Altered hypothalamic metabolism in early multiple sclerosis - MR spectroscopy study

Multiple sclerosis (MS) is a disease characterized by overlapping processes of neuroinflammation and neuroaxonal degeneration. Disturbances of the hypothalamo-pituitary axis in MS are supposed to modulate nettroinflammatory circuits, however, there is insufficient knowledge about the hypothalamic metabolism alterations in early MS. This H-1 MRS study performed on a 1.5 T MR-scanner was focused on the hypothalamus of 31 pre-treatment patients after their first clinical MS episode/s, compared to 31 healthy controls. The metabolite ratios of N-acetyl-aspartate & N-acetyl-aspartyl-glutarnate (tNAA), glutamate & glutamine (Glx), myo-Inositol (mins), choline- and creatine-containing compounds (tCho, tCr) were further correlated with the Expanded Disability Status Scale (EDSS). In the hypothalamus of early MS patients compared to controls, we found decreased tNAA/tCr and increased tCho/tNAA, mins/tNAA, Glx/tCr, and Glx/tNAA. In addition, tCho/tNAA, Glx/tNAA, and mins/tNAA were positively and tNAA/tCr was negatively correlated with EDSS. Results suggest that the decline of the tNAA ratio, indicating neuro-axonal dysfunction in the hypothalamus, may be linked with glutamate excitotoxicity. Excessive glutamate concentrations may cause microglial activation and myelinated tracts degradation with subsequent gliosis, paralleled by increased mins and tCho ratios. This indicates that glutamate excitotoxicity can play an important role in MS from its earliest stages.