Clinical Trial to Compare VIM vs PSA Bilateral Deep Brain Stimulation in Patients With Essential Tremor

Randomised, Double-Blind, Crossover Clinical Trial Comparing Bilateral Deep Brain Stimulation of the Posterior Subthalamic Area Versus the Ventral Intermediate Nucleus of the Thalamus in Essential Tremor

Deep brain stimulation (DBS) of both ventral intermediate nucleus (VIM) and the posterior subthalamic area (PSA) has shown to be an effective treatment for essential tremor (ET). Characterizing the differences between both targets is necessary. The aim of the study is comparison of efficacy, safety, energy efficiency, neuropsychological status and quality of life of bilateral PSA-DBS vs bilateral VIM-DBS in the treatment of ET. The study hypothesis is that PSA-DBS is not inferior to VIM-DBS in terms of efficacy in controlling tremor, but has superior energy efficiency and safety.

Deep brain stimulation (DBS) of the ventral intermediate (VIM) nucleus of the thalamus is an effective treatment for disabling essential tremor (ET). In recent years, the posterior subthalamic area (PSA) has emerged as a potentially more effective target. There is a need for specific research into the clinical efficacy, efficiency, as well as the mid-term cognitive and quality-of-life outcomes of VIM-DBS and PSA-DBS. The aim of this study is: 1) to compare the efficacy and safety of bilateral PSA-DBS versus bilateral VIM-DBS in the treatment of ET. 2) to determine the impact of bilateral PSA-DBS versus bilateral VIM-DBS on quality of life, neuropsychological status, energy efficiency of the DBS system, and durability of the tremor-suppressing effect. The hypothesis is that PSA-DBS is not inferior to VIM-DBS in terms of efficacy in controlling tremor, but has superior energy efficiency and safety. To this end, a randomized, double-blind, crossover trial will be conducted, in which bilateral octopolar DBS leads will be implanted in a single-trajectory covering the VIM and PSA in patients with disabling and refractory ET. They will be randomly assigned to group 1 (PSA-VIM) or group 2 (VIM-PSA), undergoing stimulation on each target for 3 months. A blinded assessment will be carried out at the end of each period.

Inclusion Criteria:

• Confirmed diagnosis of bilateral ET or ET-plus according to the Movement Disorders Society criteria.
• Refractoriness to medication: at least two attempts at medical treatment with at least two groups of different medication (fundamentally propranolol and primidone), which were ineffective (insufficient tremor control or adverse effects).
• Subjects of both sexes, older than 18 years old.
• Sufficient competence to collaborate and comply with the study protocols.
• Ability to provide informed consent.

Exclusion Criteria:

• Clinically relevant cognitive decline which may interfere with the study.
• Clinically relevant active psychiatric disorder.
• Contraindication for general surgery or bilateral DBS.
• Unsuitable electrode location according to neuroimaging.
• Participation in other interventional study.
• Cerebral atrophy (width of the third ventricle >10 mm) or other anatomical anomalies that would interfere with optimal stereotactic localization.