IN-VIVO DEMONSTRATION OF ALTERED BENZODIAZEPINE RECEPTOR DENSITY IN PATIENTS WITH GENERALIZED EPILEPSY

Electrophysiological data suggest that an abnormal oscillatory pattern of discharge in cortical and thalamic neurons may be the major mechan ism underlying primary generalised epilepsy. No neurochemical or anato mical substrate for this theory has hitherto been demonstrated in huma ns and the pathophysiology of primary generalised epilepsy remains unk nown. By means of PET and the benzodiazepine (BZ) ligand [C-11]flumaze nil it has been previously shown that the BZ receptor density is reduc ed in the epileptic foci of patients with partial epilepsy. In the pre sent study the method was further developed and used in a comparative analysis of cortical, cerebellar, and subcortical BZ receptor binding in patients with primary generalised tonic and clonic seizures (n = 8) , and healthy controls (n = 8). Patients with generalised seizures had an increased BZ receptor density in the cerebellar nuclei (p = 0.006) and decreased density in the thalamus (p = 0.003). No significant cha nges were seen in the cerebral and cerebellar cortex or in the basal g anglia. The observed alterations suggest that the gamma-amino-butyric acid (GABA)-BZ system may be affected in the cerebello-thalamocortical loop of patients with generalised epilepsy and indicate possible targ ets for selective pharmacological treatment.