Focused ultrasound thalamotomy produced short-term improvement in hand tremor in patients with essential tremor, researchers reported.

In a randomized sham-controlled trial, patients who received the therapy had greater improvements in physician-rated hand tremor scores at 3 months (47% improvement versus 0.1% improvement, P<0.001), Jeffrey Elias, MD, of the University of Virginia Health Sciences Center, and colleagues reported in the New England Journal of Medicine.

But editorialist Elan Louis, MD, of Yale, noted that data reported in a supplementary appendix (available only online) showed that overall tremor scores (i.e., not just hand tremor) rose by 23% and physician-rated tremor scores rose by 38% at month 12, relative to their nadir at one month post-treatment.
“Whether this loss of efficacy, which is also seen to some extent with deep-brain stimulation, is due to disease progression or tolerance is not clear,” Louis wrote, adding that he considered the former “less likely.”
The investigators also noted that the treatment came with sensory and gait disturbances affecting roughly one-third of patients.
The FDA approved the device used in the current study for MRI-guided focused ultrasound thalamotomy in essential tremor last month. The current study was the manufacturer’s primary registration trial.
The procedure involves ablating tissue with high-intensity sound waves. Medical therapies for essential tremor include beta blockers — particularly propranolol — the antiepileptic drug primidone, and other drugs that enhance GABA transmission.

However, efficacy of these treatments is limited, so some patients try deep brain stimulation, which is the standard surgical procedure for this condition. It was approved by the FDA in 1997 for this indication, but there have been few randomized controlled trials of the technology, so evidence of its efficacy remains scant, Elias and colleagues wrote.
To assess whether focused ultrasound thalamotomy could provide another option for patients with moderate-to-severe essential tremor who don’t responded to other medical therapies, the researchers enrolled 76 patients, mean age 71 with a mean disease duration of 17 years, and randomized them in a 3:1 fashion to unilateral focused ultrasound (which, if effective, would improve tremor in only the contralateral hand) or to a sham procedure.
The primary outcome was difference in change from baseline to 3 months in hand tremor, rated on a 32-point scale in which higher scores indicate a more severe tremor.
After 3 months, patients in the sham group were allowed to cross over to the active treatment.
Overall, the researchers found that scores improved more after focused ultrasound than with the sham procedure (from scores of 18.1 to 9.6 versus 16 to 15.8) — a 47% improvement compared with a 0.1% improvement, and a mean difference of 8.3 points (P<0.001). No significant change in tremor scores for the ipsilateral hand was seen in treated patients.
The improvement in the focused ultrasound group persisted at one year, with a 40% improvement from baseline, they reported (P<0.001).
Patients who crossed over into the treatment group improved by 55% at 3 months and by 52% at 6 months, they found (P<0.001).
In terms of secondary outcomes, those who had focused ultrasound had greater improvements in disability (62% reduction versus 3% reduction, P<0.001) and in quality of life (46% improvement versus 3% improvement, P<0.001) at 3 months.
The researchers did note that higher rates of adverse events in thalamotomy group included gait disturbance (36%) and paresthesias or numbness (38%), and these persisted at one year in 9% and 14% of patients, respectively.
In the accompanying editorial, Louis highlighted “several important concerns.” First, the study was limited to 1 year, so the benefits further down the road aren’t clear, which requires more studies with longer follow-up, he said.
In addition to the overall tremor scores and physician-reported tremor scores increasing, Louis noted that not all patients benefitted from the procedure, with a percent change below 20% in 9 of 56 patients. Some skulls may be too thick for the procedure to work properly, he added.
Unlike with deep-brain stimulation, he warned, a thalamotomy creates a fixed brain lesion — and altered sensation remained in 14% of patients at 1 year, he wrote.
“Even with these concerns and caveats, pros and cons, the procedure will take its place among other surgical procedures for medically refractory essential tremor,” Louis wrote. “Given the perception that it is less invasive than other approaches because it does not involve burr holes and intracerebral electrodes, as well as the evidence that patients with essential tremor are perhaps particularly harm avoidant, the procedure may allow more patients to avail themselves of a surgical option for the treatment of this often disabling disease.”
He also called for a head-to-head comparison with deep-brain stimulation.