MRI markers of destructive pathology in multiple sclerosis-related cognitive dysfunction
Introduction
The use of brain magnetic resonance imaging (MRI) for monitoring disease evolution in patients with multiple sclerosis (MS) is still hampered by the highly variable correlation with clinical findings [1]. The low reliability and precision of the Expanded Disability Status Scale, its dependence upon locomotor impairment rather than upon brain “hemispheric” dysfunctions and the poor pathological specificity of conventional T2-weighted MRI scans are perhaps the most important explanations for this clinical-MRI discrepancy.
Neuropsychological testing of MS patients is a reliable procedure, which reveals the presence of cognitive impairment in 40–60% of subjects with an established form of the disease [2]. The limited pathological specificity of T2-weighted MRI, as well as its inability to quantify MS-related normal-appearing white (NAWM) and grey matter (NAGM) damage, have been, at least partially, overcome by quantitative MR-based techniques [3]. Thus, the assessment of the correlation between cognitive deficits and the severity of the abnormalities disclosed by the latter techniques might provide new insights into the mechanisms underlying the development of dementia in patients with MS.
In this review, the results of studies correlating the degree of cognitive impairment in patients with MS with the extent and the severity of MR-detectable abnormalities are critically discussed, with the ultimate goal to achieve a better understanding of the disease pathobiology.
Section snippets
Conventional MRI studies of MS-related cognitive dysfunction
In patients with MS, the extent of white matter abnormalities detected on conventional brain MRI scans correlates with the performance on a wide variety of neuropsychological tests and the degree of this correlation is higher than that found with physical disability [4], [5], [6], [7], [8], [9], [10]. These findings suggest that a widespread damage of white matter might lead to functional disconnection of different cortical areas and of deep grey matter structures, such as the thalamus and the
Toward an increased pathological specificity: T1-weighted hypointense lesion load and brain atrophy assessment
Chronically hypointense lesions on T1-weighted images (known as “black holes”) represent areas where severe demyelination and axonal loss have occurred [18]. However, the definition of what constitutes a “black hole” is arbitrary and highly operator-dependent, T1-hypointense lesion volume does not provide graded information about the intrinsic pathology of individual lesions nor about pathology outside MRI-visible lesions. It is, therefore, not surprising that studies correlating “black hole”
Destructive MS pathology and cognitive impairment: quantitative MR-based studies
Several quantitative MR-based techniques, with the potential for increased specificity to the more destructive pathological features of brain damage, have been applied to the study of MS. Among these techniques, magnetization transfer (MT) MRI [27] and diffusion-weighted (DW) MRI [28] enable us to quantify the extent of structural changes of T2-visible lesions and tissue which appears normal on conventional MR images. Proton MR spectroscopy (1H-MRS) [29] can add information on the biochemical
Conclusions
The overall burden of brain MRI-visible lesions does not fully account for the severity of MS cognitive impairment. The role played by regional damage seems to have a high inter-subject variability, even though the importance of cortical/subcortical pathology appears relevant.
Quantitative MRI studies have provided fundamental in vivo insight into the pathogenesis of cognitive disturbances in MS, suggesting that brain tissue damage beyond the resolution of conventional MRI significantly
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