HUMAN BRAIN GABA LEVELS RISE AFTER INITIATION OF VIGABATRIN THERAPY BUT FAIL TO RISE FURTHER WITH INCREASING DOSE

Using H-1 spectroscopy, we measured occipital lobe GABA levels seriall y in 18 patients enrolled in an ongoing open label trial of vigabatrin . Brain GABA levels were elevated twofold in patients taking vigabatri n (3 to 4 g/d) compared with nonepileptic subjects, Serial measurement s suggested that brain GABA rose in proportion to vigabatpin dose up t o 3 g/d. Doubling the dose from 3 to 6 g/d failed to increase brain GA BA further. Serial measurements on three patients taking 6 g/d showed a gradual decrease in brain GABA in two patients over 1 to 2 years of treatment. These observations suggest that GABA synthesis may decrease at high GABA levels.