From enhancing lesions to brain atrophy in relapsing MS
Introduction
Magnetic resonance (MR) imaging and spectroscopy studies have made important contributions to our understanding of the events in the brain that occur as a result of multiple sclerosis (MS). Longitudinal study designs in particular have been especially important in clarifying the course and tempo of events, based on the perspective of the individual enhancing MS lesion, and dynamic changes affecting the brain in general, such as the accumulation of the T2 hyperintense (T2) lesion load over time.
The purpose of this discussion is to review the natural history of events in the brain observed in an untreated population of patients with relapsing MS—with emphasis on the relationships between several MR-based measures of disease, and the development of cerebral atrophy. With an understanding of the natural history of MS-related events in the brain, it has become feasible to evaluate several factors that may become important in predicting the course and prognosis of the disease.
Section snippets
The natural history of MS by MR imaging
Longitudinal MR studies reveal that subsequent to the first appearance of the acute, enhancing MS lesion in the brain, the lesion undergoes a series of relatively characteristic changes over periods of days to months. The acute lesion in relapsing and/or progressive MS has a leaky blood–brain barrier, and as a result shows contrast enhancement on T1-weighted MR imaging after intravenous administration of gadolinium-chelate (Simon, 1997). Correlative studies show that these contrast enhancing
Methodology
Details of the MSCRG trial design and primary outcomes have been reported (Jacobs et al., 1995, Jacobs et al., 1996). All patients had relapsing MS, and prior to entrance had had at least two exacerbations over the previous 3 years. By protocol, the last exacerbations were required to have occurred at least 2 months prior to study entry. High field MR studies of the brain were acquired at baseline and at 1 and 2 years after treatment initiation. These included 5-mm thick sagittal T1-weighted
Results
Because of the known intra-individual variation in enhancing lesions seen on monthly MR imaging studies (McFarland et al., 1992), strong relationships at a single observation in time between enhancing lesions and T2 lesion loads were not originally anticipated. However, we did observe a modest correlation between enhancing lesions and T2 lesion load (r=0.43; p<0.001) on the baseline studies. Fig. 1 shows that there is, in fact, a reasonably strong relationship between the T2 lesion volume that
Discussion
The natural history of the MS lesion in the brain based primarily on MR imaging and neuropathology studies is now understood to include evolution from an acute inflammatory lesion, with blood–brain barrier disruption as indicated by gadolinium-enhancing lesions, to relatively stable, smaller lesions with variable amounts of tissue damage. Over time, multiple independent attacks result in progressive increases in the overall lesion load in the brain and spinal cord. T2 lesion load increases are
Acknowledgements
This work was supported by National Institutes of Health, NINDS grant RO1-26321 and by Biogen, Cambridge, MA. The author wishes to acknowledge the invaluable contributions of the MSCRG collaborators, including Lawrence Jacobs, Richard Rudick, Robert Herndon, Andres Salazar, John Richert, Diane Cookfair, Jill Fischer and including the special efforts in statistical analysis and guidance provided by Marilyn Campion, Karl Wende and Anna Martens-Davidson.
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