November 21, 2019
Three years after unilateral transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy using the ExAblate Neuro (InSightec) device, there was improvement from baseline in hand tremors, postural tremor, disability, and quality of life remained significant. On average, hand tremors had improved by 50%, disability by 56%, and quality of life by 42%.
"This study was the first to demonstrate that focused ultrasound thalamotomy could induce durable benefit up to 3 years after the procedure," Casey Halpern, MD, assistant professor of neurosurgery, Stanford University Medical Center in California, told Medscape Medical News.
The results suggest that this "incisionless treatment is capable of having long-term effects for patients, a critical novel finding in support of this exciting advance for patients with essential tremor," said Halpern.
The findings were published online November 20 in Neurology.
The trial was supported by InSightec, the Focused Ultrasound Foundation, and the Binational Industrial Research and Development (BIRD) Foundation, and Halpern has received research funding from InSightec.
As previously reported by Medscape Medical News, initial positive findings of the 76-patient study were presented in June 2016 at the 20th International Congress of Parkinson's Disease and Movement Disorders.
Based on these initial results, in July 2016, the US Food and Drug Administration (FDA) approved the ExAblate Neuro device to treat ET refractory to other treatments.
The full 1-year results of the study were published a month later in the New England Journal of Medicine.
The study included 76 patients (68% men; mean age, 71 years) with long-standing moderate-to-severe ET between August 2013 and September 2014 at eight centers in the United States, Canada, Sweden, Japan, and South Korea.
All had previously failed to respond adequately in at least two medical therapy trials. The patients were randomly assigned to unilateral focused ultrasound thalamotomy using the ExAblate Neuro system (n = 56) or a sham procedure (n = 20).
In the procedure, energy is converged onto a spot that is heated to approximately 55 to 60°C for 10 to 30 seconds.
At 3 years, the range of improvement from baseline on standard measures was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life.
Hand tremor disability scores showed a slight increase at 3 years compared with 6 months, indicating a slight return of tremor symptoms.
However, whether assessing the cohort or on a rigorous per-patient basis, the majority of patients at 3 years maintained a 50% improvement in hand tremor, the investigators note.
They point out that a reduction in improvement is "not unexpected as ET is a progressive disease; in addition, diminishing performance of motor–functional tasks over time, particularly in this elderly population, may be multifactorial."
Improvement in postural tremor and quality of life scores at 3 years remained stable.
A limitation of the study is that 23 patients (31%) did not complete the entire 3-year follow-up. The researchers determined that patients who later dropped out of the study were not responding as well to the treatment after 3 months as those who completed the trial.
Based on these findings, the investigators support the use of the procedure in patients with medication-refractory, disabling ET. The procedure, they note, can "be considered as a safe and effective therapeutic option, in suitable patients, for example, patients who refuse DBS [deep brain stimulation], patients with predominantly unilateral tremor, elderly patients, patients with slow progressing tremor, patients with comorbidities that increase surgical risk, or patients who live far from experienced DBS programming centers."
"There is a growing availability of this treatment nationwide," Halpern told Medscape Medical News, although Stanford is the only site in California that offers it. "Our finding, suggestive of long-term relief, will motivate new centers to invest in this technology as well," he added.
Will Effect Wear Off?
Reached for comment, David Weintraub, MD, director of functional neurosurgery at North Shore University Hospital in Manhasset, New York, said the findings add to the literature supporting the use of transcranial MRI-guided focused ultrasound thalamotomy in the treatment of essential tremor.
"The main result of this study is that the treatment effect from focused ultrasound thalamotomy is durable, with sustained tremor improvement in most patients at 3 years' follow-up. It is important to note that there was some loss of effectiveness in some patients, suggesting that the effect may wear off to some extent over time," said Weintraub.
"One must interpret the results with some caution since there was a significant percentage of patients who did not complete the 3-year follow-up," he also said.