GABA changes with vigabatrin in the developing human brain

Purpose. Changes in gamma-aminobutyric acid (GABA) physiology are important in determining seizure susceptibility in the developing nervous system. No ninvasive measurements of brain GABA in adults with epilepsy have demonstra ted important relations among seizure control, brain GABA levels, and chang es in brain GABA with drugs designed to alter GABA metabolism. The purpose of this study was to demonstrate the changes in GABA in the occipital lobes of children with epilepsy after treatment with vigabatrin (VGB). Methods: Ten proton nuclear magnetic resonance spectroscopic (NMRS) studies were obtained on four subjects with epilepsy. The subjects were between ag es 1 and 5 years. Occipital lobe GABA levels were measured before and after treatment with VGB. Results: Brain GABA levels increased significantly in these subjects after VGB treatment (p < 0.05, paired Student's t test). In one subject, brain GA BA was decreased in the region of the epileptic focus compared with the hom ologous region of the opposite hemisphere. A nearly fivefold increase in GA BA occurred in the epileptic region after VGB treatment in this subject. Conclusions: VGB increases brain GABA levels in children with epilepsy. NMR S can be used to monitor the response of brain GABA levels to drugs known t o alter GABA physiology and serve as an important tool to understand the ro le of GABA-mediated inhibition in pediatric epilepsies.