Abstracts

RATIONALE: The objective of our study is to assess abnormalities in 5HT1A receptors density in epileptic patients suffering from refractory temporal lobe epilepsy.
Experimental data in animals show that 5HT1A receptors are mainly located in limbic areas and that serotonin, via 5HT1A receptors, mediates an antiepileptic and anticonvulsivant effect. In TLE patients, we quantified 5HT1A receptor density in epileptogenic and non epileptogenic areas as defined by intracranial recordings with stereo-electroencephalography (SEEG).
METHODS: Five patients and 24 control subjects (4 groups of 6 controls sex and age matched with patients) were studied by PET using a 5HT1A receptor antagonist ([18F]-pMPPF). Dynamic PET data were acquired during 70 minutes. PET and MRI data were coregistered for anatomical identification. A series of 34 anatomical Regions of Interest (ROI) were drawn on patient and control MRIs. PET data were quantified using a simplified model (Gunn et al. 1998, Neuroimage 8:426-440) to assess Binding Potential (BP) values in each ROI with cerebellum as a reference. For each patient, a normalized percent of BP change was calculated as the relative variation of BP in each ROI compared to the corresponding ROI in control subjects (%=(BPpatients-BPcontrols)/BP control). In patients, ROIs explored by SEEG, were categorized as showing (1) Ictal dischages and interictal spikes, (2) only interictal spikes, and (3) no epileptic activity activity. Percent of BP change were then averaged over patients within each of these three ROI groups.
RESULTS: Compared to control values, BP were on average decreased by 35 [plusminus] 19 % in ROI showing discharges and spikes, by 16 [plusminus] 32 % in ROI only showing spikes, and by 8 [plusminus] 20 % in ROI showing no epileptic activity. ANOVA performed on these 3 groups revealed that 5HT1A binding was significantly more decreased in ROI in which discharges and spikes were recorded compared to (1) ROI showing no epileptic activity (p[lt]0.003) and (2) ROI in which only interictal spikes were recorded (p[lt]0.03). No significant difference in BP change was found between regions in which only spikes were recorded and regions with no epileptic activity.
CONCLUSIONS: This study shows that in vivo disponibility of 5HT1A receptors is decreased in epileptic patients as compared to normal subjects. This decrease is highly correlated to the degree of epileptogenicity of cortical areas explored by intracerebral recordings. Our data suggest that the serotonin neurotransmission might be more impaired in regions involved in epileptic discharges than in regions only generating interictal paroxysms. This study raises the question of the potential use of [18F]-pMPPF-PET in the presurgical evaluation of refractory partial epilepsies.
[Supported by: Claude Bernard University Lyon1. Hospices Civils of Lyon (HCL). National Center for Sientific Research (CNRS).]