Focused ultrasound treatment for essential tremor has been approved by the Food and Drug Administration (FDA) in July 2016.
Essential tremor (ET) is the most common movement disorder, affecting an estimated 3% of the population, or approximately 10 million individuals in the United States. ET is commonly viewed as a relatively benign disease.
However, the associated disabling aspects of ET, such as significant tremor of the hands, can impair patients’ ability to eat, shave, write, perform household activities, and function in the workplace.
The underlying etiology of ET is unclear, but cases often run in families (familial tremor). It has been estimated that approximately 50% of all cases are due to a genetic mutation, and the pattern of inheritance is most consistent with autosomal dominant transmission (i.e. dominant trait).
Focused Ultrasound Therapy
Focused ultrasound is a completely non-invasive method of thalamotomy - a procedure in which a predefined small volume of brain tissue containing nerve cells causing the tremor is destroyed - that could be an effective option for certain patients. It is performed while the patient is awake and involves no anesthesia, no incisions in the scalp, and no burr holes through the skull or insertion of electrodes into the brain.
The target is a region in the thalamus called the ventral intermediate nucleus (Vim). Current treatments are being performed on one side of the brain, but a study is underway doing staged bilateral Vim treatments.
Focused ultrasound may offer the following benefits in treating ET:
- It is a non-invasive, single treatment that enables patients to recover rapidly and quickly return to activities of normal life (usually the next day).
- Compared to RF ablation or DBS, focused ultrasound offers a reduced risk of infection, of damage to the non-targeted area, and of blood clot formation.
- Focused ultrasound offers rapid resolution of symptoms.
- In contrast to lesioning performed with stereotactic radiosurgery, focused ultrasound does not use ionizing radiation, thus avoiding the side effects of exposure to radiation.
- Because it is non-invasive, focused ultrasound could be an option for medically refractory ET patients (those who do not respond well to medication) who do not want to undergo surgery.
Phase 3 Pivotal Clinical Study
Enrollment has been completed in a multi-center pivotal randomized study to evaluate the safety and efficacy of focused ultrasound for the treatment of medication-refractory essential tremor patients. Results of this study have been reviewed and approved by the FDA.
A clinical trial at The Ohio State University is looking at pre-targeting images to see if this can help in long term sustainability of ET treatments.
A clinical trial in the UK and Spain has begun and is doing staged bilateral treatments. This group will treat the second side after at least nine months have passed after the first treatment.
Please see a list of possible treatment sites here.
Regulatory & Reimbursement
The Exablate system manufactured by Insightec earned FDA approval to treat essential tremor in July 2016. It is also approved for treating essential tremor in Europe, Korea, Canada, Japan, Russia, Taiwan, and the Middle East.
In the US, Medicare, at a national level, allows payment, of approximately and most regional payment centers for Medicare are covering this procedure. However, there are still a few regions that are not, so patients should inquire from their physician regarding payment.
Although the code for this care (0398T) has been approved to move to the payable class, it will not transition to the updated codes until late 2019. Until then, it is more likely that payment rejections will have to be appealed in order to ensure payment.
Commercial coverage and Medicaid will typically follow Medicare but should be evaluated with each company and region. Some facilities have a cash payment option, for those who are not willing to wait for insurance decisions for payment. Prices vary, but a rough estimate is $40,000.
Insightec has established an informational website, including patient stories and access to treatment site information. They have also set up a Reimbursement Support Manager, who can help with questions about the status of reimbursements. Her contact information is: Kim Martin, Reimbursement Support Manager, 1-(866) 392-8478 or .
Gallay MN, Moser D, Jeanmonod D. MR-guided focused ultrasound cerebellothalamic tractotomy for chronic therapy-resistant essential tremor: anatomical target reappraisal and clinical results. J Neurosurg. 2020 Feb 7:1-10. doi: 10.3171/2019.12.JNS192219.
Parras O, Domínguez P, Tomás-Biosca A, Guridi J. The role of tractography in the localization of the Vim nucleus of the thalamus and the dentato-rubro-thalamic tract for the treatment of tremor. Neurologia. 2020 Jan 5. pii: S0213-4853(19)30131-8. doi: 10.1016/j.nrl.2019.09.006. [Epub ahead of print] Review. English, Spanish.
Pouratian N, Baltuch G, Elias WJ, Gross R. American Society for Stereotactic and Functional Neurosurgery Position Statement on Magnetic Resonance-Guided Focused Ultrasound for the Management of Essential Tremor. Neurosurgery. 2019 Dec 12. pii: nyz510. doi: 10.1093/neuros/nyz510.
Halpern CH, Santini V, Lipsman N, Lozano AM, Schwartz ML, Shah BB, Elias WJ, Cosgrove GR, Hayes MT, McDannold N, Aldrich C, Eisenberg HM, Gandhi D, Taira T, Gwinn R, Ro S, Witt J, Jung NY, Chang JW, Rosenberg J, Ghanouni P. Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor. Neurology. 2019 Dec 10;93(24):e2284-e2293. doi: 10.1212/WNL.0000000000008561. Epub 2019 Nov 20.
Krishna V, Sammartino F, Cosgrove R, Ghanouni P, Schwartz M, Gwinn R, Eisenberg H, Fishman P, Chang JW, Taira T, Kaplitt M, Rezai A, Rumià J, Gedroyc W, Igase K, Kishima H, Yamada K, Ohnishi H, Halpern C. Predictors of Outcomes After Focused Ultrasound Thalamotomy. Neurosurgery. 2019 Nov 6. pii: nyz417. doi: 10.1093/neuros/nyz417.
Sharma S, Pandey S. Treatment of essential tremor: current status. Postgrad Med J. 2019 Oct 1. pii: postgradmedj-2019-136647. doi: 10.1136/postgradmedj-2019-136647.
Pineda-Pardo JA, Urso D, Martínez-Fernández R, Rodríguez-Rojas R, Del-Alamo M, Millar Vernetti P, Máñez-Miró JU, Hernández-Fernández F, de Luis-Pastor E, Vela-Desojo L, Obeso JA. Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy in Essential Tremor: A Comprehensive Lesion Characterization. Neurosurgery. 2019 Oct 1. pii: nyz395. doi: 10.1093/neuros/nyz395.
Ranjan M, Elias GJB, Boutet A, Zhong J, Chu P, Germann J, Devenyi GA, Chakravarty MM, Fasano A, Hynynen K, Lipsman N, Hamani C, Kucharczyk W, Schwartz ML, Lozano AM, Hodaie M. Tractography-based targeting of the ventral intermediate nucleus: accuracy and clinical utility in MRgFUS thalamotomy. J Neurosurg. 2019 Sep 27:1-8. doi: 10.3171/2019.6.JNS19612.
Miller TR, Zhuo J, Eisenberg HM, Fishman PS, Melhem ER, Gullapalli R, Gandhi D. Targeting of the dentato-rubro-thalamic tract for MR-guided focused ultrasound treatment of essential tremor. Neuroradiol J. 2019 Aug 13:1971400919870180. doi: 10.1177/1971400919870180.
Chang KW, Park YS, Chang JW. Skull Factors Affecting Outcomes of Magnetic Resonance-Guided Focused Ultrasound for Patients with Essential Tremor. Yonsei Med J. 2019 Aug;60(8):768-773. doi: 10.3349/ymj.2019.60.8.768.
Levi V, Eleopra R, Franzini A, Romito L. Is Deep Brain Stimulation still an option for tremor recurrence after Focused Ultrasound thalamotomy? A case report. J Clin Neurosci. 2019 Jul 18. pii: S0967-5868(19)30831-8. doi: 10.1016/j.jocn.2019.07.035.
Sinai A, Nassar M, Eran A, Constantinescu M, Zaaroor M, Sprecher E, Schlesinger I. Magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: a 5-year single-center experience. J Neurosurg. 2019 Jul 5:1-8. doi: 10.3171/2019.3.JNS19466.
Jones RM, Kamps S, Huang Y, Scantlebury N, Lipsman N, Schwartz ML, Hynynen K. Accumulated thermal dose in MRI-guided focused ultrasound for essential tremor: repeated sonications with low focal temperatures. J Neurosurg. 2019 May 10:1-8. doi: 10.3171/2019.2.JNS182995. [Epub ahead of print] PMID: 31075781
D'Souza M, Chen KS, Rosenberg J, Elias WJ, Eisenberg HM, Gwinn R, Taira T, Chang JW, Lipsman N, Krishna V, Igase K, Yamada K, Kishima H, Cosgrove R, Rumià J, Kaplitt MG, Hirabayashi H, Nandi D, Henderson JM, Butts Pauly K, Dayan M, Halpern CH, Ghanouni P. Impact of skull density ratio on efficacy and safety of magnetic resonance-guided focused ultrasound treatment of essential tremor. J Neurosurg. 2019 Apr 26:1-6. doi: 10.3171/2019.2.JNS183517. [Epub ahead of print]
Boutet A, Gwun D, Gramer R, Ranjan M, Elias GJB, Tilden D, Huang Y, Li SX, Davidson B, Lu H, Tyrrell P, Jones RM, Fasano A, Hynynen K, Kucharczyk W, Schwartz ML, Lozano AM. The relevance of skull density ratio in selecting candidates for transcranial MR-guided focused ultrasound. J Neurosurg. 2019 May 3:1-7. doi: 10.3171/2019.2.JNS182571. [Epub ahead of print]
Yang AI, Chaibainou H, Wang S, Hitti FL, McShane BJ, Tilden D, Korn M, Blanke A, Dayan M, Wolf RL, Baltuch GH. Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of a Ventricular Shunt: Technical Report. Oper Neurosurg (Hagerstown). 2019 Mar 19. pii: opz013. doi: 10.1093/ons/opz013.
Pineda-Pardo JA, Martínez-Fernández R, Rodríguez-Rojas R, Del-Alamo M, Hernández F, Foffani G, Dileone M, Máñez-Miró JU, De Luis-Pastor E, Vela L, Obeso JA. Microstructural changes of the dentato-rubro-thalamic tract after transcranial MR guided focused ultrasound ablation of the posteroventral VIM in essential tremor. Hum Brain Mapp. 2019 Mar 13. doi: 10.1002/hbm.24569.
Gasca-Salas C, Guida P, Piredda R, Obeso I, Vela Desojo L, Martínez-Fernández R, Hernández-Fernández F, Máñez-Miró J, Pineda-Pardo JA, Del Álamo M, Rodriguez-Rojas R, Mata-Marín D, Alonso-Frech F, de Luis E, Obeso JA. Cognitive safety after unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor. J Neurol Neurosurg Psychiatry. 2019 Mar 8. pii: jnnp-2018-320129. doi: 10.1136/jnnp-2018-320129.
Harary M, Segar DJ, Hayes MT, Cosgrove GR. Unilateral Thalamic Deep Brain Stimulation vs. Focused Ultrasound Thalamotomy for Essential Tremor. World Neurosurg. 2019 Feb 19. pii: S1878-8750(19)30400-0. doi: 10.1016/j.wneu.2019.01.281.
Park YS, Jung NY, Na YC, Chang JW. Four-year follow-up results of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor. Mov Disord. 2019 Feb 13. doi: 10.1002/mds.27637.
Weidman EK, Kaplitt MG, Strybing K, Chazen JL. Repeat magnetic resonance imaging-guided focused ultrasoundthalamotomy for recurrent essential tremor: case report and review of MRI findings. J Neurosurg. 2019 Jan 25:1-6. doi: 10.3171/2018.10.JNS181721.
Boutet A, Ranjan M, Zhong J, Germann J, Xu D, Schwartz ML, Lipsman N, Hynynen K, Devenyi GA, Chakravarty M, Hlasny E, Llinas M, Lozano CS, Elias GJB, Chan J, Coblentz A, Fasano A, Kucharczyk W, Hodaie M, Lozano AM. Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor. Brain. 2018 Nov 17. doi: 10.1093/brain/awy278.
Meng Y, Solomon B, Boutet A, Llinas M, Scantlebury N, Huang Y, Hynynen K, Hamani C, Fasano A, Lozano AM, Lipsman N, Schwartz ML. Magnetic resonance-guided focused ultrasound thalamotomy for treatment of essential tremor: A 2-year outcome study. Mov Disord. 2018 Oct 4. doi: 10.1002/mds.99.
Krishna V, Sammartino F, Agrawal P, Changizi BK, Bourekas E, Knopp MV, Rezai A. Prospective Tractography-Based Targeting for Improved Safety of Focused Ultrasound Thalamotomy. Neurosurgery. 2018 Mar 21. doi: 10.1093/neuros/nyy020.
Jung NY, Park CK, Chang WS, Jung HH, Chang JW. Effects on cognition and quality of life with unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor. Neurosurg Focus. 2018 Feb;44(2):E8. doi: 10.3171/2017.11.FOCUS17625.
Click here for additional references from PubMed.
Pre- and post-treatment assessment videos courtesy of University of Virginia