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Summary: Purpose: 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.