Axonal Damage But No Increased Glial Cell Activity in the Normal-Appearing White Matter of Patients with Clinically Isolated Syndromes Suggestive of Multiple Sclerosis Using High-Field Magnetic Resonance Spectroscopy

Abstract

Proton MR spectroscopy ((1)H-MR spectroscopy) is a well-established method for the in vivo investigation of the normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS). Metabolic changes in NAWM are of special interest in patients with clinically isolated syndromes (CIS) suggestive of MS regarding further prognostic classifications. The purpose of this study was to investigate metabolic alterations in NAWM in patients with CIS with use of high-field (1)H-MR spectroscopy and to compare the results to those in patients with an early course of MS. With use of a 3T whole-body MR imaging system, single-voxel (1)H-MR spectroscopy (PRESS; TR: 2000 ms; TE: 38 ms and 140 ms) of the parietal NAWM was performed in 20 control subjects, 36 patients with CIS, and 12 patients with MS. Metabolite ratios and concentrations of N-acetylaspartate (tNAA), myo-inositol (mIns), choline, and total creatine (tCr) were determined. Compared with the control group, mean NAWM mIns concentrations were significantly elevated in the MS group (4.56 mmol/L versus 3.75 mmol/L, P = .02) but not in the CIS group (4.04 mmol/L, P = .44). The higher concentration of mIns in the MS group was also reflected in the increased Ins/tCr ratio (P = .02). The mean NAWM tNAA was significantly decreased in both patient groups compared with the control group (CIS, 13.42 mmol/L, P = .02; MS, 12.77 mmol/L versus 14.51 mmol/L, P = .008). A significant increase of the activity of the glial cells can only be observed in patients with an established diagnosis of MS but not in patients with CIS. Axonal damage occurs already during the first demyelinating episode in patients with CIS as well as in patients with definite MS.