title: Anatomy of disturbed sleep in pallido-ponto-nigral degeneration.
abstract: OBJECTIVE
  Pallido-ponto-nigral degeneration (PPND), caused by an N279K mutation of the MAPT gene, is 1 of a family of disorders collectively referred to as frontotemporal dementia and parkinsonism linked to chromosome 17. This study aims to characterize the nature of the sleep disturbance in PPND and compare these findings to those in other progressive neurological illnesses. Pathological findings are also provided.
  
  
  METHODS
  Ten subjects were recruited from the PPND kindred; 5 affected and 5 unaffected. The subjects underwent clinical assessment, polysomnography, and wrist actigraphy. Available sleep-relevant areas (pedunculopontine/laterodorsal tegmentum, nucleus basalis of Meynert, thalamus, and locus ceruleus) of affected subjects were analyzed postmortem.
  
  
  RESULTS
  The affected group's total sleep time was an average of 130.8 minutes compared to 403.6 minutes in the control group (p < 0.01). Initial sleep latency was significantly longer in affected subjects (range, 58-260 minutes vs 3-34 minutes). Affected subjects also had an increase in stage I sleep (8.5% vs 1%), and less stage III/IV sleep (8.5% vs 17%). At the time of autopsy, all cases had severe neuronal tau pathology in wake-promoting nuclei, as well as decreases in thalamic cholinergic innervations. There was no difference in orexinergic fiber density in nucleus basalis of Meynert or locus ceruleus compared to controls.
  
  
  CONCLUSIONS
  The PPND kindred showed severe sleep disturbance. Sleep abnormalities are common in neurodegenerative illnesses, but this is the first study of sleep disorders in PPND. Unlike most neurodegenerative conditions, PPND is characterized by decreased total sleep time, increased sleep latency, and decreased sleep efficiency, without daytime hypersomnolence.
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Spector
authors.affiliation: Department of Pathology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Brittany N
authors.initials: BN
authors.lastname: Dugger
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.affiliation: Sleep Disorders Center, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Paul
authors.initials: P
authors.lastname: Fredrickson
authors.affiliation: Department of Neurology, Mayo Clinic Rochester, Rochester, MN.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kaplan
authors.affiliation: Department of Neurology, Mayo Clinic Rochester, Rochester, MN.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: Department of Pathology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.affiliation: Department of Neurology, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Audrey
authors.initials: A
authors.lastname: Strongosky
authors.affiliation: Sleep Disorders Center, Mayo Clinic Florida, Jacksonville, FL.
authors.forename: Siong-Chi
authors.initials: SC
authors.lastname: Lin
mesh_terms: D056044:Actigraphy / Q000379:methods; D000328:Adult; D001216:Asparagine / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005917:Globus Pallidus / Q000473:pathology*; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000473:pathology; D017286:Polysomnography; D011149:Pons / Q000473:pathology*; D012720:Severity of Illness Index; D012893:Sleep Wake Disorders / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D055815:Young Adult; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; D001216:Asparagine; D014446:Tyrosine 3-Monooxygenase; D008239:Lysine