title: Restless legs syndrome associated with major diseases: A systematic review and new concept.
abstract: Recent publications on both the genetics and environmental factors of restless legs syndrome (RLS) defined as a clinical disorder suggest that overlapping genetic risk factors may play a role in primary (idiopathic) and secondary (symptomatic) RLS. Following a systematic literature search of RLS associated with comorbidities, we identified an increased prevalence of RLS only in iron deficiency and kidney disease. In cardiovascular disease, arterial hypertension, diabetes, migraine, and Parkinson disease, the methodology of studies was poor, but an association might be possible. There is insufficient evidence for conditions such as anemia (without iron deficiency), chronic obstructive pulmonary disease, multiple sclerosis, headache, stroke, narcolepsy, and ataxias. Based on possible gene-microenvironmental interaction, the classifications primary and secondary RLS may suggest an inappropriate causal relation. We recognize that in some conditions, treatment of the underlying disease should be achieved as far as possible to reduce or eliminate RLS symptoms. RLS might be seen as a continuous spectrum with a major genetic contribution at one end and a major environmental or comorbid disease contribution at the other.
authors.affiliation: From Center of Parkinsonism and Movement Disorders (C.T.), Paracelsus-Elena Hospital, Kassel; Departments of Neurosurgery (C.T.) and Clinical Neurophysiology (W.P.), University Medical Center, Göttingen, Germany; Department of Neurology (R.A.), The Johns Hopkins Bayview Medical Center, Baltimore, MD; Department of Neurology (B.H.), Medical University of Innsbruck, Austria; Institute for Neurogenomic (J.W.), Helmholtz Zentrum München, Neuherberg; Neurologische Klinik und Poliklinik (J.W.), Klinikum rechts der Isar, Technische Universität München, Munich; and Munich Cluster for Systems Neurology (SyNergy) (J.W.), Munich, Germany. trenkwalder@paracelsus-kliniken.de winkelmann@lrz.tu-muenchen.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.affiliation: From Center of Parkinsonism and Movement Disorders (C.T.), Paracelsus-Elena Hospital, Kassel; Departments of Neurosurgery (C.T.) and Clinical Neurophysiology (W.P.), University Medical Center, Göttingen, Germany; Department of Neurology (R.A.), The Johns Hopkins Bayview Medical Center, Baltimore, MD; Department of Neurology (B.H.), Medical University of Innsbruck, Austria; Institute for Neurogenomic (J.W.), Helmholtz Zentrum München, Neuherberg; Neurologische Klinik und Poliklinik (J.W.), Klinikum rechts der Isar, Technische Universität München, Munich; and Munich Cluster for Systems Neurology (SyNergy) (J.W.), Munich, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Allen
authors.affiliation: From Center of Parkinsonism and Movement Disorders (C.T.), Paracelsus-Elena Hospital, Kassel; Departments of Neurosurgery (C.T.) and Clinical Neurophysiology (W.P.), University Medical Center, Göttingen, Germany; Department of Neurology (R.A.), The Johns Hopkins Bayview Medical Center, Baltimore, MD; Department of Neurology (B.H.), Medical University of Innsbruck, Austria; Institute for Neurogenomic (J.W.), Helmholtz Zentrum München, Neuherberg; Neurologische Klinik und Poliklinik (J.W.), Klinikum rechts der Isar, Technische Universität München, Munich; and Munich Cluster for Systems Neurology (SyNergy) (J.W.), Munich, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Högl
authors.affiliation: From Center of Parkinsonism and Movement Disorders (C.T.), Paracelsus-Elena Hospital, Kassel; Departments of Neurosurgery (C.T.) and Clinical Neurophysiology (W.P.), University Medical Center, Göttingen, Germany; Department of Neurology (R.A.), The Johns Hopkins Bayview Medical Center, Baltimore, MD; Department of Neurology (B.H.), Medical University of Innsbruck, Austria; Institute for Neurogenomic (J.W.), Helmholtz Zentrum München, Neuherberg; Neurologische Klinik und Poliklinik (J.W.), Klinikum rechts der Isar, Technische Universität München, Munich; and Munich Cluster for Systems Neurology (SyNergy) (J.W.), Munich, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
authors.affiliation: From Center of Parkinsonism and Movement Disorders (C.T.), Paracelsus-Elena Hospital, Kassel; Departments of Neurosurgery (C.T.) and Clinical Neurophysiology (W.P.), University Medical Center, Göttingen, Germany; Department of Neurology (R.A.), The Johns Hopkins Bayview Medical Center, Baltimore, MD; Department of Neurology (B.H.), Medical University of Innsbruck, Austria; Institute for Neurogenomic (J.W.), Helmholtz Zentrum München, Neuherberg; Neurologische Klinik und Poliklinik (J.W.), Klinikum rechts der Isar, Technische Universität München, Munich; and Munich Cluster for Systems Neurology (SyNergy) (J.W.), Munich, Germany. trenkwalder@paracelsus-kliniken.de winkelmann@lrz.tu-muenchen.de.
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
mesh_terms: D015897:Comorbidity; D006801:Humans; D012148:Restless Legs Syndrome / Q000453:epidemiology / Q000209:etiology / Q000235:genetics