Longitudinal Brain Volume Measurement in Multiple Sclerosis

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Abstract
BRAIN VOLUME measurement on magnetic resonance images (MRIs) in multiple sclerosis (MS) has been proposed as a surrogate marker for axonal loss, the presumed underlying pathologic process leading to irreversible disability in MS. Axonal loss occurs not only inside but also outside focal lesions, perhaps explaining why measures of focal lesion load on MRI may fail to show good correlations with disability. Evidence from pathology and spectroscopy studies (demonstrating a decrease in the neuronal marker N-acetyl-aspartate in lesions and normal-appearing white matter of MS) indicate that axonal injury is substantial in MS.1-3 Speculations have been made as to the origin of brain atrophy; Simon4 suggests a linkage between gadolinium-enhancing lesions on T1-weighted imaging with atrophy, whereas Saindane et al5 could not confirm this finding. The diffuse pathologic process may result from local degeneration and subsequent contraction due to gliosis.6 Axonal loss may be caused by wallerian degeneration, by diffuse low-grade inflammation, or by primary neurodegeneration.