BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the betweengroup difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the openlabel extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances.
Bibliographical noteFunding Information:
(Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.) Supported by InSightec, the Focused Ultrasound Foundation, and the Binational Industrial Research and Development (BIRD) Foundation. Dr. Elias reports receiving grant support from InSightec and the Focused Ultrasound Foundation; Dr. Lipsman, receiving fees from the Focused Ultrasound Foundation for serving on a steering committee; Dr. Ghanouni and Dr. Butts Pauly, receiving grant support from InSightec and GE Healthcare; Dr. Hynynen, receiving royalties from a patent related to ultrasound therapy (US6770031 B2); Dr. Lozano, receiving grant support from In-Sightec; Dr. Gwinn, receiving teaching fees from NeuroPace and Boston Scientific; Dr. Cosgrove, receiving consulting fees from InSightec; and Dr. Taira, receiving lecture fees from Daiichi-Sankyo, Eisai, GlaxoSmithKline, Otsuka, Pfizer, Hisamitsu, Dainippon-Sumitomo, Takeda, and Kyowa-Hakko, and grant support from St. Jude Medical. No other potential conflict of interest relevant to this article was reported. We thank Rodger Elble, M.D., Ludy Shih, M.D., Peter Lewitt, M.D., Raj Pahwa, M.D., Dan Tarsy, M.D., and Theresa Zesiewicz, M.D., of the Tremor Research Group for performing videotape tremor ratings, and Vera Hashem, Ph.D., for coordinating the core laboratory.
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