According to recent research from the United States, "Succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder of GABA degradation with subsequent elevations in brain GABA and GHB, is a neurometabolic disorder with intellectual disability, epilepsy, hypotonia, ataxia, sleep disorders, and psychiatric disturbances. Neuroimaging reveals increased T2-weighted MRI signal usually affecting the globus pallidus, cerebellar dentate nucleus, and subthalamic nucleus, and often cerebral and cerebellar atrophy."

"EEG abnormalities are usually generalized spike-wave, consistent with a predilection for generalized epilepsy. The murine phenotype is characterized by failure-to-thrive, progressive ataxia, and a transition from generalized absence to tonic-clonic to ultimately fatal convulsive status epilepticus. Binding and electrophysiological studies demonstrate use-dependent downregulation of GABA(A) and (B) receptors in the mutant mouse. Translational human studies similarly reveal downregulation of GABAergic activity in patients, utilizing flumazenil-PET and transcranial magnetic stimulation for GABA(A) and (B) activity, respectively. Sleep studies reveal decreased stage REM with prolonged REM latencies and diminished percentage of stage REM. An ad libitum ketogenic diet was reported as effective in the mouse model, with unclear applicability to the human condition. Acute application of SGS-742, a GABA(B) antagonist, leads to improvement in epileptiform activity on electrocorticography," wrote P.L. Pearl and colleagues, George Washington University, Medical Department (see also Epilepsy).

The researchers concluded: "Promising mouse data using compounds available for clinical use, including taurine and SGS-742, form the framework for human trials."

Pearl and colleagues published their study in the Journal of Inherited Metabolic Disease (Succinic semialdehyde dehydrogenase deficiency: Lessons from mice and men. Journal of Inherited Metabolic Disease, 2009;32(3):343-352).

For additional information, contact P.L. Pearl, George Washington University, Children's National Med Center, School Medical, Dept. of Neurology, 111 Michigan Avenue NW, Washington, DC 20010, USA.

Publisher contact information for the Journal of Inherited Metabolic Disease is: Springer, Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands.

<>

Return to Epilepsy News