Anatomy of disturbed sleep in pallido-ponto-nigral degeneration

Andrew R. Spector, Brittany N. Dugger, Zbigniew K Wszolek, Ryan J. Uitti, Paul Fredrickson, Joseph Kaplan, Bradley F Boeve, Dennis W Dickson, Audrey Strongosky, Siong Chi Lin

Research output: Contribution to journalArticle

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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. Interpretation: 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.

Original languageEnglish (US)
Pages (from-to)1014-1025
Number of pages12
JournalAnnals of Neurology
Volume69
Issue number6
DOIs
StatePublished - Jun 2011

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Substantia Nigra
Anatomy
Sleep
Basal Nucleus of Meynert
Locus Coeruleus
Actigraphy
Disorders of Excessive Somnolence
Frontotemporal Dementia
Chromosomes, Human, Pair 17
Polysomnography
Sleep Stages
Parkinsonian Disorders
Wrist
Thalamus
Cholinergic Agents
Autopsy
Pathology
Control Groups
Mutation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Spector, A. R., Dugger, B. N., Wszolek, Z. K., Uitti, R. J., Fredrickson, P., Kaplan, J., ... Lin, S. C. (2011). Anatomy of disturbed sleep in pallido-ponto-nigral degeneration. Annals of Neurology, 69(6), 1014-1025. https://doi.org/10.1002/ana.22340

Anatomy of disturbed sleep in pallido-ponto-nigral degeneration. / Spector, Andrew R.; Dugger, Brittany N.; Wszolek, Zbigniew K; Uitti, Ryan J.; Fredrickson, Paul; Kaplan, Joseph; Boeve, Bradley F; Dickson, Dennis W; Strongosky, Audrey; Lin, Siong Chi.

In: Annals of Neurology, Vol. 69, No. 6, 06.2011, p. 1014-1025.

Research output: Contribution to journalArticle

Spector, AR, Dugger, BN, Wszolek, ZK, Uitti, RJ, Fredrickson, P, Kaplan, J, Boeve, BF, Dickson, DW, Strongosky, A & Lin, SC 2011, 'Anatomy of disturbed sleep in pallido-ponto-nigral degeneration', Annals of Neurology, vol. 69, no. 6, pp. 1014-1025. https://doi.org/10.1002/ana.22340
Spector AR, Dugger BN, Wszolek ZK, Uitti RJ, Fredrickson P, Kaplan J et al. Anatomy of disturbed sleep in pallido-ponto-nigral degeneration. Annals of Neurology. 2011 Jun;69(6):1014-1025. https://doi.org/10.1002/ana.22340
Spector, Andrew R. ; Dugger, Brittany N. ; Wszolek, Zbigniew K ; Uitti, Ryan J. ; Fredrickson, Paul ; Kaplan, Joseph ; Boeve, Bradley F ; Dickson, Dennis W ; Strongosky, Audrey ; Lin, Siong Chi. / Anatomy of disturbed sleep in pallido-ponto-nigral degeneration. In: Annals of Neurology. 2011 ; Vol. 69, No. 6. pp. 1014-1025.
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