Abstracts

In animal models of temporal lobe epilepsy (TLE) activation of D1- has a pro- and of D2-receptors anticonvulsant effects. Evidence for an alteration of the extrastriatal dopaminergic system in human focal epilepsy is missing. We hypothesized reduction of D2/D3 receptor binding in mesial temporal structures reflecting increased excitability in patients with TLE due to hippocampal sclerosis. We studied seven patients (31.6 [underline]+[/underline] 5.5 yrs) with mesial TLE and nine aged-matched (32.3 [underline]+[/underline] 8.4) controls by PET using the dopamine D2/D3 receptor ligand ¹⁸F-Fallypride (18F-FP). TLE was defined by ictal Video-EEG, MRI and 18F-FDG PET and was due to hippocampus sclerosis based on histology. Comparison with controls was performed by a voxel-based analysis using statistical parametric mapping (SPM, stat. threshold p [lt] 0.05, corr. for mult. comparisons at cluster level, minimal cluster size [gt]20 voxels). Anatomical regions of interest (ROIs) were drawn on MRIs. We than calculated a normalized the percentage binding potential (BP) of 18F-FP using the simplified reference tissue model and compared epileptogenic and unaffected hemispheres in each ROI. Comparison controls vs. patients revealed a decreased regional 18F-FP BP in anterior lateral areas of the temporal lobe of the epileptogenic hemisphere ([-34, 4, -37]; Z = 4.23 and [-46, 10, -31]; Z = 3.84). In ROI analysis 18F-FP BP was significantly decreased at the temporal pole (-34.2%, 0.50 [underline]+[/underline] 0.05 vs. 0.84 [underline]+[/underline] 0.12, p = 0.012, 2-sided paired t-test), and anterior-lateral temporal cortex (-32.9 %; 0.37 [underline]+[/underline] 0.06 vs. 0.60 [underline]+[/underline] 0.10, p = 0.036). 18F-FP BP reduction in para-hippocampal (-17.7%, 0.50 [underline]+[/underline] 0.05 vs. 0.68 [underline]+[/underline] 0.12, p = 0.09) and posterior temporal (-20.6%, 0.38 [underline]+[/underline] 0.05 vs. 0.55 [underline]+[/underline] 0.10, p = 0.11) areas was not significant. In contrast, 18F-FP BP in the hippocampus - despite considerable hippocampal atrophy on MR volumetry (mean -35.1% [underline]+[/underline] 5.3%) and significantly reduced FDG-uptake (- 8.1%, p = 0.003) - were not significant (0.92 [underline]+[/underline] 0.14 vs. 0.83 [underline]+[/underline] 0.10, p = 0.41). D2/D3 receptor binding is reduced in mTLE and hippocampus sclerosis. The decreased specific binding may reflect reduced receptor concentration, lower affinity, or a decreased occupancy of the D2/D3 receptors. Experiments using glutamate-induced seizures suggest that the absence of D2 receptors lowers the threshold for limbic seizures in dopamine D2 receptor knock-out mice (Bozzi et al. J Neurosci 2000). Alterations of D2/D3 binding may play a role in the pathophysiology of human mTLE. (Supported by Deutsche Forschungsgemeinschaft (Grant Ba 1011/2-1).)