Focused Ultrasound for Treatment of Movement Disorders: A Review of Non-Food and Drug Administration Approved Indications

Abstract

<b><i>Introduction:</i></b> MRI-guided focused ultrasound (FUS) is an incisionless thermo-ablative procedure that may be used to treat medication-refractory movement disorders, with a growing number of potential anatomic targets and clinical applications. As of this article’s publication, the only US Food and Drug Administration (FDA)-approved uses of FUS for movement disorders are thalamotomy for essential tremor (ET) and tremor-dominant Parkinson’s Disease (PD), and pallidotomy for other cardinal symptoms of PD. We present a state-of-the-art review on all non-FDA approved indications of FUS for movement disorders, beyond the most well-described indications of ET and PD. Our objective was to summarize the safety and efficacy of FUS in this setting and provide a roadmap for future directions of FUS for movement disorders. <b><i>Methods:</i></b> A state-of-the-art review was conducted on use of FUS for non-FDA approved movement disorders. All movement disorders excluding FDA-approved uses for ET and PD were included. <b><i>Results:</i></b> A total of 25 studies on 172 patients were included. In patients with tremor plus dystonia syndromes (<i>n</i> = 6), ventralis intermediate nucleus of the thalamus (VIM)-FUS gave &gt;50% tremor reduction, with no improvement in dystonia and worsened dystonia in 2/6 patients. Ventral-oralis complex (VO)-FUS gave &gt;50% improvement for focal hand dystonia (<i>n</i> = 6) and 100% return to musical performance in musician’s dystonia (<i>n</i> = 6). In patients with multiple sclerosis (MS) and tremor (<i>n</i> = 3), improvement in tremor was seen in 2 patients with a favorable skull density ratio; no MS disease change was noted after VIM-FUS. In patients with tremor and comorbid ataxia syndromes (<i>n</i> = 3), none were found to have worsened ataxia after VIM-FUS; all had clinically significant tremor improvement. Subthalamic nucleus (STN)-FUS for PD (<i>n</i> = 49) gave approximately 50% improvement in PD motor symptoms, with dystonia and mild dyskinesias as possible adverse effects. Cerebellothalamic tract (CTT-FUS) for ET (<i>n</i> = 42) gave 55–90% tremor improvement, with gait dysfunction as a rare persistent adverse effect. Pallidothalamic tract (PTT-FUS) for PD (<i>n</i> = 50) gave approximately 50% improvement in motor symptoms, with mild speech dysfunction as a possible adverse effect. <b><i>Conclusion:</i></b> VIM-FUS appeared safe and effective for heterogenous tremor etiologies, and VO-FUS appeared most effective for isolated segmental dystonia. STN-FUS was effective for PD symptom reduction; postoperative dystonia and mild on-medication dyskinesias required medical management. Tractography-based targeting with CTT-FUS for ET and PTT-FUS for PD demonstrated promising early results. Larger prospective trials with long-term follow-up are needed to the evaluate the safety and efficacy non-FDA approved indications for FUS.