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 between-group 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 open-label 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. (Funded by InSightec and others; ClinicalTrials.gov number, 
NCT01827904.).