REGIONAL INCREASES IN [C-11] FLUMAZENIL BINDING AFTER EPILEPSY SURGERY

Introduction - Animal experiments suggest that epileptic seizures alte r the expression of mRNA for neuro-receptors. PET measurements with [C -11]flumazenil show that patients with partial seizures have a reduced density of benzodiazepine (BZ) receptors in the epileptogenic regions (ER) and some of the target areas for seizure activity, the so called projection areas. Recent data suggest that the degree of BZ receptor reduction in ER is correlated to seizure frequency. We therefore hypot hesized that seizure activity can alter the BZ receptor binding, and t hat some of these changes could normalize when the seizures disappeare d. Methods - In 4 patients whose seizures were generated by mesial tem poral lobe structures, BZ receptor density was measured with [C-11]flu mazenil PET before, and 1 year after the epilepsy surgery and cessatio n of seizures. By use of a computerized anatomical brain atlas the sam e regions were analyzed in both PET scans, and the results related to data from 7 healthy controls. Results - Presurgical PET scans showed r eductions in BZ receptor density in the epileptogenic region and some of its primary projection areas. Other cortical regions had normal val ues. Postsurgically, the calculated BZ receptor density normalized (29 +/-17% increase) in several of the affected projection areas, whereas the values in other cortical regions remained unaltered. Conclusion - Regional reductions in BZ receptor density may be dynamic and related to seizures. The present preliminary observations encourage further st udies on seizure-related changes in regional receptor binding in human s.