Serial proton MR spectroscopy of gray and white matter in relapsing-remitting MS

Objective: To characterize and follow the diffuse gray and white matter (GM/WM) metabolic abnormalities in early relapsing-remitting multiple sclerosis using proton magnetic resonance spectroscopic imaging (¹H-MRSI).

Methods: Eighteen recently diagnosed, mildly disabled patients (mean baseline time from diagnosis 32 months, mean Expanded Disability Status Scale [EDSS] score 1.3), all on immunomodulatory medication, were scanned semiannually for 3 years with T1-weighted and T2-weighted MRI and 3D ¹H-MRSI at 3 T. Ten sex- and age-matched controls were followed annually. Global absolute concentrations of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and myo-inositol (mI) were obtained for all GM and WM in the 360 cm^{3 1}H-MRSI volume of interest.

Results: Patients' average WM Cr, Cho, and mI concentrations (over all time points), 5.3 ± 0.4, 1.6 ± 0.1, and 5.1 ± 0.7 mM, were 8%, 12%, and 11% higher than controls' (p ≤ 0.01), while their WM NAA, 7.4 ± 0.7 mM, was 6% lower (p = 0.07). There were increases with time of patients' WM Cr: 0.1 mM/year, Cho: 0.02 mM/year, and NAA: 0.1 mM/year (all p < 0.05). None of the patients' metabolic concentrations correlated with their EDSS score, relapse rate, GM/WM/CSF fractions, or lesion volume.

Conclusions: Diffuse WM glial abnormalities were larger in magnitude than the axonal abnormalities and increased over time independently of conventional clinical or imaging metrics and despite immunomodulatory treatment. In contrast, the axonal abnormalities showed partial recovery, suggesting that patients' lower WM NAA levels represented a dysfunction, which may abate with treatment. Absence of detectable diffuse changes in GM suggests that injury there is minimal, focal, or heterogeneous between cortex and deep GM nuclei.