Pathophysiology of Gait and Posture in Progressive Supranuclear Palsy

Study Overview
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Brief Summary
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The main hypothesis is that the gait and postural deficits in the Caribbean form of PSP may be associated with a dysfunction of the cerebral cortex, as they result from sub-cortical involvement in classical forms. The investigators will characterize the gait and posture with a force platform to collect biomechanical gait parameters, coupled with the kinematic and electromyographic (EMG) study. Then the investigators realize a multimodal imaging study [structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)] that allow us to determine if a correlation can be found between the clinical characteristics of postural control and walking on one hand, and morphological changes and structural MRI changes in cortico-subcortical pathways on the other hand. The study of performance on neuropsychological tests, registration of ocular movements and the analysis of functional cortical activity will complete our multimodal approach. A better understanding of these disorders is expected to propose new drug treatment and rehabilitative strategies.

Detailed Description
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Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease (6/100 000 inhabitants) characterized by the association of Parkinson's syndrome, a paralysis of the verticality of the gaze and an alteration early balance and walking with the onset of falls during the first year of evolution of the disease. From a neuropathological point of view, it is characterized by a tauopathy with neurodegeneration within the basal ganglia, cerebellum, and midbrain (which includes the mesencephalic locomotor region-MLR). In the Caribs this pathology is abnormally frequent (incidence over 3 times higher than expected), and represents 1/3 of the total Parkinsonian syndromes. In these patients, cortical pathology predominates leading to different cognitive deficit relative to patients with the classical form of PSP. Conversely, in PSP patients, imaging data suggest a preferential midbrain-thalamocortical pathway dysfunction. Pathophysiological mechanisms causing gait disturbances and postural control presented by these patients remains however not fully elucidated . In patients with Caribbean PSP, of which the clinical features are specific, gait disorders and falls appear later in the course of the disease (2.5 years on average) suggesting perhaps a different physiopathological mechanism. Consequently weak knowledge of the mechanisms involved, none specific treatment is currently available and the taking in therapeutic charge of these disorders rests essentially on a re-educative approach that remains poorly codified. In this study, gait and balance disorders will be recorded using a force platform, coupled with kinematic study and EMG in patients with classical form of PSP and Caribbean one, and in controls. The functional and anatomy of brain will be examined using a multimodal brain imaging approach (with DTI. Performance in neuropsychological tests and oculomotor movements will also be measured. A comparative and correlation analyses will be performed to assess the link between gait, balance, oculomotor and cognitive performances and brain anatomy, and the differences between subjects groups. Caribbean PSP patients are recruited from Neurology and Physical Medicine and Rehabilitation of University Hospital of Pointe-à-Pitre and Fort de France, Classical PSP patients are be recruited from the Centre d'Investigation Clinique (CIC) of the Pitié-Salpêtrière hospital, and healthy volunteers from both centers.

Official Title
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Pathophysiology of Gait and Posture in Progressive Supranuclear Palsy

Conditions
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Progressive Supranuclear Palsy

Intervention / Treatment
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* Other: gait recordings
* Other: brain magnetic resonance imaging
* Other: oculomotor movement recordings


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient : Patients who met the clinical criteria for PSP and Gd-PSP Walking and standing alone without assistance Patient or responsible third party who received information about the study and who signed the informed consent French Patients over 40 years Clinically detectable eye movement anomaly Witnesses : To be affiliated or beneficiary of social security scheme French person Major subjects, matched for age (± 3 years) and sex, showing no neurological or psychiatric disease or severe progressive disease No Indication against MRI Exclusion Criteria: Patient : Patient not affiliated with the social security system Cognitive impairment: MMSE ≤ 20; FAB ≤ 12 psychiatric disorders likely to interfere with exploration; severe postural disorders MRI not feasible Witnesses Not affiliated or benificiary of social security scheme Not a french person Somebody showing neurological or psychiatric disease or severe progressive disease

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: PSP Classic<br>15 patients with a classical form of PSP are recruited to realize all the tests of the multimodal approach. | Other: gait recordings<br>* gait recordings<br>Other: brain magnetic resonance imaging<br>* brain magnetic resonance imaging<br>Other: oculomotor movement recordings<br>* oculomotor movement recordings<br>|
| Other: Caribbean PSP<br>15 patients with a Caribbean PSP are recruited to realize all the tests of the multimodal approach. | Other: gait recordings<br>* gait recordings<br>Other: brain magnetic resonance imaging<br>* brain magnetic resonance imaging<br>Other: oculomotor movement recordings<br>* oculomotor movement recordings<br>|
| Other: Healthy controls<br>15 persons with no PSP are recruited to realize all the tests of the multimodal approach. | Other: gait recordings<br>* gait recordings<br>Other: brain magnetic resonance imaging<br>* brain magnetic resonance imaging<br>Other: oculomotor movement recordings<br>* oculomotor movement recordings<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gait velocity | gait recordings | at inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| brain anatomy | magnetic resonance imaging | at inclusion | 
| oculomotor movements recordings | oculomotor movements recordings | at inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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progressive supranuclear palsy PSP, atypical parkinsonism, gait disorders, neurophysiology, imaging