Clinical Trial: Brain Excitability in Patients With Succinic Semialdehyde Dehydrogenase Deficiency

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Cortical Excitability in Succinic Semialdehyde Dehydrogenase Deficiency

Brief Summary:

This study will measure brain excitability in patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, and in their parents. SSADH is a rare inherited disease in which changes in certain brain chemicals affect brain cell activity. Symptoms vary greatly among patients, and may include mental retardation, impaired ability to coordinate movements, and delays in language and speech development. Other symptoms may include poor muscle tone, uncontrolled seizures and other neurological or behavioral abnormalities. Test findings in patients and their parents will be compared with those of healthy normal volunteers.

The following individuals may be eligible for this study: patients with SSADH who are between 5 and 24 years of age; parents of patients who are between 18 and 55 years of age; healthy normal children who are between 10 and 17 years of age; and healthy normal adults who are between 18 and 55 years of age. Candidates are screened with blood and urine tests.

All participants undergo the following:

• Transcranial magnetic stimulation (TMS): This procedure maps brain function. A wire coil is held on the scalp, and a brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. During the stimulation, the subject may be asked to tense certain muscles slightly or perform other simple actions to help position the coil properly. The stimulation may cause a twitch in muscles of the face, arm, or leg, and the subject may hear a click and feel a pulling sensation on the skin under the coil. During the test, electrical activity of muscles is recorded with a computer or other recording device, using electrodes attached to the skin with tape.
• Magnetic resonance ima
  

  Detailed Summary:

  Objective: To study cortical excitability, electroencephalography patterns, nerve conduction velocity, and sleep patterns, in succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare autosomal recessive pediatric neurotransmitter disease associated with elevated levels of brain gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter. The clinical phenotype includes mental retardation, epilepsy, and neuropsychiatric manifestations.

  Study Population: Patients with SSADH deficiency, parents of patients (who are obligate heterozygotes), and healthy volunteers.

  Design: This is a natural history study in which subjects will have a series of neurophysiological tests. Transcranial magnetic stimulation (TMS) is a non-invasive technique that allows for measures of cortical excitation and inhibition. Electroencephalography (EEG) measures baseline brain electrical activity. Nerve conduction studies measure the speed of conduction of impulses by peripheral nerves. Polysomnography records sleep cycles and associated eye movements, muscle potentials, heart rate, and respiration.

  Outcome measures: Motor cortex excitability threshold, paired pulse facilitation, and paired pulse inhibition on TMS will be the main outcome measures. Values will be compared across the 4 groups of patients, carriers, adult and child healthy volunteers. Additional measures will include nerve conduction velocity, EEG frequency, and sleep patterns.

  
  Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
  

  Current Primary Outcome:
  
  

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  Original Secondary Outcome:
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: August 18, 2005
  Date Started: August 16, 2005
  Date Completion:
  Last Updated: January 24, 2017
  Last Verified: June 25, 2009