title: Human brain gamma-aminobutyric acid levels and seizure control following initiation of vigabatrin therapy.
abstract: Vigabatrin is a novel antiepileptic drug designed to control seizures by raising brain gamma-aminobutyric acid (GABA) concentrations. Seizure control is not improved significantly when the daily dose is increased beyond 50 mg/kg. Serial, in vivo measurements of GABA levels in human occipital lobe were made using 1H NMR spectroscopy before and after the start of vigabatrin treatment. We used a 2.1-T magnetic resonance imagerspectrometer and an 8-cm surface coll to examine serially a 14-cm3 volume in the occipital lobe of 26 patients with complex partial seizures. Brain GABA content increased following the start of vigabatrin treatment up to a daily dose of 60 mg/kg. Additional increases in dose falled to increase brain GABA content further. GABA synthesis may decrease with sustained elevations of human brain GABA levels. Starting vigabatrin treatment reduced seizure frequency by > 50%, from six to seven per month to three. Improved seizure control was not associated with further increases of vigabatrin dose. Increased brain GABA concentration was associated with improved seizure control. Starting vigabatrin treatment improved seizure control twofold when GABA levels increased above 1.8 mmol/kg. Further increases in brain GABA content above 2.5 mmol/kg provided less protection. Measuring occipital lobe GABA concentrations may predict improved seizure control when using antiepileptic drugs designed to increase brain GABA levels.
authors.affiliation: Department of Neurology, Yale University, New Haven, Connecticut 06510, USA.
authors.forename: O A
authors.initials: OA
authors.lastname: Petroff
authors.forename: K L
authors.initials: KL
authors.lastname: Behar
authors.forename: R H
authors.initials: RH
authors.lastname: Mattson
authors.forename: D L
authors.initials: DL
authors.lastname: Rothman
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D017029:Epilepsy, Complex Partial / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000737:chemistry / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy; D013057:Spectrum Analysis; D013997:Time Factors; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin