Optimization of Parameters of Subthalamic Nucleus Stimulation

Study Overview
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Brief Summary
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Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease. The analysis of cerebral signals of the subthalamic nucleus by local field potentials, provides one of the main electrophysiological markers of the success of the stimulation. This marker can be used to evaluate new paradigms of stimulation. So far, little studied, the temporal characteristics of the stimulation are very important in the effectiveness of the stimulation of the subthalamic nucleus, in Parkinson's disease. The first objective (Study I) is to compare the effectiveness of the stimulation when it is applied with biphasic symmetrical pulses and when applied with the standard pulses applied so far. The second objective (Study II) is to see if, by applying pseudo-random time intervals between each stimulation pulse, if it would be possible to improve the efficiency and to limit the side effects of the stimulation. The third objective (Study III) is to evaluate the electrophysiological changes of the subthalamic nucleus caused by the general anesthesia, in the anticipation of the realization of the surgery of the stimulation of the subthalamic nucleus under general anesthesia.

Detailed Description
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Study I and II: Patients who participate undergo pulse generator change under sedation. Four sets of stimulation parameters will be compared. The efficacy of every set will be measured on induced changes in LFP recorded from the STN electrodes. LFP will be compared between before, during and right after each stimulation conditions. The stimulation order will be randomized. All other stimulation parameters will be the same (macrocontact with most beta-oscillations, 1 minute, 1.5mA) . Study III: Patients who participate undergo their first pulse generator implantation, performed under general anesthesia because of wire tunnelisation. The depth of anesthesia will be documented, recording the BIS spectral analysis index. The difference in spectral amplitude density of LFP, in particular in beta band oscillations will be correlated with the depth of anesthesia as measured with the BIS index at the time of 2 minutes recordings.

Official Title
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Optimization of Parameters of Subthalamic Nucleus Stimulation

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: biphasic stimulation
* Device: standard stimulation
* Device: Uniform distribution
* Device: Poisson distribution
* Device: Recordings of LFP oscillations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients suffering from Parkinson's disease, who must undergo surgery for the replacement of their neurostimulator (under sedation) or for the first positioning of it capacity of discernment informed signed consent Exclusion Criteria: Health considerations in regard to adding 13' in surgery room (e.g. pain or incomfort).

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Different stimulation paradigm tested sequentially in every patient of the group
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pulse generator change under sedation<br>The efficacy of every set will be measured on induced changes in LFP recorded from the STN electrodes.LFP will be compared between before, during and right after each stimulation conditions. The stimulation order will be randomized. All other stimulation parameters will be the same (macrocontact with most beta-oscillations, 1 minute, 1.5mA) . Hence 4 sets of 1 minutes of STN stimulation will be performed, for: Symmetrical biphasic pulses versus standard pseudo monophasic pulses (study I; 2 sets). Pseudorandom uniform distribution stimulation paradigms versus pseudorandom Poisson distribution stimulation paradigms (study II: 2 sets). | Device: biphasic stimulation<br>* Fixed 70Hz symmetrical biphasic pulses<br>Device: standard stimulation<br>* Fixed 70Hz pseudo-monophasic pulses<br>Device: Uniform distribution<br>* Uniform distribution 70Hz Biphasic pulses<br>Device: Poisson distribution<br>* Poisson distribution 70Hz Biphasic pulses<br>|
| Experimental: First pulse generator implantation under general an<br>The depth of anesthesia will be documented, recording the BIS spectral analysis index. The difference in spectral amplitude density of LFP, in particular in beta band oscillations will be correlated with the depth of anesthesia as measured with the BIS index. | Device: Recordings of LFP oscillations<br>* Two minutes of recordings of LFP oscillations will be performed from the contacts of the implanted electrode. Recordings of the depth of anaesthesia (BIS) all along the measurements performed under general anaesthesia.The correlation between the depth of anaesthesia and the cerebral oscillations recorded at the site of subthalamic nucleus will be studied.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of quantity of Beta oscillations after biphasic pulses vs standard monophasic pulses | % of changes in the energy of Beta oscillations | 10 minutes per patient | 
| Comparison of quantity of Beta oscillations after pseudo random (Poisson distribution) vs uniform distribution of pulse time intervals | % of changes in the energy of Beta oscillations | 10 minutes per patient | 
| Observe the evolution of Beta oscillations during deep anesthesia | Energy of Beta oscillations | 2 minutes per patient |