Role of the Striatal Cholinergic System in the Pathophysiology of Dystonia (DYSCHOL)

University Hospital of Bordeaux

Status

Completed

Conditions

Dystonia

Treatments

Radiation: PET (Positron Emission Tomography) imaging

Other: MRI : Magnetic Resonance Imaging

Study type

Interventional

Funder types

Other

Identifiers

NCT02727361

CHUBX2014/20

Details and patient eligibility

About

Dystonia is defined as a syndrome of sustained muscle contractions resulting in repetitive movements and abnormal postures. DYT1 is the most common form of genetic dystonia, but the link between genomic mutations and phenotypic expression remains largely unknown. Furthermore, secondary forms of dystonia have highlighted the role of the basal ganglia, particularly the putamen in the pathophysiology of the disease. Experimental results in a genetic model of dystonia in rodents suggest that cholinergic inter-neurons (ACh-I) of the putamen play a critical role in the pathological process of plasticity in the cortico-striatal synapse. However, these results have not been demonstrated in humans.

Full description

The purpose of this study is to demonstrate that the phenotype of dystonia is associated with the degree of striatal ACh-I alterations.

In this molecular imaging study, the investigators will directly test this hypothesis using a PET radiotracer of the vesicular acetylcholine transporter (VAT). Their goal is to explore the relationships between cholinergic dysfunction and clinical disease expression and the associated morphological and functional alterations. The experimental protocol will also include multimodal MRI, MRI diffusion tensor (to study the microscopic structure of white matter) and functional MRI of the resting state (to study the functional organization of cerebral cholinergic networks at rest).

Enrollment

40 patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Man or woman 18 to 75 years, with health insurance European health insurance card (for resident patients in EU), insurance by bilateral social security agreement signed between his country and France (for resident patients outside the EU)
Diagnosis of dystonia DYT1 confirmed by molecular biology (TORSINE- A gene mutation)
Patient who stopped his anticholinergic treatment 48 hours before imaging

Exclusion criteria

Patients who underwent surgery for deep brain stimulation or under cholinergic treatment.
Presence of a counter-indication for MRI
Presence of a counter-indication for TEP Scan with [18F]-FEOBV
Woman premenopausal without effective ongoing contraception (intrauterine device or combined hormonal)
Patient who underwent a PET examination in the previous month
Presence of any health problem preventing travel to the imaging service of the University Hospital
Being under the legal guardianship of another person or being unable to provide consent to participate
Pregnant or breastfeeding woman