title: Reduced D2/D3 Receptor Binding of Extrastriatal and Striatal Regions in Temporal Lobe Epilepsy.
abstract: OBJECTIVE
  Dopamine is an endogenous neuromodulator in cortical circuits and the basal ganglia. In animal models of temporal lobe epilepsy (TLE), seizure threshold is modulated to some extent by dopamine, with D1-receptors having a pro- and D2-receptors an anticonvulsant effect. We aimed to extend our previously reported results on decreased D2/D3 receptor binding in the lateral epileptogenic temporal lobe and to correlate them with demographic and seizure variables to gain a more comprehensive understanding of the underlying involvement of the dopaminergic system in the epileptogenesis of TLE.
  
  
  METHODS
  To quantify D2/D3 receptor binding, we studied 21 patients with TLE and hippocampal sclerosis (13 left- and eight right-sided) and 18 controls using PET with the high-affinity dopamine D2/D3-receptor ligand 18F-Fallypride to image striatal and extrastriatal binding. TLE was defined by interictal and ictal video-EEG, MRI and 18F-Fluorodeoxyglucose PET. Voxel-based statistical and regions-of-interest analyses were performed.
  
  
  RESULTS
  18F-Fallypride binding potential was significantly reduced in the affected temporal lobe and bilateral putamen. A positive correlation between age at onset of epilepsy and [18F]FP BPnd (binding potential non-displaceable) in temporal regions on the epileptogenic side was found, as well as a negative correlation between epilepsy duration and [18F]FP BPnd in the temporal pole on the epileptogenic side and a positive correlation between the estimated number of lifetime GTCS and [18F]FP BPnd in the hippocampus on the epileptogenic side.
  
  
  CONCLUSIONS
  The areas of reduced D2/D3 receptor availability correspond to "the irritative zone" surrounding the epileptogenic area. Moreover, reduced D2/D3 receptor availability was detectable in the basal ganglia, which are suspected to be involved in a control circuit for epileptic seizures. The correlational analysis additionally suggests that increased epilepsy duration leads to increasing impairment of the dopaminergic system.
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Viviane E
authors.initials: VE
authors.lastname: Bernedo Paredes
authors.affiliation: Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.affiliation: Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gartenschläger
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Breimhorst
authors.affiliation: Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Schreckenberger
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Konrad J
authors.initials: KJ
authors.lastname: Werhahn
mesh_terms: D000328:Adult; D000818:Animals; D001931:Brain Mapping; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019788:Fluorodeoxyglucose F18; D004298:Dopamine