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Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy
Univ Hosp Geneva, Nucl Med & Mol Imaging Div, Dept Med Imaging, Geneva, Switzerland; Univ Geneva, Fac Med, Geneva, Switzerland.
Univ Hosp Geneva, Nucl Med & Mol Imaging Div, Dept Med Imaging, Geneva, Switzerland.
Advantis Med Imaging, Eindhoven, Netherlands.
Univ Hosp Geneva, EEG & Epilepsy Unit, Dept Neurol, Geneva, Switzerland.
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2019 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 46, no 2, p. 385-395Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 46, no 2, p. 385-395
Keywords [en]
F-A-85380, Focal epilepsy, Idiopathic generalized epilepsy, Nicotinic receptors, PET
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-362194DOI: 10.1007/s00259-018-4175-0ISI: 000455817600014PubMedID: 30269157OAI: oai:DiVA.org:uu-362194DiVA, id: diva2:1252605
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2019-02-05Bibliographically approved

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