Diffuse white matter (WM) injury is prominent in primary progressive multiple sclerosis (PPMS). Diffusion Kurtosis Imaging (DKI) allows the quantification of non-Gaussian water diffusion, offering the possibility of more detailed characterization of WM damage, in comparison with that provided by diffusion tensor imaging metrics. Here we present application of DKI metrics in PPMS using a Tract-Based Spatial Statistics approach. We observed a diffuse WM microstructural damage, manifested as axonal water fraction, mean kurtosis and fractional anisotropy decrease. In line with histopathological studies, our results suggest the prevalence of axonal damage over demyelination in progressive MS.