Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients

Abstract

Brain atrophy measurement can provide an estimate of the amount of tissue destruction due to the pathologic processes in multiple sclerosis. The potential usefulness of atrophy as a marker of disease progression depends upon the concurrent and predictive relationships between atrophy and disability. A follow-up study was performed to measure atrophy and disability scores in patients from the Multiple Sclerosis Collaborative Research Group's phase III trial of IFNbeta-1a (Avonex) in relapsing- remitting multiple sclerosis. New data were obtained on 160 out of 172 eligible patients from the original trial were enrolled in the follow-up study approximately 8 years after randomization. The follow-up visit consisted of several tests and questionnaires including a clinical exam to determine Expanded Disability Status Score (EDSS) and Multiple Sclerosis Functional Composite (MSFC), and a magnetic resonance imaging exam to calculate the brain parenchymal fraction. Brain parenchymal fraction was correlated with both EDSS and MSFC at each of the four time points for which data were available (baseline 1, 2 and 8 years). Furthermore, the change in BPF was correlated with the changes in disability scores from the end of the phase III trial to the follow-up exam. These data suggest that brain atrophy may be a useful and clinically relevant marker of disease progression in relapsing--remitting MS.

Interferon-β Treatment for Multiple Sclerosis

“…Early accumulation of brain atrophy has been shown to correlate with physical disability, 75 and brain atrophy measures are now common secondary outcome measures in MS clinical trials. 76 In the pivotal trial of IFN␤1a-IM, whole-brain atrophy was measured using the brain parenchymal fraction method in 68 patients randomized to interferon-␤1a and 72 patients randomized to placebo.…”

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

“…33,34 Generally speaking, brain volume changes can be an important measure of tissue damage in patients with MS. 32 Indeed, baseline atrophy and high rates of subsequent volume loss are associated with cognitive impairment, fatigue and disability progression over the long term. 32,[35][36][37][38][39][40][41] In a complex disease such as MS, brain volume loss results from the sum of and interactions between various destructive pathological processes, 42 including irrever sible demyelination, and axonal and/or neuronal loss. The neurodegenerative pathology that occurs in MS is an important target for treatment; thus, MRI brain volume measures have been used in randomized clinical trials to monitor the effects of disease modifying thera pies on these parameters.…”

Oligoclonal bands in the cerebrospinal fluid and increased brain atrophy in early stages of relapsing-remitting multiple sclerosis

“…A possible explanation could be that the presence of Ig in the CSF, independently of whether it is IgG or IgM, is related to an immunological phenomenon that may be producing brain tissue damage, which would consequently lead to a reduction in measured volumes. Studies are currently demonstrating that the reduction in brain volume (brain atrophy) is related to physical disability in the short and mid-term follow-ups, with this marker being considered as a possible biomarker in the near future that may help to predict the course of the disease in MS patients 3,5,18,19 . On the other hand, the reduction of brain volumes in MS patients could be related to other unexplored and unknown phenomena like reduction of the inflammation (pseudoatrophy) instead of neurodegeneration.…”

“…Considering the relevance that brain atrophy, which may be termed as neurodegeneration, might have in predicting the disease evolution at MS onset 3,5 and the role that IgG-OB could have in producing such damage 9 , the aim of this study was to evaluate the relationship between CSF IgG-OB positivity, and the presence of brain atrophy in the MS early onset.…”