In multiple sclerosis (MS), persistent chronic inflammation at the edges of old non-gadolinium-enhancing white matter lesions, is identified with a paramagnetic rim on susceptibility-based-MRI sequences. Serum neurofilaments (sNfL) levels are associated with disease activity and neurodegeneration in acute and chronic phases of MS. Whether the presence of chronic inflammation is accompanied by increased in neuroaxonal destruction is currently unknown. We showed that MS patients featuring chronic inflammation at the lesions edges have higher neuroaxonal destruction than patients without. The combination of paramagnetic rim and sNfL may help in the selection of “chronically” active MS patients who may benefit from disease-modifying-treatments.