Research progress on magnetic resonance guided focused ultrasound therapy for drug-resistant epilepsy_Journal of Epilepsy

Authors：

SONG Tingting ¹ , JIA Chunlan ² , ZHAO Yue ¹ , WANG Qi ¹ ,  MU Jie ^1,3

1. West China Xiamen Hospital of Sichuan University, Department of Neurology, Xiamen 361000, China;
2. West China Xiamen Hospital of Sichuan University, Center for Neurological Function Test and Neuromodulation, Xiamen 361000, China;
3. West China Hospital, Sichuan University, Department of Neurology, Chengdu 610000, China;

Corresponding author：

MU Jie, Email: mujie2010@foxmail.com

Keywords：

Drug refractory epilepsy; Magnetic resonance-guided focused ultrasound; Low intensity focused ultrasound; High intensity focused ultrasound

DOI：

10.7507/2096-0247.202501001

Video：

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Abstract Full text Figures/Tables Video References Cited by

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging therapeutic ultrasound modality that integrates the precise localization capabilities of magnetic resonance imaging with the non-invasive therapeutic properties of focused ultrasound (FUS). This technology enables accurate targeting of deep brain structures and facilitates the treatment of various central nervous system disorders, including essential tremor, Parkinson's disease, and chronic neuropathic pain, through mechanisms such as ablation of diseased tissue, modulation of neural activity, and disruption of the blood-brain barrier. However, its efficacy and safety in the treatment of drug-resistant epilepsy (DRE) remain subjects of ongoing research. Consequently, MRgFUS is under investigation to ascertain its effectiveness and safety profile for treating DRE. This review aims to summarize the current progress in the application of MRgFUS for DRE therapy.

1.	Organization WH. Epilepsy: a public health imperative. 2019.
2.	Ding D, Zhou D, Sander JW, et al. Epilepsy in China: major progress in the past two decades. Lancet Neurol, 2021, 20(4): 316-326.
3.	Beghi E, Giussani G, Nichols E, et al. Global, regional, and national burden of epilepsy, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol, 2019, 18(4): 357-375.
4.	Karabacak M, Jagtiani P, Jain A, et al. Tracing topics and trends in drug-resistant epilepsy research using a natural language processing-based topic modeling approach. Epilepsia, 2024, 65(4): 861-872.
5.	Chen Z, Brodie MJ, Liew D, et al. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol, 2018, 75(3): 279-286.
6.	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(6): 1069-1077.
7.	Lerche H. Drug-resistant epilepsy—time to target mechanisms. Nat Rev Neurol, 2020, 16(11): 595-596.
8.	王泽青, 张祎年. P-糖蛋白在药物难治性癫痫中作用机制的研究进展. 中华神经外科杂志, 2019, 35(6): 642-645.
9.	Smolarz B, Makowska M, Romanowicz H. Pharmacogenetics of drug-resistant epilepsy (review of literature). Int J Mol Sci, 2021, 22(21): 11696.
10.	Fang M, Xi ZQ, Wu Y, et al. A new hypothesis of drug refractory epilepsy: neural network hypothesis. Med Hypotheses, 2011, 76(6): 871-876.
11.	Löscher W, Potschka H, Sisodiya SM, et al. Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol Rev, 2020, 72(3): 606-638.
12.	Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia, 2011, 52(4): 657-678.
13.	Rogawski MA. The intrinsic severity hypothesis of pharmacoresistance to antiepileptic drugs. Epilepsia, 2013, 54(s2): 33-40.
14.	中国抗癫痫协会. 临床诊疗指南•癫痫病分册. 北京: 人民卫生出版社, 2023.
15.	Sheng J, Liu S, Qin H, et al. Drug-Resistant Epilepsy and Surgery. Curr Neuropharmacol, 2017, 16(1): 17-28.
16.	Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA, 2015, 313(3): 285-293.
17.	Lescrauwaet E, Vonck K, Sprengers M, et al. Recent advances in the use of focused ultrasound as a treatment for epilepsy. Front Neurosci, 2022, 16: 886584.
18.	王中鸣, 彭琼, 黄亚辉, 李振光, 卢军. SEEG引导下多电极立体交叉射频热凝损毁治疗药物难治性癫痫的研究进展. 立体定向和功能性神经外科杂志, 2023, 36(4): 250-256.
19.	Grewal SS, Tatum WO. Laser thermal ablation in epilepsy. Expert Rev Neurother, 2019, 19(12): 1211-1218.
20.	Andrew H Milby, Gordon H Baltuch. Vagus nerve stimulation in the treatment of refractory epilepsy. Neurotherapeutics, 2009, 6(2): 228-237.
21.	Yang H, Shi W, Fan J, et al. Transcutaneous auricular vagus nerve stimulation (ta-vns) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial. Neurotherapeutics, 2023, 20(3): 870-880.
22.	Cukiert A, Lehtimäki K. Deep brain stimulation targeting in refractory epilepsy. Epilepsia, 2017, 58(S1): 80-84.
23.	Carrette S, Boon P, Dekeyser C, et al. Repetitive transcranial magnetic stimulation for the treatment of refractory epilepsy. Expert Rev Neurother, 2016, 16(9): 1093-1110.
24.	Sudbrack-Oliveira P, Barbosa MZ, Thome-Souza S, et al. Transcranial direct current stimulation (tDCS) in the management of epilepsy: a systematic review. Seizure, 2021, 86: 85-95.
25.	Leinenga G, Langton C, Nisbet R, et al. Ultrasound treatment of neurological diseases — current and emerging applications. Nat Rev Neurol, 2016, 12(3): 161-174.
26.	Bowary P, Greenberg BD. Noninvasive focused ultrasound for neuromodulation: a review. Psychiatr Clin North Am, 2018, 41(3): 505-514.
27.	Cornelssen C, Finlinson E, Rolston JD, et al. Ultrasonic therapies for seizures and drug-resistant epilepsy. Front Neurol, 2023, 14: 1301956.
28.	LeWitt PA, Lipsman N, Kordower JH. Focused ultrasound opening of the blood–brain barrier for treatment of Parkinson's disease. Mov Disord, 2019, 34(9): 1274-1278.
29.	Aubry JF, Tanter M. MR-guided transcranial focused ultrasound. Adv Exp Med Biol, 2016, 880: 97-111.
30.	Quadri SA, Waqas M, Khan I, et al. High-intensity focused ultrasound: past, present, and future in neurosurgery. Neurosurg Focus, 2018, 44(2): E16.
31.	董生, 王劲. 磁共振引导聚焦超声在中枢神经系统疾病治疗中的应用进展中华神经外科杂志, 2021, 37(3): 319-321.
32.	Stavarache MA, Chazen JL, Kaplitt MG. Innovative applications of MR-guided focused ultrasound for neurological disorders. World Neurosurg, 2021, 145: 581-589.
33.	左保廷, 范熙明, 张卫星, 等. 聚焦超声治疗脑功能区局灶性癫痫的实验研究. 国际外科学杂志 2011, 38(9): 618-621.
34.	左保廷. 聚焦超声治疗猫功能区局灶性癫痫的可行性研究. 立体定向和功能性神经外科杂志, 2011, 24(4): 202-205.
35.	Manlapaz JS, Ballantine HT, Astrom KE, et al. Effects of ultrasonic radiation in experimental focal epilepsy in the cat. Exp Neurol, 1964, 10(4): 345-356.
36.	Monteith S, Snell J, Eames M, et al. Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study. J Neurosurg, 2016, 125(6): 1557-1564.
37.	Parker WE, Weidman EK, Chazen JL, et al. Magnetic resonance-guided focused ultrasound for ablation of mesial temporal epilepsy circuits: modeling and theoretical feasibility of a novel noninvasive approach. J Neurosurg, 2020, 133(1): 63-70.
38.	Abe K, Yamaguchi T, Hori H, et al. Magnetic resonance-guided focused ultrasound for mesial temporal lobe epilepsy: a case report. BMC Neurol, 2020, 20(1): 160.
39.	Yamaguchi T, Hori T, Hori H, et al. Magnetic resonance-guided focused ultrasound ablation of hypothalamic hamartoma as a disconnection surgery: a case report. Acta Neurochir (Wien), 2020, 162(10): 2513-2517.
40.	Krishna V, Mindel J, Sammartino F, et al. A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy. Epilepsia, 2023, 64(4): 831-842.
41.	Colucci V, Strichartz G, Jolesz F, et al. Focused ultrasound effects on nerve action potential in vitro. Ultrasound Med Biol, 2009, 35(10): 1737-1747.
42.	Munoz F, Aurup C, Konofagou EE, et al. Modulation of brain function and behavior by focused ultrasound. Curr Behav Neurosci Rep, 2018, 5(2): 153-164.
43.	van Vliet EA, da Costa Araújo S, Redeker S, et al. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain, 2007, 130(Pt 2): 521-534.
44.	Zhang Y, Zhou H, Qu H, et al. Effects of non-invasive, targeted, neuronal lesions on seizures in a mouse model of temporal lobe epilepsy. Ultrasound Med Biol, 2020, 46(5): 1224-1234.
45.	Zou J, Meng L, Lin Z, et al. Ultrasound neuromodulation inhibits seizures in acute epileptic monkeys. iScience, 2020, 23(5): 101066.
46.	Lin Z, Meng L, Zou J, et al. Non-invasive ultrasonic neuromodulation of neuronal excitability for treatment of epilepsy. Theranostics, 2020, 10(12): 5514-5526.
47.	Zhang M, Li B, Lv X, et al. Low-intensity focused ultrasound-mediated attenuation of acute seizure activity based on EEG brain functional connectivity. Brain Sci, 2021, 11(6): 711.
48.	Kim T, Kim T, Joo J, et al. Modulation of EEG frequency characteristics by low-intensity focused ultrasound stimulation in a Pentylenetetrazol-induced epilepsy model. IEEE Access, 2021, 9: 59900-59909.
49.	Kim E, Kim HC, Van Reet J, et al. Transcranial focused ultrasound-mediated unbinding of phenytoin from plasma proteins for suppression of chronic temporal lobe epilepsy in a rodent model. Sci Rep, 2023, 13(1): 4128.
50.	Min BK, Bystritsky A, Jung KI, et al. Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. BMC Neurosci, 2011, 12: 23.
51.	Brinker ST, Preiswerk F, White PJ, et al. Focused ultrasound platform for investigating therapeutic neuromodulation across the human hippocampus. Ultrasound Med Biol, 2020, 46(5): 1270-1274.
52.	Lee CC, Chou CC, Hsiao FJ, et al. Pilot study of focused ultrasound for drug-resistant epilepsy. Epilepsia, 2022, 63(1): 162-175.

1. Organization WH. Epilepsy: a public health imperative. 2019.
2. Ding D, Zhou D, Sander JW, et al. Epilepsy in China: major progress in the past two decades. Lancet Neurol, 2021, 20(4): 316-326.
3. Beghi E, Giussani G, Nichols E, et al. Global, regional, and national burden of epilepsy, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol, 2019, 18(4): 357-375.
4. Karabacak M, Jagtiani P, Jain A, et al. Tracing topics and trends in drug-resistant epilepsy research using a natural language processing-based topic modeling approach. Epilepsia, 2024, 65(4): 861-872.
5. Chen Z, Brodie MJ, Liew D, et al. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol, 2018, 75(3): 279-286.
6. 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(6): 1069-1077.
7. Lerche H. Drug-resistant epilepsy—time to target mechanisms. Nat Rev Neurol, 2020, 16(11): 595-596.
8. 王泽青, 张祎年. P-糖蛋白在药物难治性癫痫中作用机制的研究进展. 中华神经外科杂志, 2019, 35(6): 642-645.
9. Smolarz B, Makowska M, Romanowicz H. Pharmacogenetics of drug-resistant epilepsy (review of literature). Int J Mol Sci, 2021, 22(21): 11696.
10. Fang M, Xi ZQ, Wu Y, et al. A new hypothesis of drug refractory epilepsy: neural network hypothesis. Med Hypotheses, 2011, 76(6): 871-876.
11. Löscher W, Potschka H, Sisodiya SM, et al. Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol Rev, 2020, 72(3): 606-638.
12. Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia, 2011, 52(4): 657-678.
13. Rogawski MA. The intrinsic severity hypothesis of pharmacoresistance to antiepileptic drugs. Epilepsia, 2013, 54(s2): 33-40.
14. 中国抗癫痫协会. 临床诊疗指南•癫痫病分册. 北京: 人民卫生出版社, 2023.
15. Sheng J, Liu S, Qin H, et al. Drug-Resistant Epilepsy and Surgery. Curr Neuropharmacol, 2017, 16(1): 17-28.
16. Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA, 2015, 313(3): 285-293.
17. Lescrauwaet E, Vonck K, Sprengers M, et al. Recent advances in the use of focused ultrasound as a treatment for epilepsy. Front Neurosci, 2022, 16: 886584.
18. 王中鸣, 彭琼, 黄亚辉, 李振光, 卢军. SEEG引导下多电极立体交叉射频热凝损毁治疗药物难治性癫痫的研究进展. 立体定向和功能性神经外科杂志, 2023, 36(4): 250-256.
19. Grewal SS, Tatum WO. Laser thermal ablation in epilepsy. Expert Rev Neurother, 2019, 19(12): 1211-1218.
20. Andrew H Milby, Gordon H Baltuch. Vagus nerve stimulation in the treatment of refractory epilepsy. Neurotherapeutics, 2009, 6(2): 228-237.
21. Yang H, Shi W, Fan J, et al. Transcutaneous auricular vagus nerve stimulation (ta-vns) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial. Neurotherapeutics, 2023, 20(3): 870-880.
22. Cukiert A, Lehtimäki K. Deep brain stimulation targeting in refractory epilepsy. Epilepsia, 2017, 58(S1): 80-84.
23. Carrette S, Boon P, Dekeyser C, et al. Repetitive transcranial magnetic stimulation for the treatment of refractory epilepsy. Expert Rev Neurother, 2016, 16(9): 1093-1110.
24. Sudbrack-Oliveira P, Barbosa MZ, Thome-Souza S, et al. Transcranial direct current stimulation (tDCS) in the management of epilepsy: a systematic review. Seizure, 2021, 86: 85-95.
25. Leinenga G, Langton C, Nisbet R, et al. Ultrasound treatment of neurological diseases — current and emerging applications. Nat Rev Neurol, 2016, 12(3): 161-174.
26. Bowary P, Greenberg BD. Noninvasive focused ultrasound for neuromodulation: a review. Psychiatr Clin North Am, 2018, 41(3): 505-514.
27. Cornelssen C, Finlinson E, Rolston JD, et al. Ultrasonic therapies for seizures and drug-resistant epilepsy. Front Neurol, 2023, 14: 1301956.
28. LeWitt PA, Lipsman N, Kordower JH. Focused ultrasound opening of the blood–brain barrier for treatment of Parkinson's disease. Mov Disord, 2019, 34(9): 1274-1278.
29. Aubry JF, Tanter M. MR-guided transcranial focused ultrasound. Adv Exp Med Biol, 2016, 880: 97-111.
30. Quadri SA, Waqas M, Khan I, et al. High-intensity focused ultrasound: past, present, and future in neurosurgery. Neurosurg Focus, 2018, 44(2): E16.
31. 董生, 王劲. 磁共振引导聚焦超声在中枢神经系统疾病治疗中的应用进展中华神经外科杂志, 2021, 37(3): 319-321.
32. Stavarache MA, Chazen JL, Kaplitt MG. Innovative applications of MR-guided focused ultrasound for neurological disorders. World Neurosurg, 2021, 145: 581-589.
33. 左保廷, 范熙明, 张卫星, 等. 聚焦超声治疗脑功能区局灶性癫痫的实验研究. 国际外科学杂志 2011, 38(9): 618-621.
34. 左保廷. 聚焦超声治疗猫功能区局灶性癫痫的可行性研究. 立体定向和功能性神经外科杂志, 2011, 24(4): 202-205.
35. Manlapaz JS, Ballantine HT, Astrom KE, et al. Effects of ultrasonic radiation in experimental focal epilepsy in the cat. Exp Neurol, 1964, 10(4): 345-356.
36. Monteith S, Snell J, Eames M, et al. Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study. J Neurosurg, 2016, 125(6): 1557-1564.
37. Parker WE, Weidman EK, Chazen JL, et al. Magnetic resonance-guided focused ultrasound for ablation of mesial temporal epilepsy circuits: modeling and theoretical feasibility of a novel noninvasive approach. J Neurosurg, 2020, 133(1): 63-70.
38. Abe K, Yamaguchi T, Hori H, et al. Magnetic resonance-guided focused ultrasound for mesial temporal lobe epilepsy: a case report. BMC Neurol, 2020, 20(1): 160.
39. Yamaguchi T, Hori T, Hori H, et al. Magnetic resonance-guided focused ultrasound ablation of hypothalamic hamartoma as a disconnection surgery: a case report. Acta Neurochir (Wien), 2020, 162(10): 2513-2517.
40. Krishna V, Mindel J, Sammartino F, et al. A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy. Epilepsia, 2023, 64(4): 831-842.
41. Colucci V, Strichartz G, Jolesz F, et al. Focused ultrasound effects on nerve action potential in vitro. Ultrasound Med Biol, 2009, 35(10): 1737-1747.
42. Munoz F, Aurup C, Konofagou EE, et al. Modulation of brain function and behavior by focused ultrasound. Curr Behav Neurosci Rep, 2018, 5(2): 153-164.
43. van Vliet EA, da Costa Araújo S, Redeker S, et al. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain, 2007, 130(Pt 2): 521-534.
44. Zhang Y, Zhou H, Qu H, et al. Effects of non-invasive, targeted, neuronal lesions on seizures in a mouse model of temporal lobe epilepsy. Ultrasound Med Biol, 2020, 46(5): 1224-1234.
45. Zou J, Meng L, Lin Z, et al. Ultrasound neuromodulation inhibits seizures in acute epileptic monkeys. iScience, 2020, 23(5): 101066.
46. Lin Z, Meng L, Zou J, et al. Non-invasive ultrasonic neuromodulation of neuronal excitability for treatment of epilepsy. Theranostics, 2020, 10(12): 5514-5526.
47. Zhang M, Li B, Lv X, et al. Low-intensity focused ultrasound-mediated attenuation of acute seizure activity based on EEG brain functional connectivity. Brain Sci, 2021, 11(6): 711.
48. Kim T, Kim T, Joo J, et al. Modulation of EEG frequency characteristics by low-intensity focused ultrasound stimulation in a Pentylenetetrazol-induced epilepsy model. IEEE Access, 2021, 9: 59900-59909.
49. Kim E, Kim HC, Van Reet J, et al. Transcranial focused ultrasound-mediated unbinding of phenytoin from plasma proteins for suppression of chronic temporal lobe epilepsy in a rodent model. Sci Rep, 2023, 13(1): 4128.
50. Min BK, Bystritsky A, Jung KI, et al. Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. BMC Neurosci, 2011, 12: 23.
51. Brinker ST, Preiswerk F, White PJ, et al. Focused ultrasound platform for investigating therapeutic neuromodulation across the human hippocampus. Ultrasound Med Biol, 2020, 46(5): 1270-1274.
52. Lee CC, Chou CC, Hsiao FJ, et al. Pilot study of focused ultrasound for drug-resistant epilepsy. Epilepsia, 2022, 63(1): 162-175.

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Latest ArticlesResearch progress on magnetic resonance guided focused ultrasound therapy for drug-resistant epilepsy

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