Pathophysiology of Gait and Posture in Progressive Supranuclear Palsy (Gait-PSP)

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.

Study Overview

• Status: Completed
• Conditions: Progressive Supranuclear Palsy
• Intervention / Treatment: Other: gait recordings; Other: brain magnetic resonance imaging; Other: oculomotor movement recordings

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Pointe-a-Pitre
• Collaborators: Groupe Hospitalier Pitie-Salpetriere; University Hospital Center of Martinique
• Investigators: Principal Investigator: Marie-Laure WELTER, PU-PH, Groupe Hospitalier Pitie-Salpetriere

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 28, 2015
• Primary Completion (ACTUAL): July 12, 2018
• Study Completion (ACTUAL): July 12, 2018

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (ACTUAL): September 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 17, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: imaging; gait disorders; neurophysiology; progressive supranuclear palsy PSP; atypical parkinsonism
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Tauopathies; Cranial Nerve Diseases; Ocular Motility Disorders; Ophthalmoplegia; Paralysis; Supranuclear Palsy, Progressive
• Other Study ID Numbers: RBM-PAP-2015/19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No