Abstract
Next to the disseminated clinical symptoms, cognitive dysfunctions are common features of multiple sclerosis (MS). Over the recent years several different MRI measures became available representing the various features of the pathology, but the contribution to various clinical and cognitive functions is not yet fully understood. In this multiparametric MRI study we set out to identify the set of parameters that best predict the clinical and cognitive disability in MS. High resolution T1 weighted structural and high angular resolution diffusion MRI images were measured in 53 patients with relapsing remitting MS and 53 healthy controls. Clinical disability was inflicted by EDSS and cognitive functions were evaluated with the BICAMS tests. The contribution of lesion load, partial brain, white matter, gray matter and subcortical volumes as well as the diffusion parameters in the area of the lesions and the normal appearing white matter were examined by model free, partial least square (PLS) approach. Significance of the predictors was tested with Variable Importance in the Projection (VIP) score and 1 was used for threshold of significance. The PLS analysis indicated that the axial diffusivity of the NAWM contributed the most to the clinical disability (VIP score: 1.979). For the visuo-spatial working memory the most critical contributor was the size of the bilateral hippocampi (VIP scores: 1.183 and 1.2 left and right respectively). For the verbal memory the best predictors were the size of the right hippocampus (VIP score: 1.972), lesion load (VIP score: 1.274) and the partial brain volume (VIP score: 1.119). In case of the information processing speed the most significant contribution was from the diffusion parameters (fractional anisotropy, mean and radial diffusivity, VIP scores: 1.615, 1.321 respectively) of the normal appearing white matter. Our results indicate that various MRI measurable factors of MS pathology contribute differently to clinical and cognitive disability. These results point out the importance of the volumetry of the subcortical structures and the diffusion measures of the white matter in understanding the disability progression.
Highlights
Multiple sclerosis (MS) is an inflammatory, demyelinating disease, which affects the central nervous system
Cognitive functions were influenced by several factors in the various domains: (i) the most critical MR contributor to the visuo-spatial working memory was the size of the bilateral hippocampi and the demyelination-like diffusion profile of the lesions, and the axon loss of the normal appearing white matter (NAWM); (ii) the best predictor of the verbal memory was the size of the right hippocampus and the brain, gray and white matter volumes, and (iii) information processing speed as measured on the symbol digit modalities test (SDMT) test was best predicted by the demyelination like diffusion parameter alterations of the white matter
In our previous analysis we showed that the demyeliniation like diffusion parameter changes can be detected in most of investigated white matter skeleton if high number of diffusion directions are investigated [12]
Summary
Multiple sclerosis (MS) is an inflammatory, demyelinating disease, which affects the central nervous system. Increasing interest is shown about the gray matter (GM) atrophy, which has become an approach to follow-up of the therapeutic effectiveness [8, 9] The fact that it correlates stronger with the clinico-cognitive functioning gives the real importance of the GM [10, 11]. While lesions and gray matter atrophy are non-specific to the underlying pathology, there are novel methods which better approximate the pathological processes One of those is diffusion tensor imaging, which non-invasively depicts the diffusion of water in biological tissues. With appropriate parameters was able to detect widespread alterations of the white matter, even in the non-lesioned, normal appearing white matter (NAWM) [12] These alterations were correlating with various clinical and cognitive functions [13, 14]
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