Objective: To evaluate heterogeneity of outcomes following magnetic resonance-guided focused ultrasound (MRgFUS) for essential tremor (ET), highlighting differences in assessment time points, thresholds and definitions.

Background: MRgFUS thalamotomy is established for medication-refractory ET, yet studies report varied outcome definitions for treatment “success” and “recurrence”. Follow-up intervals to assess initial success range from immediately post-procedure to six months, and studies use clinical measures including tremor severity (e.g., CRST/FTM), functional disability scores, and patient-reported outcomes like quality-of-life assessments. This heterogeneity limits cross-study comparisons and retrospective analyses, warranting a literature review to better characterize its extent.

Method: A comprehensive PubMed search was performed using search terms like “MRgFUS”, “focused ultrasound”, “essential tremor”, “outcomes”, and “recurrence”. Full text articles were reviewed and data on assessment time points, outcome measures, success thresholds, and recurrence criteria were compiled, summarized, and grouped to identify patterns and variability.

Results: Success definitions vary. The pivotal trial used CRST Part A+B scores at 3 months,¹ and reported those achieving ≥50% improvement.^2,3 Other studies report >80% at 6 months,⁴ or >90% patient-reported improvement.⁵ Early improvements may reflect transient edema,^6,7 leading some to favor 6-month assessments.⁴ Recurrence is reported in 4 –11% of cases,^5,8 with definitions ranging from >33% loss of efficacy,⁸ ≥50% loss,⁹ >5-point increase in FTM,¹⁰ >3-point increases in FTM Part A,¹¹ <30% CRST reduction from baseline,¹² return to baseline,⁵ functional impact,¹³ seeking other therapies,³ to no clear definition.⁷ Timing is key: early recurrence may reflect suboptimal treatment, while late recurrence may reflect disease progression.^3,14,15

Conclusion: The lack of standardized definitions limits cross-study comparisons, hinders treatment optimization, and complicates clinician and patient education. Consensus on assessment time points, efficacy thresholds, and recurrence criteria is critical to improve outcome evaluation and guide clinical decision-making. Ongoing international modified-Delphi efforts aim to address these gaps by establishing standardized terminology and a unified clinical framework.

References: 1) Elias, W. Jeffrey, et al. “A randomized trial of focused ultrasound thalamotomy for essential tremor.” New England Journal of Medicine 375.8 (2016): 730-739.
2) Chang, Jin Woo, et al. “A prospective trial of magnetic resonance–guided focused ultrasound thalamotomy for essential tremor: results at the 2‐year follow‐up.” Annals of neurology 83.1 (2018): 107-114.
3) Halpern, Casey H., et al. “Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.” Neurology 93.24 (2019): e2284-e2293.
4) Arcadi, Alana, et al. “Magnetic Resonance‐Guided Focused Ultrasound (MRgFUS)‐Thalamotomy for Essential Tremor: Lesion Location and Clinical Outcomes.” Movement Disorders 39.6 (2024): 1015-1025.
5) Kim, Minsoo, et al. “Comparative evaluation of magnetic resonance-guided focused ultrasound surgery for essential tremor.” Stereotactic and functional neurosurgery 95.4 (2017): 279-286.
6) Wintermark, M., et al. “Imaging findings in MR imaging–guided focused ultrasound treatment for patients with essential tremor.” American journal of neuroradiology 35.5 (2014): 891-896.Stouwe 2024
7) Zaaroor, Menashe, et al. “Magnetic resonance–guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson’s disease and essential tremor cases.” Journal of neurosurgery 128.1 (2017): 202-210.
8) Kapadia, Anish N., et al. “Multimodal MRI for MRgFUS in essential tremor: post-treatment radiological markers of clinical outcome.” Journal of Neurology, Neurosurgery & Psychiatry 91.9 (2020): 921-927.Lak 2022
9) Lak, Asad M., et al. “Magnetic resonance image guided focused ultrasound thalamotomy. A single center experience with 160 procedures.” Frontiers in Neurology 13 (2022): 743649.
10) Bruno, Federico, et al. “Comprehensive evaluation of factors affecting tremor relapse after MRgFUS thalamotomy: a case-control study.” Brain sciences 11.9 (2021): 1183.
11) Bruno, Federico, et al. “Early re-emerging tremor after MRgFUS thalamotomy: case–control analysis of procedural and imaging features.” Frontiers in Neurology 15 (2024): 1356613.
12) Tamburin, Stefano, et al. “Magnetic resonance-guided focused ultrasound unilateral thalamotomy for medically refractory essential tremor: 3-year follow-up data.” Frontiers in Neurology 15 (2024): 1360035.Sinai 2019
13) Sinai, Alon, et al. “Magnetic resonance–guided focused ultrasound thalamotomy for essential tremor: a 5-year single-center experience.” Journal of neurosurgery 133.2 (2019): 417-424.
14) Krishna, Vibhor, et al. “Predictors of outcomes after focused ultrasound thalamotomy.” Neurosurgery 87.2 (2020): 229-237.
15) van der Stouwe, A. M. M., et al. “Double lesion MRgFUS thalamotomy for essential tremor: 4.5-year outcomes and framework for assessing loss of efficacy and tremor progression.” British journal of neurosurgery (2024): 1-4.

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