Brain damage and motor and cognitive function in MS

MRI is the window in the MSer brain; it is surprising how much damage MS causes. #MSBlog #MSResearch

Sbardella et al. Assessing the Correlation between Grey and White Matter Damage with Motor and Cognitive Impairment in Multiple Sclerosis Patients.PLoS One. 2013 May 16;8(5):e63250.

BACKGROUND: MS is characterized by demyelinating and degenerative processes within the central nervous system. Unlike conventional MRI, new advanced imaging techniques improve pathological specificity and better highlight the relationship between anatomical damage and clinical impairment.

OBJECTIVE: To investigate the relationship between clinical disability and both grey (GM) and white matter (WM) regional damage in MSers.

METHODS: Thirty-six RRMSers and 25 sex- and age-matched controls were enrolled. All MSers were clinically evaluated by the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite (MSFC) scale, which includes the 9-hole peg test (9HPT), the timed 25-feet walking test (T25FW) and the paced auditory serial addition test (PASAT). All subjects were imaged by a 3.0 T scanner: dual-echo fast spin-echo, 3DT1-weighted and diffusion-tensor imaging (DTI) sequences were acquired. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses were run for regional GM and WM assessment, respectively. T2 lesion volumes were also calculated, by using a semi-automated technique.

3D = three-dimensional; 3D imaging is higher resolution.

T1-weighted = The MRI sequence that shows up MS lesions as black holes.

DTI = diffusion tensor imaging allows you to measure the integrity of  white matter tracts to see if they are intact or damaged.


VBM = voxel based morphometry morphs the brain onto a standard template and looks for subtle anatomical variations, for example shrinkage of the brain in a specific region.


TBSS = tract-based spatial statistics is a measure of how intact a particular nerve pathway is as well as its connections, for example the corticospinal tract from the cerebral cortex in the brain to the spinal cord, this is the tract that carries motor fibres. Damage to the corticospinal tract results in weakness, spasticity and so called clonic spasms.


RESULTS: Brain volumetric assessment of GM and DTI measures revealed significant differences between MSers and controls. In MSers, different measures of WM damage correlated each-other (p<0.0001), whereas none of them correlated with GM volume. In MSers, focal GM atrophy and widespread WM damage significantly correlated with clinical measures. In particular, VBM analysis revealed a significant correlation (p<0.05) between GM volume and 9HPT in cerebellum and between GM volume and PASAT in orbito-frontal cortex. TBSS showed significant correlations between DTI metrics with 9HPT and PASAT scores in many WM bundles (p<0.05), including corpus callosum, internal capsule, posterior thalamic radiations, cerebral peduncles.

CONCLUSIONS: Selective GM atrophy and widespread WM tracts damage are associated with functional impairment of upper-limb motion and cognition. The combined analysis of volumetric and DTI data may help to better understand structural alterations underlying physical and cognitive dysfunction in MS.

"This study is showing what we already know; MS is associated with widespread damage on MRI that correlates with clinical outcomes, for example upper-limb function (speed and accuracy of movement) and cognition. Cognition refers to the complex mental processes that include attention, memory, producing and understanding language, learning, reasoning, problem solving, and decision making."

"It is becoming increasingly clear that MRI is a window into the brain; what we are seeing on MRI is the pathology. This is not what some people in the field would like you to believe. What you see clinically is the tip of the iceberg and often reflects how well you adapt to damage. Some MSers have incredible functional reserve and cope with extraordinary amount of damage when their MRIs show major damage. The problem with this is that ultimately that MSer's coping mechanisms eventually fail and they develop overt disabilities and often appear to go downhill very rapidly. They go down rapidly because they accumulated so much damage in the past and it manifests itself as soon as a threshold is seen."

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