Objective A previous 1H-MR spectroscopy (MRS) study reported elevated levels of glutamate, an excitatory neurotransmitter, in acute lesions and normal-appearing white matter, which may relate to the presence of inflammatory cells and astrocytosis. We aim to assess whether glutamate levels (1) change in the grey matter (GM), and (2) relate to cognitive dysfunction.
Methods Single-voxel MRS was performed at 3 T in 18 patients with relapsing-remitting MS [12 women, age 43.5 years, median EDSS 2.8] and 17 healthy subjects [11 women, age 39.7], using PRESS [TR6000, TE30, water suppression]. Voxels were located in the right cingulate and parietal cortices, right hippocampus and thalamus. Concentrations of metabolites were obtained using LCModel, scaled using the water signal amplitude, and corrected for fractions of different tissue compartments and their T1 and T2 relaxation times. Visual and verbal memory and speed of information processing were assessed.
Results Patients showed significantly worse performance on the visual memory test (total errors p<0.01, trials completed at the 1st attempt p<0.05, and total no. of trials p<0.01), on verbal learning (p<0.01), delayed verbal recall (p<0.05), and on processing speed (SDMT, p<0.001), compared to controls. Patients showed lower glutamate concentration in the cingulate (6.3 institutional unit (iu) vs 7.7, p<0.001) and parietal cortices (6.4 iu vs 7.5, p=0.001), and in the hippocampus (3.2 iu vs 4.4, p=0.05), compared to controls. Patients also showed significantly lower N-Acetyl-Aspartate (NAA) levels in the thalamus and cortical GM, compared to controls. Lower hippocampal glutamate levels correlated with worse visual memory (trials at 1st attempt: r=0.5, p<0.05; total trials: r=0.5, p<0.05).
Discussion Glutamate neurotransmission is reduced in the cortical and hippocampal regions of people with MS and is linked to cognitive impairment. Reduced levels of glutamate and NAA in cortical GM agree with post-mortem findings of GM neuronal loss in MS. MR spectroscopy of cortical glutamate may provide a surrogate marker for assessing the efficacy of future therapies in reducing memory decline in people with MS.