Objective:  Essential or parkinsonian tremor is frequently refractory to medical therapy. There are no currently available non-invasive, incisionless treatments for refractory tremor. A cost effective, safe, and incisionless treatment is highly desired.

Methods:  We conducted a single-arm single-institutional pilot prospective trial from 2013 to 2019 with one-year follow-up to provide foundational evidence necessary prior to randomized controlled trials. Adult patients with medically refractory essential or parkinsonian tremor determined by a movement-disorder neurologist without prior surgical thalamotomy or radiation treatment to the thalamus were eligible. All patients were treated with frameless, image-guided unilateral radiosurgical ablation of the thalamic ventral intermediate nucleus.

The Fahn-Tolosa-Marin tremor rating scale, performed by a movement-disorder neurologist, and patient-reported quality of life using the disease-specific Quality of Life in Essential Tremor or PD Questionnaire were obtained prior to treatment and at 3, 6, 9, and 12 months following treatment to evaluate efficacy and safety.

Results:  Thirty-three patients, including 23 with essential tremor and 10 with Parkinson's disease, were enrolled. Overall treatment response rate was 83% (n=15/18) at 6 months. There was a marked improvement in tremor, with average total FTM reduction of 21% at 3 months (from 46 to 30 points, p=0·003) and 41% at 6 months (from 46 to 24 points, p=0·001); at 6 months, functional decline regressed by 54% (from 15 to 7 points, p=0·001). Quality of life improved by 57% (p=0·001) at 6 months in patients with essential tremor. Mild neurologic adverse events were observed in 6% (n=2/33) of patients; these resolved with supportive measures. No serious adverse events occurred.

Conclusion:  In a pilot trial, noninvasive, frameless radiosurgical thalamotomy appears safe and efficacious treatment for patients with tremor, with benefits in physical symptoms and quality of life. Accomplishing this with cost-effective frameless linear accelerator approach would make this more accessible globally for patients at more centers than currently available. Randomized controlled trials are merited.