Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

Dileep R. Nair; Martha J. Morrell; Tara L. Skarpaas; Anthony M. Murro; Yong D. Park; Gregory L. Barkley; Brien J. Smith; Ryder P. Gwinn; Michael J. Doherty; Katherine H. Noe; Richard S. Zimmerman; Gregory K. Bergey; William S. Anderson; Christianne Heck; Charles Y. Liu; Ricky W. Lee; Toni Sadler; Robert B. Duckrow; Lawrence J. Hirsch; Robert E. Wharen; William Tatum; Shraddha Srinivasan; Guy M. McKhann; Mark A. Agostini; Andreas V. Alexopoulos; Barbara C. Jobst; David W. Roberts; Vicenta Salanova; Thomas C. Witt; Sydney S. Cash; Andrew J. Cole; Gregory A. Worrell; Brian N. Lundstrom; Jonathan C. Edwards; Jonathan J. Halford; David C. Spencer; Lia Ernst; Christopher T. Skidmore; Michael R. Sperling; Ian Miller; Eric B. Geller; Michel J. Berg; A. James Fessler; Paul Rutecki; Alica M. Goldman; Eli M. Mizrahi; Robert E. Gross; Donald C. Shields; Theodore H. Schwartz; Douglas R. Labar; Nathan B. Fountain; W. Jeff Elias; Piotr W. Olejniczak; Nicole R. Villemarette-Pittman; Stephan Eisenschenk; Steven N. Roper; Jane G. Boggs; Tracy A. Courtney; Felice T. Sun; Cairn G. Seale; Kathy L. Miller; Tara L. Skarpaas

doi:10.1212/WNL.0000000000010154

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

Dileep R. Nair, Martha J. Morrell, Tara L. Skarpaas, Anthony M. Murro, Yong D. Park, Gregory L. Barkley, Brien J. Smith, Ryder P. Gwinn, Michael J. Doherty, Katherine H. Noe, Richard S. Zimmerman, Gregory K. Bergey, William S. Anderson, Christianne Heck, Charles Y. Liu, Ricky W. Lee, Toni Sadler, Robert B. Duckrow, Lawrence J. Hirsch, Robert E. WharenWilliam Tatum, Shraddha Srinivasan, Guy M. McKhann, Mark A. Agostini, Andreas V. Alexopoulos, Barbara C. Jobst, David W. Roberts, Vicenta Salanova, Thomas C. Witt, Sydney S. Cash, Andrew J. Cole, Gregory A. Worrell, Brian N. Lundstrom, Jonathan C. Edwards, Jonathan J. Halford, David C. Spencer, Lia Ernst, Christopher T. Skidmore, Michael R. Sperling, Ian Miller, Eric B. Geller, Michel J. Berg, A. James Fessler, Paul Rutecki, Alica M. Goldman, Eli M. Mizrahi, Robert E. Gross, Donald C. Shields, Theodore H. Schwartz, Douglas R. Labar, Nathan B. Fountain, W. Jeff Elias, Piotr W. Olejniczak, Nicole R. Villemarette-Pittman, Stephan Eisenschenk, Steven N. Roper, Jane G. Boggs, Tracy A. Courtney, Felice T. Sun, Cairn G. Seale, Kathy L. Miller, Tara L. Skarpaas

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Abstract

ObjectiveTo prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.MethodsAdults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-Term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.ResultsOf 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-Targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-Tailed χ2).ConclusionsAdjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.ClinicalTrials.gov identifierNCT00572195.Classification of evidenceThis study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

Original language	English (US)
Pages (from-to)	E1244-E1256
Journal	Neurology
Volume	95
Issue number	9
DOIs	https://doi.org/10.1212/WNL.0000000000010154
State	Published - Sep 1 2020

ASJC Scopus subject areas

Clinical Neurology

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Nair, D. R., Morrell, M. J., Skarpaas, T. L., Murro, A. M., Park, Y. D., Barkley, G. L., Smith, B. J., Gwinn, R. P., Doherty, M. J., Noe, K. H., Zimmerman, R. S., Bergey, G. K., Anderson, W. S., Heck, C., Liu, C. Y., Lee, R. W., Sadler, T., Duckrow, R. B., Hirsch, L. J., ... Skarpaas, T. L. (2020). Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. Neurology, 95(9), E1244-E1256. https://doi.org/10.1212/WNL.0000000000010154

Nair, DR, Morrell, MJ, Skarpaas, TL, Murro, AM, Park, YD, Barkley, GL, Smith, BJ, Gwinn, RP, Doherty, MJ, Noe, KH, Zimmerman, RS, Bergey, GK, Anderson, WS, Heck, C, Liu, CY, Lee, RW, Sadler, T, Duckrow, RB, Hirsch, LJ, Wharen, RE, Tatum, W, Srinivasan, S, McKhann, GM, Agostini, MA, Alexopoulos, AV, Jobst, BC, Roberts, DW, Salanova, V, Witt, TC, Cash, SS, Cole, AJ, Worrell, GA , Lundstrom, BN, Edwards, JC, Halford, JJ, Spencer, DC, Ernst, L, Skidmore, CT, Sperling, MR, Miller, I, Geller, EB, Berg, MJ, Fessler, AJ, Rutecki, P, Goldman, AM, Mizrahi, EM, Gross, RE, Shields, DC, Schwartz, TH, Labar, DR, Fountain, NB, Elias, WJ, Olejniczak, PW, Villemarette-Pittman, NR, Eisenschenk, S, Roper, SN, Boggs, JG, Courtney, TA, Sun, FT, Seale, CG, Miller, KL & Skarpaas, TL 2020, 'Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy', Neurology, vol. 95, no. 9, pp. E1244-E1256. https://doi.org/10.1212/WNL.0000000000010154

@article{6ce286a471f54c04a58d9bf7a72fc66a,

title = "Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy",

abstract = "ObjectiveTo prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.MethodsAdults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-Term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.ResultsOf 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-Targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-Tailed χ2).ConclusionsAdjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.ClinicalTrials.gov identifierNCT00572195.Classification of evidenceThis study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.",

author = "Nair, {Dileep R.} and Morrell, {Martha J.} and Skarpaas, {Tara L.} and Murro, {Anthony M.} and Park, {Yong D.} and Barkley, {Gregory L.} and Smith, {Brien J.} and Gwinn, {Ryder P.} and Doherty, {Michael J.} and Noe, {Katherine H.} and Zimmerman, {Richard S.} and Bergey, {Gregory K.} and Anderson, {William S.} and Christianne Heck and Liu, {Charles Y.} and Lee, {Ricky W.} and Toni Sadler and Duckrow, {Robert B.} and Hirsch, {Lawrence J.} and Wharen, {Robert E.} and William Tatum and Shraddha Srinivasan and McKhann, {Guy M.} and Agostini, {Mark A.} and Alexopoulos, {Andreas V.} and Jobst, {Barbara C.} and Roberts, {David W.} and Vicenta Salanova and Witt, {Thomas C.} and Cash, {Sydney S.} and Cole, {Andrew J.} and Worrell, {Gregory A.} and Lundstrom, {Brian N.} and Edwards, {Jonathan C.} and Halford, {Jonathan J.} and Spencer, {David C.} and Lia Ernst and Skidmore, {Christopher T.} and Sperling, {Michael R.} and Ian Miller and Geller, {Eric B.} and Berg, {Michel J.} and Fessler, {A. James} and Paul Rutecki and Goldman, {Alica M.} and Mizrahi, {Eli M.} and Gross, {Robert E.} and Shields, {Donald C.} and Schwartz, {Theodore H.} and Labar, {Douglas R.} and Fountain, {Nathan B.} and Elias, {W. Jeff} and Olejniczak, {Piotr W.} and Villemarette-Pittman, {Nicole R.} and Stephan Eisenschenk and Roper, {Steven N.} and Boggs, {Jane G.} and Courtney, {Tracy A.} and Sun, {Felice T.} and Seale, {Cairn G.} and Miller, {Kathy L.} and Skarpaas, {Tara L.}",

note = "Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2020",

month = sep,

day = "1",

doi = "10.1212/WNL.0000000000010154",

language = "English (US)",

volume = "95",

pages = "E1244--E1256",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "9",

}

TY - JOUR

T1 - Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

AU - Nair, Dileep R.

AU - Morrell, Martha J.

AU - Skarpaas, Tara L.

AU - Murro, Anthony M.

AU - Park, Yong D.

AU - Barkley, Gregory L.

AU - Smith, Brien J.

AU - Gwinn, Ryder P.

AU - Doherty, Michael J.

AU - Noe, Katherine H.

AU - Zimmerman, Richard S.

AU - Bergey, Gregory K.

AU - Anderson, William S.

AU - Heck, Christianne

AU - Liu, Charles Y.

AU - Lee, Ricky W.

AU - Sadler, Toni

AU - Duckrow, Robert B.

AU - Hirsch, Lawrence J.

AU - Wharen, Robert E.

AU - Tatum, William

AU - Srinivasan, Shraddha

AU - McKhann, Guy M.

AU - Agostini, Mark A.

AU - Alexopoulos, Andreas V.

AU - Jobst, Barbara C.

AU - Roberts, David W.

AU - Salanova, Vicenta

AU - Witt, Thomas C.

AU - Cash, Sydney S.

AU - Cole, Andrew J.

AU - Worrell, Gregory A.

AU - Lundstrom, Brian N.

AU - Edwards, Jonathan C.

AU - Halford, Jonathan J.

AU - Spencer, David C.

AU - Ernst, Lia

AU - Skidmore, Christopher T.

AU - Sperling, Michael R.

AU - Miller, Ian

AU - Geller, Eric B.

AU - Berg, Michel J.

AU - Fessler, A. James

AU - Rutecki, Paul

AU - Goldman, Alica M.

AU - Mizrahi, Eli M.

AU - Gross, Robert E.

AU - Shields, Donald C.

AU - Schwartz, Theodore H.

AU - Labar, Douglas R.

AU - Fountain, Nathan B.

AU - Elias, W. Jeff

AU - Olejniczak, Piotr W.

AU - Villemarette-Pittman, Nicole R.

AU - Eisenschenk, Stephan

AU - Roper, Steven N.

AU - Boggs, Jane G.

AU - Courtney, Tracy A.

AU - Sun, Felice T.

AU - Seale, Cairn G.

AU - Miller, Kathy L.

AU - Skarpaas, Tara L.

PY - 2020/9/1

Y1 - 2020/9/1

N2 - ObjectiveTo prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.MethodsAdults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-Term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.ResultsOf 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-Targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-Tailed χ2).ConclusionsAdjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.ClinicalTrials.gov identifierNCT00572195.Classification of evidenceThis study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

AB - ObjectiveTo prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.MethodsAdults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-Term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.ResultsOf 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-Targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-Tailed χ2).ConclusionsAdjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.ClinicalTrials.gov identifierNCT00572195.Classification of evidenceThis study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

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DO - 10.1212/WNL.0000000000010154

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JO - Neurology

JF - Neurology

IS - 9

ER -

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

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