Correlation of Hippocampal Glucose Oxidation Capacity and Interictal FDG‐PET in Temporal Lobe Epilepsy

Abstract

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.

Metabolism is Normal in Astrocytes in Chronically Epileptic Rats: A 13C NMR Study of Neuronal—Glial Interactions in a Model of Temporal Lobe Epilepsy

“…However, this was only statistically significant for unlabeled glucose, not for [1-13 C]glucose, likely because the percentage of enrichment in glucose was only 18%, thus the differences might have been too small to be detectable. This decreased consumption is in agreement with animal and human data showing interictal hypometabolism within the hippocampus, which could extend to extratemporal cortical and subcortical regions (Arnold et al, 1996;Dube et al, 2001;Vielhaber et al, 2003b;Chassoux et al, 2004). Moreover, in these areas neuronal loss does not necessarily correlate with interictal hypometabolism (Ryvlin et al, 1991;O'Brien et al, 1997;Foldvary et al, 1999;Dube et al, 2001).…”

Cytochrome c oxidase deficit is associated with the seizure onset zone in young patients with focal cortical dysplasia Type II

“…Other investigators used CIV histochemistry, estimated by optical density, to demonstrate neuronal loss and a non-homogenous decrease in CIV activity in piriform cortex of adult rats after pilocarpine- (Otáhal et al 2005). Others have shown that interictal FDG-PET hypometabolism in adult patients with temporal lobe epilepsy was correlated with decreased respiratory chain glucose-oxidation capacity, suggesting the possibility of an intrinsic metabolic abnormality (Vielhaber et al 2003). Although ETC biochemistry was not determined by the investigators, their histological examination suggested CIV deficiency in pyramidal neurons in the CA3 region of hippocampal resections (Vielhaber et al 2003).…”

Brain areas involved in medial temporal lobe seizures: A principal component analysis of ictal SPECT data

“…A special element of the paralimbic system, the insula-orbital-temporal complex, projects from the temporal pole cortex to insular cortex, i.e., to the long anterior and posterior gyrus of the insula [Augustine, 1996;Eberstaller, 1887;Mesulam and Mufson, 1982a]. The negatively loaded parahippocampal gyrus in the PC3 image, extending bilaterally from the basis of temporal lobe medially and probably including the dentate gyrus, is known to show suppressed metabolism in interictal PET studies of fluorodeoxyglucose [Foldvary et al, 1999;Vielhaber et al, 2003]. The implication of the dentate gyrus in the inhibition of seizures is substantiated by studies of rodents and humans.…”