神经调控治疗药物难治性癫痫：从开环到闭环刺激

doi:10.3969/j.issn.1672-6731.2026.01.007

摘要/Abstract

摘要： 电刺激疗法作为癫痫的神经调控方式近年发展迅速。尽管开环刺激（如迷走神经刺激术和丘脑前核脑深部电刺激术）治疗药物难治性癫痫取得一定效果，但其固定参数、持续刺激的模式存在时机与剂量不匹配、个体适应性差等局限。闭环刺激（如反应性神经电刺激）通过实时监测脑电信号，并在发作前或发作时进行响应性刺激，显著提高治疗精准性和效果，并借助长期数据推动参数优化和脑网络重塑。本文阐述药物难治性癫痫神经调控治疗从开环刺激到闭环刺激的发展历程、机制与进展，探讨未来更具预测性、自适应和网络化的癫痫调控前景，为实现癫痫治疗的个体化和精准化提供理论基础。

关键词: 耐药性癫痫, 电刺激疗法, 丘脑髓板内核, 前丘脑核, 丘脑枕, 综述

Abstract: Over the recent years, electrical stimulation therapy has rapidly evolved as a commonly used neuromodulation therapy for epilepsy. Although open-loop stimulation [such as vagus nerve stimulation (VNS) and anterior nucleus of the thalamus deep brain stimulation (ANT-DBS)] has achieved certain success in treating drug-resistant epilepsy, its fixed-parameters, continuous stimulation paradigm suffers from limitations such as a mismatch between timing and dosage, poor individual adaptability, and more. In contrast, closed-loop stimulation [exemplified by responsive neurostimulator system (RNS)] significantly enhances treatment precision and energy efficiency by monitoring brain activity in real time and delivering responsive stimulation before or during seizures. It also leverages long-term data to optimize stimulation parameters and promote brain network remodeling. This review outlines the development, mechanisms, and recent advances in drug-resistant epilepsy neuromodulation from open-loop stimulation to closed-loop stimulation, and discusses future prospects for more predictive, adaptive, and network- oriented approaches, providing a theoretical foundation for personalized and precise epilepsy treatment.

Key words: Drug resistant epilepsy, Electric stimulation therapy, Intralaminar thalamic nuclei, Anterior thalamic nuclei, Pulvinar, Review

中图分类号:

R741
R651

平安, 朱君明. 神经调控治疗药物难治性癫痫：从开环到闭环刺激[J]. 中国现代神经疾病杂志, 2026, 26(1): 50-56.

PING An, ZHU Jun-ming. Advances in neuromodulation for drug-resistant epilepsy: transitioning from open-loop stimulation to closed-loop stimulation[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2026, 26(1): 50-56.

https://journal11.magtechjournal.com/cjcnn/CN/Y2026/V26/I1/50

参考文献

[1] Liu W, Xu Y, Lin Y, Wang L, Zhou M, Yin P, Zhao G. Burden of epilepsy in China and its provinces, 1990 to 2019: findings from the Global Burden of Disease Study 2019[J]. Chin Med J (Engl), 2023, 136:305-312.
[2] Perucca E, Perucca P, White HS, Wirrell EC. Drug resistance in epilepsy[J]. Lancet Neurol, 2023, 22:723-734.
[3] Afra P, Adamolekun B, Aydemir S, Watson GDR. Evolution of the vagus nerve stimulation (VNS) therapy system technology for drug-resistant epilepsy[J]. Front Med Technol, 2021, 3:696543.
[4] Bouwens van der Vlis TAM, Schijns OEMG, Schaper FLWVJ, Hoogland G, Kubben P, Wagner L, Rouhl R, Temel Y, Ackermans L. Deep brain stimulation of the anterior nucleus of the thalamus for drug-resistant epilepsy[J]. Neurosurg Rev, 2019, 42:287-296.
[5] Sun FT, Morrell MJ. The RNS system: responsive cortical stimulation for the treatment of refractory partial epilepsy[J]. Expert Rev Med Devices, 2014, 11:563-572.
[6] Chen S, Yang X, Xu S, Li B, Li C, Yang N, Yang X, Wang X, Xu S, Zhao X. Long-term outcome of vagus nerve stimulation therapy in drug-resistant epilepsy: a retrospective single-center study[J]. Front Neurol, 2025, 16:1564735.
[7] Kaufmann E, Peltola J, Colon AJ, Lehtimäki K, Majtanik M, Mai JK, Bóné B, Bentes C, Coenen V, Gil-Nagel A, Goncalves-Ferreira AJ, Ryvlin P, Taylor R, Brionne TC, Gielen F, Song S, Boon P; MORE Study Group. Long-term evaluation of anterior thalamic deep brain stimulation for epilepsy in the European MORE registry[J]. Epilepsia, 2024, 65:2438-2458.
[8] Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, Labar D, Sperling MR, Sharan A, Sandok E, Handforth A, Stern JM, Chung S, Henderson JM, French J, Baltuch G, Rosenfeld WE, Garcia P, Barbaro NM, Fountain NB, Elias WJ, Goodman RR, Pollard JR, Tröster AI, Irwin CP, Lambrecht K, Graves N, Fisher R; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy[J]. Neurology, 2015, 84:1017-1025.
[9] Nair DR, Laxer KD, Weber PB, 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 Jr, 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, Morrell MJ; RNS System LTT Study. Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy[J]. Neurology, 2020, 95:e1244-e1256.
[10] Eliashiv D, Jobst B, Morrell M. Multicenter post-approval study of the RNS system in focal epilepsy (S20.009)[J]. Neurology, 2025, 104(7_Supplement_1):5244.
[11] Falach R, Geva-Sagiv M, Eliashiv D, Goldstein L, Budin O, Gurevitch G, Morris G, Strauss I, Globerson A, Fahoum F, Fried I, Nir Y. Annotated interictal discharges in intracranial EEG sleep data and related machine learning detection scheme [J]. Sci Data, 2024, 11:1354.
[12] Baumgartner C, Baumgartner J, Duarte C, Lang C, Lisy T, Koren JP. Role of specific interictal and ictal EEG onset patterns[J]. Epilepsy Behav, 2025, 164:110298.
[13] Tomlinson SB, Davis P, Armstrong C, Baumgartner ME, Kennedy BC, Marsh ED. Interictal spikes and evoked cortical potentials share common spatiotemporal constraints in human epilepsy[J]. Front Netw Physiol, 2025, 5:1602124.
[14] Schevon C, Michalak A. Demystifying interictal discharges and seizure initiation in focal epilepsy[J]. Brain, 2023, 146: 1734-1736.
[15] Jarosiewicz B, Morrell M. The RNS system: brain-responsive neurostimulation for the treatment of epilepsy[J]. Expert Rev Med Devices, 2021, 18:129-138.
[16] Sharma E, Pomianoski BW, Jabbar R, Ayesha A, Silva YP, Łajczak P, Ahmed AR, Sahin OK, Majeed MW, Raake M, Fagundes W, Noll G. Responsive neurostimulation for patients with refractory mesial temporal lobe epilepsy: a systematic review and meta-analysis[J]. Epilepsy Behav Rep, 2025, 30: 100774.
[17] Malaga M, Modiano Y, Haneef Z. Neuropsychological and neurobehavioral outcomes of responsive neurostimulation in epilepsy: a systematic review and meta-analysis[J]. Epilepsia, 2025, 66:3585-3601.
[18] Yang Y, Wei P, Shi J, Mao Y, Zhang J, Lei D, Yang Z, Song S, Qian R, Li W, Shan Y, Zhao G. Early assessment of responsive neurostimulation for drug-resistant epilepsy in China: a multicenter, self-controlled study[J]. Chin Med J (Engl), 2025, 138:430-440.
[19] Geller EB, Skarpaas TL, Gross RE, Goodman RR, Barkley GL, Bazil CW, Berg MJ, Bergey GK, Cash SS, Cole AJ, Duckrow RB, Edwards JC, Eisenschenk S, Fessler J, Fountain NB, Goldman AM, Gwinn RP, Heck C, Herekar A, Hirsch LJ, Jobst BC, King-Stephens D, Labar DR, Leiphart JW, Marsh WR, Meador KJ, Mizrahi EM, Murro AM, Nair DR, Noe KH, Park YD, Rutecki PA, Salanova V, Sheth RD, Shields DC, Skidmore C, Smith MC, Spencer DC, Srinivasan S, Tatum W, Van Ness PC, Vossler DG, Wharen RE Jr, Worrell GA, Yoshor D, Zimmerman RS, Cicora K, Sun FT, Morrell MJ. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy[J]. Epilepsia, 2017, 58:994-1004.
[20] Jobst BC, Kapur R, Barkley GL, Bazil CW, Berg MJ, Bergey GK, Boggs JG, Cash SS, Cole AJ, Duchowny MS, Duckrow RB, Edwards JC, Eisenschenk S, Fessler AJ, Fountain NB, Geller EB, Goldman AM, Goodman RR, Gross RE, Gwinn RP, Heck C, Herekar AA, Hirsch LJ, King -Stephens D, Labar DR, Marsh WR, Meador KJ, Miller I, Mizrahi EM, Murro AM, Nair DR, Noe KH, Olejniczak PW, Park YD, Rutecki P, Salanova V, Sheth RD, Skidmore C, Smith MC, Spencer DC, Srinivasan S, Tatum W, Van Ness P, Vossler DG, Wharen RE Jr, Worrell GA, Yoshor D, Zimmerman RS, Skarpaas TL, Morrell MJ. Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas[J]. Epilepsia, 2017, 58:1005-1014.
[21] Elder C, Friedman D, Devinsky O, Doyle W, Dugan P. Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment-resistant multifocal epilepsy[J]. Epilepsia Open, 2019, 4:187-192.
[22] Li A, Huynh C, Fitzgerald Z, Cajigas I, Brusko D, Jagid J, Claudio AO, Kanner AM, Hopp J, Chen S, Haagensen J, Johnson E, Anderson W, Crone N, Inati S, Zaghloul KA, Bulacio J, Gonzalez-Martinez J, Sarma SV. Neural fragility as an EEG marker of the seizure onset zone[J]. Nat Neurosci, 2021, 24:1465-1474.
[23] Kokkinos V, Sisterson ND, Wozny TA, Richardson RM. Association of closed-loop brain stimulation neurophysiological features with seizure control among patients with focal epilepsy [J]. JAMA Neurol, 2019, 76:800-808.
[24] Pohodich AE, Yalamanchili H, Raman AT, Wan YW, Gundry M, Hao S, Jin H, Tang J, Liu Z, Zoghbi HY. Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity[J]. Elife, 2018, 7: e34031.
[25] Jiang H, Cai Z, Worrell GA, He B. Multiple oscillatory push-pull antagonisms constrain seizure propagation[J]. Ann Neurol, 2019, 86:683-694.
[26] Jiang H, Kokkinos V, Ye S, Urban A, Bagić A, Richardson M, He B. Interictal SEEG resting-state connectivity localizes the seizure onset zone and predicts seizure outcome[J]. Adv Sci (Weinh), 2022, 9:e2200887.
[27] Gregg NM, Pal Attia T, Nasseri M, Joseph B, Karoly P, Cui J, Stirling RE, Viana PF, Richner TJ, Nurse ES, Schulze-Bonhage A, Cook MJ, Worrell GA, Richardson MP, Freestone DR, Brinkmann BH. Seizure occurrence is linked to multiday cycles in diverse physiological signals[J]. Epilepsia, 2023, 64: 1627-1639.
[28] Baud MO, Kleen JK, Mirro EA, Andrechak JC, King-Stephens D, Chang EF, Rao VR. Multi-day rhythms modulate seizure risk in epilepsy[J]. Nat Commun, 2018, 9:88.
[29] Chiang S, Khambhati AN, Tcheng TK, Loftman AP, Hasulak NR, Mirro EA, Morrell MJ, Rao VR. State-dependent effects of responsive neurostimulation depend on seizure localization[J]. Brain, 2025, 148:521-532.
[30] Fields MC, Eka O, Schreckinger C, Dugan P, Asaad WF, Blum AS, Bullinger K, Willie JT, Burdette DE, Anderson C, Quraishi IH, Gerrard J, Singh A, Lee K, Yoo JY, Ghatan S, Panov F, Marcuse LV. A multicenter retrospective study of patients treated in the thalamus with responsive neurostimulation[J]. Front Neurol, 2023, 14:1202631.
[31] Skelton HM, Bullinger K, Isbaine F, Lau JC, Willie JT, Gross RE. Optimal hippocampal targeting in responsive neurostimulation for mesial temporal lobe epilepsy [J]. J Neurosurg, 2024, 141:1105-1114.
[32] Kobayashi K, Taylor KN, Shahabi H, Krishnan B, Joshi A, Mackow MJ, Feldman L, Zamzam O, Medani T, Bulacio J, Alexopoulos AV, Najm I, Bingaman W, Leahy RM, Nair DR. Effective connectivity relates seizure outcome to electrode placement in responsive neurostimulation[J]. Brain Commun, 2024, 6:fcae035.
[33] Weiss SA, Sperling MR, Engel J, Liu A, Fried I, Wu C, Doyle W, Mikell C, Mofakham S, Salamon N, Sim MS, Bragin A, Staba R. Simulated resections and responsive neurostimulator placement can optimize postoperative seizure outcomes when guided by fast ripple networks[J]. Brain Commun, 2024, 6: fcae367.
[34] Nanda P, Sisterson N, Walton A, Chu CJ, Cash SS, Moura LMVR, Oster JM, Urban A, Richardson RM. Centromedian region thalamic responsive neurostimulation mitigates idiopathic generalized and multifocal epilepsy with focal to bilateral tonic-clonic seizures[J]. Epilepsia, 2024, 65:2626-2640.
[35] Mohanty D, Houck KM, Trandafir C, Haneef Z, Karakas C, Lee S, Curry DJ, Riviello JJ, Ali I. Responsive neurostimulation of thalamic nuclei for regional and multifocal drug-resistant epilepsy in children and young adults[J]. J Neurosurg Pediatr, 2024, 34:40-48.
[36] Wong GM, Hofmann K, Shlobin NA, Tsuchida TN, Gaillard WD, Oluigbo CO. Stimulation of the pulvinar nucleus of the thalamus in epilepsy: a systematic review and individual patient data (IPD) analysis[J]. Clin Neurol Neurosurg, 2023, 235: 108041.
[37] Pizzo F, Carron R, Laguitton V, Clement A, Giusiano B, Bartolomei F. Medial pulvinar stimulation for focal drug-resistant epilepsy: interim 12-month results of the PULSE study [J]. Front Neurol, 2024, 15:1480819.
[38] Wang R, Sacknovitz A, Vazquez S, Dominguez J, McGoldrick P, Wolf S, Sukul V, Muh C, Patra SE, Burdette DE. Bilateral pulvinar responsive neurostimulation for bilateral multifocal posteriorly dominant drug resistant epilepsy[J]. Epilepsia Open, 2024, 9:2263-2273.
[39] Cole ER, Connolly MJ, Ghetiya M, Sendi MES, Kashlan A, Eggers TE, Gross RE. SAFE-OPT: a Bayesian optimization algorithm for learning optimal deep brain stimulation parameters with safety constraints[J]. J Neural Eng, 2024, 21:046054.
[40] Cole ER, Connolly MJ, Park S, Grogan DP, Buxton W, Eggers TE, Nealen G. Laxpati NG, Gross RE. Autonomous state inference for data-driven optimization of neural modulation[C] // 202110th International IEEE/EMBS Conference on Neural Engineering (NER), Italy, 2021. Italy: IEEE, 2021: 950-953.

选择文件类型/文献管理软件名称

选择包含的内容

2 神经调控治疗药物难治性癫痫：从开环到闭环刺激

Advances in neuromodulation for drug-resistant epilepsy: transitioning from open-loop stimulation to closed-loop stimulation

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	明东. 神经调控医工融合创新研究[J]. 中国现代神经疾病杂志, 2026, 26(1): 8-12.
[2]	支迪暄, 金磊, 王逸鹤, 单永治. 脑机接口临床实践与展望[J]. 中国现代神经疾病杂志, 2026, 26(1): 13-20.
[3]	杨艺, 何蕲恒, 柴晓珂, 赵继宗. 慢性意识障碍与脑机接口：神经调控医工融合新范式[J]. 中国现代神经疾病杂志, 2026, 26(1): 21-29.
[4]	靳卓, 任小欣, 王浩婷, 乔羿静, 赵玉超, 郑晨光. 非侵入性电磁神经调控治疗创伤后应激障碍认知损害研究进展[J]. 中国现代神经疾病杂志, 2026, 26(1): 30-39.
[5]	王承恩, 李雪辉, 耿子涵, 赵飞, 杨佳佳. 神经调控治疗脊髓小脑性共济失调3型临床进展[J]. 中国现代神经疾病杂志, 2026, 26(1): 40-49.
[6]	胡天棋, 解虎涛, 张建国. 脑深部电刺激术治疗药物难治性癫痫进展与展望[J]. 中国现代神经疾病杂志, 2026, 26(1): 57-64.
[7]	魏新明, 冯珂珂. 脑深部电刺激术在脑卒中后运动功能障碍中应用进展[J]. 中国现代神经疾病杂志, 2026, 26(1): 65-68.
[8]	吴静超, 梁思泉. 脑深部电刺激术在难治性精神疾病中应用进展[J]. 中国现代神经疾病杂志, 2026, 26(1): 69-76.
[9]	张昀昇, 王琦, 杨文强, 于炎冰, 张黎. 脊髓电刺激术临床应用进展[J]. 中国现代神经疾病杂志, 2026, 26(1): 77-84.
[10]	冯善刚, 史烨童, 尹绍雅. 迷走神经刺激术临床应用现状[J]. 中国现代神经疾病杂志, 2026, 26(1): 85-91.
[11]	杨鑫, 王书哲, 李申. 经颅交流电刺激治疗抑郁症机制研究与应用进展[J]. 中国现代神经疾病杂志, 2026, 26(1): 92-98.
[12]	邱炳辉, 杜佳澍, 钟晴蕾, 卓杰, 何山. 应重视下丘脑垂体功能障碍对重型颅脑创伤患者长期预后的影响[J]. 中国现代神经疾病杂志, 2025, 25(9): 779-783.
[13]	韩佳良, 张国斌. 小胶质细胞在颅脑创伤发病机制中的作用[J]. 中国现代神经疾病杂志, 2025, 25(9): 784-789.
[14]	潘景锡, 李文福, JalalKhan, 杜佳澍, 钟晴蕾, 包贇. 创伤性脑水肿病理学特征与治疗进展[J]. 中国现代神经疾病杂志, 2025, 25(9): 790-797.
[15]	廖希贤, 梅芬, 邱炳辉, 漆松涛, 钟晴蕾, 包贇. 生长激素在颅脑创伤的应用进展[J]. 中国现代神经疾病杂志, 2025, 25(9): 798-806.

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

2 神经调控治疗药物难治性癫痫：从开环到闭环刺激

Advances in neuromodulation for drug-resistant epilepsy: transitioning from open-loop stimulation to closed-loop stimulation

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价