title: A Four-Year Longitudinal Study on Restless Legs Syndrome in Parkinson Disease.
abstract: OBJECTIVE
  Restless legs syndrome (RLS) prevalence estimates range from 0% to 52% in Parkinson disease (PD), but the causal relationship between the two disorders is still debated. The present study aims to evaluate RLS prevalence in de novo PD subjects, its incidence during the first 4 years from diagnosis, and possible relationships with clinical, laboratory, and neuroradiological data.
  
  
  METHODS
  One hundred nine newly diagnosed, drug-naïve PD subjects were evaluated at the time of PD diagnosis, and after 2- and 4-years. RLS diagnosis was performed with the RLS Diagnostic Index at each visit. Motor features, additional non-motor symptoms (NMS), and concomitant dopaminergic and nondopaminergic treatments were also gathered. Moreover, at baseline, 65 subjects were randomly selected to undergo a FP-CIT SPECT to study dopamine transporter availability.
  
  
  RESULTS
  RLS prevalence rose from 4.6% at baseline evaluation to 6.5% after 2 years and to 16.3% after 4 years (P = 0.007). A multinomial logistic stepwise regression model selected NMS Questionnaire items more likely to be associated with RLS at diagnosis (insomnia, OR = 15.555; P = 0.040) and with occurrence of RLS during follow-up (dizziness, OR = 1.153; P = 0.022; and daytime sleepiness; OR = 9.557; P = 0.001), as compared to patients without RLS. Older age was more likely associated to increased RLS occurrence during follow-up in a random effect logistic regression model (OR = 1.187; P = 0.036). A multinomial logistic stepwise model found increased dopaminergic transporter availability of affected caudate and putamen to be more likely associated with RLS presence at diagnosis (n = 5; OR = 75.711; P = 0.077), and RLS occurrence during follow-up (n = 16; OR = 12.004; P = 0.059), respectively, as compared to patients without RLS (n = 88).
  
  
  CONCLUSIONS
  RLS is present since PD diagnosis, and increases in prevalence during the course of PD. PD subjects with RLS have higher age at PD onset, more preserved dopaminergic pathways, and worse sleep and cardiovascular disturbances.
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Moccia
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK.|Department of Neurological and Movement Sciences, University of Verona, Policlinico Borgo Roma, Verona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Erro
authors.affiliation: Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, Department of Medicine, University of Salerno, Salerno, Italy.|Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marina
authors.initials: M
authors.lastname: Picillo
authors.affiliation: Department of Psychology, Neuropsychology Laboratory, Second University of Naples, Caserta, Italy.|IDC Hermitage-Capodimonte, Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Santangelo
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Spina
authors.affiliation: Department of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Allocca
authors.affiliation: IDC Hermitage-Capodimonte, Naples, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Longo
authors.affiliation: IDC Hermitage-Capodimonte, Naples, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Amboni
authors.affiliation: Department of Primary Care and Public Health, Imperial College, London, UK.|Department of Public Health, Federico II University, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palladino
authors.affiliation: Department of Advanced Biomedical Sciences, University Federico II, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Assante
authors.affiliation: Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Pappatà
authors.affiliation: Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, Department of Medicine, University of Salerno, Salerno, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Pellecchia
authors.affiliation: Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, Department of Medicine, University of Salerno, Salerno, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.affiliation: IDC Hermitage-Capodimonte, Naples, Italy.|Department of Motor Sciences, University Parthenope, Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Vitale
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D015995:Prevalence; D011897:Random Allocation; D012148:Restless Legs Syndrome / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D012893:Sleep Wake Disorders / Q000150:complications; D011795:Surveys and Questionnaires; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins
keywords: DAT; Parkinson; RLS; SPECT; progression; restless; sleep