Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias

Although dysfunctions in both basal ganglia and cerebellum in dystonia are well documented, the functional relationships between these two important motor control networks remains unclear in the context of dystonia. Here the investigators propose to tackle this issue by associating cerebellar stimulations with functional analysis using fMRI in dystonic patients.

The working hypothesis is that the primary torsion dystonia (PTD) pathophysiology involves dysfunction of striatum that is amplified by dysregulation of the cerebello-thalamo-striatal pathway.

The project is to study dystonia forms resulting primarily from dysfunctions of the striatum (patients with mutation of the ADCY5 gene) and compare them with patients with putative dysfunction of the cerebellum (patients with mutation of the PRRT2 gene) and healthy controls. In these patients, the investigators will look for (1) how cerebello-thalamo striatal pathway can be influenced by striatal dysfunctions and (2) whether cerebellar stimulation may prevent (or worsen?) the disrupted activity in the basal ganglia and (3) whether striatum-related dystonia share the same abnormal network with another form of dystonia resulting from another dysfunction (patients with PRRT2 mutation).

Inclusion criteria

• clinical diagnosis of Dystonia
• characterized ADCY5 or PRRT2 mutation
• must have a European Social Security card or a parent having an European Social Security card
• must be older than > 15 years 3 months
• must be able to give informed consent or, for minor patients, parents must be able to give informed consent
• must be able to comply with all study procedures, based on the judgment by the investigator(s).

Exclusion criteria

• major depression or any major mental disorders (axis I disorders)
• neurologic disorder other than dystonia
• presence of pacemaker, intracardiac lines, implanted pumps or stimulators, or metal objects inside the eye or skull, cochlear implant
• Permanent makeup of lips or eyelids
• Black large tattoo close to the head
• Severe claustrophobia
• Current pregnancy or breast feeding
• Copper intrauterine device Subjects with one of the following exclusion criteria will not receive cerebellar stimulation
• Open scalp wounds or scalp infection,
• epilepsy or seizures
• Taking at the time of the study: ketamine, antidepressants, ganciclovir, ritonavir, amphetamines, antiemetic.