Valentina Garibotto1,2, Michael Wissmeyer3, Zoi Giavri4, Rachel Goldstein5, Yann Seimbille3, Margitta Seeck6,5, Osman Ratib3, Sven Haller6,7,8, Fabienne Picard9,10. 1. Nuclear Medicine and Molecular Imaging Division, Department of Medical Imaging, University Hospitals of Geneva, 4 rue Gabrielle-Perret-Gentil, 1211, Genève 14, Switzerland. valentina.garibotto@hcuge.ch. 2. Faculty of Medicine, Geneva University, 1211, Geneva, Switzerland. valentina.garibotto@hcuge.ch. 3. Nuclear Medicine and Molecular Imaging Division, Department of Medical Imaging, University Hospitals of Geneva, 4 rue Gabrielle-Perret-Gentil, 1211, Genève 14, Switzerland. 4. Advantis Medical Imaging, Eindhoven, The Netherlands. 5. EEG and Epilepsy Unit, Department of Neurology, University Hospitals of Geneva, 4 rue Gabrielle-Perret-Gentil, 1211, Genève 14, Switzerland. 6. Faculty of Medicine, Geneva University, 1211, Geneva, Switzerland. 7. CIRD - Centre d'Imagerie Rive Droite, Rue Chantepoulet 21, 1201, Genève, Switzerland. 8. Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden. 9. Faculty of Medicine, Geneva University, 1211, Geneva, Switzerland. Fabienne.Picard@hcuge.ch. 10. EEG and Epilepsy Unit, Department of Neurology, University Hospitals of Geneva, 4 rue Gabrielle-Perret-Gentil, 1211, Genève 14, Switzerland. Fabienne.Picard@hcuge.ch.
Abstract
PURPOSE: Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4β2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy. METHODS: We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis. RESULTS: In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy. CONCLUSIONS: We observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4β2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.
PURPOSE: Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4β2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy. METHODS: We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis. RESULTS: In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy. CONCLUSIONS: We observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4β2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.
Entities:
Keywords:
F-A-85380; Focal epilepsy; Idiopathic generalized epilepsy; Nicotinic receptors; PET
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