BENZODIAZEPINE-GABA(A) RECEPTORS IN IDIOPATHIC GENERALIZED EPILEPSY MEASURED WITH [C-11] FLUMAZENIL AND POSITRON EMISSION TOMOGRAPHY

The neurochemical basis of absence seizures and the mechanism of their suppression by valproate (VPA) are uncertain. We used positron emissi on tomography (PET) to determine whether an abnormality of [C-11]fluma zenil binding to benzodiazepine (BZD)-GABA(A) receptors exists in pati ents with childhood and juvenile absence epilepsy and to examine the e ffects of VPA on [C-11]flumazenil binding. The regional cerebral volum e of distribution (V-d) of [C-11]flumazenil in patients not treated wi th VPA was not different from that in normal controls; V-d was lower i n patients treated with VPA, and the number of receptors available for binding was significantly reduced in such patients as compared with n ormal controls. There was no evidence of a primary abnormality of the BZD-GABA(A) receptor in childhood and juvenile absence epilepsy (CAE/J AE), but the data suggest that treatment with VPA is associated with a reduction in [C-11]flumazenil binding that may be relevant to its mod e of action in CAE/JAE.