Relationships between gray matter metabolic abnormalities and white matter inflammation in patients at the very early stage of MS

Abstract

Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) was used to study metabolic abnormalities inside the gray matter (GM) during or distant to white matter (WM) inflammatory processes reflected by T(1) gadolinium-enhancing lesions in patients at the very early stage of multiple sclerosis (MS). The spectroscopic examination was performed in the axial plane using a home-designed acquisition-weighted, hamming shape, 2D-SE pulse sequence (TE = 135 ms; TR = 1,600 ms). Bilateral thalami and the medial occipital cortex were explored in 35 patients (15 with and 20 without T(1)-Gd enhancing lesions) with clinically isolated syndrome suggestive of MS and in 30 controls. The mean duration since the first presenting symptom was 9.1 (+/-6.7) months. The two groups of patients (with or without T(1) Gd-enhancing lesions) did not differ in terms of time elapsed since the first clinical onset and T(2) lesion load. The spatial contamination of surrounding WM tissues was obtained in each GM region by determining the tissue component in the ROI from GM and WM probability maps smoothed with the point spread function of the MRSI acquisition. Contribution of WM signal was important (60%) inside thalami while the region centered on the medial occipital cortex was well representative of GM metabolism (>70%). Comparisons of relative metabolite levels (ratios of each metabolite over the sum of all metabolites) between all patients and controls showed significant decrease in relative N-acetyl aspartate (NAA) levels, increase in relative choline-containing compounds (Cho) levels and no change in relative creatine/phosphocreatine levels inside the three ROIs. Decrease in relative NAA levels and increase in relative Cho levels were found in patients with inflammatory activity, while no metabolic alterations were present in patients without T(1) Gd-enhancing lesions. These results suggest that abnormalities in GM metabolism observed in patients at the very early stage of MS are mainly related to neuronal dysfunction occurring during acute inflammatory processes.

High field MR imaging and 1H-MR spectroscopy in clinically isolated syndromes suggestive of multiple sclerosis

“…Nevertheless, conventional MR imaging and consequently current MR imaging criteria do not sufficiently reflect special aspects of disease activity, in particular grey matter pathology which occurs abundantly in MS [41]. However, grey matter changes in MS can not be sufficiently visualized on conventional MR imaging techniques but may substantially contribute to metabolic changes (e.g.…”

1H-MRSI evidence for cortical gray matter pathology that is independent of cerebral white matter lesion load in patients with secondary progressive multiple sclerosis

“…Similarly, whereas some studies have found statistically-significant correlations between cGM-NA and clinical status [42] and between cGM-NA/Cr and memory impairment in patients with MS, [46] other studies have failed to find statistically-significant correlations between cGM-NA and clinical disability in such patients [38,39,36,40,41,37]. It should be noted, however, that all of these studies had relatively-low sample sizes and some of them had a very limited range of cerebral WM-LL values [38,47] or scores on Kurtzke's Expanded Disability Status Scale [53] (EDSS) [38] -either of which would make it very difficult to find statistically-significant correlations. Thus, to the best of our knowledge, the relationship of 1 H-MRS(I) measures of cGM neuro-axonal integrity to cerebral WM-LL and clinical status in patients with MS has not yet been definitively established.…”

“…With regards to the relationship between cerebral WM lesions and 1 H-MRS(I) measures of cGM pathology, Van Au Duong et al [47] studied cGM-NA/Cr values and cerebral WM inflammation in patients with CIS and found a significantly-lower mean NA/Cr value in the cGM of those 15 patients who had gadolinium-enhancing cerebral WM lesions than in the 25 patients who did not have any such lesions (and whose mean cGM-NA/Cr value did not differ from that of their normal controls). On the other hand, a number of 1 H-MRS(I) studies of cGM neuro-axonal integrity in patients with MS have failed to find statistically-significant correlations between cerebral WM lesion-load (WM-LL) and cGM-NA [38,40,37,44] or between cerebral WM-LL and cGM-NA/Cr [47]. Similarly, whereas some studies have found statistically-significant correlations between cGM-NA and clinical status [42] and between cGM-NA/Cr and memory impairment in patients with MS, [46] other studies have failed to find statistically-significant correlations between cGM-NA and clinical disability in such patients [38,39,36,40,41,37].…”

“…Although a small number of studies have found values of 1 H-MRS(I)-measured NA to be statistically unaffected in the cGM of patients with MS, [35][36][37] the majority of such studies have provided evidence for decreased cGM NA: [38][39][40][41][42][43][44] and NA/Cr [45][46][47]. This is true for: (i) patients with clinically-isolated syndromes indicative of MS (CIS); [47] (ii) patients in the early, relapsing-remitting stage of the disease; [38,46,44] and (iii) patients with more-severe, progressive MS [40][41][42][43]. Importantly, in each of the studies that explicitly compared groups of patients with relapsing-remitting MS to those with progressive MS and found a significant decrease in cGM NA, this decrease was far greater in the group of patients with progressive MS [40,41,43].…”

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: The Hydrostatic-Immune Paradigm and the Flow Cytometry as a Diagnostic Tool

“…On a more macroscopic scale, MS has been associated with diffuse brain hypoperfusion [16] and decreased cerebral metabolism [17] even in the initial stages of the disease [18]. Using dynamic susceptibility contrast-enhanced magnetic resonance imaging, Law et al [19] found significantly decreased cerebral blood flow (CBF) and significantly prolonged mean transit time throughout the normal appearing white matter (NAWM) in patients with relapsing-remitting MS. Adhya et al [20] also found significantly decreased CBF and cerebral blood volume (CBV) in NAWM regions of patients with either relapsingremitting or primary progressive MS compared with healthy subjects.…”