Focused Ultrasound Therapy
Focused ultrasound is a rapidly evolving, noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with epilepsy. This novel technology focuses beams of ultrasound energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue.
How it Works
Where the beams converge, focused ultrasound produces two therapeutic effects that are being evaluated. One mechanism is thermal ablation, which heats and destroys the targeted tissue. Another is the use of neuromodulation, where focused ultrasound is able to lower the impact of epileptic impulses.
Advantages
Current treatments for epilepsy include medication, surgery, radiofrequency or laser ablation, deep brain stimulation, and stereotactic radiosurgery, all of which have limitations and side effects.
Focused ultrasound has the potential to provide an alternative or complement to conventional therapy, with several advantages.
- Focused ultrasound is non-invasive, so it does not carry added concerns like surgical wound healing or infection.
- It can reach the desired target without damaging surrounding tissue.
- Focused ultrasound does not use any ionizing radiation.
- It can be repeated, if necessary.
Clinical Trials
A current clinical trial is underway at the University of Virginia, Stanford University, the University of Kansas, and the Mayo Clinic. This study is treating patients with medication-refractory, focal epilepsy.
Another clinical trial at the Brigham and Women’s University is enrolling patients with drug resistant temporal lobe epilepsy.
A clinical trial that began at The Ohio State University is transitioning to its new home at University of North Carolina and will resume recruitment soon. It is designed to prevent the secondary generalization from focal onset epilepsy.
See here for a list of clinical trials sites
Preclinical Laboratory Studies
Preclinical studies are underway to investigate the use of various mechanisms of focused ultrasound in the treatment of epilepsy. Examples of these studies include:
- Focused ultrasound to temporarily disrupt the BBB and deliver promising drug therapies, including the dosing and timing (e.g. frequency) of drug administration.
- Focused ultrasound to induce neuromodulation, to stimulate or block signals in a specific area of the brain that are causing symptoms such as seizure.
Regulatory Approval and Reimbursement
Focused ultrasound is not approved by any regulatory bodies worldwide as a treatment for epilepsy, nor is the treatment reimbursed by medical insurance providers.
Notable Papers
Suggested Reading: Focused Ultrasound for Epilepsy (PDF), June 2020.
Mathon B, Navarro V, Lecas S, Roussel D, Charpier S, Carpentier A. Safety Profile of Low-Intensity Pulsed Ultrasound-Induced Blood-Brain Barrier Opening in Non-epileptic Mice and in a Mouse Model of Mesial Temporal Lobe Epilepsy. Ultrasound Med Biol. 2023 May;49(5):1327-1336. doi: 10.1016/j.ultrasmedbio.2023.02.002. Epub 2023 Mar 4.
Kim E, Kim HC, Van Reet J, Böhlke M, Yoo SS, Lee W. Transcranial focused ultrasound-mediated unbinding of phenytoin from plasma proteins for suppression of chronic temporal lobe epilepsy in a rodent model. Sci Rep. 2023 Mar 13;13(1):4128. doi: 10.1038/s41598-023-31383-4.
Chu PC, Huang CS, Ing SZ, Yu HY, Fisher RS, Liu HL. Pulsed Focused Ultrasound Reduces Hippocampal Volume Loss and Improves Behavioral Performance in the Kainic Acid Rat Model of Epilepsy. Neurotherapeutics. 2023 Mar 14. doi: 10.1007/s13311-023-01363-7.
Krishna V, Mindel J, Sammartino F, Block C, Dwivedi AK, Van Gomple JJ, Fountain N, Fisher R. A Phase-1 Open-label Trial Evaluating Focused Ultrasound Unilateral Anterior Thalamotomy for Focal Onset Epilepsy. Epilepsia. 2023 Feb 6. doi: 10.1111/epi.17535.
Afif S, Rehan ST, Ul Hussain H, Islam MS. Low-intensity focused ultrasound, a novel approach to epilepsy treatment in developing countries. Brain Behav. 2022 Dec 21:e2852. doi: 10.1002/brb3.2852.
Bex A, Bex V, Carpentier A, Mathon B. Therapeutic ultrasound: The future of epilepsy surgery? Rev Neurol (Paris). 2022 Dec;178(10):1055-1065. doi: 10.1016/j.neurol.2022.03.015. Epub 2022 Jul 17.
Murphy KR, Farrell JS, Gomez JL, Stedman QG, Li N, Leung SA, Good CH, Qiu Z, Firouzi K, Butts Pauly K, Khuri-Yakub BPT, Michaelides M, Soltesz I, de Lecea L. A tool for monitoring cell type-specific focused ultrasound neuromodulation and control of chronic epilepsy. Proc Natl Acad Sci U S A. 2022 Nov 16;119(46):e2206828119. doi: 10.1073/pnas.2206828119. Epub 2022 Nov 7.
Maguire MJ. Wired for sound: The effect of sound on the epileptic brain. Seizure. 2022 Sep 24;102:22-31. doi: 10.1016/j.seizure.2022.09.016.
Bex A, Bex V, Carpentier A, Mathon B. Therapeutic ultrasound: The future of epilepsy surgery? Rev Neurol (Paris). 2022 Jul 16:S0035-3787(22)00641-5. doi: 10.1016/j.neurol.2022.03.015.
Chu PC, Yu HY, Lee CC, Fisher R, Liu HL. Pulsed-Focused Ultrasound Provides Long-Term Suppression of Epileptiform Bursts in the Kainic Acid-Induced Epilepsy Rat Model. Neurotherapeutics. 2022 May 17. doi: 10.1007/s13311-022-01250-7.
Zhang M, Li B, Liu Y, Tang R, Lang Y, Huang Q, He J. Different Modes of Low-Frequency Focused Ultrasound-Mediated Attenuation of Epilepsy Based on the Topological Theory. Micromachines (Basel). 2021 Aug 23;12(8):1001. doi: 10.3390/mi12081001.
Stern JM, Spivak NM, Becerra SA, Kuhn TP, Korb AS, Kronemyer D, Khanlou N, Reyes SD, Monti MM, Schnakers C, Walshaw P, Keselman I, Cohen MS, Yong W, Fried I, Jordan SE, Schafer ME, Engel J Jr, Bystritsky A. Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy. Brain Stimul. 2021 Jun 23;14(4):1022-1031. doi: 10.1016/j.brs.2021.06.003.
Zhang M, Li B, Lv X, Liu S, Liu Y, Tang R, Lang Y, Huang Q, He J. Low-Intensity Focused Ultrasound-Mediated Attenuation of Acute Seizure Activity Based on EEG Brain Functional Connectivity. Brain Sci. 2021 May 27;11(6):711. doi: 10.3390/brainsci11060711.
Zhang Y, Buckmaster PS, Qiu L, Wang J, Keunen O, Ghobadi SN, Huang A, Hou Q, Li N, Narang S, Habte FG, Bertram EH, Lee KS, Wintermark M. Non-invasive, neurotoxic surgery reduces seizures in a rat model of temporal lobe epilepsy. Exp Neurol. 2021 May 12:113761. doi: 10.1016/j.expneurol.2021.113761.
Barragan A, Preston C, Alvarez A, Bera T, Qin Y, Weinand M, Kasoff W, Witte RS. Acoustoelectric imaging of deep dipoles in a human head phantom for guiding treatment of epilepsy. J Neural Eng. 2020 Oct 30;17(5):056040. doi: 10.1088/1741-2552/abb63a.
Yamaguchi T, Hori T, Hori H, Takasaki M, Abe K, Taira T, Ishii K, Watanabe K. Magnetic resonance-guided focused ultrasound ablation of hypothalamic hamartoma as a disconnection surgery: a case report. Acta Neurochir (Wien). 2020 Jul 2. doi: 10.1007/s00701-020-04468-6.
Lin Z, Meng L, Zou J, Zhou W, Huang X, Xue S, Bian T, Yuan T, Niu L, Guo Y, Zheng H. Non-invasive ultrasonic neuromodulation of neuronal excitability for treatment of epilepsy. Theranostics 2020; 10(12):5514-5526. doi:10.7150/thno.40520
Abe K, Yamaguchi T, Hori H, Sumi M, Horisawa S, Taira T, Hori T. Magnetic resonance-guided focused ultrasound for mesial temporal lobe epilepsy: a case report. BMC Neurol. 2020 Apr 29;20(1):160. doi: 10.1186/s12883-020-01744-x.
Zhang Y, Zhou H, Qu H, Liao C, Jiang H, Huang S, Ghobadi SN, Telichko A, Li N, Habte FG, Doyle T, Woznak JP, Bertram EH, Lee KS, Wintermark M. Effects of Non-invasive, Targeted, Neuronal Lesions on Seizures in a Mouse Model of Temporal Lobe Epilepsy. Ultrasound Med Biol. 2020 Feb 17. pii: S0301-5629(20)30010-7. doi: 10.1016/j.ultrasmedbio.2020.01.008.
Chen SG, Tsai CH, Lin CJ, Lee CC, Yu HY, Hsieh TH, Liu HL.Transcranial focused ultrasound pulsation suppresses pentylenetetrazol induced epilepsy in vivo. Brain Stimul. 2019 Sep 24. pii: S1935-861X(19)30374-2. doi: 10.1016/j.brs.2019.09.011.
Agnese V, Costa V, Scoarughi GL, Corso C, Carina V, De Luca A, Bellavia D, Raimondi L, Pagani S, Midiri M, Stassi G, Alessandro R, Fini M, Barbato G, Giavaresi G. Focused Ultrasound Effects on Osteosarcoma Cell Lines. Biomed Res Int. 2019 May 19;2019:6082304. doi: 10.1155/2019/6082304. eCollection 2019.
Parker WE, Weidman EK, Chazen JL, Niogi SN, Uribe-Cardenas R, Kaplitt MG, Hoffman CE. Magnetic resonance-guided focused ultrasound for ablation of mesial temporal epilepsy circuits: modeling and theoretical feasibility of a novel noninvasive approach. J Neurosurg. 2019 Jun 14:1-8. doi: 10.3171/2019.4.JNS182694. [Epub ahead of print] PMID: 31200385
Vejay N. Vakharia, MRCS , John S. Duncan, FRCP, Juri-Alexander Witt, PhD, Christian E. Elger, FRCP, Richard Staba, PhD, and Jerome Engel Jr, PhD. Getting the Best Outcomes from Epilepsy Surgery. ANN NEUROL 2018;83:676–690
Piper RJ, Hughes MA, Moran CM, Kandasamy J. Focused ultrasound as a non-invasive intervention for neurological disease: a review. Br J Neurosurg. 2016 Jun;30(3):286-93. doi: 10.3109/02688697.2016.1173189. Epub 2016 Apr 22.
Monteith S, Snell J, Eames M, Kassell NF, Kelly E, Gwinn R. Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study. J Neurosurg. 2016 Feb 12:1-8.
Kang JY, Wu C, Tracy J, Lorenzo M, Evans J, Nei M, Skidmore C, Mintzer S, Sharan AD, Sperling MR. Laser interstitial thermal therapy for medically intractable mesial temporal lobe epilepsy. Epilepsia. 2016 Feb;57(2):325-34. doi: 10.1111/epi.13284. Epub 2015 Dec 24.
Quigg M, Harden C. Minimally invasive techniques for epilepsy surgery: stereotactic radiosurgery and other technologies. J Neurosurg. 2014 Dec;121 Suppl:232-40. doi: 10.3171/2014.8.GKS141608. Review.
Wynn Legon, Tomokazu F Sato, Alexander Opitz, Jerel Mueller, Aaron Barbour, Amanda Williams & William J Tyler. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nature Neuroscience (2014).
Jolesz FA, McDannold NJ. Magnetic resonance-guided focused ultrasound: a new technology for clinical neurosciences. Neurol Clin. 2014 Feb;32(1):253-69.
Dallapiazza R, McKisic MS, Shah B, Elias WJ. Neuromodulation for movement disorders. Neurosurg Clin N Am. 2014 Jan;25(1):47-58.
Click here for additional references from PubMed.
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