Essential Tremor

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Focused ultrasound treatment for essential tremor has been approved by the Food and Drug Administration (FDA) in July 2016.

Medicare approved the treatment in all US states as of July 12, 2020.

The FDA approved staged bilateral treatment for essential tremor on December 20, 2022. Treatments are approved for the second side at least 9 months after the initial treatment.

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 rapidly evolving, noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with essential tremor. This novel technology focuses multiple beams of ultrasound energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue.

How it Works
Where the focused ultrasound beams converge, they produce precise ablation (thermal destruction of tissue), enabling ET to be treated noninvasively. The primary target is a region in the thalamus called the ventral intermediate nucleus (Vim), but other adjacent targets and white matter pathways are also in use.

Current treatments are being performed on one side of the brain, but there is a study underway of staged bilateral treatments.



Advantages

  • It is a noninvasive, 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.

Clinical Trials

A clinical trial in Los Angeles is using transcranial ultrasound neuromodulation to treat patients with essential tremor.

clinical trial in France is using focused ultrasound to treat ET.

A multi-site US clinical trial investigating staged bilateral treatments for ET has been completed.

clinical trial in the UK and Spain is testing staged bilateral treatments. This group will treat the second side after at least nine months have passed after the first treatment.

There are two clinical trials in Canada for bilateral treatments of essential tremor. These studies are only open to Canadian Citizens.

Treatment Sites

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, all treatment sites have been approved for payment under Medicare.

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.

Device manufacturer, 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.

Additional Information 

Notable Papers

Suggested Reading: Focused Ultrasound: Transforming treatment of Neurodegenerative Diseases August 2022

Suggested Reading: Focused Ultrasound for Essential Tremor Market Study (2021)

Bernstock JD, Torio EF, Raghu ALB, Chua M, Chen JA, Segar D, Gupta S, White PJ, McDannold N, Golby AJ, Cosgrove GR. Transcranial MR-Guided Focused Ultrasound and Hyperostosis Calvariae Diffusa: Case Report and Systematic Review of the Literature. Stereotact Funct Neurosurg. 2022 Dec 15;100(5-6):331-339. doi: 10.1159/000527232. PMID: 36521432

Lu H, Lin J, Xiong Y, Deng L, Wang X, Zhang D, Bian X, Zhou J, Pan L, Lou X. Assessing the impact of MR-guided focused ultrasound thalamotomy on brain activity and connectivity in patients with essential tremor. Neurosurg Focus. 2022 Dec;53(6):E5. doi: 10.3171/2022.9.FOCUS22228. PMID: 36455269

Visani E, Panzica F, Eleopra R, Rossi Sebastiano D, Lanteri P, Devigili G, Dotta S, Rinaldo S, Franceschetti S. MRI-guided focused-ultrasound thalamotomy in essential tremor: Immediate and delayed changes in cortico-muscular coherence and cortico-cortical out-strength. Clin Neurophysiol. 2022 Dec;144:67-71. doi: 10.1016/j.clinph.2022.10.001. Epub 2022 Oct 12. PMID: 36283222

Giammalva GR, Maugeri R, Umana GE, Paolini F, Bonosi L, Meccio F, Scalia G, Palmisciano P, Gerardi RM, Iacopino DG. DBS, tcMRgFUS, and gamma knife radiosurgery for the treatment of essential tremor: a systematic review on techniques, indications, and current applications. J Neurosurg Sci. 2022 Dec;66(6):476-484. doi: 10.23736/S0390-5616.22.05524-2. Epub 2022 Mar 17. PMID: 35301835

Jameel A, Meiwald A, Bain P, Patel N, Nandi D, Jones B, Weston G, Adams EJ, Gedroyc W. The cost-effectiveness of unilateral magnetic resonance-guided focused ultrasound in comparison with unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England. Br J Radiol. 2022 Dec 1;95(1140):20220137. doi: 10.1259/bjr.20220137. Epub 2022 Oct 12. PMID: 36125247

Rohringer CR, Sewell IJ, Gandhi S, Isen J, Davidson B, McSweeney M, Swardfager W, Scantlebury N, Swartz RH, Hamani C, Giacobbe P, Nestor SM, Yunusova Y, Lam B, Schwartz ML, Lipsman N, Abrahao A, Rabin JS. Cognitive effects of unilateral thalamotomy for tremor: a meta-analysis. Brain Commun. 2022 Nov 4;4(6):fcac287. doi: 10.1093/braincomms/fcac287. eCollection 2022. PMID: 36440102

Parras O, Domínguez P, Tomás-Biosca A, Guridi J. The role of tractography in the localisation of the Vim nucleus of the thalamus and the dentatorubrothalamic tract for the treatment of tremor. Neurologia (Engl Ed). 2022 Oct;37(8):691-699. doi: 10.1016/j.nrleng.2019.09.008. Epub 2021 Sep 23.

Visani E, Panzica F, Eleopra R, Rossi Sebastiano D, Lanteri P, Devigili G, Dotta S, Rinaldo S, Franceschetti S. MRI-guided focused-ultrasound thalamotomy in essential tremor: Immediate and delayed changes in cortico-muscular coherence and cortico-cortical out-strength. Clin Neurophysiol. 2022 Oct 12;144:67-71. doi: 10.1016/j.clinph.2022.10.001.

Unadkat P, Eidelberg D. Commentary on: A Network Approach to Understanding the Effects of Focused Ultrasound for Essential Tremor: Insights into Pathophysiology, Treatment, and Imaging Biomarkers. Neurotherapeutics. 2022 Oct 27. doi: 10.1007/s13311-022-01321-9.

Pohl EDR, Upadhyay N, Kobeleva X, Purrer V, Maurer A, Keil VC, Kindler C, Borger V, Pieper CC, Groetz S, Scheef L, Maciaczyk J, Schild H, Vatter H, Klockgether T, Radbruch A, Attenberger U, Wüllner U, Boecker H. Coherent Structural and Functional Network Changes after Thalamic Lesions in Essential Tremor. Mov Disord. 2022 Sep;37(9):1924-1929. doi: 10.1002/mds.29130. Epub 2022 Jun 23.

Xiong Y, Lin J, Bian X, Lu H, Zhou J, Zhang D, Pan L, Lou X. Treatment-Specific Network Modulation of MRI-Guided Focused Ultrasound Thalamotomy in Essential Tremor : Modulation of ET-Related Network by MRgFUS Thalamotomy. Neurotherapeutics. 2022 Sep 9. doi: 10.1007/s13311-022-01294-9.

Jameel A, Meiwald A, Bain P, Patel N, Nandi D, Jones B, Weston G, Adams EJ, Gedroyc W. The Cost-Effectiveness of unilateral magnetic Resonance-Guided focused ultrasound in comparison to unilateral deep brain stimulation for the treatment of medically refractory essential tremor in England. Br J Radiol. 2022 Sep 20:20220137. doi: 10.1259/bjr.20220137.

Leung SA, Moore D, Gilbo Y, Snell J, Webb TD, Meyer CH, Miller GW, Ghanouni P, Butts Pauly K. Comparison between MR and CT imaging used to correct for skull-induced phase aberrations during transcranial focused ultrasound. Sci Rep. 2022 Aug 4;12(1):13407. doi: 10.1038/s41598-022-17319-4.

Moosa S, Craver A, Asuzu D, Eames M, Wang TR, Elias WJ. Patient-Reported Outcomes and Predictive Factors following Focused Ultrasound Thalamotomy for Essential Tremor. Stereotact Funct Neurosurg. 2022 Aug 26:1-9. doi: 10.1159/000525763.

Tani N, Oshino S, Hosomi K, Hattori N, Mihara M, Yanagisawa T, Khoo HM, Kanemoto M, Watanabe Y, Mochizuki H, Kishima H. Altered Thalamic Connectivity Due to Focused Ultrasound Thalamotomy in Patients with Essential Tremor. World Neurosurg. 2022 Aug;164:e1103-e1110. doi: 10.1016/j.wneu.2022.05.113. Epub 2022 May 31.

Cosgrove GR, Lipsman N, Lozano AM, Chang JW, Halpern C, Ghanouni P, Eisenberg H, Fishman P, Taira T, Schwartz ML, McDannold N, Hayes M, Ro S, Shah B, Gwinn R, Santini VE, Hynynen K, Elias WJ Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results.  J Neurosurg. 2022 Aug 5:1-6. doi: 10.3171/2022.6.JNS212483. Online ahead of print.

Gauthier-Lafreniere E, Aljassar M, Rymar VV, Milton J, Sadikot AF. A standardized accelerometry method for characterizing tremor: Application and validation in an ageing population with postural and action tremor. Front Neuroinform. 2022 Aug 4;16:878279. doi: 10.3389/fninf.2022.878279. eCollection 2022.

Yamamoto K, Sarica C, Elias GJB, Boutet A, Germann J, Loh A, Joel SE, Bigioni L, Gwun D, Gramer R, Li SX, Zemmar A, Vetkas A, Algarni M, Devenyi G, Chakravarty M, Hynynen K, Scantlebury N, Schwartz ML, Lozano AM, Fasano A. Ipsilateral and axial tremor response to focused ultrasound thalamotomy for essential tremor: clinical outcomes and probabilistic mapping. J Neurol Neurosurg Psychiatry. 2022 Aug 22:jnnp-2021-328459. doi: 10.1136/jnnp-2021-328459.

Purrer V, Borger V, Pohl E, Upadhyay N, Boecker H, Schmeel C, Pieper CC, Wüllner U. Transcranial high-intensity Magnetic Resonance-guided focused ultrasound (tcMRgFUS) – safety and impacts on tremor severity and quality of life. Parkinsonism Relat Disord. 2022 Jul;100:6-12. doi: 10.1016/j.parkreldis.2022.05.017. Epub 2022 May 23.

Pae C, Kim MJ, Chang WS, Jung HH, Chang KW, Eo J, Park HJ, Chang JW. Differences in intrinsic functional networks in patients with essential tremor who had good and poor long-term responses after thalamotomy performed using MR-guided ultrasound. J Neurosurg. 2022 Jul 22:1-11. doi: 10.3171/2022.5.JNS22324.

Kato S, Maesawa S, Bagarinao E, Nakatsubo D, Tsugawa T, Mizuno S, Kawabata K, Tsuboi T, Suzuki M, Shibata M, Takai S, Ishizaki T, Torii J, Mutoh M, Saito R, Wakabayashi T, Katsuno M, Ozaki N, Watanabe H, Sobue G. Magnetic resonance-guided focused ultrasound thalamotomy restored distinctive resting-state networks in patients with essential tremor. J Neurosurg. 2022 Jul 8:1-12. doi: 10.3171/2022.5.JNS22411.

Yuen J, Goyal A, Kaufmann TJ, Jackson LM, Miller KJ, Klassen BT, Dhawan N, Lee KH, Lehman VT. Comparison of the impact of skull density ratio with alternative skull metrics on magnetic resonance-guided focused ultrasound thalamotomy for tremor. J Neurosurg. 2022 Jul 1:1-8. doi: 10.3171/2022.5.JNS22350.

Thaler C, Tian Q, WIntermark M, Ghanouni P, Halpern C, Henderson J, Airan R, Zeineh M, Goubran M, Leuze C, Fiehler J, Butts Pauly K, McNab JA. Changes In The Cerebello-thalamo-cortical Network After MR-guided Focused Ultrasound Thalamotomy. Brain Connect. 2022 Jun 9. doi: 10.1089/brain.2021.0157.

Pohl EDR, Upadhyay N, Kobeleva X, Purrer V, Maurer A, Keil VC, Kindler C, Borger V, Pieper CC, Groetz S, Scheef L, Maciaczyk J, Schild H, Vatter H, Klockgether T, Radbruch A, Attenberger U, Wüllner U, Boecker H. Coherent Structural and Functional Network Changes after Thalamic Lesions in Essential Tremor. Mov Disord. 2022 Jun 23. doi: 10.1002/mds.29130.

Erro R, Fasano A, Barone P, Bhatia KP. Milestones in Tremor Research: 10 Years Later. Mov Disord Clin Pract. 2022 Feb 26;9(4):429-435. doi: 10.1002/mdc3.13418. eCollection 2022 May.

Sasaki T, Date I. Essential Tremor That is Difficult to Improve with Standard Medical Treatment-Suppression: Surgical Treatment of Tremor. Brain Nerve. 2022 May;74(5):645-651. doi: 10.11477/mf.1416202092.

Boutet A, Loh A, Germann J, Machnowska M, Scantlebury N, Vetkas A, Elias GJB, Lozano AM, Katzberg HD, Fasano A, Schwartz ML. A Cautionary Tale of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy-Induced White Matter Lesions. Mov Disord. 2022 May 26. doi: 10.1002/mds.29040.

Purrer V, Borger V, Pohl E, Upadhyay N, Boecker H, Schmeel C, Pieper CC, Wüllner U. Transcranial high-intensity Magnetic Resonance-guided focused ultrasound (tcMRgFUS) – safety and impacts on tremor severity and quality of life. Parkinsonism Relat Disord. 2022 May 23;100:6-12. doi: 10.1016/j.parkreldis.2022.05.017.

Binder DK, Shah BB, Elias WJ. Focused ultrasound and other lesioning in the treatment of tremor. J Neurol Sci. 2022 Apr 15;435:120193. doi: 10.1016/j.jns.2022.120193. Epub 2022 Feb 19.

Alshimemeri S, Vargas-Méndez D, Chen R, Lipsman N, Schwartz ML, Lozano AM, Fasano A. Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor. J Neurol Neurosurg Psychiatry. 2022 Apr 26:jnnp-2021-327524. doi: 10.1136/jnnp-2021-327524.

Páez-Nova M, Spiegelmann R, Korn-Israeli S, Zibly Z, Illera-Rivera D, Daza-Cordoba C, Alcazar-Daza JC, Garcia-Ballestas E. Targeting the vim by direct visualization of the cerebello-thalamo-cortical pathway in 3 T proton density MRI: correlation with focused ultrasound lesioning. Neurosurg Rev. 2022 Feb 11. doi: 10.1007/s10143-022-01752-0.

Mensah-Brown KG, Yang AI, Hitti FL, Henry L, Heman-Ackah SM, Chaibainou H, Baltuch GH. Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Under General Anesthesia: Technical Note. Oper Neurosurg (Hagerstown). 2022 Feb 11. doi: 10.1227/ONS.0000000000000119.

Campbell JM, Ballard J, Duff K, Zorn M, Moretti P, Alexander MD, Rolston JD. Balance and cognitive impairments are prevalent and correlated with age in presurgical patients with essential tremor. Clin Park Relat Disord. 2022 Jan 23;6:100134. doi: 10.1016/j.prdoa.2022.100134. eCollection 2022.

Ahmed AK, Guo S, Kelm N, Clanton R, Melhem ER, Gullapalli RP, Ksendzovsky A, Eisenberg HM, Miller TR, Gandhi D. Technical Comparison of Treatment Efficiency of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy and Pallidotomy in Skull Density Ratio-Matched Patient Cohorts. Front Neurol. 2022 Jan 21;12:808810. doi: 10.3389/fneur.2021.808810. eCollection 2021.

Yamamoto K, Lozano AM, Fasano A. Commentary: Feasibility of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of Prior Craniotomy. Oper Neurosurg (Hagerstown). 2022 Mar 1;22(3):e147-e149. doi: 10.1227/ONS.0000000000000087.

Wathen C, Yang AI, Hitti FL, Henry L, Chaibainou H, Baltuch GH. Feasibility of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of Prior Craniotomy. Oper Neurosurg (Hagerstown). 2021 Dec 22. doi: 10.1227/ONS.0000000000000012.

Yuen J, Miller KJ, Klassen BT, Lehman VT, Lee KH, Kaufmann TJ. Hyperostosis in Combination With Low Skull Density Ratio: A Potential Contraindication for Magnetic Resonance Imaging-Guided Focused Ultrasound Thalamotomy. Mayo Clin Proc Innov Qual Outcomes. 2021 Dec 20;6(1):10-15. doi: 10.1016/j.mayocpiqo.2021.11.007. eCollection 2022 Feb.

Sammartino F, Yeh FC, Krishna V. Intraoperative lesion characterization after focused ultrasound thalamotomy. J Neurosurg. 2021 Dec 31:1-9. doi: 10.3171/2021.10.JNS211651.

Iorio-Morin C, Yamamoto K, Sarica C, Zemmar A, Levesque M, Brisebois S, Germann J, Loh A, Boutet A, Elias GJB, Azevedo P, Adam E, Patel U, Lenis M, Kalia SK, Hodaie M, Fasano A, Lozano AM. Bilateral Focused Ultrasound Thalamotomy for Essential Tremor (BEST-FUS Phase 2 Trial). Mov Disord. 2021 Nov;36(11):2653-2662. doi: 10.1002/mds.28716. Epub 2021 Jul 20.

Segar DJ, Lak AM, Lee S, Harary M, Chavakula V, Lauro P, McDannold N, White J, Cosgrove GR. Lesion location and lesion creation affect outcomes after focused ultrasound thalamotomy. Brain. 2021 Nov 9:awab176. doi: 10.1093/brain/awab176.

Click here for additional references from PubMed.

Pre- and post-treatment assessment videos courtesy of University of Virginia

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