ayesha.jameel@nhs.net;w.gedroyc@imperial.ac.uk

Essential Tremor (ET) is estimated to affect 10 million people in the United States. Magnetic Resonance guided focused ultrasound (MRgFUS) is a non-invasive treatment for ET that allows targeted thermal ablation of brain tissue under real time image guidance. Previous studies have demonstrated successful targeting of the thalamic Ventral Intermedius Nucleus (Vim) to be an effective treatment in ET; this paper describes the world's first trial using MRgFUS to target both the thalamic Vim and the subthalamic Zona Incerta (ZI).

This prospective study enrolled 13 patients with medication refractory ET for unilateral MRgFUS procedure. Tremor severity and functional impairment were assessed at baseline and regular intervals post-treatment for 24 months, using the Clinical Rating Scale for Tremor (CRST), Quality of Life in Essential Tremor (QUEST) and Bain-Findley Spirals (BFS) scores. BFS Spirals were also collated intraoperatively: immediately pre-procedure, after targeting the Vim and after targeting the ZI. All spirals were scored by 3 blinded movement disorder Neurologists. The percentage improvement in the spiral scores after Vim ablation and after ZI ablation were compared and analysed.

In all patients there was successful thermal ablation of the target tissue at both Vim and ZI, with improvement in all parameters over the 24months: CRST tremor score of the treated arm 73.5% and the non-treated arm 38.4%, QUEST 38%, BFS 46.9%. The intraoperative BFS scores demonstrated the additional benefit of targeting the ZI was 21.8% - improvement after Vim lesioning 27.9% but after both Vim and ZI lesioning was 49.7%. One patient (7.69%) experienced a significant adverse event; post-treatment unilateral hemi-chorea persistent at 2 years.

Our study provides further evidence that MRgFUS is an effective curative treatment for ET and demonstrates the additional benefit of targeting the subthalamic ZI with the thalamic Vim. Furthermore improvement in the tremor scores of non-treated arm shows the positive bilateral effects of targeting the ZI.

MRgFUS has the potential to revolutionise the treatment of movement disorders such as ET It provides an non-invasive alternative to current surgical therapies such as DBS.