Association of decreased thalamic neurotransmitter level with sensorimotor tract damage in patients with relapsing-remitting multiple sclerosis

Thalamic microstructural damage and neurotransmission dysfunction are present in patients with multiple sclerosis (MS). The aim of this study was to investigate the relationship of altered γ-aminobutyric acid (GABA) and glutamate + glutamine (Glx) levels in the thalamus with the white-matter (WM) microstructural damage of the sensorimotor tract in patients with relapsing-remitting MS (RRMS). In this cross-sectional study, 50 patients with RRMS and 43 healthy controls (HCs) were scanned using Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) to quantify the GABA+ and Glx level of the thalamus. Metrics derived from diffusion tensor imaging (DTI) were calculated to reflect the degree of WM microstructural damage of the sensorimotor tract. The correlation between neurotransmitter level and diffusion metrics was determined in patients with RRMS and HCs, respectively. Thalamic GABA+ and Glx levels were significantly decreased in patients with RRMS as compared with HCs (GABA+: 2.859±0.451 vs. 3.092±0.283 IU, P=0.002; Glx: 5.787±1.307 vs. 6.439±0.680 IU, P=0.002), and the neurotransmitter levels were significantly and negatively correlated with total lesion volume and disease duration in patients with RRMS (P<0.05). With the exception of the tract of right supplementary motor area, other sensorimotor tracts of patients with RRMS showed extensive WM microstructural damage. In addition, there was a significant correlation between decreased thalamic GABA+ and Glx levels and sensorimotor tract damage in patients with RRMS (corrected P<0.05). Analysis in HCs showed that the thalamic neurotransmitter level was not correlated with diffusion metrics in any of the sensorimotor tracts. Neurotransmitters may play an important role in the pathophysiologic mechanisms of MS. Our study suggests an association between altered GABA and glutamate levels in deep gray-matter and WM microstructural damage in the sensorimotor tract.