The unique impact of changes in normal appearing brain tissue on cognitive dysfunction in secondary progressive multiple sclerosis patients
Cox D, Pelletier D, Genain C, Majumdar S, Lu Y, Nelson S and Mohr DC;
Commented by , 24 Jan 2005
Background
It is well described that the normal appearing white matter (NAWM) seen on conventional MRI contain pathological changes in MS.
There is reason to believe these changes has considerable consequences for brain function, since magnetic transfer ratio (MTR) and magnetic resonance spectroscopy (MRS) of NAWM correlate with clinical disability in MS. The association with cognitive dysfunction is not well described which this study aims at doing.
Aim
To examine the association between MTR and cognitive dysfunction in MS patients with secondary progressive disease course (SPMS).
Methods
The authors examined 19 patients with clinically definite secondary progressive MS (SPMS). The neuropshychological assessment covered several cognitive domains. MRI was conducted using a 1.5 T scanner acquiring T1 – and T2 weighted images, magnetic transfer ratio (MTR) images and magnetic resonance spectroscopy (MRS) images (only 14 patients).
In the statistical analysis a composite cognitive function score was assessed using the results of a factor analysis as an integrated measure of cognitive impairment. Subsequently a multiple regression analysis was applied with T2 and T1 lesion load, MTR and MRS (NAA/Cr) as independent variables.
Results
The results of the multiple regression analysis showed that MTR significantly correlate to cognitive function (DR2=0.22, p=0.02) after accounting for T2 and T1-lesion load. Unresidualized MTR also correlate with cognitive function (r=-0.68, p=0.002).
MRS was not related to cognitive function (p=0.90) in the multiple regression analysis or in the unresidualized analysis (p=0.17).
Dr Blinkenberg's comments
The study shows that cognitive testing predict the outcome of global MTR. This was true for MTR measurements containing T2 and T1 - lesions as well as NAWM.
The authors found no relationship with MRS (NAA/Cr) with or without effect of lesions. In this regard they refer to an older study supporting their findings, although a recent study by Gadea et al. (ref. 1), find a relation between brainstem NAWM NAA/Cr and attention impairment. Sample size was smaller in the MRS analysis, which may have affected the outcome of statistics.
It is hypothesized that appearance of cognitive symptoms in MS may indicate the transition to a more diffuse disease involvement with growing disease burden. It can be argued that approximately 60% of all MS patients have cognitive dysfunction and this number increases in SPMS where diffuse disease burden is more pronounced.
In this way, the proposed hypothesis bears little interest and it would have been more interesting if the authors had incorporated remitting relapsing MS (RRMS) patients in order to look for differences between early and chronic disease.
It is evident that we need better clinical markers in order to differentiate between predominantly focal or diffuse MS pathology, which will have impact on therapeutic strategies as well as prognosis.
It is interesting that cognitive testing could determine a shift in disease course although it is hard to imagine how such a complex measure could act as a screening toll.
Furthermore, it may be anticipated that the specificity of the test is low, since focal lesions, especially in frontotemporal regions, also cause cognitive decline. NAWM and cortical grey matter pathology in MS may prove to be a more accurate measure of disease activity compared with lesion burden, although better markers are needed in order to determine this.
Reference
1. Gadea M, Martinez-Bisbal MC, Marti-Bonmati L, et al. Spectroscopic axonal damage of the right locus coeruleus relates to selective attention impairment in early stage relapsing-remitting multiple sclerosis. Brain 2004; 127; 89-98