Optimization of VIM Targeting in Essential Tremor Surgery

Study Overview
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Brief Summary
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Deep brain stimulation (DBS) for essential tremor is based on the intermedius ventralis nucleus of the thalamus (VIM) stimulation. This structure is however very difficult to target, as it remains invisible on imaging. The current procedure based on awake surgery with clinical and electrophysiological testings has several limitations that lead us to develop a probabilistic model to locate precisely the target. This study aims to show that asleep DBS surgery based on this new targeting method leads to at least the same clinical results than the classical procedure.

Detailed Description
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The intermedius ventralis nucleus of the thalamus (VIM), which represents the target for deep brain stimulation (DBS) in essential tremor, still remains invisible on 1,5 tesla MRI (the only magnetic field available for stereotactic surgery). The target coordinates currently used are based on stereotactic atlases or mean coordinates from retrospective series. They are so imprecise that intra-operative clinical testing and micro-electrode recordings are mandatory to locate the exact position of the VIM. This procedure is long lasting, requires that the patient is awake, and increases the risk of intracerebral haemorrhage and nosocomial infections. Furthermore, some patients are not improved despite a DBS lead implanted in the electrophysiologically and clinically defined target. To overcome these limitations, investigators developed a probabilistic model based on data extracted from imaging of patients with particularly good outcomes after DBS surgery. This machine-learning model allows calculating to coordinates of the VIM according to the position of radio-anatomical landmarks with a mean precision of 1,65mm. The aim of this study is to validate this new targeting method on a prospective cohort of patients. DBS surgery will be performed under general anaesthesia, without intra-operative clinical and electrophysiological testing, with a surgical robot and under CT-scan guidance (O-Arm ©). Neurostimulation device programming will be performed as usual. Patients' tremor and quality of life will be evaluated pre and post-operatively at 3 months, according to the Fahn-Tolosa-Marin (FTM) scale and with an accelerometry recording (for tremor) and with the mPDQ-39 scale for quality of life. Surgical complications and side effects related to neurostimulation will be gathered all along the follow-up.

Official Title
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Optimization of VIM Targeting in Essential Tremor Surgery

Conditions
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Essential Tremor

Intervention / Treatment
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* Procedure: Opti-VIM targeting in DBS surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe essential tremor despite the optimal medical management Age between 18 and 75 years Normal MRI scan Mattis Dementia Rating Scale (MDRS) score ≥ 130 Affiliation to the social security Signed informed consent Exclusion Criteria: Depression (Beck Depression Inventory scale > 20) Contra-indication to surgery or general anesthesia Cerebral atrophy on MRI scan Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Severe essential tremor treated by DBS<br> | Procedure: Opti-VIM targeting in DBS surgery<br>* DBS surgery will be performed under general anaesthesia, without intra-operative clinical and electrophysiological testing, with a surgical robot and under CT-scan guidance (O-Arm ©). The VIM coordinates will be calculated with the probabilistic model that have been developed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Fahn-Tolosa-Marin (FTM) scale score | Scale global range : min=0 / max=160 Higher values represent worse tremor | Before and 3 month after DBS surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accelerometry recordings : spectral analysis | Accelerometry recordings at the pre-inclusion visit and at 3 months after surgery in ON and OFF-stimulation conditions with spectral analysis. | Before and 3 month after DBS surgery | 
| Accelerometry recordings : calculation of the total accelerometry power | Accelerometry recordings at the pre-inclusion visit and at 3 months after surgery in ON and OFF-stimulation conditions with calculation of the total accelerometry power. | Before and 3 month after DBS surgery | 
| Surgical complications | Onset of infection, hematoma or seizure | Up to 3 month after DBS surgery | 
| Device complications and dysfunction | rupture or displacement of electrode, pain at the stimulation box implantation site or along the subcutaneous cable if they require further intervention, infection. | Up to 3 month after DBS surgery | 
| Neurostimulation-related side effects | Onset of dysarthria and ataxia assessed by the items 1 to 4 of the Scale for Assessment and Rating of Ataxia (SARA), ataxia assessed by a posturometry analysis, paresthesia, muscular contractions | Up to 3 month after DBS surgery | 
| Quality of life: change of modified Parkinson's Disease Questionnaire-39 (mPDQ-39) scale score | Adaptation of Parkinson's Disease Questionnaire-39 to essential tremor Scale global range : min=0 / max=156 Higher values represent worse Quality of life | Before and 3 month after DBS surgery | 
| Coordinates of active contacts | Coordinates of active contacts (i.e; the contact with the best effect on tremor without side effects) These coordinates (x, y, z) are obtained by merging the images of the 3-month postoperative scanner with the images of the preoperative MRI. | 3 month after DBS surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Essential Tremor, Deep brain stimulation, Ventro-intermediate nucleus of the thalamus, Targeting, Asleep surgery