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International Psychogeriatrics Aug 2019Prion diseases are rare dementias that most commonly occur sporadically, but can be inherited or acquired, and for which there is no cure. We sought to understand which... (Observational Study)
Observational Study
OBJECTIVES
Prion diseases are rare dementias that most commonly occur sporadically, but can be inherited or acquired, and for which there is no cure. We sought to understand which prion disease symptoms are most problematic for carers, to inform the development of outcome measures.
DESIGN
Self-completed questionnaire with follow-up of a subset of participants by structured interview.
SETTING
A nested study in the UK National Prion Monitoring Cohort, a longitudinal observational study.
PARTICIPANTS AND MEASUREMENTS
71 carers, of people with different prion diseases with a wide range of disease severity, identified 236 of their four most problematic symptoms by questionnaire which were grouped into ten domains. Structured interviews were then done to qualitatively explore these experiences. Eleven family carers of people with prion disease were selected, including those representative of a range of demographics and disease subtypes and those who cared for people with prion disease, living or recently deceased. Interviews were transcribed and formally studied.
RESULTS
The six most problematic symptom domains were: mobility and coordination; mood and behavior; personal care and continence; eating and swallowing; communication; and cognition and memory. The prevalence of these symptoms varied significantly by disease stage and type. A formal analysis of structured interviews to explore these domains is reported.
CONCLUSIONS
We make suggestions about how healthcare professionals can focus their support for people with prion disease. Clinical trials that aim to generate evidence regarding therapies that might confer meaningful benefits to carers should consider including outcome measures that monitor the symptomatic domains we have identified as problematic.
Topics: Activities of Daily Living; Adult; Affect; Aged; Caregivers; Cognition; Communication; Deglutition; Disease Progression; Eating; Fecal Incontinence; Female; Humans; Interviews as Topic; Longitudinal Studies; Male; Memory; Middle Aged; Mobility Limitation; Prion Diseases; Self Care; United Kingdom
PubMed: 30353798
DOI: 10.1017/S1041610218001588 -
Folia Neuropathologica 2012Human prion diseases are a unique group of transmissible neurodegenerative diseases that occur as sporadic, familial or acquired disorders and show a wide range of... (Review)
Review
Human prion diseases are a unique group of transmissible neurodegenerative diseases that occur as sporadic, familial or acquired disorders and show a wide range of phenotypic variation. The latter has been attributed to the existence of distinct strains of the agent or prion, and the genetic background of the host, namely the primary sequence of the gene encoding the prion protein, which is the site of mutations and polymorphisms. The characterization of distinct isoforms of the abnormal prion protein in the brain of affected patients, which has been shown to correlate with the disease phenotype, has recently led to the concept of molecular strain typing, in which the different prion protein isoforms or "types", possibly enciphering the strain variability in their conformation, may serve as surrogate markers for individual prion strains. In sporadic Creutzfeldt-Jakob disease, the most common human prion disease, there are at least six distinct clinico-pathological disease phenotypes that largely correlate at a molecular level with two prion protein types with distinctive physicochemical properties and the genotype at the methionine/valine polymorphic codon 129 in the prion protein gene. Recent results of transmission studies indicate that five prion strains with distinctive biological properties can be isolated from these six disease variants. It has also been shown that about a third of sporadic cases show a mixed phenotype and the co-occurrence of prion protein types. The origin of prion strains and their co-occurrence as well as the mechanisms underlying the strain-specific neuronal targeting remain largely unexplained and their understanding constitute, together with the development of successful therapies and more sensitive and specific clinical biomarkers, the major challenges that this disease poses for the future.
Topics: Humans; Pathology, Molecular; PrPSc Proteins; Prion Diseases
PubMed: 22505361
DOI: No ID Found -
Handbook of Clinical Neurology 2018Chronic 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...
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 Korea, and most recently Norway, marking the first time this disease was detected in Europe. Its unparalleled efficiency of contagious transmission, combined with high densities of deer in certain areas, complicates strategies for controlling CWD, raising concerns about its potential for spread to new species. Because there is a high prevalence of CWD in deer and elk, which are commonly hunted and consumed by humans, and since prions from cattle with bovine spongiform encephalopathy have been transmitted to humans causing variant Creutzfeldt-Jakob disease, the possibility of zoonotic transmission of CWD is particularly concerning. Here we review the clinical and pathologic features of CWD and its disturbing epidemiology, and discuss features that affect its transmission, including genetic susceptibility, pathogenesis, and agent strain variability. Finally, we discuss evidence that speaks to the potential for zoonotic transmission of this emerging disease.
Topics: Animals; Deer; Genetic Predisposition to Disease; Humans; Prion Diseases; Prions; Wasting Disease, Chronic
PubMed: 29887133
DOI: 10.1016/B978-0-444-63945-5.00008-8 -
Cell May 1997
Review
Topics: Amino Acid Sequence; Animals; Humans; In Vitro Techniques; Models, Biological; Models, Molecular; Molecular Sequence Data; PrPC Proteins; PrPSc Proteins; Prion Diseases; Prions; Protein Conformation; Species Specificity
PubMed: 9160742
DOI: 10.1016/s0092-8674(00)80232-9 -
Transfusion Medicine (Oxford, England) Sep 1996
Topics: Animals; Cattle; Creutzfeldt-Jakob Syndrome; Encephalopathy, Bovine Spongiform; Humans; Incidence; Mice; Prion Diseases; Prions; Risk Factors; Species Specificity; Transfusion Reaction
PubMed: 8885149
DOI: 10.1111/j.1365-3148.1996.tb00070.x -
Rinsho Shinkeigaku = Clinical Neurology Nov 2008There have been identified 1051 cases of prion dsease in Japan since 1999 by the surveillance committee, of which idiopathic prion disease held 77.8%, hereditary 15.9%... (Review)
Review
There have been identified 1051 cases of prion dsease in Japan since 1999 by the surveillance committee, of which idiopathic prion disease held 77.8%, hereditary 15.9% and infectious 6.6%. Idiopathic prion disease is sporadic Creutzfeldt-Jakob disease (sCJD) and most sCJD cases were classified into MM1 presenting with classical clinical features. MM2, MV2, VV1 and VV2 sCJD cases were rare and showed atypical features including prolonged course, lack of myoclonus and absence of PSD. In such occasions, high signal intensities on DW-MRI as well as increased 14-3-3 and tau proteins in CSF were very helpful. MM2 tharamic sCJD may lack all these laboratory findings but reduction of tharamic CBF in SPECT or PET would support the diagnosis. Hereditary prion disease are classified into 3 major phenotypes such as familial CJD, Gerstmann-Straeussler-Scheinker disease (GSS) mainly showing spinocerebellar ataxia, and fatal familial insomunia. While there have been known many mutations of prion protein gene, only V180I (fCJD), E200K (fCJD), M232R (fCJD) and P102L (GSS) mutations were common. Because most cases did not have family history, genetic test is mandatory in all the cases of prion disease including seemingly "sporadic" CJD. All the cases but 1 case of variant CJD were dura-grafted CJD in infectious prion disease.
Topics: 14-3-3 Proteins; Animals; Biomarkers; Humans; Japan; Magnetic Resonance Imaging; Mutation; Prion Diseases; Prions; tau Proteins
PubMed: 19198101
DOI: 10.5692/clinicalneurol.48.861 -
Handbook of Clinical Neurology 2018The cellular prion protein, PrP, is a small, cell surface glycoprotein with a function that is currently somewhat ill defined. It is also the key molecule involved in... (Review)
Review
The cellular prion protein, PrP, 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 PrP to a conformationally altered isoform, designated PrP, is the main molecular process involved in pathogenesis and appears to precede many other pathologic and clinical manifestations of disease, including neuronal loss, astrogliosis, and cognitive loss. PrP is also believed to be the major component of the infectious "prion," the agent responsible for disease transmission, and preparations of this protein can cause prion disease when inoculated into a naïve host. Thus, understanding the biochemical and biophysical properties of both PrP and PrP, and ultimately the mechanisms of their interconversion, is critical if we are to understand prion disease biology. Although entire books could be devoted to research pertaining to the protein, herein we briefly review the state of knowledge of prion biochemistry, including consideration of prion protein structure, function, misfolding, and dysfunction.
Topics: Animals; Humans; Prion Diseases; Prion Proteins; Protein Folding
PubMed: 29887138
DOI: 10.1016/B978-0-444-63945-5.00002-7 -
Communicable Diseases Intelligence... Jun 2023Nationwide surveillance of Creutzfeldt-Jakob disease (CJD) and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry...
Nationwide surveillance of Creutzfeldt-Jakob disease (CJD) and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2022. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2022, a total of 599 domestic CSF specimens were referred for diagnostic testing and 79 persons with suspected human prion disease were formally added to the national register. As of 31 December 2022, just under half of the 79 suspect case notifications (36/79) remain classified as 'incomplete'; 15 cases were classified as 'definite' and 23 as 'probable' prion disease; five cases were excluded through neuropathological examination. For 2022, fifty-five percent of all suspected human-prion-disease-related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. The SARS-CoV-2 pandemic did not affect prion disease surveillance outcomes in Australia during 2022.
Topics: Humans; Creutzfeldt-Jakob Syndrome; Prospective Studies; Disease Notification; Australia; COVID-19; SARS-CoV-2; Prion Diseases
PubMed: 37357180
DOI: 10.33321/cdi.2023.47.37 -
Neurobiology of Disease Oct 2019Prion diseases typically involve brain deposition of abnormally folded prion protein, which is associated with activated glia and increased cytokine production....
Prion diseases typically involve brain deposition of abnormally folded prion protein, which is associated with activated glia and increased cytokine production. Cyclophilin A (CypA) is a ubiquitous protein with peptidyl prolyl cis-trans isomerase activity, which regulates protein folding, and can be secreted by cells in response to inflammatory stimuli. On the basis of in vitro studies, CypA was proposed to mediate glial activation during prion infection. To investigate the role of CypA in vivo, we inoculated CypA, CypA and CypA mice with the RML prion strain, and recorded the time to onset of neurological signs and to terminal disease, and the astrocyte and microglia response at presymptomatic and symptomatic stages. Time to onset of disease and survival were significantly shorter in CypA-deficient mice than CypA-expressing controls. CypA-deficient mice had significantly greater microglial activation in the presymptomatic stage, and analysis of anti- and pro-inflammatory microglial markers indicated a shift towards a pro-inflammatory phenotype. There was no difference in astrocyte activation. This suggests that CypA contributes to dampening the pro-inflammatory microglial response during the early stage of RML-induced prion disease.
Topics: Animals; Brain; Mice; Mice, Knockout; Microglia; Peptidylprolyl Isomerase; Prion Diseases
PubMed: 31181281
DOI: 10.1016/j.nbd.2019.104498 -
Nihon Naika Gakkai Zasshi. the Journal... Jul 2006