CENTRAL BENZODIAZEPINE GAMMA-AMINOBUTYRIC ACID(A) RECEPTORS IN IDIOPATHIC GENERALIZED EPILEPSY - AN [C-11] FLUMAZENIL POSITRON-EMISSION-TOMOGRAPHY STUDY/

Purpose: Previous [C-11]flumazenil (FMZ) positron emission tomography (PET) investigations in patients with idiopathic generalized epilepsy (IGE) have demonstrated nonsignificant global cortical decreases in ce ntral benzodiazepine gamma-aminobutyric acid(A) (GABA(A)) receptor (cB ZR) binding or focal decreases in the thalamus and increases in the ce rebellar nuclei with no changes in cerebral cortex. We previously repo rted lower [C-11]FMZ binding in cerebral cortex of IGE patients treate d with valproate (VPA) than in cerebral cortex of controls. We now rep ort high-resolution three-dimensional [C-11]FMZ PET studies in a large r number of subjects using an improved method to detect differences in cBZR between IGE patients and controls and a more powerful longitudin al design to determine the functional effect of VPA. Methods: We compa red parametric images of [C-11]FMZ volume of distribution (FMZVD) in 1 0 IGE patients before and after addition of VPA and in 20 normal subje cts. Results: Mean FMZVD was significantly higher in the cerebral cort ex (11%, p = 0.009), thalamus (14%, p = 0.018), and cerebellum (15%, p = 0.027) of the 10 IGE patients as compared with that of 20 normal co ntrols. Using statistical parametric mapping, no significant areas of focal abnormality of FMZVD were detected. Addition of VPA was not asso ciated with a significant change in mean FMZVD in any brain area. Conc lusions: Our finding of increased FMZVD in IGE could reflect microdysg enesis or a state of cortical hyperexcitability. Our data suggest that short-term VPA therapy does not affect the number of available cBZR i n patients with IGE.