Ziliotto N, Zivadinov R, Baroni M, et al. - Since there has been scarcely any investigation into the participation of protein C (PC) pathway components in multiple sclerosis (MS), researchers examined their levels in patients in relation to clinical and neurodegenerative MRI outcomes. A total of 138 patients with MS and 42 healthy people have been analyzed. By multiplex assays and enzyme-linked immunosorbent assay, PC, protein S and soluble endothelial protein C receptor (sEPCR) have been assessed. Regression analyses were performed between 3 T MRI outcomes and PC pathway components. An association was found between PC concentration, mainly reflecting the zymogen PC, and MRI measures for volumes of total gray matter (GM), thalamus, cortex, deep GM and whole brain. Findings suggested that protein C plasma concentrations could be linked to neurodegenerative MRI outcomes in MS. Several correlation variations between protein plasma concentrations in patients with MS indicate dysregulation of PC pathway elements. PC concentration stability over time promotes a PC investigation of GM atrophy in MS.