Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy

Valentina Garibotto*, Michael Wissmeyer, Zoi Giavri, Rachel Goldstein, Yann Seimbille, Margitta Seeck, Osman Ratib, Sven Haller, Fabienne Picard

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Scopus)

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 [ 18 F]-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 [ 18 F]-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 (BP RI , corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BP RI 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.

Original languageEnglish
Pages (from-to)385-395
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume46
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

Bibliographical note

Funding Information:
Funding The work was funded by the Swiss National Science Foundation (n° 320030_127608).

Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

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