Brain Changes in Patients With Focal Hand Dystonia
Condition: Focal Dystonia
MeSH terms: Dystonia; Dystonic Disorders
Study type: Observational

Summary: 
      This study will examine how chemical changes in the brain produce symptoms of hand dystonia.
      Patients with dystonia have muscle spasms that cause uncontrolled twisting and repetitive
      movement or abnormal postures. In focal dystonia, just one part of the body, such as the
      hand, neck or face, is involved. The study will use positron emission tomography (PET) to
      find our which areas of the brain in patients with focal hand dystonia differ from healthy
      volunteers without focal hand dystonia.

      Healthy volunteers and patients with focal hand dystonia between 18 and 65 years of age may
      be eligible for this study. Candidates are screened with a medical history and physical and
      neurological examinations.

      Participants undergo the following procedures:

        -  PET scanning: The PET scanner is shaped like a doughnut. The subject lies on a bed that
           can slide in and out of the scanner. A custom-molded plastic mask is placed on the face
           and head to support the head and prevent it from moving during scanning. Two radioactive
           substances - five doses (one per scan) of [15 O] water and one dose of [11C] flumazil
           are injected into the body through a vein. The dose of injected radioactive substance is
           very small, and they are not harmful to the body. The [15 O] water doses are injected
           during the first hour and scans are taken every 10 minutes. The [11C] flumazil is
           injected during the second hour. The radioactive substances are detected by the PET
           scanner and provide information on the functioning of the brain chemistry.

        -  MRI scanning: MRI uses a magnetic field and radio waves to produce images of body
           tissues and organs. The patient lies on a table that is moved into the scanner (a narrow
           cylinder), wearing earplugs to muffle loud knocking and thumping sounds that occur
           during the scanning process. Scanning time for this study will be less than one hour.
           Subjects may be asked to lie still for up to 10 minutes at a time.
    

Detailed description: 
      Objective

      The purpose of this study is to determine if in focal hand dystonia there is disinhibition
      involving key structures of the motor control system (basal ganglia, thalamus, cerebellum and
      motor cortex) caused by dysfunction of the GABA-ergic neurons. The major inhibitory
      neurotransmitter in the central nervous system is gamma-amino butyric acid (GABA), which acts
      mainly through GABA A receptors, the majority of which possess the benzodiazepine binding
      site. Pathological processes involving GABA-ergic neurons will cause alterations in the
      density of GABA receptors, which can be visualized and measured with positron emission
      tomography (PET) using as a radioactive ligand [(11)C] Flumazenil.

      Study Population

      This research will be conducted using 20 patients with primary focal hand dystonia and 20
      healthy volunteers that are matched by age and gender.

      Design

      By using positron emission tomography (PET) using radioactive ligand [(11)C] Flumazenil, we
      will detect alterations in the density of GABA receptors in patients with primary focal hand
      dystonia in comparison with control subjects.

      Outcome Measures

      We will be able to determine the density of GABA A receptors of the various Regions of
      Interest as measured by PET analysis among these groups of subjects. This study should
      provide new information concerning localization and degree of dysfunction of GABA-ergic
      neurons in movement related structures in dystonia, which might open new possibilities for
      pharmacological treatment of this disorder.
    

Time perspective: Other
Keywords: Neurotransmitter; Neuroimaging; Movement Disorder; Focal Hand Dystonia; FHD; HV