MR correlates of cerebral atrophy in patients with multiple sclerosis

Objective: To investigate the in-vivo correlates of brain atrophy in patients with multiple sclerosis (MS) by assessing the relationship between normalized measures of brain volume (NBV) and other magnetic resonance (MR) measures of tissue damage. Background: Brain atrophy diffusely occurs and progressively increases in patients with MS. Nevertheless, the mechanisms leading to brain atrophy in this disease are not fully understood. Methods: MR examinations were performed in 20 patients with relapsing-remitting MS. Conventional MRI was used to assess NBV and total brain T2-hyper-intense and T1-hypointense lesion volumes. Proton MR spectroscopic imaging and diffusion tensor MR imaging were also performed for large portions of brain containing mainly normal-appearing tissue to provide indices of tissue damage, including N-acetylaspartate to creatine ratio (NAA/Cr) and mean diffusivity (D̄). Results: Values of NBV correlated significantly with those of average brain D̄ (r = -0.58, p = 0.007) and NAA/Cr (r = 0.67, p <0.001). The relationship of these markers of tissue damage to NBV was also found when NAA/Cr and D̄ were computed together in a composite MR score (r = 0.70, p <0.001). In contrast, NBV values did not correlate with measurements of average lesion D̄, T₂ and T₁ weighted total brain MRI lesion volumes. Conclusions: This study suggests that brain atrophy in MS is not simply due to axonal loss, but rather reflects a more generalized process that involves various brain tissue components. Damage to the normal-appearing tissue rather than the extent and intrinsic pathology of macroscopic lesions seems to be important in the destructive process leading to MS-related irreversible cerebral atrophy.