GABA changes with vigabatrin in the developing human brain.
OBJECTIVE
Changes in gamma-aminobutyric acid (GABA) physiology are important in determining seizure susceptibility in the developing nervous system. Noninvasive measurements of brain GABA in adults with epilepsy have demonstrated important relations among seizure control, brain GABA levels, and changes 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 ages 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 GABA was decreased in the region of the epileptic focus compared with the homologous region of the opposite hemisphere. A nearly fivefold increase in GABA occurred in the epileptic region after VGB treatment in this subject.


CONCLUSIONS
VGB increases brain GABA levels in children with epilepsy. NMRS can be used to monitor the response of brain GABA levels to drugs known to alter GABA physiology and serve as an important tool to understand the role of GABA-mediated inhibition in pediatric epilepsies.
Novotny
E J
EJ
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Hyder
F
F
Shevell
M
M
Rothman
D L
DL
D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000254:growth & development*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009778:Occipital Lobe / Q000737:chemistry* / Q000187:drug effects; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000032:analysis* / Q000494:pharmacology / Q000627:therapeutic use
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin