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Human Brain γ‐Aminobutyric Acid Levels and Seizure Control Following Initiation of Vigabatrin Therapy
Author(s) -
Petroff Ognen A. C.,
Behar Kevin L.,
Mattson Richard H.,
Rothman Douglas L.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67062399.x
Subject(s) - vigabatrin , epilepsy , anticonvulsant , aminobutyric acid , gamma aminobutyric acid , human brain , occipital lobe , temporal lobe , medicine , endocrinology , anesthesia , psychology , pharmacology , neuroscience , receptor
Vigabatrin is a novel antiepileptic drug designed to control seizures by raising brain γ‐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 1 H NMR spectroscopy before and after the start of vigabatrin treatment. We used a 2.1‐T magnetic resonance imagerspectrometer and an 8‐cm surface coil to examine serially a 14‐cm 3 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 failed 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.