Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy.

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.

• Authors: Valentina Garibotto, Michael Wissmeyer, Zoi Giavri, Rachel Goldstein, Yann Seimbille, Margitta Seeck, Osman Ratib, Sven Haller, Fabienne Picard
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 46 Issue 2 Pg. 385-395 (02 2019) ISSN: 1619-7089 [Electronic] Germany
• PMID: 30269157 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Receptors, Nicotinic

Topics

• Adolescent
• Adult
• Biomarkers (metabolism)
• Case-Control Studies
• Epilepsy, Generalized (diagnostic imaging, metabolism)
• Female
• Humans
• Image Processing, Computer-Assisted
• Magnetic Resonance Imaging
• Middle Aged
• Positron Emission Tomography Computed Tomography
• Receptors, Nicotinic (metabolism)
• Young Adult