MRI-Guided Focused Ultrasound Demonstrates Efficacy for Essential Tremor, But Effect Decreases Over Time

Antonella Macerollo, MD, PhD

(Credit: LinkedIn)

Findings from a recent meta-analysis published in Movement Disorders revealed that although MRI-guided focused ultrasound, an approved noninvasive therapy for essential tremor (ET), initially showed an effect in tremor relief, the treatment’s benefits tended to decrease over time, which may necessitate further investigation into its long-term durability for patients living with the movement disorder.¹

The meta-analysis included 45 studies, with 42 qualifying for the final analysis, assessing the long-term efficacy and safety of MRI-guided focused ultrasound for ET. All told, the study reported significant improvements in tremor severity, disability, and quality of life scores 1 year following the procedure in patients with ET. Specifically, pooled standardized mean differences were -2.36 for hand tremor, -2.08 for total tremor, -2.85 for disability scores, and -1.41 for quality of life (all, P < .0001). However, the analysis also revealed a decrease in treatment effects over time.

“The results of this meta-analysis highlight the need to standardize the reporting of patient outcomes and adverse events (AEs). This could be achieved with the use of digital, objective measures of the tremor to monitor the outcome of the surgery,” senior author Antonella Macerollo, MD, PhD, consultant neurologist at the Walton Centre NHS Foundation Trust, and colleagues wrote.¹ “In addition, there is a need to objectively monitor AEs such as gait and balance impairments, which would benefit from technological solutions. Attaining this aim will minimize heterogeneity across studies and will enhance our understanding of the benefits and limitations of the procedure.”

The study utilized a systematic search across major databases including PubMed, Scopus, Web of Science, and Cochrane Library, following referred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines.² Researchers analyzed the data using both random-effects models for meta-analysis and mixed-effects models for meta-regression. Safety outcomes revealed common adverse events (AEs), with sensory symptoms observed in 22% of cases (95% CI 15%; 31%) and unsteadiness in 23% of cases (95% CI 16%; 31%) one month after treatment.

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These findings indicate that although MRI-guided focused ultrasound could be a promising option for patients with ET, clinicians should potentially consider the possibility of diminishing treatment effects over time and the occurrence of adverse symptoms. Notably, the decrease in efficacy seen in the meta-regression suggests that ongoing research could be essential to refine the procedure and better understand how long the benefits of MRI-guided focused ultrasound last.

“In addition, our results showed that there is a lack of RCTs that assess long-term efficacy. Indeed, there is only one published study reporting 5-year follow-up outcomes. We therefore suggest that there is an urgent need for extended follow-up studies and longitudinal patient monitoring that focuses on patient-centered outcomes as well as clinical efficacy,” Macerollo et al noted.¹

The variability in reporting AEs and the lack of standardization in assessments led to high heterogeneity in the meta-analysis, according to the authors. Many AEs were self-reported without clinical examination, and differences in patient demographics, sample sizes, and outcome measures contributed to this variability. Additionally, the exclusion of non-English studies and potential overlap of cohorts could have impacted the results. Limited long-term follow-up data restricted comprehensive analysis, and the inclusion of studies with varying quality highlights the need for more standardized, multicenter research.

“Overall, this work provides a robust and up-to-date meta-analysis of the treatment effect of [MRI-guided focused ultrasound] in ET patients, including improvements in terms of tremor, disability, and QOL measures, in which effect sizes were significant. It also provides an analysis of AEs, including those reported intraoperatively and up to 1-year post-procedure,” Macerollo et al noted.¹ “Our results suggest a decline in efficacy over time across 5 years, and a decline in the proportions of AEs across 1 year, but further evidence is needed to substantiate these findings. Future work could also investigate this intervention based upon patient characteristics such as SDR and cognitive impairment, target area, and unilateral versus bilateral procedures.”

REFERENCES
1. Shiramba A, Lane S, Ray N, et al. Efficacy and Safety of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy in Essential Tremor: A Systematic Review and Metanalysis. Mov Disord. Published online April 17, 2025. doi:10.1002/mds.30188
2. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. Published 2021 Mar 29. doi:10.1136/bmj.n71