LOCALIZED CEREBELLAR REDUCTIONS IN BENZODIAZEPINE RECEPTOR DENSITY INHUMAN PARTIAL EPILEPSY

Background: Previous studies suggest that the morphological substrate for cerebellar dysfunction is destruction of Purkinje cells, but disag ree on whether this is caused by seizure- or drug-related toxicity. Th e benzodiazepine (BZ) receptor antagonist flumazenil tagged with carbo n 11 is a sensitive marker of Purkinje cells. Objective: To investigat e whether cerebellar dysfunction in partial epilepsy is related to sei zures through cerebrocerebellar connections. Design: Positron emission tomography with [C-11]flumazenil conducted in 5 patients with frontal lobe seizures, 12 patients with mesial temporal lobe seizures, and 7 healthy men. Eight patients also had [F-18]fluorodeoxyglucose positron emission tomography. Cerebellar regions of interest were delineated u sing magnetic resonance imaging and a computerized anatomical brain at las, and the epileptogenic regions were determined with a multimethod assessment. Results: Patients with frontal lobe seizures had a signifi cantly reduced BZ receptor density in the anterior cerebellum contrala teral to the seizure onset region (P less than or equal to.001, 2-way repeated-measure analysis of variance). Patients with mesial temporal lobe seizures had reductions in the ipsilateral (posterior and anterio r) cerebellum (P less than or equal to.001 for both). No significant a symmetries were found in regional glucose metabolism. Conclusions: The observed distribution of BZ receptor reductions is congruent with ani mal experiments showing that frontal lobe projections to the cerebellu m are crossed, whereas projections from mesial temporal lobe are predo minantly ipsilateral. The results thus indicate a functional relation with seizures and may reflect excitotoxic lesions or specific changes in the gamma-aminobutyric BZ system.