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

Abstract

Article abstract-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 ␤-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 ␤-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 ␤-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 atrophyInterferon beta. NEUROLOGY 1999;53:1698-1704 Individual MS patients face an unpredictable future during the relapsing-remitting stage of the disease, because severity is highly variable and accurate predictors of long-term outcome are lacking. Recurrent inflammation in optic nerves, brain, and spinal cord damages myelin and axons, leading to intermittent neurologic symptoms initially, and progressive disability later in the disease. Over 50% of patients with relapsing-remitting MS (RRMS) enter the secondary progressive disease stage, which is associated with more continuous physical, neuropsychologic, and socioeconomic decline. Clinical features during the early relapsing-remitting stage are not very accurate in predicting when an individual patient will enter the secondary progressive disease stage.The poor predictive value of clinical features during RRMS may relate to ongoing subclinical disease activity, evident on MRI. Serial MRI scans demonstrate that new lesions occur 5 to 10 times as often as clinical relapses.1-3 The predictive value of MRIbased disease markers has been studied for T2 hyperintense lesions. It was shown that the volume of T2 hyperintense lesions seen on cranial MRI scans at the time of first symptoms predicted subsequent clinical disease progression. 4 This supports the use of MRI as a surrogate marker in MS, but the optimal MRI measure is unknown.Recent studie...

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