title: Sleep Disorders in Parkinsonian and Nonparkinsonian LRRK2 Mutation Carriers.
abstract: OBJECTIVE
  In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC).
  
  
  METHODS
  A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD.
  
  
  RESULTS
  Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC.
  
  
  CONCLUSIONS
  Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD.
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Claustre
authors.initials: C
authors.lastname: Pont-Sunyer
authors.affiliation: MultidisciplinarySleepDisordersUnit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Iranzo
authors.affiliation: MultidisciplinarySleepDisordersUnit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Gaig
authors.affiliation: MultidisciplinarySleepDisordersUnit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Arcos
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Vilas
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Valldeoriola
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Yaroslau
authors.initials: Y
authors.lastname: Compta
authors.affiliation: Laboratory of Neurodegenerative Disorders, Department of Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Universitat de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Fernández-Santiago
authors.affiliation: Laboratory of Neurodegenerative Disorders, Department of Clinical and Experimental Neurology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Universitat de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Fernández
authors.affiliation: Unidad de Parkinson Teknon, Barcelona, Spain.
authors.forename: Angels
authors.initials: A
authors.lastname: Bayés
authors.affiliation: NeurologyService, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Calopa
authors.affiliation: Hospital Mateu Orfila, Maó, Menorca, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Casquero
authors.affiliation: Neurology Service, Hospital Universitari Vall D'Hebron, Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: de Fàbregues
authors.affiliation: NeurologyService, Hospital Universitari de Bellvitge, Barcelona, Spain.
authors.forename: Serge
authors.initials: S
authors.lastname: Jaumà
authors.affiliation: Neurology Service, Hospital Del Mar, Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Puente
authors.affiliation: PsychologyService, Hospital Clinic,Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Salamero
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: José Martí
authors.affiliation: MultidisciplinarySleepDisordersUnit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Santamaría
authors.affiliation: Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigacions BiomediquesAugust Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Tolosa
mesh_terms: D000328:Adult; D003710:Demography; D004576:Electromyography; D005260:Female; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D017286:Polysomnography; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020187:REM Sleep Behavior Disorder / Q000150:complications / Q000235:genetics; D012148:Restless Legs Syndrome / Q000150:complications / Q000235:genetics; D012893:Sleep Wake Disorders / Q000150:complications* / Q000201:enzymology / Q000235:genetics*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases