DOI: 10.1007/s00259-018-4175-0Pages: 1-11

Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy

1. University Hospitals of Geneva, Nuclear Medicine and Molecular Imaging Division, Department of Medical Imaging

2. Geneva University, Faculty of Medicine

3. Advantis Medical Imaging

4. University Hospitals of Geneva, EEG and Epilepsy Unit, Department of Neurology

5. CIRD - Centre d’Imagerie Rive Droite

6. Uppsala University, Department of Surgical Sciences, Radiology

Correspondence to:
Fabienne Picard
Tel: +41.22.37.25.258
Email: Fabienne.Picard@hcuge.ch

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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.

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  • Accepted: Sep 18, 2018
  • Online: Sep 29, 2018

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