ARTICLE CLASS OF EVIDENCE Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor Casey H. Halpern, MD, Veronica Santini, MD, Nir Lipsman, MD, PhD, Andres M. Lozano, MD, PhD, Michael L. Schwartz, MD, Binit B. Shah, MD, W. Jeff Elias, MD, Garth R. Cosgrove, MD, Michael T. Hayes, MD, Nathan McDannold, PhD, Christina Aldrich, RN, MSN, Howard M. Eisenberg, MD, Dheeraj Gandhi, MD, Takaomi Taira, MD, PhD, Ryder Gwinn, MD, Susie Ro, MD, Jennifer Witt, MD, Na Young Jung, MD, Jin Woo Chang, MD, Jarrett Rosenberg, PhD, and Pejman Ghanouni, MD, PhD Neurology ® 2019;93:e1-e10. doi:10.1212/WNL.0000000000008561 Correspondence Dr. Halpern chalpern@stanford.edu or Dr. Ghanouni ghanouni@stanford.edu Abstract Objective To test the hypothesis that transcranial magnetic resonance–guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication- refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a con- trolled multicenter prospective trial. Methods Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor–motor (scale of 0–32), functional disability (scale of 0–32), and postural tremor (scale of 0–4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0–100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. Results Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0–2, p = 0.0098) and disability (95% CI 1–4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. Conclusions Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. Clinicaltrials.gov identifier NCT01827904. Classification of evidence This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years. MORE ONLINE Class of Evidence Criteria for rating therapeutic and diagnostic studies NPub.org/coe Podcast Dr. Jason Crowell talks with Dr. Casey Halpern about his paper on a 3-year follow-up of a prospective trial of focused ultrasound thalamotomy for essential tremor. NPub.org/021x7d From the Departments of Neurosurgery (C.H.H.), Neurology (V.S.), and Radiology (J.R., P.G.), Stanford University School of Medicine, CA; Department of Neurosurgery (N.L., A.M.L., M.L.S.), University of Toronto, Canada; Department of Neurology (B.B.S., W.J.E.), University of Virginia, Charlottesville; Departments of Neurosurgery (G.R.C.), Neurology (M.T.H.), and Radiology (N.M.), Brigham and Women’s Hospital, Boston, MA; Departments of Neurosurgery (C.A., H.M.E.) and Radiology (D.G.), University of Maryland, Baltimore; Department of Neurosurgery (T.T.), Tokyo Women’s Medical University, Japan; Departments of Neurosurgery (R.G.) and Neurology (S.R., J.W.), Swedish Hospital Seattle, WA; and Department of Neurosurgery (N.Y.J., J.W.C.), Yonsei University, Seoul, Republic of Korea. Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. Copyright © 2019 American Academy of Neurology e1 Copyright © 2019 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Published Ahead of Print on November 20, 2019 as 10.1212/WNL.0000000000008561