Pathophysiology of Focal Hand Dystonia
Condition: Dystonia
MeSH terms: Dystonia; Dystonic Disorders
Study type: Interventional

Summary: 
      Background:

      Little is known about the problems in brain function in focal hand dystonia (FHD) or complex
      regional pain syndrome (CRPS) dystonia. It is unclear why some CRPS patients develop dystonia
      but others do not. Researchers want to learn which area of the brain is involved in CRPS
      dystonia compared with FHD.

      Objectives:

      To understand why people with CRPS develop dystonia, and if these reasons are different in
      people with FHD.

      Eligibility:

      Adults ages 18 - 70 with CRPS dystonia OR with CRPS without dystonia OR with FHD and Healthy
      volunteers of similar age.

      Design:

      Participants will be screened with physical exam, neurological exam, and medical history.
      They may give a urine sample and will answer questions.

      Participants can have 4 - 5 outpatient visits or stay at the clinical center for
      approximately 5-6 days.

      Participants will have MRI scans. They will lie on a table that slides in and out of a
      scanner that takes pictures of their brain. They will do small tasks or be asked to imagine
      things during the scanning.

      Participants will have transcranial magnetic stimulation (TMS) sessions for a few hours, with
      breaks. A brief electrical current passing through a well insulated wire coil on the scalp
      creates a magnetic pulse. This affects brain activity. Participants may do small tasks during
      TMS.

      Participants will have the electrical activity of their muscles measured during TMS sessions.
      Small sticky pads will be attached to their hands and arms.

      Participants ability to feel 2 separate stimuli as different will be tested by using a weak
      electrical shock to their fingers. They will also be asked to feel small plastic domes with
      ridges, that may cause discomfort.
    

Detailed description: 
      Objective: detailed evaluation of pathophysiology of Focal Hand Dystonia (FHD) with focus on
      the involvement of the parietal area, and to investigate differences in cortical mapping in
      the sensory and motor cortices between FHD and healthy volunteers.

      Study population: The study will enroll patients with FHD and Healthy Volunteers (HVs).

      Design: Prospective study using MRI and Physiology experiments using EMG and TMS based
      protocols to evaluate the differences between the groups.

      Outcome measures: The evaluation using fMRI will be performed under 3 conditions; 1. Rest 2.
      Voluntary activity 3. Motor imagery task.

      Outcome measures (fMRI based):

      We will explore the differences in BOLD signal in the parietal lobe, in FHD compared to HVs,
      in the different conditions. We will look for changes in the BOLD signal in the parietal
      sensorimotor integration area.

      We will use vascular occupancy imaging (VASO) to explore differences of detailed cortical
      mapping of neural structures between FHD and healthy volunteers.

      The Physiology experiments aim to explore abnormalities and differences in the baseline motor
      cortical excitability between the groups and evaluate the influence of continuous Theta Burst
      Stimulation (cTBS) on these measures. We will study the influence of cTBS on the phenomenon
      Cortical Silent Period (cSP) in FHD.

      We will also be studying the baseline Spatial and Temporal Discrimination (SDTs and TDTs),
      which are measures of sensory surround inhibition and have been noted to be endophenotypic of
      dystonia.

      Physiology outcomes:

      Baseline differential influences of PMv and IPL on motor cortical excitability and changes
      after cTBS of dIPL.

      Baseline cortical Silent Period (cSP) in the involved and uninvolved limb in FHD and the
      influence of cTBS on cSP in the involved limb.

      The TDTs/ SDTs in both the involved and uninvolved limbs in FHD compared to HVs.
    

Intervention name(s): TMS; MRI; VASO Imaging
Intervention type(s): Device; Device; Device
Intervention description(s): Single pulse TMS, IPL-M1 Interaction, IPL-M1 Interaction, Inhibitory Theta Burst Protocol (cTBS); High-resolution MRI for anatomical reference; fMRI scan as per research fMRI protocol will be conducted under 3 conditions. 1. Rest 2. Voluntary activity 3. Motor imagery task.; The voluntary activity condition will involve 4 tasks: a. individual tapping of two fingers (index and little), b. individual tapping of four fingers (index, middle, ring, and little; no thumb) interspaced with rest periods, c. individual tapping of all five fingers (index, middle, ring, little, and thumb) interspaced with rest periods and d. Alternating grasping or retraction of a rubber ball interspaced with rest periods.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Dystonia