Protocol Number: 02-N-0181

Title:

Evaluation of Density and Pattern of Distribution of GABA A Receptors in Brain of Patients with Tourette's Syndrome Studied with PET using [11C] Flumazenil

Number:

02-N-0181

Summary:

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.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility 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.

Special Instructions: Currently Not Provided

Keywords:

Basal Ganglia

Neuroimaging

Inhibitory Neurons

Disinhibition

Tics

Recruitment Keywords:

Tourette's Syndrome

Tourette Syndrome

Tics

Healthy Volunteer

HV

Normal Control

Conditions:

Tourette Syndrome

Investigational Drug(s):

flumazenil

H215O

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Biswal B, Ulmer JL, Krippendorf RL, Harsch HH, Daniels DL, Hyde JS, Haughton VM Abnormal cerebral activation associated with a motor task in Tourette PMID#9763386

Bolam JP, Hanley JJ, Booth PA, Bevan MD Synaptic organisation of the basal ganglia J Anat 2000 May;196 ( Pt 4):527-42 Review PMID#10923985

Hevers W, Luddens H The diversity of GABAA receptors Pharmacological and electrophysiological properties of GABAA channel subtypes Mol Neurobiol 1998 Aug;18(1):35-86 PMID#982848

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