To comprehensively review safety outcomes reported following unilateral and staged, bilateral magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of medication-refractory essential tremor (ET).

MRgFUS is FDA-approved for the unilateral and staged, bilateral treatment of medication-refractory ET. To date, over 20,000 MRgFUS neurosurgical procedures have been performed worldwide. In the United States, MRgFUS has surpassed deep brain stimulation to become the most common procedural intervention for ET. In clinical trials, MRgFUS treatment results in immediate, signi?cant, long-lasting improvements in tremor, with favorable safety profile.

We summarized long-term safety findings of unilateral and staged, bilateral MRgFUS treatment using data from clinical trials, published literature, company-reported safety data and surveys.

In pivotal trials, most related adverse events (AEs) were classified as mild (74% unilateral; 85% staged, bilateral), with no related severe events. The most common AEs were paresthesias (38%; 33%) and gait disturbance (36%; 24%). Dysarthria and taste disturbance were reported more commonly after staged, bilateral MRgFUS (2%; 24% and 4%; 22%, respectively). Many related AEs resolved within 6 months (48%; 56%). At long-term follow-ups, there were no new or worsening AEs. Results from the literature indicate a similar safety profile, with mild transitory procedure-related AEs (e.g., headache, nausea) and mild-to-moderate paresthesias and gait disturbances, weakness, dysmetria, and dysgeusia (mainly after bilateral treatments), which mostly diminish over time. No declines in cognition have been reported. In post marketing surveillance, 226 AEs (1.5% of 15,200 procedures) were reported, mostly related to gait disturbance and paresthesias. Surveys conducted with treating physicians indicated a good to excellent perception of safety, without unexpected safety events.

The safety data continuously collected in real-world, everyday clinical practice, suggests that unilateral and staged, bilateral MRgFUS is safe and well-tolerated, without new or unexpected safety events. This evidence supports the leading role of MRgFUS among advanced therapies to treat ET.