Chapter 15 Fatal familial insomnia and sporadic fatal insomnia
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Laura Cracco, Brian S. Appleby, Pierluigi Gambetti Fatal familial insomnia (FFI) and sporadic fatal insomnia (sFI), or thalamic form of sporadic Creutzfeldt–Jakob disease MM2 (sCJDMM2T), are prion diseases originally named and characterized in 1992 and 1999, respectively. FFI is genetically determined and linked to a D178N mutation coupled with the M129 genotype in the prion protein gene (PRNP) at chromosome 20. sFI is a phenocopy of FFI and likely its sporadic form. Both diseases are primarily characterized by progressive sleep impa...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 14 Dominantly inherited prion protein cerebral amyloidoses – a modern view of Gerstmann–Sträussler–Scheinker
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Bernardino Ghetti, Pedro Piccardo, Gianluigi Zanusso Among genetically determined neurodegenerative diseases, the dominantly inherited prion protein cerebral amyloidoses are characterized by deposition of amyloid in cerebral parenchyma or blood vessels. Among them, Gerstmann–Sträussler–Scheinker disease has been the first to be described. Their clinical, neuropathologic, and molecular phenotypes are distinct from those observed in Creutzfeldt–Jakob disease (CJD) and related spongiform encephalopathies. It is not understood why s...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 13 Genetic Creutzfeldt –Jakob disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Anna Ladogana, Gabor G. Kovacs Genetic Creutzfeldt–Jakob disease (CJD) is associated with mutations in the human PrP gene (PRNP) on chromosome 20p12-pter. Pathogenic mutations have been identified in 10–15% of all CJD patients, who often have a family history of autosomal-dominant pattern of inheritance and variable penetrance. However, the use of genetic tests implemented by surveillance networks all over the world increasingly identifies unexpectedly PRNP mutations in persons apparently presenting with a sporadic form of CJD. A hi...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 12 Iatrogenic Creutzfeldt –Jakob disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Atsushi Kobayashi, Tetsuyuki Kitamoto, Hidehiro Mizusawa Iatrogenic transmission of Creutzfeldt–Jakob disease (CJD) has occurred through particular medical procedures. Among them, dura mater grafts and pituitary-derived growth hormone obtained from human cadavers undiagnosed as CJD are the most frequent sources of infection. Recent advances in our knowledge about dura mater graft- and human pituitary-derived growth hormone-associated CJD patients have revealed that the combination of the infected CJD strain and the PRNP genotype of t...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 11 Variant Creutzfeldt –Jakob disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Jean-Philippe Brandel, Richard Knight Variant CJD (vCJD) was described first in the United Kingdom in 1996. It is a zoonotic form of human prion disease, originating from dietary contamination of human food with material from bovine spongiform encephalopathy (BSE)-affected cattle. It has important epidemiologic, clinical, and neuropathogic differences from other forms of human prion disease. Cases have occurred in several countries but the United Kingdom and France have been most affected. Following the decline in BSE in cattle and the ...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 10 Variably protease-sensitive prionopathy
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Silvio Notari, Brian S. Appleby, Pierluigi Gambetti Variably protease-sensitive prionopathy (VPSPr), originally identified in 2008, was further characterized and renamed in 2010. Thirty-seven cases of VPSPr have been reported to date, consistent with estimated prevalence of 0.7–1.7% of all sporadic prion diseases. The lack of gene mutations establishes VPSPr as a sporadic form of human prion diseases, along with sporadic Creutzfeldt–Jakob disease (sCJD) and sporadic fatal insomnia. Like sCJD, VPSPr affects patients harboring any of...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 9 Sporadic Creutzfeldt –Jakob disease
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Inga Zerr, Piero Parchi Sporadic Creutzfeldt–Jakob disease (CJD), the most common human prion disease, is generally regarded as a spontaneous neurodegenerative illness, arising either from a spontaneous PRNP somatic mutation or a stochastic PrP structural change. Alternatively, the possibility of an infection from animals or other source remains to be completely ruled out. Sporadic CJD is clinically characterized by rapidly progressive dementia with ataxia, myoclonus, or other neurologic signs and, neuropathologically, by the presence...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 8 Chronic wasting disease: an evolving prion disease of cervids
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Sylvie L. Benestad, Glenn C. Telling Chronic wasting disease (CWD) is a relatively new and burgeoning prion epidemic of deer, elk, reindeer, and moose, which are members of the cervid family. While the disease was first described in captive deer, its subsequent discovery in various species of free-ranging animals makes it the only currently recognized prion disorder of both wild and farmed animals. In addition to its expanding range of host species, CWD continues to spread from North America to new geographic areas, including South Kore...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 7 Atypical and classic bovine spongiform encephalopathy
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Cristina Casalone, James Hope This chapter describes the prion diseases of cattle, or bovine transmissible spongiform encephalopathies (BoTSEs). “Classic” bovine spongiform encephalopathy (C-BSE), the major prion protein disorder of Bovidae, was first described in 1986. We also describe the spatiotemporal correlation of C-BSE to a novel form of human prion disease, variant Creutzfeldt–Jakob disease (vCJD), which led to the classification of BSE as a zoonotic disease (and the “cause” of vCJD) in 1996. From isolated cases first ...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 6 Classic and atypical scrapie – a genetic perspective
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Wilfred Goldmann Scrapie was the first prion disease to be recognised and the study of this disease in sheep and goats has provided a wealth of information not only for scrapie but also for the other prion diseases. All prion diseases are under strong genetic control of the prion gene PRNP, independent of whether they are typical or atypical scrapie and which of the different prion strains is causing infection. Decades of studies using experimental disease challenges and field surveys have established disease association models, in which...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 5 The role of the immune system in prion infection
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Neil A. Mabbott, James D. Alibhai, Jean Manson Prion diseases are a unique group of chronic neurodegenerative diseases that affect humans and certain domestic and free-ranging animal species. Many natural prion diseases are acquired peripherally, such as by ingestion of contaminated food or pasture. Although the pathology during prion disease appears to be restricted to the central nervous system, where it causes extensive neurodegeneration, some prion diseases accumulate to high levels within the secondary lymphoid tissues of the host...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 4 Experimental models of human prion diseases and prion strains
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Abigail B. Diack, Jason C. Bartz Prion strains occur in natural prion diseases, including prion diseases of humans. Prion strains can correspond with differences in the clinical signs and symptoms of disease and the distribution of prion infectivity in the host and are hypothesized to be encoded by strain-specific differences in the conformation of the disease-specific isoform of the host-encoded prion protein, PrPTSE. Prion strains can differ in biochemical properties of PrPTSE that can include the relative sensitivity to digestion wit...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 3 Cell biology of prion infection
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Suzette A. Priola The development of multiple cell culture models of prion infection over the last two decades has led to a significant increase in our understanding of how prions infect cells. In particular, new techniques to distinguish exogenous from endogenous prions have allowed us for the first time to look in depth at the earliest stages of prion infection through to the establishment of persistent infection. These studies have shown that prions can infect multiple cell types, both neuronal and nonneuronal. Once in contact with th...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 2 The cellular and pathologic prion protein
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): Andrew C. Gill, Andrew R. Castle The cellular prion protein, PrPC, is a small, cell surface glycoprotein with a function that is currently somewhat ill defined. It is also the key molecule involved in the family of neurodegenerative disorders called transmissible spongiform encephalopathies, which are also known as prion diseases. The misfolding of PrPC to a conformationally altered isoform, designated PrPTSE, is the main molecular process involved in pathogenesis and appears to precede many other pathologic and clinical manifestations ...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
Chapter 1 Human transmissible spongiform encephalopathies: historic view
Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 153 Author(s): David M. Asher, Luisa Gregori The first of several pivotal moments leading to current understanding of human transmissible spongiform encephalopathies (TSEs) occurred in 1959 when veterinary pathologist W.J. Hadlow first recognized several similarities between scrapie—a slow infection of sheep caused by an unusual infectious agent—and kuru, a fatal exotic neurodegenerative disease affecting only people of a single language group in the remote mountainous interior of New Guinea, described two years earlier by D.C. Gajdusek and V. Zig...
Source: Handbook of Clinical Neurology - June 8, 2018 Category: Neurology Source Type: research
