Interactions Between Striatum and Cerebellum in ADCY5 and PRRT2 Dystonias
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Resting state functional connectivity between the cerebellum and the striatum
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
盲法说明
Participants will be blinded to the TMS procedure (SHAM or real stimulation).
入排标准
- 年龄范围
- 15 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
Sham cerebellar stimulation
Participants will receive a Sham stimulation (inefficient probe) applied over the cerebellum.
干预措施: transcranial magnetic stimulation of the cerebellum (Other)
Real cerebellar stimulation
Participants will receive a real continuous theta burst stimulation (cTBS) applied over the cerebellum.
干预措施: transcranial magnetic stimulation of the cerebellum (Other)
结局指标
主要结局
Resting state functional connectivity between the cerebellum and the striatum
时间窗: 6 weeks
Synchrony between the cerebellum and the striatum, calculated from resting state fMRI done at visit2 will be compared between the 3 groups (healthy controls, ADCY5 patients, PRTT2 patients)
次要结局
- Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the cerebellum(6 weeks)
- Fractional anisotropy (FA) of the cerebello-striatal tract(1 day)
- Creatine concentration in the striatum measured with diffusion weighted spectroscopy.(6 weeks)
- Amplitude of Low Frequency Fluctuation (ALFF) of blood oxygen level-dependent signal in the striatum(6 weeks)
- Resting state functional connectivity between the cerebellum and the thalamus(6 weeks)