Neurology, Vol 45, Issue 6 1068-1075, Copyright © 1995 by American Academy of Neurology

ARTICLES

Clinical and genetic studies of fatal familial insomnia

AT Reder, AS Mednick, P Brown, JP Spire, E Van Cauter, RL Wollmann, L Cervenakova, LG Goldfarb, A Garay and F Ovsiew
Department of Neurology, University of Chicago School of Medicine, IL, USA.

We report a 42-year-old man who, for 8 months, had intermittent motor abnormalities and mild difficulty falling asleep. A diagnosis of fatal familial insomnia (FFI) became evident over the next 6 months when he developed progressive insomnia, myoclonus, sympathetic hyperactivity, and dementia. The amyloid or prion protein (PrP) genotype showed features typically seen in FFI, with a 178Asn mutation and a 129Met polymorphism. There was also a deletion of one octapeptide repeat, suggesting that the association of 178Asn mutation with the 129Met polymorphism is not due to "founder effect." Western immunoblot showed a trace of protease-resistant PrP in the thalamus--which had the most significant neuronal loss and gliosis--a moderate amount of PrP in the fronto-temporal area, and no detectable protein elsewhere in the brain. Endocrine studies showed that a circadian modulation of hormonal levels could be maintained despite a near-total absence of sleep. Administration of gamma-hydroxybutyrate induced a remarkable increase in slow-wave sleep.

This article has been cited by other articles:

				H. -P. Landolt, M. Glatzel, T. Blattler, P. Achermann, C. Roth, J. Mathis, J. Weis, I. Tobler, A. Aguzzi, and C. L. Bassetti Sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease Neurology, May 9, 2006; 66(9): 1418 - 1424. [Abstract] [Full Text] [PDF]

				J J Zarranz, A Digon, B Atares, A B Rodriguez-Martinez, A Arce, N Carrera, I Fernandez-Manchola, M Fernandez-Martinez, C Fernandez-Maiztegui, I Forcadas, et al. Phenotypic variability in familial prion diseases due to the D178N mutation J. Neurol. Neurosurg. Psychiatry, November 1, 2005; 76(11): 1491 - 1496. [Abstract] [Full Text] [PDF]

				C Tabernero, J M Polo, M D Sevillano, R Munoz, J Berciano, A Cabello, B Baez, J R Ricoy, R Carpizo, J Figols, et al. Fatal familial insomnia: clinical, neuropathological, and genetic description of a Spanish family J. Neurol. Neurosurg. Psychiatry, June 1, 2000; 68(6): 774 - 777. [Abstract] [Full Text] [PDF]

				J. A. Mastrianni, R. Nixon, R. Layzer, G. C. Telling, D. Han, S. J. DeArmond, and S. B. Prusiner Prion Protein Conformation in a Patient with Sporadic Fatal Insomnia N. Engl. J. Med., May 27, 1999; 340(21): 1630 - 1638. [Full Text] [PDF]

				G. Almer, J. A. Hainfellner, T. Brucke, K. Jellinger, R. Kleinert, G. Bayer, O. Windl, H. A. Kretzschmar, A. Hill, K. Sidle, et al. Fatal familial insomnia: a new Austrian family Brain, January 1, 1999; 122(1): 5 - 16. [Abstract] [Full Text] [PDF]

				I. Tobler, T. Deboer, and M. Fischer Sleep and Sleep Regulation in Normal and Prion Protein-Deficient Mice J. Neurosci., March 1, 1997; 17(5): 1869 - 1879. [Abstract] [Full Text] [PDF]