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Neurology 1999;53:1698
© 1999 American Academy of Neurology
Articles

Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS

R. A. Rudick, MD, E. Fisher, PhD, J.-C. Lee, MS, J. Simon, MD, PhD, L. Jacobs, MD and the Multiple Sclerosis Collaborative Research Group*

From the Departments of Neurology (Mellen Center) (Dr. Rudick), Biomedical Engineering (Dr. Fisher), and Biostatistics and Epidemiology (J.-C. Lee), Cleveland Clinic Foundation, Cleveland, OH; the Department of Radiology–MRI (Dr. Simon), University of Colorado Health Sciences Center, Denver, CO; and the Department of Neurology (Dr. Jacobs), Buffalo General Hospital, Buffalo, NY.

Address correspondence and reprint requests to Dr. Rudick, Area U100, Mellen Center, Cleveland Clinic Foundation, Cleveland, OH 44195.

BACKGROUND: Episodic inflammation in the CNS during the early stages of MS results in progressive disability years later, presumably due to myelin and axonal injury. MRI demonstrates ongoing disease activity during the early disease stage, even in some patients who are stable clinically. The optimal MRI measure for the destructive pathologic process is uncertain, however.

METHODS: In this post-hoc study, MRI scans were analyzed from patients with relapsing MS participating in a placebo-controlled trial of interferon ß-1a. The brain parenchymal fraction, defined as the ratio of brain parenchymal volume to the total volume within the brain surface contour, was used to measure whole brain atrophy. The relationship between disease features and brain atrophy and effect of interferon ß-1a were determined.

RESULTS: MS patients had significant brain atrophy that worsened during each of 2 years of observation. In many patients, brain atrophy worsened without clinical disease activity. Baseline clinical and MRI abnormalities were not strongly related to the rate of brain atrophy during the subsequent 2 years. Treatment with interferon ß-1a resulted in a reduction in brain atrophy progression during the second year of the clinical trial.

CONCLUSIONS: Patients with relapsing-remitting MS have measurable amounts of whole brain atrophy that worsens yearly, in most cases without clinical manifestations. The brain parenchymal fraction is a marker for destructive pathologic processes ongoing in relapsing MS patients, and appears useful in demonstrating treatment effects in controlled clinical trials.

Key words: MS—MRI—Brain atrophy—Interferon beta.




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