Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor

Abstract

ObjectiveTo test the hypothesis that transcranial magnetic resonance–guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial.MethodsOutcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor–motor (scale of 0–32), functional disability (scale of 0–32), and postural tremor (scale of 0–4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0–100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported.ResultsMeasured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0–2, p = 0.0098) and disability (95% CI 1–4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred.ConclusionsResults at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant.Clinicaltrials.gov identifierNCT01827904.Classification of evidenceThis study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

A Population Model of Deep Brain Stimulation in Movement Disorders From Circuits to Cells

“…Hence, it appears that the thalamus acts as a hub for the support of these low-frequency oscillations. This is consistent with the clinical practice of thalamotomy, thalamic DBS and MRI guided focussed ultrasound of the thalamus for relieving tremor (Bretsztajn and Gedroyc, 2018;Halpern et al, 2019). Furthermore, it is also supported by the targeting of zona incerta (ZI) during STN DBS (Yousif et al, 2012), a region highly connected with the thalamus.…”

Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation

“…It is noteworthy that despite suboptimal targeting and premature cessation of sonications due to dysarthria, the initial MRgFUS treatment resulted in tremor relief, albeit temporarily. The onset of tremor recurrence within 1 year postoperatively has been reported in numerous cases in the literature, even without lesions complicated by dysarthria (Wang et al, 2018;Halpern et al, 2019). This suggests several plausible explanations for loss of tremor suppression efficacy over time after MRgFUS.…”

“…In a 2-year follow up study, however, 4% of the original cohort subsequently received DBS due to unsuccessful or suboptimal treatment with MRgFUS (Chang et al, 2018). A retrospective comparative evaluation of RF thalamotomy, DBS, or MRgFUS for ET patients revealed this loss of effect is shared across modalities (Halpern et al, 2019). Moreover, compared to 6-months post-procedure, the 3-year follow-up study found that even though the primary outcome metric for the trial (i.e., the hand combined tremor-motor score) was significantly improved, there was a slight but significant increase in the median total Clinical Rating Scale for Tremor (CRST) score over time (Kim et al, 2017).…”

Improved Vim targeting for focused ultrasound ablation treatment of essential tremor: A probabilistic and patient‐specific approach

“…Evaluation with clinical outcomes at later timepoints will be critical for assessing the ability of our probabilistic target region to predict longer term therapeutic effects. As MRgFUS becomes more widespread, studies with larger numbers of patients and examining farther timepoints from surgery are becoming more common (Halpern et al, 2019). Future work would benefit from a larger patient cohort and from the correlation of image‐derived features with clinical outcome at multiple timepoints post‐treatment.…”

“…In these situations, intervention was previously limited to radiofrequency or radiosurgical thalamotomy, deep‐brain stimulation (DBS) (Benabid et al, 1996), or most recently, magnetic resonance‐guided focused ultrasound (MRgFUS) of the ventral intermediate (Vim) nucleus of the thalamus, although improvements tend to decrease over time for all methods. In the present study, we focused on MRgFUS thalamotomy, a promising new technology that was recently FDA‐approved as an incisionless ablation therapy for the relief of medically refractory ET (Elias et al, 2016; Halpern et al, 2019). Like DBS, preoperative imaging is used to determine an initial target location and awake intraoperative testing is used to refine the target location.…”