Revisiting Brain Atrophy and Its Relationship to Disability in Multiple Sclerosis

Brain atrophy is a well-accepted imaging biomarker of multiple sclerosis (MS) that partially correlates with both physical disability and cognitive impairment.Based on MRI scans of 60 MS cases and 37 healthy volunteers, we measured the volumes of white matter (WM) lesions, cortical gray matter (GM), cerebral WM, caudate nucleus, putamen, thalamus, ventricles, and brainstem using a validated and completely automated segmentation method. We correlated these volumes with the Expanded Disability Status Scale (EDSS), MS Severity Scale (MSSS), MS Functional Composite (MSFC), and quantitative measures of ankle strength and toe sensation. Normalized volumes of both cortical and subcortical GM structures were abnormally low in the MS group, whereas no abnormality was found in the volume of the cerebral WM. High physical disability was associated with low cerebral WM, thalamus, and brainstem volumes (partial correlation coefficients ~0.3-0.4) but not with low cortical GM volume. Thalamus volumes were inversely correlated with lesion load (r = -0.36, p<0.005).The GM is atrophic in MS. Although lower WM volume is associated with greater disability, as might be expected, WM volume was on average in the normal range. This paradoxical result might be explained by the presence of coexisting pathological processes, such as tissue damage and repair, that cause both atrophy and hypertrophy and that underlie the observed disability

Clinical correlates of grey matter pathology in multiple sclerosis

Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect

Association between MRI parameters and the MS severity scale: a 12 year follow-up study

Contains fulltext : 80250.pdf (publisher's version ) (Closed access)BACKGROUND: Several magnetic resonance imaging (MRI) parameters are known to be associated with short-term outcome in multiple sclerosis (MS) patients. MS-related disability typically progresses over decades, stressing the need for longer follow-up studies. Until now, these studies are relatively sparse and, therefore, the predictive value of MRI parameters for clinical disability remains largely unknown. OBJECTIVE: To assess the predictive value of brain MRI parameters, which are obtained during the first 3.3 years of the study for overall disease severity as measured by the MS Severity Score (MSSS) after 12.2 years follow-up. METHODS: Forty-six MS patients were included in the study. MRI parameters included both lesion loads and atrophy measures. Average and change parameters were calculated for MRI parameters and subsequently used as independent variables in regression models, while MSSS was the dependent variable. RESULTS: Follow-up (FU) was obtained in 43/46 patients (94%) and median expanded disability status scale (EDSS) score increased significantly from 2.5 to 4.0. At last FU median MSSS was 4.3 (range 2.2-6.9). In univariate analyses, both change and cross-sectional T1-hypointense lesion load and ventricular atrophy measures were associated with MSSS. A multiple regression model included the change parameter of hypointense T1-lesion load (BHLL). This model explained 20% of variance in MSSS, which increased to 34% when type of disease (relapsing remitting or secondary progressive), age, and sex were entered additionally. CONCLUSION: MRI measures of axonal loss are associated with higher overall disease severity in MS patients