Assessment of normal-appearing white and gray matter in patients with primary progressive multiple sclerosis - A diffusion-tensor magnetic resonance imaging study

Background: Diffusion-tensor magnetic resonance imaging is sensitive to the more destructive aspects of multiple sclerosis (MS) evolution occurring outside and within T2-visible lesions and, as a consequence, holds promise for providing a more complete picture of primary progressive (PP) MS-related tissue damage than conventional magnetic resonance imaging. Objective: To improve our understanding of PPMS by assessing the extent of occult pathological features in the normal-appearing white and gray matter of the brain using diffusion-tensor magnetic resonance imaging. Methods: Ninety-six patients with PPMS, 47 patients with secondary progressive (SP) MS, and 44 healthy control subjects were studied. T2-hyperintense and T1-hypointense lesion volumes were calculated, and the volume of the whole brain tissue was measured. Diffusion-tensor magnetic resonance imaging scans were postprocessed and analyzed to obtain the mean diffusivity and fractional anisotropy histograms from the brain and from the normal-appearing white and gray matter in isolation. Results: The mean T2-hyperintense and T1-hypointense lesion volumes were lower in patients with PPMS than in patients with SPMS, while the mean absolute brain volumes were similar in the 2 groups. The average lesion diffusivity was significantly higher in patients with SPMS than in patients with PPMS (P<.001). Histogram-derived metrics of the brain tissue and normal-appearing white and gray matter were significantly different between patients with PPMS and healthy subjects (range, P=.004 to <001). Average diffusivity values were significantly higher in patients with SPMS than in patients with PPMS for all the tissues studied (range, P=.001 to <001). Fractional anisotropy histogram-derived quantities did not significantly differ between the 2 patient groups (range, P=.94 to .03). Conclusion: This study confirms that, in patients with PPMS, normal-appearing white and gray matter are not spared by disease-related pathological processes, although they are affected to a lesser degree than in patients with SPMS.