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" ... A priori causal models encoded by the investigators to explore the mechanism of action of... [+] simvastatin in progressive multiple sclerosis. The cholesterol-mediated model (A) assumes that the cholesterol-lowering effect of simvastatin is the cause of the slowing of the brain atrophy and disability worsening. The cholesterol-independent model (B) makes the assumption the cholesterol-lowering effect of simvastatin is independent of its effect on brain atrophy and clinical outcomes. In both models, a lower rate of brain atrophy development has an effect on the clinical change. ... "