Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate

Abstract

Introduction: The purpose of this study was to investigate whether single-voxel (SV) proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) detected differences between fibromyalgia (FM) patients and healthy controls. We also searched for correlations between neuroimaging abnormalities and neuropsychological variables.

Methods: Ten patients with FM and 10 gender- and age-matched control subjects were studied. A neuropsychological examination, DWI, DTI, and proton MRS were performed on the brain areas known to be associated with pain processing.

Results: Compared with healthy controls, FM patients had significantly higher levels of glutamate + glutamine (Glx) (mean ± SD, 10.71 ± 0.50 arbitrary institutional units versus 9.89 ± 1.04; P = 0.049) and higher glutamate + glutamine/creatine (Glx/Cr) ratios (1.90 ± 0.12 versus 1.72 ± 0.23; P = 0.034) in the posterior gyrus. Myoinositol (Ins) levels of the right and left hippocampi were significantly lower in FM patients (4.49 ± 0.74 versus 5.17 ± 0.62; P = 0.008 and 4.91 ± 0.85 versus 6.09 ± 0.78; P = 0.004, respectively). In FM patients, decreased myoinositol/creatine (Ins/Cr) ratios were found in the left sensorimotor area (P = 0.05) and the left hippocampus (P = 0.002) and lower levels of choline (P = 0.019) and N-acetyl aspartate + N-acetyl aspartyl glutamate (NAA + NAG) (P = 0.034) in the left hippocampus. Significant correlations between depression, pain, and global function and the posterior gyrus Glx levels and Glx/Cr ratios were observed.

Conclusions: Glx within the posterior gyrus could be a pathologic factor in FM. Hippocampal dysfunction may be partially responsible for the depressive symptoms of FM. Additional studies with larger samples are required to confirm these preliminary data.

Figure 1

Voxel placement in the different brain regions. The hippocampus (a, b), thalamus (c, d), posterior gyrus (e), and left sensorimotor (f) (red) after functional magnetic resonance imaging during finger-tapping tasks.

Figure 2

Left hippocampus spectrum. A control patient (a) and a patient with fibromyalgia (FM) (b). For the patient with FM, a decrease in the myoinositol peak amplitude and in the relation to creatine was noted. The black line indicates the averaged spectrum; the red line indicates the LCModel fit. The residuals, calculated as a subtraction of the fit from the average spectrum, are plotted at the top.

Figure 3

Axial images showing the different locations of the equal-sized regions of interest (ROIs). The ROI placements for the periaqueductal gray and amygdale (a), the orbitofrontal cortex and insular cortex (b), the internal capsule and ventral and dorsolateral thalamus (c), the gyrus cortex and corpus callosum (d), the frontal white matter, parietal white matter, and dorsolateral prefrontal cortex (e), and the sensorimotor area (f).

Figure 4

Scatterplot of the correlations between brain metabolites and psychological variables in patients with FM. FIQ, Fibromyalgia Impact Questionnaire; Glx, glutamate+glutamine; Glx-Cr, glutamate+glutamine/creatine; HADS-dep: Hospital Anxiety Depression Scale (depression subscale); Sphig, pain assessed with sphygmomanometer (the pressure that is needed to evoke pain). Blue circles represent patients with FM.