Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to characterize through spectral analysis intra-thalamic local field potentials (LFPs) recorded through implanted DBS leads during periods with and without tremor in patients suffering from severe essential tremor.

Detailed Description
-----------------
Essential tremor (ET) is one of the most common adult movement disorders with a prevalence of 4% in the general population. Although several medications (primidone, beta-adrenergic blockers, benzodiazepines…) are commonly used, few of them are truly effective for controlling the severe forms of ET. Since 1987, an alternative has emerged with the development of high frequency deep brain stimulation (DBS) of the thalamic nucleus ventralis intermedius (VIM). This surgical technique now represents the gold standard treatment for tremor-disabled ET patients. Although VIM-DBS is clearly effective for treatment of essential tremor (ET) a partial loss of DBS effectiveness may occur over time in some patients. This loss of DBS effectiveness could be related to an adaptation of the local neuronal network to chronic stimulation (changes in synaptic plasticity). In order to avoid this problem, investigators plan to develop a intermittent mode of VIM stimulation using a new Medtronic device combining a DBS system with local field potential (LFPs) sensing capability. First, investigators propose to analyse VIM LFPs in order to define a tremor biomarker in 10 patients operated for severe ET. Thereafter, investigators will automatically detect this biomarker using a specific algorithm and use it to trigger stimulation at the onset of tremor only. Thus, this project will allow us to optimize DBS therapy in ET, by improving the longevity of implantable devices and avoiding the loss of efficacy previously reported

Official Title
-----------------
Thalamic LFPs and VIM DBS in Essential Tremor: Correlation, Evolution, and Therapeutic Perspectives

Conditions
-----------------
Essential Tremor

Intervention / Treatment
-----------------
* Device: Deep Brain Stimulation with Medtronic Activa PC+S systems


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients suffering from severe and disabling ET with serious impact on their quality of life (QoL). 18-70 years old Free of evolutive and untreated psychiatric disorder Tremor must be predominant in the upper limbs although it can affect the lower limbs, head and voice. Affiliation to a social security system Written informed consent signed by the participant and the investigator (prior to any examination required by research) Exclusion Criteria: Parkinsonian tremor Pregnancy or lactating women Severe co-morbidity (cardiac, renal or respiratory failures, evolutive cancer) Impaired cognitive functions (score <130 on Mattis scale). Patients with severe atrophy or lesions on MRI Depression (Beck > 10) Participation in another clinical research for 18 months (after surgery)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deep Brain Stimulation<br>All of included patients will receive a standard deep brain stimulation of the thalamus in order to reduce their essential tremor | Device: Deep Brain Stimulation with Medtronic Activa PC+S systems<br>* Deep Brain Stimulation of VIM.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LFPs records 3 month after implantation | in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity | 3 month after implantation | 
| LFPs records 12 month after implantation | in order to characterize the features of tremor-related thalamic activity during the initiation of movement-related tremor-induced activity | 12 month after implantation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Essential tremor, Deep brain stimulation (DBS), Ventral intermediate Thalamus (VIM), Local field potentials (LFPs), Closed loop therapy