Multiple Sclerosis Research Repository

1. “Brain Atrophy Assessment in Multiple Sclerosis: Importance and Limitations”: Antonio Giorgio, MD et al

-cortical GM pathology is also present

-selective regional measures have demonstrated differences in brain regional involvement in the progressive and relapsing forms of MS, or a progressive involvement of the cortical regions in patients with long disease duration or increasing disability.  Atrophy seems to start in frontotemporal areas, specifically involving the superior temporal gyrus and superior and middle frontal gyri and to extend to other clinically relevant areas (eg, the motor cortex) in the more advanced disease phases

-there are specific deep GM regions (eg, thalamus and caudate nuclei) that can be involved earlier and more strongly than other regions in the pathologic process, provide additional evidence of the high relevance of GM pathology from the earliest stages of MS

-both RRMS and SPMS patients have comparable ex vivo loss of the thalamic neurons and in vivo thalamic volume decrease

-the midsagittal corpus callosum size decreased independently of the disease course at the rate of about 1.8% per year.  This decrease adds to the significant atrophy of central brain regions (ie, lateral ventricles) that also largely progresses over time in all MS stages and subtypes

-brain atrophy is greater in patients who show sustained progression of disability than in those who are clinically stable; in longitudinal studies of relapsing and progressive MS patients, brain volume at early stages seems to be a good predictor of disability status at follow up, suggesting that atrophy is a relevant marker of disease progression and may even precede the development of measurable disability 

-longitudinal studies have shown a persisting association between segmental callosal atrophy and disability status even at early disease stages.  Also the decline in ambulatory function (ie, Timed Walk Test) has been related to atrophy of periventricular and brainstem regions, whereas a focal thinning of the precentral gyrus and primary visual cortex has been related to the motor and visual scores of the EDSS

-the magnitude of the correlation between neuropsychologic scores and T2 lesion volume has been found to be weak or moderate.  By contrast, cognitive impairment has been found to be associated with measures of cerebral atrophy and importance of decreasing brain volumes (rather than increasing lesion load) to MS-related cognitive impairment has been suggested in several studies

-In particular, cortical atrophy has been found to be significantly higher in cognitively impaired than in cognitive preserved RRMS patients and in both RRMS and SPMS patients, has been the best predictor of verbal memory impairment and neurobehavioral symptoms

-in other studies, the atrophy of the frontal cortex has been found to be related to reduced cognitive functions and right and left frontal atrophy has been associated with auditory/verbal memory and episodic and working memory deficits

-brain atrophy (in particular, selective GM atrophy) is a good marker of unfavoralbe disease outcome in MS

-widespread neocortical loss and thinning can be found even in patients with minimal cerebral lesion load.  This observation suggest that retrograde changes from focal WM lesions cannot explain the full range of findings.  Pathologic studies have shown that neuroaxonald amage and loss may occur via mechanisms that are independent of those causing demyelination and are likely related to the presence of an abnormal glia-axonal interaction even with low or absent inflammation; in agreement with this, apoptotic neuronal death unrelated to axonal transection has been found in the cortex of MS patients; it is possible that factors that are not directly connected with lesion formation may also have a significant role in determining brain atrophy in MS

-the expansion of the extracellular space over the course of the disease

-some evidence that ApoE genotype, by influencing the ability to respond to injury, may have a significant role in tissue damage leading to atrophy