Brain Excitability in Patients With Succinic Semialdehyde Dehydrogenase Deficiency

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.