Summary:Purpose: Interictal [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography (PET) demonstrates temporal hypometabolism in the epileptogenic zone of 60-90% of patients with temporal lobe epilepsy. The pathophysiology of this finding is still unknown. Several studies failed to show a correlation between hippocampal FDG-PET hypometabolism and neuronal cell loss. Because FDG is metabolized by hexokinase bound to the outer mitochondrial membrane, we correlated the glucose-oxidation capacity of hippocampal subfields obtained after surgical resection with the corresponding hippocampal presurgical FDG-PET activity.Methods: In 16 patients with electrophysiologically confirmed temporal lobe epilepsy, we used high-resolution respirometry to determine the basal and maximal glucose-oxidation rates in 400-m-thick hippocampal subfields obtained after dissection of human hippocampal slices into the CA1 and CA3 pyramidal subfields and the dentate gyrus.Results: We observed a correlation of the FDG-PET activity with the maximal glucose-oxidation rate of the CA3 pyramidal subfields (r p ‫ס‬ 0.7, p ‫ס‬ 0.003) but not for the regions CA1 and dentate gyrus. In accordance with previous studies, no correlation of the FDG-PET to the neuronal cell density of CA1, CA3, and dentate gyrus was found.Conclusions: The interictal hippocampal FDG-PET hypometabolism in patients with temporal lobe epilepsy is correlated to the glucose-oxidation capacity of the CA3 hippocampal subfield as result of impaired oxidative metabolism. Key Words: Temporal lobe epilepsy-FDG-PET-Mitochondrial oxidative phosphorylation.With [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET), interictal hypometabolism is found among 60-90% of patients with the clinical syndrome of temporal lobe epilepsy (TLE) (1-3). FDG-PET has become an accepted tool for localization of temporal lobe foci and for prediction of surgical outcome (4-7). FDG-PET hypometabolism is proposed to be associated with the presence of underlying mesial temporal sclerosis (MTS) and seems to correlate with the degree of hippocampal volume loss measured by volumetric magnetic resonance imaging (MRI) (8,9). Conversely, several studies failed to show a clear relation between hippocampal neuronal cell loss, associated atrophy, and interictal hypometabolism (10-12). The pathophysiologic mechanism accounting for the FDG-PET hypometabolism is therefore still under discussion. The purpose of our study was to examine the existence of a relation between regional FDG metabolism in PET scans and intrinsic glucose metabolism in surgical specimens in TLE patients. Because FDG is metabolized in the brain by hexokinase bound to the outer mitochondrial membrane (13), we tried to correlate the glucoseoxidation capacity quantified in resected hippocampal subfield specimens with the corresponding hippocampal FDG-PET in patients with TLE.