Clinical trial NCT03481491: Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias
Official title: Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dystonia
Keywords: Cerebellum
Striatum
Human
fMRI
Transcranial magnetic stimulation
Genetic dystonia
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2018-03-29
Enrollment: 104
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The investigators will study the relationship between the basal ganglia and the cerebellum in dystonia by associating cerebellar stimulations with functional magnetic resonance imaging analysis.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Resting state functional connectivity between the cerebellum and the striatum
timeFrame: 6 weeks
Secondary outcomes:
measure: Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the cerebellum
timeFrame: 6 weeks
measure: Fractional anisotropy (FA) of the cerebello-striatal tract
timeFrame: 1 day
measure: Creatine concentration in the striatum measured with diffusion weighted spectroscopy.
timeFrame: 6 weeks
measure: Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the striatum
timeFrame: 6 weeks
measure: Resting state functional connectivity between the cerebellum and the thalamus
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Paris
country: France
facility: Département de Neurologie, Fédération des Maladies du Système Nerveux, GH Pitié-Salpêtrière, 47 Bd de l'Hôpital
Study officials:
affiliation: Pitié-Salpêtrière
name: Emmanuel Flamand-Roze, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ekmen A, Meneret A, Valabregue R, Beranger B, Worbe Y, Lamy JC, Mehdi S, Herve A, Adanyeguh I, Temiz G, Damier P, Gras D, Roubertie A, Piard J, Navarro V, Mutez E, Riant F, Welniarz Q, Vidailhet M, Lehericy S, Meunier S, Gallea C, Roze E. Cerebellum Dysfunction in Patients With PRRT2-Related Paroxysmal Dyskinesia. Neurology. 2022 Mar 8;98(10):e1077-e1089. doi: 10.1212/WNL.0000000000200060. Epub 2022 Jan 20.