In vivo Quantitative Imaging and Postmortem Protein Analysis Reveal CNS Hypomyelination in the Restless Legs Syndrome

Introduction: Restless Legs Syndrome (RLS) is a sensorimotor disorder with a prevalence of 5-10% in western countries [1]. The disorder is characterized by uncomfortable leg sensations with an irresistible urge to move the legs, causing chronic sleep disruption at night. Evidence from a number of analytical approaches has suggested that insufficient brain iron may underlie the pathophysiology of this syndrome [2-3]. Iron is essential for normal myelination in the brain. Disruption of iron availability in the brain can affect oligodendroglial cell maturation and myelinogenesis. Therefore, we hypothesized that hypomyelination should be present in the brain in individuals with RLS. To test the hypothesis, we investigated the expression of myelin-related proteins, including myelin basic protein (MBP), 3’5’-cyclic nucleotide phosphohydrolase (CNPase), and proteolipid protein (PLP). In addition, to expand the postmortem findings to an in vivo evaluation, we analyzed the brain imaging of RLS patients and controls using voxel-based morphometry (VBM).