MRgFUS thalamotomy is an effective treatment for patients with medically refractory essential tremor (ET) although the lesion location for optimal tremor control and minimal side effects is unknown.

We reviewed 200 consecutive ET patients who underwent unilateral MRgFUS thalamotomy at our center. Clinical outcomes including Fahn-Tolosa-Marin (FTM) tremor scores and side effects were collected prospectively at 1 day, 3 months, and 1 year post-procedure. Lesions were manually segmented on thin-cut T2 axial images 24 hours after surgery and mapped to standard MNI space using the Lead-DBS platform. The Sweetspot Explorer tool within Lead-DBS was used to investigate sites corresponding to optimal tremor outcomes (i.e., “sweetspot) and side effects (i.e., “sourspots”). The Fiber Filtering Explorer tool within Lead-DBS was used to investigate fiber tracts associated with optimal tremor control and side effects.

The average FTM score reduction at 1-year in our cohort was 86.01%. We identified a specific subregion within the Vim associated with highest 1-year FTM score improvements. This sweetspot intersected with the dentatorubrothalamic tract (DRTT) defined by either of two normative tract atlases. Additionally, only streamlines forming part of the DRTT were positively associated with tremor improvement.

The frequency of side effects was highest on day 1 and gradually improved over time. Weakness was associated with lesions extending laterally into the internal capsule and associated with the corticospinal tract (CST). Sensory deficits and dysgeusia were associated with posterior lesions associated with medial lemniscal fibers. Dysgeusia also revealed fibers corresponding to the trigeminothalamic tract. Gait imbalance was associated with ventrolateral lesions and fibers corresponding to the DRTT and CST. Dysarthria was associated with superomedial lesions.

We report a clinical and radiological analysis of 200 MRgFUS thalamotomy cases that demonstrates an optimal target area for tremor control as well as regions associated with specific side effects which could help refine current targeting methods and improve future outcomes.