Abstracts

RATIONALE: Animal seizure models and intracellular recording studies suggest that serotonin (5-HT) exerts an anticonvulsant effect mediated by activation of 5-HT[sub]1A[/sub] receptors, which are abundant in hippocampus, raphe nuclei and neocortex. We used Positron Emission Tomography (PET) using [F-18]FCWAY, a selective 5-HT[sub]1A[/sub] receptor antagonist, to compare 5-HT[sub]1A[/sub] receptor binding in patients with temporal lobe epilepsy to normal controls.
METHODS: [F-18]FCWAY PET was performed in 11 adults with medically refractory temporal lobe epilepsy (age 20-56 years; 5 women; 9 with right and 2 with left medial temporal lobe seizure onset based on surface ictal recordings; 9/11 had mesial temporal sclerosis on MRI) and 9 normal controls. Data were corrected for partial volume averaging from F-18 activity in skull and for uptake of a radiolabeled acid metabolite, and fitted to a one-tissue compartment model. Quantitative PET image anaylsis was performed to obtain regional values for volume of distribution (Vd), representing total binding, and K1, the delivery rate from plasma to tissue. [F-18]FDG PET was performed in all patients and quantitative data obtained. Using paired t tests, within patient comparisons of Vd were made between the ipsilateral vs. contralateral inferior medial (IMT) and lateral (ILT) temporal regions. Grouped patient vs. control comparisons were made in these regions and in the raphe region using 2 sample t tests. In patients, absolute asymmetry indices (|AI|), |(ipsilateral-contralateral)/[0.5*(ipsilateral+contralateral)]|, for [F-18]FCWAY Vd and normalized regional cerebral metabolic rate for glucose (rCMRglu) in the IMT and ILT regions were compared using paired t tests. P values were adjusted for multiple comparison.
RESULTS: Within patient comparison revealed significantly lower Vd in the ipsilateral IMT and ILT compared to the contralateral regions (IMT and ILT, P=0.04). No side to side difference was seen in controls. The Vd in ipsilateral but not contralateral IMT and ILT regions was decreased in patients compared to corresponding regions in controls (IMT, P=0.006; ILT, P=0.05). There was no significant difference in Vd in the raphe region of patients compared to controls. 7 patients had ipsilateral hypometabolism on [F-18]FDG PET based on quantitative data. Mean Vd |AI| in the IMT (0.27) and ILT (0.34) regions was greater than mean rCMRglu (IMT, 0.13; ILT, 0.12) |AI| (IMT, P=0.11; ILT, P=0.02).
CONCLUSIONS: Vd of 5-HT[sub]1A[/sub] receptor binding is decreased in the epileptogenic temporal lobe and to a greater degree than the rCMRglu (ILT[gt]IMT). These findings suggest that there may be specific 5-HT[sub]1A[/sub] receptor loss.