Advertisement

Fatal Familial Insomnia: A Disease Model Emphasizing the Role of the Thalamus in the Regulation of the Sleep-Wake Cycle and Other Circadian Rhythms

  • Patrizia Avoni
  • Pietro Cortelli
  • Elio Lugaresi
  • Pasquale Montagna

Abstract

Fatal Familial Insomnia (FFI) is a human hereditary prion disease due to a mutation at codon 178 of the prion protein gene located on chromosome 20, which cosegregates with a methionine polymorphism at codon 129 of the same gene on the mutated allele (Lugaresi et al., 1986; Medori et al., 1992). Prion diseases are characterized by the presence in the brain of an isoform of the prion protein, which is partially resistant to the action of proteases, so called PrPres, and is transmissible. The brains of FFI patients indeed demonstrate accumulation of a 19 kDa (after deglycosylation) PrPres (Parchi et al 1998), and FFI has been transmitted to transgenic mice. FFI has been found in at least 21 pedigrees around the world, and probably represents the third most common inherited human prion disease. FFI is also characterized by a unique set of clinical symptoms and pathological findings, which give rise to peculiar clinico-pathological correlations and interesting physiopathological conclusions concerning the role of the thalamus, especially its anterior and mediodorsal nuclei, in the regulation of circadian activities such as the sleep-wake cycle and the attending hormonal and vegetative functions.

Keywords

Prion Protein Prion Disease NREM Sleep Fatal Familial Insomnia Human Prion Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cortelli, P., Perani, D., Parchi, P., Grassi, F., Montagna, P., De Martin, M, Castellani, R., Tinuper, P., Gambetti, P., Lugaresi, E., Fazio, F., 1997, Cerebral metabolism in fatal familial insomnia: relation to duration, neuropathology, and distribution of protease-resistent prion protein,Neurology,49:126.PubMedCrossRefGoogle Scholar
  2. Hess, W.R., 1944, Das Schlaf syndrom als Folge diencephaler Reizung,Helv. Physiol. Pharmacol. Acta,2:305.Google Scholar
  3. Lugaresi, E., Medori, R., Montagna, P., Baruzzi, A., Cortelli, P., Lugaresi, A., Tinuper, P., Zucconi, M., Gambetti, P., 1986, Fatal familial insomnia and dysautonomia with selective degeneration of thalamic nuclei,New Engl. J. Med.315:997.PubMedCrossRefGoogle Scholar
  4. Lugaresi, E., Tobler, I., Gambetti, P., Montagna, P., 1998, The pathophysiology of fatal familial insomnia,Brain Pathol.8:521.PubMedCrossRefGoogle Scholar
  5. Manetto, V., Medori, R., Cortelli, P., Montagna, P., Baruzzi, A., Hauw, J J., Rancurel, G., Vanderhaeghen, J.J., Mailleux, P., Bugiani, O., Tagliavini, F., Bouras, C, Rizzuto, N., Lugaresi, E., Gambetti, P., 1992, Fatal familial insomnia: clinical and pathological study of five new cases,Neurology,42:312.PubMedCrossRefGoogle Scholar
  6. Marini, G., Imeri, L., Mancia, M., 1988, Changes in sleep-waking cycle induced by lesions of medialis dorsalis thalamic nuclei in the cat,Neurosci. Lett.85:223.PubMedCrossRefGoogle Scholar
  7. Medori, R., Tritschler, H.J., LeBlanc, A., Villare, F., Manetto, V., Chen, H.Y., Xue, R., Leal, S., Montagna, P., Cortelli, P., Tinuper, P., Avoni, P., Mochi, M., Baruzzi, A., Hauw, J.J., Ott, J., Lugaresi, E., Autilio-Gambetti, L., Gambetti, P.. 1992, Fatal familial insomnia is a prion disease with a mutation at codon 178 of the prion protein gene,New Engl. J. Med.326:444.PubMedCrossRefGoogle Scholar
  8. Montagna, P., Cortelli, P., Avoni, P., Tinuper, P., Plazzi, G., Gallassi, R., Portaluppi, F., Julien, J., Vital, C, Delisle, C.B., Gambetti, P., Lugaresi, E., 1998, Clinical features of fatal familial insomnia: phenotypic variability in relation to a polymorphism at codon 129 of the prion protein gene,Brain Pathol.8:515.PubMedCrossRefGoogle Scholar
  9. Parchi, P., Petersen, R.B., Chen, S.G., Autilio-Gambetti, L., Capellari, S., Monari, L., Cortelli, P., Montagna, P., Lugaresi, E., Gambetti, P., 1998, Molecular pathology of fatal familial insomnia,Brain Pathol.8:539.PubMedCrossRefGoogle Scholar
  10. Parmeggiani, P.L., 1964, A study of the central representation of sleep behavior,Progr. Brain Res.6:180.CrossRefGoogle Scholar
  11. Villablanca, J., and Salinas-Zebalos, M.E., 1972, Sleep-wakefulness, EEG, and behavioral studies of chronic cats without the thalamus:”athalamic”,Arch. Ital. Biol.110:383.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Patrizia Avoni
    • 1
  • Pietro Cortelli
    • 1
  • Elio Lugaresi
    • 1
  • Pasquale Montagna
    • 1
  1. 1.Institute of Clinical NeurologyUniversity of Bologna Medical SchoolBolognaItaly

Personalised recommendations