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The appearance of postural instability and gait disorders is a major turning point in the evolution of Parkinson's disease (PD). These axial symptoms are usually unresponsive to L-Dopa and represent a severe impairment for the patients due to frequent falls and reduced outside mobility. There is no effective pharmacological treatment available for these symptoms, and their pathophysiology is not well known : it is currently assumed that non-dopaminergic brainstem lesions participate to axial symptoms in PD. Surgically, these patients cannot benefit from high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) since this operation tends to even aggravate axial symptoms unresponsive to L-Dopa in some patients. A dysfunction of the pedunculopontine nucleus (PPN) might be at the origin of these axial symptoms, since the PPN participates in the maintenance of posture and motion in primates. In PD patients, recent reports have suggested that low frequency stimulation of the PPN may equally improve gait and posture. However, these results are debatable due to methodological limitations, insufficient clinical evaluation and uncertain anatomical targeting. Thus, our aim is to propose a low frequency PPN stimulation to six advanced PD patients according to the usual criteria for STN DBS who are, however, unsuitable for this operation due to gait and posture disorders. We will perform a randomized, double-blind and cross over design (two months periods with and without DBS randomly assigned to each patient). The targeting will be allowed by a a three-dimensional and deformable atlas of the basal ganglia fusioned with the stereotaxic magnetic resonance imaging (MRI) of each patient. Evaluations will comprise 1 month before surgery and in "Off" and "On" stimulation condition:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| OFF PPN DBS-ON PPN DBS | Other | Patients randomly allocated to the order OFF Low frequency DBS of the pedunculopontine nucleus then ON Low frequency DBS of the pedunculopontine nucleus |
|
| ON PPN DBS - OFF PPN DBS | Other | Patients randomly allocated to the order ON Low frequency DBS of the pedunculopontine nucleus then OFF Low frequency DBS of the pedunculopontine nucleus |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low frequency DBS of the pedunculopontine nucleus | Device |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of Rating scale for gait evaluation between 'Off stim off drug" and "On stim off drug" conditions | The primary outcome criteria will be the comparison between RSGE total score in obtained 'Off' and 'On' stimulation conditions either at 4 or 6 months after surgery according to the randomized order of the cross-over | 4 months and 6 months after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events records | 1 month before surgery, 1-2-3-4-5-6 months after surgery | |
| Change of UPDRS part 3 score between "Off Stim Off drug" and "ON stim Off drug" conditions | 4 and 6 months after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in sleep architecture between "off stim" and "on stim" conditions | 4 and 6 months after surgery | |
| changes in cognitive evaluation between "Off stim" and 'On stim" conditions | 4 and 6 months after surgery |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital de la Pitié-Salpétrière | Paris | 75013 | France |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| Change of Rating scale for gait evaluation between 'Off stim on drug" and "On stim on drug" conditions | 4 and 6 months after surgery |
| Change of UPDRS part 3 score between "Off Stim On drug" and "ON stim On drug" conditions | 4 and 6 months after surgery |
| Change of UPDRS part 3 score between "Off Stim Off drug" and "No stim Off drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| Change of UPDRS part 3 score between "Off Stim On drug" and "No stim On drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| Change of Rating scale for gait evaluation between 'Off stim Off drug" and "No stim off drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| Change of Rating scale for gait evaluation between 'Off stim On drug" and "No stim on drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| Change of Rating scale for gait evaluation between 'On stim Off drug" and "No stim off drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| Change of Rating scale for gait evaluation between 'On stim On drug" and "No stim On drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| Change of gait physiological parameters between "Off Stim Off drug" and "ON stim Off drug" conditions | 4 and 6 months after surgery |
| Change of gait physiological parameters between "Off Stim On drug" and "ON stim On drug" conditions | 4 and 6 months after surgery |
| Change of gait physiological parameters between "No Stim On drug" and "Off stim On drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| Change of gait physiological parameters between "No Stim Off drug" and "On stim off drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| Change of gait physiological parameters between "No Stim Off drug" and "Off stim off drug" conditions | 1 month before surgery and 4 or 6 months after surgery |
| changes in cognitive evaluation between "No stim" and 'Off stim" conditions | 1 month before surgery and 4 or 6 months after surgery |
| changes in cognitive evaluation between "No stim" and 'On stim" conditions | 1 month before surgery and 4 or 6 months after surgery |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |