GABA deficiency in NF1: a multimodal [11C]-Flumazenil and spectroscopy study
File(s)
Published version
Accepted version
Author(s)
Ribeiro Violante, I
Type
Journal Article
Abstract
Objective: To provide a comprehensive investigation of the GABA system in
patients with Neurofibromatosis type 1 (NF1) that allows understanding the
nature of the GABA imbalance in humans at pre- and post-synaptic levels.
Methods: In this cross-sectional study, we employed multimodal imaging and
spectroscopy measures to investigate GABAA receptor binding, using [11C]-
Flumazenil positron emission tomography (PET), and GABA concentration,
using magnetic resonance spectroscopy (MRS). 14 adult patients with NF1 and
13 matched controls were included in the study. MRS was performed in the
occipital cortex and in a frontal region centered in the functionally localized
frontal-eye fields. PET and MRS acquisitions were performed in the same day.
Results: Patients with NF1 have reduced concentration of GABA+ in the
occipital cortex (P = 0.004) and frontal-eye fields (P = 0.026). PET results
showed decreased binding of GABAA receptors in patients in the parietooccipital
cortex, midbrain and thalamus, which are not explained by decreased
grey matter levels.
Conclusions: Abnormalities in the GABA system in NF1 involve both GABA
concentration and GABAA receptor density suggestive of neurodevelopmental
synaptopathy with both pre- and post-synaptic involvement.
patients with Neurofibromatosis type 1 (NF1) that allows understanding the
nature of the GABA imbalance in humans at pre- and post-synaptic levels.
Methods: In this cross-sectional study, we employed multimodal imaging and
spectroscopy measures to investigate GABAA receptor binding, using [11C]-
Flumazenil positron emission tomography (PET), and GABA concentration,
using magnetic resonance spectroscopy (MRS). 14 adult patients with NF1 and
13 matched controls were included in the study. MRS was performed in the
occipital cortex and in a frontal region centered in the functionally localized
frontal-eye fields. PET and MRS acquisitions were performed in the same day.
Results: Patients with NF1 have reduced concentration of GABA+ in the
occipital cortex (P = 0.004) and frontal-eye fields (P = 0.026). PET results
showed decreased binding of GABAA receptors in patients in the parietooccipital
cortex, midbrain and thalamus, which are not explained by decreased
grey matter levels.
Conclusions: Abnormalities in the GABA system in NF1 involve both GABA
concentration and GABAA receptor density suggestive of neurodevelopmental
synaptopathy with both pre- and post-synaptic involvement.
Date Issued
2016-07-29
Date Acceptance
2016-05-10
Citation
Neurology
ISSN
0028-3878
Publisher
American Academy of Neurology
Journal / Book Title
Neurology
Copyright Statement
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is properly cited.
use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor
Wellcome Trust
Grant Number
103045/Z/13/Z
Subjects
Neurology & Neurosurgery
1103 Clinical Sciences
1109 Neurosciences
1702 Cognitive Science
Publication Status
Published