There were two aims to this study. First, to explore how the reduction in the volume of abnormal T2-signal intensity associated with white matter (WM) lesions in multiple sclerosis (MS) relates to tissue loss resulting from focal pathology inside lesions. Second, to demonstrate that this volume of abnormal T2-signal intensity underestimates the actual size of the region to which the direct effects of lesion activity extend. For these purposes, we used deformation field analysis to quantify the evolution of local atrophy associated with a chronic peri-ventricular lesion in a patient with secondary progressive MS. This subject had particular features that may not necessarily co-exist in a group of unselected patients, which enabled interesting observations to be made. We show, quantitatively, that the focal WM lesion was associated with adjacent regional WM volume loss, which was disproportionate to concurrent diffuse atrophy in the rest of the normal appearing brain tissue, and that the loss of volume associated with the lesion was partially reciprocated by local ventricular expansion. Our observations re-emphasise the complex relationship between the change in the volume of abnormal signal intensity on magnetic resonance images and the tissue volume change directly related to lesion pathology.