MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis

Abstract

Correlation studies between various conventional and non-conventional MRI parameters and cognitive impairment in the early stages of multiple sclerosis (MS) are lacking, although it is known that a number of patients with early MS have mild cognitive impairment. Our aim was to explore whether this cognitive impairment is dependent on the extent and severity of the burden of disease, diffuse microscopic brain damage or both. We studied 63 patients with clinically definite relapsing-remitting (RR) MS, duration of disease 1-10 years and Expanded disability status scale scores < or = 5.0. Mean age was 35.4 years, mean duration of disease 5.8 years and median EDSS score 1.5. Neuropsychological performance, psychological function, neurological impairment and disability were assessed. The patients also underwent MRI, including magnetisation-transfer (MT) studies. We quantified the lesion load on T2- and T1-weighted images, the magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT) and the brain parenchymal fraction (BPF). No significant difference was found between lesion loads in patients with and without cognitive impairment. In 15 patients (23.8%) with overall cognitive impairment, median BPF and average NABT MTR were significantly lower than those in patients without cognitive impairment (0.868 vs 0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively). Multiple regression analysis models demonstrated that the only variables independently correlated with cognitive impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R = 0.76, P = 0.012). Our findings support the hypothesis that, cognitive decline in patients with MS, a low disability score and short duration of disease is directly associated with the extent and severity of diffuse brain damage. The loss of brain parenchyma did not correlate with the severity of microscopic damage in the NABT, indicating that the two processes could be distinct in the early stages of the disease.

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

“…For example, in five cross‐sectional18, 23, 24, 25, 26 and two longitudinal studies,2, 38 which included between 43 and 81 patients in very early stages of MS, no significant associations between MRI lesion burden and cognitive measures were reported. Four of these studies also examined the relationships between global or regional brain atrophy and cognitive measures but found no associations 2, 24, 25, 26.…”

Evaluation of Normal Appearing White Matter in Multiple Sclerosis

“…However, a correlation between conventional MRI findings and clinical impairment is weak. The most important factor seems to be the subtle abnormalities within normal appearing white matter (NAWM) which cannot be delineated by conventional MRI and contribute to the development of disability in MS [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Cognitive dysfunction in multiple sclerosis: Assessment, imaging, and risk factors

“…Given that cerebral atrophy is increasingly associated with worsening MS, volumetric analysis has also been the focus of much recent research on cognition. Studies looking at total brain parenchymal volume have indicated that global atrophy is strongly correlated with development of cognitive dysfunction in MS [29][30]. When the association between volume and size of individual structures (e.g., ventricle width, bicaudate ratio) and cognitive dysfunction was examined, central atrophy as measured by the third ventricle width more strongly predicted cognitive dysfunction than either global atrophy or lesion load [31].…”

“…Pan et al found significant correlations between high periventricular N-acetyl aspartate levels and impaired performance on cognitive testing [34]. In sum, mounting evidence indicates that damage to white and gray matter structures within the CNS is significantly correlated with cognitive dysfunction in MS [29][30][31][32][33][34][35]. Continued study and improved imaging techniques may better elucidate the pathology of cognitive dysfunction in MS and the compensatory mechanisms that MS patients with cognitive dysfunction use.…”