title: Brain imaging and networks in restless legs syndrome.
abstract: Several studies provide information useful to our understanding of restless legs syndrome (RLS), using various imaging techniques to investigate different aspects putatively involved in the pathophysiology of RLS, although there are discrepancies between these findings. The majority of magnetic resonance imaging (MRI) studies using iron-sensitive sequences supports the presence of a diffuse, but regionally variable low brain-iron content, mainly at the level of the substantia nigra, but there is increasing evidence of reduced iron levels in the thalamus. Positron emission tomography (PET) and single positron emission computed tomography (SPECT) findings mainly support dysfunction of dopaminergic pathways involving not only the nigrostriatal but also mesolimbic pathways. None or variable brain structural or microstructural abnormalities have been reported in RLS patients; reports are slightly more consistent concerning levels of white matter. Most of the reported changes were in regions belonging to sensorimotor and limbic/nociceptive networks. Functional MRI studies have demonstrated activation or connectivity changes in the same networks. The thalamus, which includes different sensorimotor and limbic/nociceptive networks, appears to have lower iron content, metabolic abnormalities, dopaminergic dysfunction, and changes in activation and functional connectivity. Summarizing these findings, the primary change could be the reduction of brain iron content, which leads to dysfunction of mesolimbic and nigrostriatal dopaminergic pathways, and in turn to a dysregulation of limbic and sensorimotor networks. Future studies in RLS should evaluate the actual causal relationship among these findings, better investigate the role of neurotransmitters other than dopamine, focus on brain networks by connectivity analysis, and test the reversibility of the different imaging findings following therapy.
authors.affiliation: IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Unit of Neurology, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. Electronic address: g.rizzo@unibo.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rizzo
authors.affiliation: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Galantucci
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
authors.affiliation: Department of Neurology, School of Medicine, Dongsan Medical Center, Keimyung University, Daegu, South Korea. Electronic address: neurocho@gmail.com.
authors.forename: Yong Won
authors.initials: YW
authors.lastname: Cho
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006801:Humans; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D059906:Neuroimaging; D012148:Restless Legs Syndrome / Q000000981:diagnostic imaging* / Q000503:physiopathology
keywords: Connectivity; Imaging; MRI; Network; Pathophysiology; Restless legs syndrome