GABA deficiency in NF1: a multimodal [11C]-Flumazenil and spectroscopy study

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.