Decreased dopamine D2/D3-receptor binding in temporal lobe epilepsy: an [18F]fallypride PET study.
OBJECTIVE
Although animal data are suggestive, evidence for an alteration of the extrastriatal dopaminergic system in human focal epilepsy is missing.


METHODS
To quantify D2/D3-receptor density, we studied seven patients with temporal lobe epilepsy (TLE) and nine age-matched controls with positron emission tomography (PET) by using the high-affinity dopamine D2/D3-receptor ligand [18F]Fallypride ([18F]FP) suitable for imaging extrastriatal binding. TLE was defined by interictal and ictal video-EEG, magnetic resonance imaging (MRI), and [18F]fluorodeoxyglucose ([18F]FDG)-PET and was due to hippocampal sclerosis (HS), based on histology in all patients. Primary analysis was based on regions of interest (ROIs) defined on individual MRIs. For each patient, binding potential (BP) was calculated by using the simplified reference tissue model, and the epileptogenic was compared with the unaffected hemisphere in each ROI. To confirm the results, an additional voxel-based group analysis was performed by using statistical parametric mapping.


RESULTS
Compared with controls, [18F]FP BP was significantly decreased in the epileptogenic temporal lobe in all patients. On ROI analysis, this reduction was evident in areas surrounding the seizure-onset zone at the pole (-34.2%) and lateral aspects (-32.9%) of the temporal lobe. Although the hippocampus [18F]FDG uptake (-8.1%) and hippocampal MR volume (-35.1%) were significantly reduced, no significant decrease of [18F]FP BP was found. Reduction of [18F]FP BP did not correlate with hippocampal atrophy.


CONCLUSIONS
D2/D3-receptor binding is reduced at the pole and in lateral aspects of the epileptogenic temporal lobe in patients with mesial TLE and HS. This area might correspond to "the irritative zone," indicating that D2/D3 receptors might play a specific role in the pathophysiology of mesial TLE.
Werhahn
Konrad J
KJ
Department of Neurology, Johannes Gutenberg University, Rhineland-Palatinate, Germany. werhahn@uni-mainz.de
Landvogt
Christian
C
Klimpe
Sven
S
Buchholz
Hans-Georg
HG
Yakushev
Igor
I
Siessmeier
Thomas
T
Müller-Forell
Wibke
W
Piel
Markus
M
Rösch
Frank
F
Glaser
Martin
M
Schreckenberger
Mathias
M
Bartenstein
Peter
P
D000328:Adult; D001549:Benzamides; D001931:Brain Mapping; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D007839:Functional Laterality / Q000502:physiology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000378:metabolism* / Q000502:physiology; D050637:Receptors, Dopamine D3 / Q000378:metabolism* / Q000502:physiology; D012598:Sclerosis / Q000175:diagnosis / Q000473:pathology; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D014018:Tissue Distribution; D014743:Videotape Recording
D001549:Benzamides; D005462:Fluorine Radioisotopes; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019788:Fluorodeoxyglucose F18