title: Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder.
abstract: OBJECTIVE
  To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder.
  
  
  METHODS
  The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria.
  
  
  RESULTS
  172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows - RBD, 62±14 (range, 20-93), cognitive impairment (n=147); 69±10 (range, 22-90), parkinsonism (n=151); 68±9 (range, 20-92), and autonomic dysfunction (n=42); 62±12 (range, 23-81). Death age was 75±9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n=97), Parkinson's disease with or without mild cognitive impairment or dementia (n=32), multiple system atrophy (MSA) (n=19), Alzheimer's disease (AD)(n=9) and other various disorders including secondary narcolepsy (n=2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n=1). The neuropathologic diagnoses were Lewy body disease (LBD)(n=77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n=59), MSA (n=19), AD (n=6), progressive supranulear palsy (PSP) (n=2), other mixed neurodegenerative pathologies (n=6), NBIA-1/LBD/tauopathy (n=1), and hypothalamic structural lesions (n=2). Among the neurodegenerative disorders associated with RBD (n=170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features.
  
  
  CONCLUSIONS
  In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. bboeve@mayo.edu
authors.forename: B F
authors.initials: BF
authors.lastname: Boeve
authors.forename: M H
authors.initials: MH
authors.lastname: Silber
authors.forename: T J
authors.initials: TJ
authors.lastname: Ferman
authors.forename: S C
authors.initials: SC
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authors.forename: E E
authors.initials: EE
authors.lastname: Benarroch
authors.forename: A M
authors.initials: AM
authors.lastname: Schmeichel
authors.forename: J E
authors.initials: JE
authors.lastname: Ahlskog
authors.forename: R J
authors.initials: RJ
authors.lastname: Caselli
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authors.lastname: Jacobson
authors.forename: M
authors.initials: M
authors.lastname: Sabbagh
authors.forename: C
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authors.lastname: Adler
authors.forename: B
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authors.lastname: Woodruff
authors.forename: T G
authors.initials: TG
authors.lastname: Beach
authors.forename: A
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authors.lastname: Iranzo
authors.forename: E
authors.initials: E
authors.lastname: Gelpi
authors.forename: J
authors.initials: J
authors.lastname: Santamaria
authors.forename: E
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authors.lastname: Tolosa
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authors.lastname: Singer
authors.forename: D C
authors.initials: DC
authors.lastname: Mash
authors.forename: C
authors.initials: C
authors.lastname: Luca
authors.forename: I
authors.initials: I
authors.lastname: Arnulf
authors.forename: C
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: C H
authors.initials: CH
authors.lastname: Schenck
authors.forename: M W
authors.initials: MW
authors.lastname: Mahowald
authors.forename: Y
authors.initials: Y
authors.lastname: Dauvilliers
authors.forename: N R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Z K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: J E
authors.initials: JE
authors.lastname: Parisi
authors.forename: B
authors.initials: B
authors.lastname: Dugger
authors.forename: M E
authors.initials: ME
authors.lastname: Murray
authors.forename: D W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000150:complications / Q000473:pathology; D009290:Narcolepsy / Q000150:complications / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications* / Q000473:pathology*; D020187:REM Sleep Behavior Disorder / Q000150:complications* / Q000473:pathology*; D013494:Supranuclear Palsy, Progressive / Q000150:complications / Q000473:pathology; D055815:Young Adult
keywords: Dementia with Lewy bodies; Lewy body disease; Multiple system atrophy; Parasomnia; Parkinson’s disease; REM sleep behavior disorder; Synuclein; Synucleinopathy