反应性神经刺激治疗成人局灶性药物难治性癫痫的中心试验结果_Journal of Epilepsy

Authors：

 樊京京 , 杨华俊 ,  王群

首都医科大学附属北京天坛医院神经病学中心癫痫科, 北京, 100050;

Corresponding author：

王群, Email: wangq@ccmu.edu.cn

Keywords：

皮层刺激; 部分性癫痫; 局灶性癫痫; 反应性神经刺激; 神经刺激器

DOI：

10.7507/2096-0247.20160015

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为了验证在癫痫灶进行反应性神经刺激作为减少成人癫痫起源于一个或两个致痫灶的药物难治性部分性癫痫发作频率的辅助治疗方法的安全性及有效性。反应性局灶皮层刺激(Responsive focal cortical stimulation, RNS)的多中心随机对照双盲试验。对起源于一个或两个致痫灶的药物难治性部分性癫痫受试者进行皮下植入, 植入后1个月按1∶1随机分为真刺激及假刺激组。植入后第5个月过后, 所有受试者在一个开放标签期(Open label period, OLP)接受反应性神经刺激开放标签来完成2年的植入后随访。所有191例受试者进行了随机化。盲法期结束时真刺激组癫痫发作改变的百分比为37.9%, 假刺激组为17.3%(P=0.012, 广义估计方程)。开放标签期癫痫发作减少百分比中位数第1年为44%, 第2年为53%, 代表随着时间呈进行性且显著的改善(P＜0.000 1)。严重不良事件发生率在真刺激及假刺激组间无差异。不良事件与植入医疗设备、癫痫发作及其它癫痫治疗方法的已知风险是一致的。未出现神经心理功能或情绪方面的不良效应。反应性神经刺激治疗局灶性癫痫快速减少了部分性癫痫发作的频率, 显示了随时间癫痫发作减少率的改善, 耐受性良好, 安全性可接受。RNS系统为药物难治性部分性癫痫发作患者提供了一种新的治疗选择

Citation： 樊京京, 杨华俊, 王群. 反应性神经刺激治疗成人局灶性药物难治性癫痫的中心试验结果. Journal of Epilepsy, 2016, 2(1): 81-88. doi: 10.7507/2096-0247.20160015 Copy

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11.	Lozano AM, Lipsman N. Probing and regulating dysfunctional circuits using deep brain stimulation. Neuron, 2013, 77(20): 406-424.
12.	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(16): 296-302.
13.	Boon P, Raedt R, De Herdt V, et al. Electrical stimulation for the treatment of epilepsy. Neurotherapeutics, 2009, 6(3): 218-227.
14.	Stone SS, Teixeira CM, Devito LM, et al. Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. J Neurosci, 2011, 31(13): 13469-13484.
15.	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(21):175-178.
16.	Hessen E, Lossius MI, Gjerstad L. Health concerns predicts poor quality of life in well-controlled epilepsy. Seizure, 2009, 18(6): 487-491.
17.	Loring DW, Meador KJ, Lee GP. Determinants of quality of life in epilepsy. Epilepsy Behav, 2004, 5(2): 976-980.
18.	Behrens E, Schramm J, Zentner J, et al. Surgical and neurological complications in a series of 708 epilepsy surgery procedures. Neurosurgery, 1997, 41(12): 1-9.
19.	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(23): 37-50.
20.	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(12): 1089-1093.
21.	Spencer SS, Spencer DD, Williamson PD, et al. Combined depth and subdural electrode investigation in uncontrolled epilepsy. Neurology, 1990, 40(14): 74-79.
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24.	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(16): 63-73.
25.	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(19): 956-963.
26.	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 epilepsy. Epilepsia, 2014, 55(3):432-441.
27.	Refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia, 2013, 54(2): 126-134.
28.	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(14): 1308-1317.
29.	Cereghino JJ, Biton V, Bou-Khalil B, et al. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology, 2000, 55(10): 236-242.
30.	U.S. Department of Health and Human Services. Keppra NDA 21-035. Center for Devices and Radiological Health, FDA. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21035lbl.pdf.AccessedJune14, 2013.
31.	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(13): 795-801.
32.	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 unblended randomised controlled trial. Lancet, 2007, 369(23): 1000-1015.
33.	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(11): 1261-1273.
34.	Perucca P, Carter J, Vahle V, et al. Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy. Neurology, 2009, 72(21): 1223-1229.
35.	Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia, 2007, 48(13): 1223-1244.
36.	Poochikian-Sarkissian S, Sidani S, Wennberg RA, et al. Psychological impact of illness intrusiveness in epilepsy-comparison of treatments. Psychol Health Med, 2008, 13(7): 129-145.
37.	Gilliam F. The impact of epilepsy on subjective health status. Curr Neurol Neurosci Rep, 2003, 3(1): 357-362.
38.	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(10): 148-161.
39.	Jones JE, Berven NL, Ramirez L, et al. Long-term psychosocial outcomes of anterior temporal lobectomy. Epilepsia, 2002, 43(10): 896-903.
40.	Hermann BP, Seidenberg M, Dow C, et al. Cognitive prognosis in chronic temporal lobe epilepsy. Ann Neurol, 2006, 60(18): 80-87.
41.	Leidy NK, Elixhauser A, Vickrey B, et al. Seizure frequency and the health-related quality of life of adults with epilepsy. Neurology, 1999, 53(17): 162-166.

1. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia, 2010, 51(16): 1069-1077.
2. IOM (Institute of Medicine) Epilepsy Across the Spectrum: Promoting Health and Understanding. Washington, DC: The National Academies Press, 2012.
3. Morrell MJ. RNS-system in Epilepsy Study Group Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology, 2011, 77(23): 1295-1304.
4. Devinsky O, Vickrey BG, Cramer J, et al. Development of the quality of life in epilepsy inventory. Epilepsia, 1995, 36(13): 1089-1104.
5. 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(8): 230-234.
6. Wiebe S, Matijevic S, Eliasziw M, et al. Clinically important change in quality of life in epilepsy. J Neurol Neurosurg Psychiatry, 2002, 73(14): 116-120.
7. 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(13): 478-483.
8. DeGiorgio CM, Schachter SC, Handforth A, et al. Prospective longterm study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia, 2000, 41(10): 1195-1200.
9. 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(20): 1731-1735.
10. Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia, 2010, 51(12): 899-908.
11. Lozano AM, Lipsman N. Probing and regulating dysfunctional circuits using deep brain stimulation. Neuron, 2013, 77(20): 406-424.
12. 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(16): 296-302.
13. Boon P, Raedt R, De Herdt V, et al. Electrical stimulation for the treatment of epilepsy. Neurotherapeutics, 2009, 6(3): 218-227.
14. Stone SS, Teixeira CM, Devito LM, et al. Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. J Neurosci, 2011, 31(13): 13469-13484.
15. 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(21):175-178.
16. Hessen E, Lossius MI, Gjerstad L. Health concerns predicts poor quality of life in well-controlled epilepsy. Seizure, 2009, 18(6): 487-491.
17. Loring DW, Meador KJ, Lee GP. Determinants of quality of life in epilepsy. Epilepsy Behav, 2004, 5(2): 976-980.
18. Behrens E, Schramm J, Zentner J, et al. Surgical and neurological complications in a series of 708 epilepsy surgery procedures. Neurosurgery, 1997, 41(12): 1-9.
19. 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(23): 37-50.
20. 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(12): 1089-1093.
21. Spencer SS, Spencer DD, Williamson PD, et al. Combined depth and subdural electrode investigation in uncontrolled epilepsy. Neurology, 1990, 40(14): 74-79.
22. 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(12): 538-547.
23. Wiebe S, Blume WT, Girvin JP, et al. A randomized, controlled trial of surgery for temporal-lobe epilepsy.N Engl J Med, 2001, 345(20): 311-318.
24. 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(16): 63-73.
25. 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(19): 956-963.
26. 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 epilepsy. Epilepsia, 2014, 55(3):432-441.
27. Refractory partial-onset seizures: interim results from phase III, extension study 307. Epilepsia, 2013, 54(2): 126-134.
28. 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(14): 1308-1317.
29. Cereghino JJ, Biton V, Bou-Khalil B, et al. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology, 2000, 55(10): 236-242.
30. U.S. Department of Health and Human Services. Keppra NDA 21-035. Center for Devices and Radiological Health, FDA. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21035lbl.pdf.AccessedJune14, 2013.
31. 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(13): 795-801.
32. 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 unblended randomised controlled trial. Lancet, 2007, 369(23): 1000-1015.
33. 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(11): 1261-1273.
34. Perucca P, Carter J, Vahle V, et al. Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy. Neurology, 2009, 72(21): 1223-1229.
35. Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia, 2007, 48(13): 1223-1244.
36. Poochikian-Sarkissian S, Sidani S, Wennberg RA, et al. Psychological impact of illness intrusiveness in epilepsy-comparison of treatments. Psychol Health Med, 2008, 13(7): 129-145.
37. Gilliam F. The impact of epilepsy on subjective health status. Curr Neurol Neurosci Rep, 2003, 3(1): 357-362.
38. 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(10): 148-161.
39. Jones JE, Berven NL, Ramirez L, et al. Long-term psychosocial outcomes of anterior temporal lobectomy. Epilepsia, 2002, 43(10): 896-903.
40. Hermann BP, Seidenberg M, Dow C, et al. Cognitive prognosis in chronic temporal lobe epilepsy. Ann Neurol, 2006, 60(18): 80-87.
41. Leidy NK, Elixhauser A, Vickrey B, et al. Seizure frequency and the health-related quality of life of adults with epilepsy. Neurology, 1999, 53(17): 162-166.

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反应性神经刺激治疗成人局灶性药物难治性癫痫的中心试验结果

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