Principal investigator Pr. Pierre Burbaud of the Bordeaux University Hospital, in Bordeaux, France is looking for approximately 20 patients to be included in the study.
DYT1 dystonia is a rare disease. Many of these patients have already been operated for deep brain stimulation. For technical reasons, we aim to include non-operated patients. There are few of them in each country and the 20 patients necessary for this study cannot be found in one single european country.
Why are we doing this research ?
Dystonia is defined as a syndrome of sustained muscular contractions leading to repetitive movements and abnormal postures. DYT1 dystonia is the most frequent form of primary dystonia, but the link between genomic mutation and the expression of the phenotype remains largely unknown. A line of experimental evidence suggests that acetylcholine interneurones (Ach-I) of the putamen (a part of the basal ganglia) plays a critical role in the abnormal plasticity occuring in dystonia. However, this data has not been demonstrated, so far. The aim of the present study is to demonstrate that dystonia is associated with an abnormal function of the ACh-I.
We are checking this hypothesis in DYT1 dystonic patients using a marker of the vesicular transporter of acetylcholine, [123I]iodobenzovesamicol (IBVM), with TEP imaging. MRI images are acquired allowing anatomical imaging and tensor diffusion techniques. Our primary outcome is the quantification of marker fixation (binding potential i.e. BP) and its comparison between sex- and age-matched dystonic patients DYT1 (n = 20) and normal controls (n = 20). We postulate that the level of fixation will be increased by at least 40% in dystonic versus control subjects based on previous data. Since a high phenotypic variability exists in DYT1 dystonia, we will then search for a correlation between the BP and the severity of dystonia evaluated on the dystonia clinical rating scale (BFM).
What is the objective of the study ?
This innovative study aims to demonstrate a specific pathophysiological mechanism for primary dystonia focusing on the striatal cholinergic system. Such a data will potentially open up new therapeutic avenues promoting the search for new drugs acting on the cholinergic system but devoted of the side-effects of classical anti-cholinergics treatments.
Inclusion criterias:
- Age Between 18 to 75 y.o
- Diagnostic of DYT1 dystonia documented on molecular biology
- Necessity (and possibility) to stop anti-cholinergic treatment 24 hours before PET scan.
How is organized the research protocol in Bordeaux ?
The research takes place in the Bordeaux Universitary hospital on two consecutive days.
- Travelling is organized on Tuesday morning by plane or train, depending on the distance. Patients arrive at Bordeaux in the afternoon and are transferred by taxi to the Xavier Arnozan hospital.
- They are received by a doctor who explains the objective and principles of the study. The examination includes one intra-venous injection of the biomarker (IBVM). After this injection, a first PET-scan is performed for 1h30. After à 30 mn rest session, another acquisition of images is maid for 30 mn (total duration 3 hours)
- Then, they join by taxi their hotel located close to the Pellegrin Hospital in Bordeaux.
- On Wednesday morning, they are first examined by a neurologist (Pr. P. Burbaud) and directed to the MRI unit.
- The MRI protocol does not require any preparation or injection and last 45 mn.
- Then, return travel to the airport or station by taxi.
- All aspects of organization and travels are organized by Bordeaux clinical assistants.
Why do we include patients for different European countries ?
DYT1 dystonia is a rare disease. Many of these patients have already been operated for deep brain stimulation. For technical reasons, we aim to include non-operated patients. There are few of them in each country and the 20 patients necessary for this study cannot be found in one single european country.
If you agree to be part of this study and require further information, please contact
Pierre.Burbaud@chu-bordeaux.fr tel : +33 6 70 48 86 11
