Increased NAA Concentration in the Restless Legs Syndrome: Possible Link to Hypomyelination

Introduction: Iron deficiency has been known as a contributing factor for restless legs syndrome (RLS). Iron plays a pivotal role in brain physiology as an essential component for proper myelination, as a cofactor for enzymes in neurotransmitter synthesis, lipid and DNA synthesis. Most in vivo studies on RLS have been carried out with fMRI and MR relaxation mapping [1-3]. To date, the associated neurochemical changes in the dopaminergic brain structures has not been studied in vivo such that the important experimental relationship of iron insufficiency with neurochemical distribution in RLS brains can be established. The aim of present study was to investigate the neurochemical alterations in the RLS brain, specifically in the putamen, using in vivo proton MRS. In addition, the involvement of iron in myelin synthesis and insufficient brain iron in RLS led to the hypothesis that hypomyelination could exist in RLS brains. 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).