Progressive Supranuclear Palsy Clinical Trial
Official title:
Pathophysiology of Gait and Posture in Progressive Supranuclear Palsy
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.
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.
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