Diseases Clinical Trial
Official title:
Cortical Excitability in Succinic Semialdehyde Dehydrogenase Deficiency
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 imaging (MRI): This test combines a powerful magnet with an advanced
computer system and radio waves to produce accurate, detailed pictures of organs and
tissues. During the scan, the subject lies on a table in a narrow cylinder containing a
magnetic field, wearing ear plugs to muffle loud noises that occur with electrical
switching of the magnetic fields. He or she can speak with a staff member via an
intercom system at all times during the procedure. In addition to standard MRI, subjects
may have newer MRI tests, such as diffusion tensor MRI and magnetic resonance
spectroscopy.
In addition to the above, patients and their parents may also undergo the following tests:
- Electroencephalography (EEG): This test records brain waves (electrical activity of the
brain). Electrodes are placed on the scalp and brain electrical activity is recorded
while the subject lies quietly, breathes deeply, watches flashes of light, or sleeps.
Some patients may also have video-EEG monitoring, which involves simultaneous clinical
recording using a video camera along with brain wave recording.
- Sleep study and multiple sleep latency onset testing (MSLT): Electrodes are placed on
the subject's scalp and remain there while the subject sleeps in the hospital overnight.
MSLT is done the next day, starting 2 hours after the subject wakes up from the night's
sleep. A total of five 20- to 30-minute naps are recorded, each every 2 hours, to access
daytime sleepiness.
- Nerve conduction studies: This test measures the speed with which nerves conduct
electrical impulses and the strength of the connection between the nerve and the muscle.
A probe is placed on the skin to deliver a small electrical stimulus, and wires taped on
the skin record the impulses.
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.
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