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, 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, 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, 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

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.

© 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Figures

Figure 1
Figure 1
Implanted RNS Neurostimulator and NeuroPace Depth Lead and NeuroPace Cortical Strip Lead.
Figure 2
Figure 2
RNS System Pivotal Study Design.
Figure 3
Figure 3
RNS System Pivotal Study Subject Disposition.
Figure 4
Figure 4
Responder rate and median percent reduction in seizure frequency.
Figure 5
Figure 5
Seizure frequency percent change by subject: most recent 3 months.
Figure 6
Figure 6
Changes in QOLIE-89 primary scale scores at 2 years after implantation of the RNS Neurostimulator and Leads.

References

    1. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51:1069–1077.
    1. IOM (Institute of Medicine) Epilepsy Across the Spectrum: Promoting Health and Understanding. Washington, DC: The National Academies Press; 2012.
    1. Morrell MJ. RNS® system in Epilepsy Study Group Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology. 2011;77:1295–1304.
    1. Devinsky O, Vickrey BG, Cramer J, et al. Development of the quality of life in epilepsy inventory. Epilepsia. 1995;36:1089–1104.
    1. Borghs S, de la Loge C, Cramer JA. Defining minimally important change in QOLIE-31 scores: estimates from three placebo-controlled lacosamide trials in patients with partial-onset seizures. Epilepsy Behav. 2012;23:230–234.
    1. Wiebe S, Matijevic S, Eliasziw M, et al. Clinically important change in quality of life in epilepsy. J Neurol Neurosurg Psychiatry. 2002;73:116–120.
    1. Elliott RE, Morsi A, Tanweer O, et al. Efficacy of vagus nerve stimulation over time: review of 65 consecutive patients with treatment-resistant epilepsy treated with VNS >10 years. Epilepsy Behav. 2011;20:478–483.
    1. DeGiorgio CM, Schachter SC, Handforth A, et al. Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia. 2000;41:1195–1200.
    1. Morris GL, III, Mueller WM. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05. Neurology. 1999;53:1731–1735.
    1. Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010;51:899–908.
    1. Lozano AM, Lipsman N. Probing and regulating dysfunctional circuits using deep brain stimulation. Neuron. 2013;77:406–424.
    1. Hess CW, Vaillancourt DE, Okun MS. The temporal pattern of stimulation may be important to the mechanism of deep brain stimulation. Exp Neurol. 2013;247:296–302.
    1. Boon P, Raedt R, De Herdt V, et al. Electrical stimulation for the treatment of epilepsy. Neurotherapeutics. 2009;6:218–227.
    1. Stone SS, Teixeira CM, Devito LM, et al. Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. J Neurosci. 2011;31:13469–13484.
    1. Stavrinou LC, Boviatsis EJ, Stathis P, et al. Sustained relief after discontinuation of DBS for dystonia: implications for the possible role of synaptic plasticity and cortical reorganization. J Neurol Surg A Cent Eur Neurosurg. 2012;73:175–178.
    1. Hessen E, Lossius MI, Gjerstad L. Health concerns predicts poor quality of life in well-controlled epilepsy. Seizure. 2009;18:487–491.
    1. Loring DW, Meador KJ, Lee GP. Determinants of quality of life in epilepsy. Epilepsy Behav. 2004;5:976–980.
    1. Behrens E, Schramm J, Zentner J, et al. Surgical and neurological complications in a series of 708 epilepsy surgery procedures. Neurosurgery. 1997;41:1–9.
    1. Wong CH, Birkett J, Byth K, et al. Risk factors for complications during intracranial electrode recording in presurgical evaluation of drug resistant partial epilepsy. Acta Neurochir (Wien) 2009;151:37–50.
    1. Silberbusch MA, Rothman MI, Bergey GK, et al. Subdural grid implantation for intracranial EEG recording: CT and MR appearance. AJNR Am J Neuroradiol. 1998;19:1089–1093.
    1. Spencer SS, Spencer DD, Williamson PD, et al. Combined depth and subdural electrode investigation in uncontrolled epilepsy. Neurology. 1990;40:74–79.
    1. Engel J, Jr, Wiebe S, French J, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy: report of the Quality Standards Subcommittee of the American Academy of Neurology, in association with the American Epilepsy Society and the American Association of Neurological Surgeons. Neurology. 2003;60:538–547.
    1. Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345:311–318.
    1. Weaver FM, Follett K, Stern M, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009;301:63–73.
    1. The Deep-Brain Stimulation for Parkinson's Disease Study Group. Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson's disease. N Engl J Med. 2001;345:956–963.
    1. Krauss GL, Perucca E, Ben-Menachem E, et al. Perampanel, a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia. 2013;54:126–134.
    1. Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007;48:1308–1317.
    1. Cereghino JJ, Biton V, Bou-Khalil B, et al. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000;55:236–242.
    1. U.S. Department of Health and Human Services. Center for Devices and Radiological Health, FDA. Keppra NDA 21-035. Available at: . Accessed June 14, 2013.
    1. Anhut H, Ashman P, Feuerstein TJ, et al. Gabapentin (Neurontin) as add-on therapy in patients with partial seizures: a double-blind, placebo-controlled study. The International Gabapentin Study Group. Epilepsia. 1994;35:795–801.
    1. Marson AG, Al-Kharusi A, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007;369:1000–1015.
    1. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2004;62:1261–1273.
    1. Perucca P, Carter J, Vahle V, et al. Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy. Neurology. 2009;72:1223–1229.
    1. Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia. 2007;48:1223–1244.
    1. Poochikian-Sarkissian S, Sidani S, Wennberg RA, et al. Psychological impact of illness intrusiveness in epilepsy – comparison of treatments. Psychol Health Med. 2008;13:129–145.
    1. Gilliam F. The impact of epilepsy on subjective health status. Curr Neurol Neurosci Rep. 2003;3:357–362.
    1. Jacoby A, Baker GA, Steen N, et al. The clinical course of epilepsy and its psychosocial correlates: findings from a U.K. Community study. Epilepsia. 1996;37:148–161.
    1. Jones JE, Berven NL, Ramirez L, et al. Long-term psychosocial outcomes of anterior temporal lobectomy. Epilepsia. 2002;43:896–903.
    1. Hermann BP, Seidenberg M, Dow C, et al. Cognitive prognosis in chronic temporal lobe epilepsy. Ann Neurol. 2006;60:80–87.
    1. Leidy NK, Elixhauser A, Vickrey B, et al. Seizure frequency and the health-related quality of life of adults with epilepsy. Neurology. 1999;53:162–166.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅