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Noninvasive, High-throughput Determination of Sleep Duration in Rodents
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Noninvasive, High-throughput Determination of Sleep Duration in Rodents

Published on: April 18, 2018

Familial and sporadic fatal insomnia

Pasquale Montagna1, Pierluigi Gambetti, Pietro Cortelli

  • 1Department of Neurological Sciences, University of Bologna, Bologna, Italy.

The Lancet. Neurology
|July 10, 2003
PubMed

Insights

Familial fatal insomnia (FFI) and sporadic fatal insomnia (SFI) share symptoms like disrupted sleep and motor issues. Distinct prion strains and PRNP gene variations influence these rare prion diseases.

Area of Science:

  • Neuroscience
  • Genetics
  • Pathology

Background:

  • Familial fatal insomnia (FFI) and sporadic fatal insomnia (SFI) are rare prion diseases with overlapping clinical presentations.
  • Both conditions involve severe disruptions in sleep architecture, autonomic dysfunction, and progressive motor deficits.

Purpose of the Study:

  • To delineate the clinicopathological features of FFI and SFI.
  • To investigate the role of PRNP gene mutations and polymorphisms in disease phenotype.
  • To explore the potential for distinct prion strains in FFI.

Main Methods:

  • Clinical assessment of sleep disturbances, autonomic hyperactivation, and motor abnormalities.
  • Positron Emission Tomography (PET) for metabolic activity.
  • Neuropathological examination of brain tissue.
  • Analysis of prion protein (PrP) isoforms and PRNP gene mutations (D178N) and polymorphisms (codon 129).

Main Results:

  • FFI and SFI exhibit similar phenotypes including disrupted sleep (loss of sleep spindles, slow-wave sleep, enacted dreams) and autonomic/motor signs (myoclonus, ataxia, dysarthria, dysphagia, pyramidal signs).
  • PET imaging revealed significant thalamic and limbic hypometabolism, progressing to wider brain regions.
  • Neuropathology showed severe neuronal loss and astrogliosis in the anterior medial thalamus and inferior olives, with later involvement of cerebral cortex and cerebellum.
  • Distinct PrP isoforms were identified in FFI compared to familial Creutzfeldt-Jakob disease with the same D178N mutation, highlighting the influence of the PRNP codon 129 polymorphism on prion strain characteristics.

Conclusions:

  • The thalamolimbic system plays a crucial role in regulating sleep and circadian functions, as suggested by clinicopathological findings in FFI and SFI.
  • The PRNP codon 129 polymorphism significantly impacts the phenotypic expression of the D178N mutation, potentially leading to different prion strains.
  • FFI and SFI represent distinct but related prionopathies with shared neuropathological substrates and clinical manifestations.

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