ET is a most common movement disorder affecting roughly 0.9% of individuals over age 65 years, though it can have a large range of symptom severity ranging from mildly symptomatic to sufficiently severe as to render an individual unable to self-feed.1 Although there are no curative therapies, symptoms of ET are often managed medically using a variety of available oral or injected treatments.1,2 For patients whose tremor is not adequately controlled medically, surgical treatment options are also available including stereotactic thalamotomy with radiofrequency (RF) ablation and DBS.1 Radiosurgery has also been described, though there is less data available on its efficacy.1 Both unilateral thalamotomy and DBS are acceptable surgical interventions for medically refractory ET, though DBS is thought to have fewer adverse events.3
MRgFUS has emerged as a potential non-invasive thalamotomy technique.
Food and Drug Administration (FDA) approval for MRgFUS treatment of ET4 was based on its pivotal study, a prospective, double-blind, randomized, sham-controlled trial of MRgFUS to create a unilateral thalamic ablation for the treatment of ET, for which results were published in the peer reviewed literature.5 In this study, investigators examined the impact of the ExAblate® MRgFUS device in 76 patients with ET. There were 56 patients assigned to the treatment arm with ExAblate® and 20 patients assigned to the sham control group. Patients in the sham group could crossover to active treatment after 3 months, after initial effectiveness endpoints were assessed. The primary efficacy outcome measure was the change from baseline to 3 months in the on-medication upper limb tremor subscore of the Clinical Rating Scale for Tremor (CRST A+B) for the treated limb. The baseline CRST A+B score was 18.4 in the treatment group and 16.0 in the sham group. The CRST A+B score improved 47% by 3 months in the treatment group and 0.01% in the sham group with a between group difference of 8.3 (P < 0.001). The between group difference persisted at 12 months. Following the initial 3 month outcome assessment, 19 of the 20 patients originally randomized to the sham group and 2 patients randomized to MRgFUS, in whom the procedure was not completed crossed over to receive MRgFUS treatment. The mean baseline CRST A+B score at crossover in this group was 16.5, but 3 months after the crossover, the mean dropped to 7.4 (P <0.001), similar to the 3 month outcomes in the group originally allocated to treatment.
Following the FDA approval of MRgFUS for ET, MRgFUS for unilateral thalamotomy was approved by the FDA for the treatment of medication-refractory TDPD.6,7 Research has suggested that the pathophysiology of TDPD may be different from the pathophysiology of PD in patients affected primarily by rigidity and bradykinesia.8 Additionally, a unique medication strategy is often indicated for TDPD, but for refractory patients, surgery may be considered.9
In a study patterned off of the study used in FDA approval of MRgFUS for ET, investigators studied the impact of the ExAblate® MRgFUS device in 27 patients with TDPD.6,7 There were 20 patients assigned to the treatment arm and 7 patients assigned to the sham control group. Patients in the sham group could crossover to active treatment after 3 months, after initial effectiveness endpoints were assessed. The patients in the treatment arm received a unilateral MRgFUS thalamotomy. The primary efficacy outcome measure was the change from baseline to 3 months in the on-medication upper limb tremor subscore of the CRST A+B for the treated limb. The baseline CRST A+B score was 17 (range of 10.5-27.5) in the treatment group and 23 (range of 14-27) in the sham group. The CRST A+B score improved 62% by 3 months in the treatment group and 22% in the sham group (p = 0.04). The investigators also noticed improvements in efficacy secondary outcome measures at 3 months including the CRST, UPDRS, and PD Questionnaire-39 in the treatment group. Following the initial 3 month outcome assessment, 6 of the 7 patients originally randomized to the sham group crossed over to receive MRgFUS treatment. The median baseline CRST A+B score at crossover in these 6 was 21, but 3 months after the sham group crossed over, the median dropped to 5.5, similar to the 3 month outcomes in the group originally allocated to treatment. The investigators also considered the 1 year outcome of response in on-medication CRST A+B score. Of the 20 patients enrolled in the treatment group, 14 were unblended for 1 year assessments, and the median CRST was 5. Among the sham patients who crossed over, the median CRST was 6 at 1 year.
Additionally, MRgFUS is currently being studied for use in medically-refractory dyskinesia symptoms or motor fluctuations of advanced PD as part of a study registered at clinicaltrials.gov.10 This study does not yet have results available, so evidence from it was not reviewed.