Literature Review

Benefits of focused ultrasound thalamotomy for essential tremor persist for 3 years



Reduction in improvement may have many causes

“A reduction in improvement is not unexpected, as essential tremor is a progressive disease,” wrote Dr. Halpern and colleagues. “In addition, diminishing performance of motor–functional tasks over time, particularly in this elderly population, may be multifactorial.” Decrease in tremor control has been reported after all surgical treatments for essential tremor (e.g., deep brain stimulation [DBS] and radiofrequency thalamotomy). Retreatment with invasive therapies or ionizing irradiation would be more problematic than retreatment with focused ultrasound thalamotomy, they added.

The researchers acknowledged that the main limitations of their study were the 31% dropout rate at 3 years and the fact that the cohort at 3-year follow-up differed from those at 2-year follow-up and in the original trial. The results nevertheless “demonstrate persistent, significant tremor reduction, as well as functional and quality of life improvement, with a positive safety profile,” they wrote.

Study funding was provided by the Focused Ultrasound Foundation, the Binational Industrial Research and Development Foundation of Israel, and InSightec, the maker of the focused ultrasound equipment that the researchers used. Dr. Halpern and other investigators received research funding from InSightec. One of the researchers is on the company’s medical advisory board, and another served as a consultant to the company.

Effect on axial tremor is unclear

The 50% improvement in hand tremor, disability, and quality of life that Halpern et al. report is similar to the improvement observed following DBS therapy, said Aparna Wagle Shukla, MD, director of the neurophysiology laboratory at the University of Florida in Gainesville, in an interview. Although the results are promising, neurologists should bear several points in mind, she added.

“DBS-induced side effects often are amenable to programming adjustments. However, similar to radiofrequency thalamotomy, focused ultrasound thalamotomy causes lesion effects. While the study discusses the nature of thalamotomy-induced adverse effects, the clinical practitioners also will benefit from learning about the severity of side effects and how they were individually addressed,” said Dr. Wagle Shukla. “The study acknowledges that there was a 30% dropout rate at 3 years’ follow-up. As the original plan included a 5-year follow-up, it would be beneficial to know why a large fraction of participants discontinued participation earlier than expected.”

Furthermore, the study by Halpern et al. leaves several questions unanswered. It does not indicate, for example, whether focused ultrasound thalamotomy can affect the control of axial tremor, including head and voice tremor, said Dr. Wagle Shukla. “Also, the potential of focused ultrasound thalamotomy to treat complex tremors with possible targeting of multiple brain regions such as ventralis oralis anterior and posterior and zona incerta stimulation is currently not known.

“There is no doubt that focused ultrasound thalamotomy is useful for the control of hand tremors in patients diagnosed with essential tremor, with long-term improvements in quality of life,” Dr. Wagle Shukla continued. “However, it is presently limited in its scope as a unilateral, single-target brain procedure.”

SOURCE: Halpern CH et al. Neurology. 2019 Nov 20 (Epub ahead of print).

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