Magnetic resonance imaging (MRI), an established secondary outcome for multiple sclerosis (MS) clinical trials, looms on the near horizon as a primary outcome of therapeutic efficacy. It provides a window on pathology. Gadolinium enhancements, reflecting blood-brain barrier dysfunction common in early disease, are easily quantified. Tissue involvement or disease burden is represented by increased signal intensity on T2-weighted images, and hypointense lesions on T1-weighted images capture the most extensive destruction. These are complemented by global atrophy measures, advanced imaging, and spectroscopic assessment of neuronal and myelin integrity. All reflect different aspects of the complex pathologic process that ultimately compromises function. As recent studies show, therapy may differentially affect the progression of these parameters. The interferons have early and profound effects on enhancement but lesser effects on disease burden and delayed effects on atrophy. Glatiramer has delayed and modest effects on enhancement but still affects disease burden. Linomide has dose-dependent effects on both enhancements and hypointense lesions. Cladribine has profound and long-lasting effects on enhancements not mirrored on disease burden. These varied patterns support an unweighted MRI composite incorporating different measures of the pathologic process as potentially preferable for monitoring MS trials, especially when pharmacological drug mechanisms are incompletely understood.
Wolinsky JS. Signature MRI Drug Effects in MS: the Demand for Composite MRI Outcomes. Arch Neurol. 2000;57(8):1235. doi: