cole, Andrew J.

AU - Smith, Michael C.

AU - Gwinn, Ryder P.

AU - Skidmore, Christopher

AU - Van Ness, Paul C.

AU - Bergey, Gregory K.

AU - Park, Yong D.

AU - Miller, Ian

AU - Geller, Eric

AU - Rutecki, Paul A.

AU - Zimmerman, Richard

AU - Spencer, David C.

AU - Goldman, Alica

AU - Edwards, Jonathan C.

AU - Leiphart, James W.

AU - Wharen, Robert E.

AU - Fessler, James

AU - Fountain, Nathan B.

AU - Worrell, Gregory A.

AU - Gross, Robert E.

AU - Eisenschenk, Stephan

AU - Duckrow, Robert B.

AU - Hirsch, Lawrence J.

AU - Bazil, Carl

AU - O'Donovan, Cormac A.

AU - Sun, Felice T.

AU - Courtney, Tracy A.

AU - Seale, Cairn G.

AU - Morrell, Martha J.

PY - 2014

Y1 - 2014

N2 - 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. Significance 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.

AB - 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. Significance 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.

KW - Cortical stimulation

KW - Focal seizures

KW - Neurostimulator

KW - Partial seizures

KW - Responsive stimulation

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DO - 10.1111/epi.12534

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