This study will investigate how the brain generates tics in patients with Tourette's syndrome and which areas of the brain are primarily affected. Tourette's syndrome is a neuropsychiatric disorder characterized by motor and vocal tics, and is associated with behavioral and emotional disturbances, including symptoms of attention deficit hyperactivity disorder and obsessive-compulsive disorder. This study will examine whether tic generation is related to changes in brain cell receptors for a chemical messenger called gamma-aminobutyric acid (GABA).

Healthy normal volunteers and patients with Tourette's syndrome between 21 and 65 years of age may be eligible for this study. Candidates will be screened with a medical history and physical and neurological examinations.

Participants will undergo positron emission tomography (PET) scanning to measure brain blood flow. For this procedure, the subject receives an injection of H215O, a radioactive substance similar to water. A special camera detects the radiation emitted by the H215O, allowing measurement of the blood flow. Subjects will receive up to five injections of H215O during the scanning. They will also be injected with another radioactive chemical, (11C) flumazenil, which binds to GABA receptors, to measure the density and distribution of these receptors. This will reveal which areas of the brain in patients with Tourette's syndrome have abnormal binding of flumazenil compared with the brains of healthy control subjects.

During the PET procedure, the subject lies on a table in the PET scanner. A small catheter (plastic tube) is placed in an arm vein for injecting the radioactive tracers, and a mask is placed on the face to help keep the head still during scanning. The mask has large openings for eyes, nose and mouth, so that it does not interfere with talking or breathing. The entire test takes about 3 hours.

On a separate day, participants will also undergo magnetic resonance imaging (MRI), a diagnostic test that uses a magnetic field and radio waves to produce images of the brain. For this procedure, the subject lies still on a stretcher that is moved into the scanner (a narrow cylinder containing the magnet). Earplugs are worn to muffle loud noises caused by electrical switching of radio frequency circuits used in the scanning process. The scan lasts about 45 to 60 minutes.

Condition	Treatment or Intervention
Tourette Syndrome	Drug: flumazenil  Drug: H215O

Further Study Details: 

Expected Total Enrollment:  34

The purpose of this study is to determine if symptoms of Tourette's syndrome are due to disinhibition originating in basal ganglia, and involving thalamus, prefrontal and limbic cortices, caused by dysfunction of the GABA-ergic neurons.

The major inhibitory neurotransmitter in central nervous system is gamma-aminobutyric acid (GABA), which acts mainly through the GABA A receptors, the majority of which possess the benzodiazepine binding site. Pathological processes involving GABA-ergic neurons, such as degeneration, which alters receptor structure or channelopathy, which alters function, will cause subsequent alterations in the density of GABA receptors of the targeted neurons. These changes can be visualized and measured with Positron Emission Tomography using as a radioactive ligand [11C] flumazenil. This study should provide new information concerning localization and degree of dysfunction of GABA-ergic neurons in areas involved in Tourette's syndrome, which, in turn, might open new possibilities in pharmacological treatment of this disorder.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA
Patients will have clinically documented Tourette's syndrome as defined by DSM-IV and evaluation of tics severity using Yale Tic Scale.
Patients will be in age ranges 18 to 65. Patients may be male or female. Female patients of child bearing potential will have a pregnancy test and specific interview prior to the study to ensure that pregnant patients will not participate in the study. Patients will be asked to stop for two weeks prior to exam any medication that can influence the central nervous system. Fluoxetine will be stopped for four weeks. They will be asked to abstain from alcohol for one week before the study.
Seventeen normal controls will be included; controls will be screened in the NINDS Movement Disorders Outpatient Clinic, and will have neurological and physical examination. Controls with chronic illnesses, taking any medication that affects the CNS will be excluded. They will be asked to abstain from alcohol for one week before the study.
EXCLUSION CRITERIA
Patients younger than 18 years old and older than 65 will be excluded from the study.
Patients with MRI findings consistent with brain tumors, strokes, trauma or AVMs will be excluded.
Patients with progressive neurological disorders other than Tourette's syndrome will be excluded.
Patients with a history of significant medical disorders, or requiring chronic treatment with other drugs, which, cannot be stopped, will be excluded.
Patients with cancer will be excluded.
Patients not capable of giving an informed consent will be excluded.

Maryland
      National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  020181; 02-N-0181
Record last reviewed:  April 20, 2004
Last Updated:  November 23, 2004
Record first received:  April 26, 2002
ClinicalTrials.gov Identifier:  NCT00034398
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08