scholarly journals Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic Creutzfeldt-Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009

2017 ◽  
Vol 22 (41) ◽  
Author(s):  
Laurene Peckeu ◽  
Nicole Delasnerie-Lauprètre ◽  
Jean-Philippe Brandel ◽  
Dominique Salomon ◽  
Véronique Sazdovitch ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Prion Protein ◽  
Brain Magnetic Resonance Imaging ◽  
Specific Test ◽  
System Disease ◽  
Jakob Disease ◽  
Diagnosis Criteria ◽  
Recombinant Prion Protein ◽  
Electroencephalogram Eeg ◽  
Sporadic Cjd

Diagnostic criteria of Creutzfeldt–Jakob disease (CJD), a rare and fatal transmissible nervous system disease with public health implications, are determined by clinical data, electroencephalogram (EEG), detection of 14-3-3 protein in cerebrospinal fluid (CSF), brain magnetic resonance imaging and prion protein gene examination. The specificity of protein 14-3-3 has been questioned. We reviewed data from 1,572 autopsied patients collected over an 18-year period (1992–2009) and assessed whether and how 14-3-3 detection impacted the diagnosis of sporadic CJD in France, and whether this led to the misdiagnosis of treatable disorders. 14-3-3 detection was introduced into diagnostic criteria for CJD in 1998. Diagnostic accuracy decreased from 92% for the 1992–1997 period to 85% for the 1998–2009 period. This was associated with positive detections of 14-3-3 in cases with negative EEG and alternative diagnosis at autopsy. Potentially treatable diseases were found in 163 patients (10.5%). This study confirms the usefulness of the recent modification of diagnosis criteria by the addition of the results of CSF real-time quaking-induced conversion, a method based on prion seed-induced misfolding and aggregation of recombinant prion protein substrate that has proven to be a highly specific test for diagnosis of sporadic CJD.

scholarly journals Bank vole prion protein extends the use of RT-QuIC assays to detect prions in a range of inherited prion diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tze How Mok ◽  
Akin Nihat ◽  
Connie Luk ◽  
Danielle Sequeira ◽  
Mark Batchelor ◽  
...  
Keyword(s):  
Prion Protein ◽  
Bank Vole ◽  
Prion Diseases ◽  
Post Mortem ◽  
Prion Strains ◽  
Wide Range ◽  
Jakob Disease ◽  
Recombinant Prion Protein ◽  
First Time ◽  
Sporadic Cjd

AbstractThe cerebrospinal fluid (CSF) real-time quaking-induced conversion assay (RT-QuIC) is an ultrasensitive prion amyloid seeding assay for diagnosis of sporadic Creutzfeldt–Jakob disease (CJD) but several prion strains remain unexplored or resistant to conversion with commonly used recombinant prion protein (rPrP) substrates. Here, bank vole (BV) rPrP was used to study seeding by a wide range of archived post-mortem human CSF samples from cases of sporadic, acquired and various inherited prion diseases in high throughput 384-well format. BV rPrP substrate yielded positive reactions in 70/79 cases of sporadic CJD [Sensitivity 88.6% (95% CI 79.5–94.7%)], 1/2 variant CJD samples, and 9/20 samples from various inherited prion diseases; 5/57 non-prion disease control CSFs had positive reactions, yielding an overall specificity of 91.2% (95% CI 80.1–97.1%). Despite limitations of using post-mortem samples and our results’ discrepancy with other studies, we demonstrated for the first time that BV rPrP is susceptible to conversion by human CSF samples containing certain prion strains not previously responsive in conventional rPrPs, thus justifying further optimisation for wider diagnostic and prognostic use.

scholarly journals The First Meta-Analysis of the M129V Single-Nucleotide Polymorphism (SNP) of the Prion Protein Gene (PRNP) with Sporadic Creutzfeldt–Jakob Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3132
Author(s):  
Yong-Chan Kim ◽  
Byung-Hoon Jeong
Keyword(s):  
Prion Protein ◽  
Protein Gene ◽  
Meta Analysis ◽  
Prnp Gene ◽  
Case Control ◽  
Prion Protein Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Jakob Disease ◽  
Sporadic Cjd

Prion diseases are fatal, chronic, and incurable neurodegenerative diseases caused by pathogenic forms of prion protein (PrPSc) derived from endogenous forms of prion protein (PrPC). Several case–control and genome-wide association studies have reported that the M129V polymorphism of the human prion protein gene (PRNP) is significantly associated with susceptibility to sporadic Creutzfeldt–Jakob disease (CJD). However, since some case–control studies have not shown these associations, the results remain controversial. We collected data that contain the genotype and allele frequencies of the M129V single-nucleotide polymorphism (SNP) of the PRNP gene and information on ethnic backgrounds from sporadic CJD patients. We performed a meta-analysis by collecting data from eligible studies to evaluate the association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD. We found a very strong association between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD using a meta-analysis for the first time. We validated the eligibility of existing reports and found severe heterogeneity in some previous studies. We also found that the MM homozygote is a potent risk factor for sporadic CJD compared to the MV heterozygote in the heterozygote comparison model (MM vs. MV, odds ratio = 4.9611, 95% confidence interval: 3.4785; 7.0758, p < 1 × 10−10). To the best of our knowledge, this was the first meta-analysis assessment of the relationship between the M129V SNP of the PRNP gene and susceptibility to sporadic CJD.

scholarly journals Sporadic Creutzfeldt-Jakob disease with focal findings: caveats to current diagnostic criteria

2013 ◽  
Vol 5 (1) ◽  
pp. 1 ◽  
Author(s):  
Edward C. Mader ◽  
Rima El-Abassi ◽  
Nicole R. Villemarette-Pittman ◽  
Lenay Santana-Gould ◽  
Piotr W. Olejniczak ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
San Francisco ◽  
Brain Magnetic Resonance Imaging ◽  
Brain Biopsy ◽  
World Health ◽  
Mri Findings ◽  
Epilepsia Partialis Continua ◽  
Epileptiform Discharges ◽  
History Of ◽  
Jakob Disease

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD), especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of <em>epilepsia partialis continua</em> (jerking of the left upper extremity) and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI) showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroencephalography (EEG) on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient’s focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009) will enhance the ability to recognize sCJD and implement early safety measures.

scholarly journals Creutzfeldt-Jakob Disease - a literature review

2021 ◽  
Author(s):  
Mariana Sandoval Terra Campos Guelli ◽  
Daniela Bastos de Almeida Zampier ◽  
Lorena Araújo Silva Dias ◽  
Marina de Oliveira Nunes Ibrahim
Keyword(s):  
Literature Review ◽  
Prion Protein ◽  
Neuronal Loss ◽  
Symptomatic Treatment ◽  
Immune Mediated ◽  
Extrapyramidal Signs ◽  
Weighted Magnetic Resonance Imaging ◽  
Jakob Disease ◽  
Electroencephalogram Eeg ◽  
Human Neurodegenerative Disease

Background: Creutzfeldt-Jakob disease (CJD) is a progressive, rare, fatal and rapid human neurodegenerative disease that occurs in the etiologies: sporadic (CJD), familial, iatrogenic (CJD) and CJD variant (CJV) in which cell prion protein (PrP) can be transmitted through animals. Objectives: Literature review about Creutzfeldt-Jakob diseaseDesign and setting: Literature review development in the Centro Universitário de Volta Redonda, Rio de Janeiro, Brazil. Methods: The Creutzfeldt-Jakob disease, infectious diseases and neuroinfection indexes were used in the PUBMED and Scielo databases. Results:CJD has different etiologies with different clinical and pathological phenotypes. CJDV shows psychiatric behaviors and symptoms followed by abnormalities, ataxia and dementia. The sporadic form is the most common, with a progressive clinical course with generalized brain deposition of abnormal prion protein aggregates (PrPTSE) that leads to spongiform change, gliosis and neuronal loss. CJD progresses to dementia and two or more symptoms: cerebellar or visual impairments; pyramidal or extrapyramidal signs; myoclonus; and akinetic mutism. Complex periods of acute wave in the electroencephalogram (EEG) are strongly suggestive of prionic diseases. Rapidly evolving field neuroimmune disorders have shown an increasing in autoantibody testing; attempt to diagnose a range of immune-mediated conditions. Evidence indicates that diffusion-weighted magnetic resonance imaging (DWI) is more sensitive for detecting signal abnormalities. Conclusion: The disease progresses to dementia, accompanied by myoclonus, pyramidal signs and characteristic EEG. It is a complex pathology, which has only symptomatic treatment and requires strict control of reservoirs and risk of contamination.

scholarly journals Creutzfeldt-Jakob disease associated with a missense mutation at codon 200 of the prion protein gene in Brazil

2007 ◽  
Vol 1 (2) ◽  
pp. 222-224
Author(s):  
Jerusa Smid ◽  
Vilma Regina Martins ◽  
Michele Christine Landemberger ◽  
Daniele Riva ◽  
Renato Anghinah ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Missense Mutation ◽  
Prion Protein ◽  
Clinical Picture ◽  
Protein Gene ◽  
Clinical Presentation ◽  
Prion Protein Gene ◽  
Periodic Activity ◽  
Jakob Disease ◽  
Sporadic Cjd

Abstract Genetic Creutzfeldt-Jakob disease (gCJD) represents less than 15% of CJD cases, and its clinical picture may be either indistinguishable from that of sporadic CJD (sCJD) or be atypical, usually with younger onset and longer duration. We report a case of 59-year old Brazilian man who presented rapidly progressive cognitive decline and cerebellar ataxia. EEG revealed periodic activity. A brother and a cousin of the patient had CJD. A point mutation at codon 200 (E200K) of the prion protein gene (PRNP) was found and death occurred 11 months after onset of symptoms. Autopsy was not performed. The clinical presentation of gCJD associated with E200K, which is the most frequent PRNP mutation, is quite similar to sCDJ. This is the first report of E200K mutation in Brazil, and it is possible that a more systematic search for its occurrence may show it to be relatively frequent in Brazil.

scholarly journals Immunoquantitative PCR for Prion Protein Detection in Sporadic Creutzfeldt–Jakob Disease

2005 ◽  
Vol 51 (9) ◽  
pp. 1605-1611 ◽  
Author(s):  
Stéphanie Gofflot ◽  
Manuel Deprez ◽  
Benaïssa el Moualij ◽  
Awad Osman ◽  
Jean-François Thonnart ◽  
...  
Keyword(s):  
Prion Protein ◽  
Sensitivity And Specificity ◽  
Diagnostic Tests ◽  
Detection Threshold ◽  
Protein Detection ◽  
High Specificity ◽  
Proteinase K ◽  
Jakob Disease ◽  
Sporadic Cjd ◽  
Immunohistochemical Analyses

Abstract Background: The most common human prion disorder is Creutzfeldt–Jakob disease (CJD); it includes sporadic, familial, iatrogenic, and variant subtypes. Diagnostic tests aim at detection with the highest specificity of very small deposits of abnormal prion protein (PrP). Methods: We used immunoquantitative PCR (iqPCR) to detect proteinase K–resistant PrP (PrPRes) in tissue from the middle frontal gyrus of 7 patients with sporadic CJD and 7 non-CJD cases. We compared iqPCR with routine optimized ELISA, Western blotting, and immunohistochemical analyses. Results: The 4 methods showed similar 100% sensitivity and specificity for the diagnosis of CJD. Along with high specificity, however, iqPCR had a threshold for PrPRes detection at least 10-fold lower than that of the classic ELISA. Conclusions: iqPCR is a new method for PrPRes detection that combines 100% specificity with a detection threshold at least 10-fold lower than classic techniques. This method may improve the detection of minute PrPRes deposits in tissues and body fluids and thus be useful for diagnostic and sterilization applications.

scholarly journals A field on fire: The biochemistry of mad cows

2005 ◽  
Vol 27 (4) ◽  
pp. 6-8
Author(s):  
David R. Brown
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Human Diseases ◽  
Spongiform Encephalopathy ◽  
Related Disease ◽  
Jakob Disease ◽  
Sporadic Cjd

Prion diseases are neurodegenerative diseases1 that have been linked together because they may potentially have the same cause. These include the diseases scrapie of sheep and BSE (bovine spongiform encephalopathy) of cattle, and also several human diseases that include sporadic CJD (Creutzfeldt-Jakob) disease and a variety of inherited forms. The inherited forms of prion diseases are linked to mutations within the gene for the prion protein. Around 85% of all human cases of prion disease are sporadic CJD, which is a disease affecting people of around 60 years of age. The cause of this disease remains unknown. Unfortunately, the name of this disease causes some confusion, as it is similar to vCJD (variant CJD), a related disease of much younger people.

scholarly journals Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions

2016 ◽  
Vol 90 (21) ◽  
pp. 9558-9569 ◽  
Author(s):  
Joel C. Watts ◽  
Kurt Giles ◽  
Daniel J. Saltzberg ◽  
Brittany N. Dugger ◽  
Smita Patel ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Guinea Pigs ◽  
Spongiform Encephalopathy ◽  
Prolonged Incubation ◽  
Rapid Propagation ◽  
Incubation Periods ◽  
Jakob Disease ◽  
Sporadic Cjd

ABSTRACTThe biochemical and neuropathological properties of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) prions are faithfully maintained upon transmission to guinea pigs. However, primary and secondary transmissions of BSE and vCJD in guinea pigs result in long incubation periods of ∼450 and ∼350 days, respectively. To determine if the incubation periods of BSE and vCJD prions could be shortened, we generated transgenic (Tg) mice expressing guinea pig prion protein (GPPrP). Inoculation of Tg(GPPrP) mice with BSE and vCJD prions resulted in mean incubation periods of 210 and 199 days, respectively, which shortened to 137 and 122 days upon serial transmission. In contrast, three different isolates of sporadic CJD prions failed to transmit disease to Tg(GPPrP) mice. Many of the strain-specified biochemical and neuropathological properties of BSE and vCJD prions, including the presence of type 2 protease-resistant PrPSc, were preserved upon propagation in Tg(GPPrP) mice. Structural modeling revealed that two residues near the N-terminal region of α-helix 1 in GPPrP might mediate its susceptibility to BSE and vCJD prions. Our results demonstrate that expression of GPPrP in Tg mice supports the rapid propagation of BSE and vCJD prions and suggest that Tg(GPPrP) mice may serve as a useful paradigm for bioassaying these prion isolates.IMPORTANCEVariant Creutzfeldt-Jakob disease (vCJD) and bovine spongiform encephalopathy (BSE) prions are two of the prion strains most relevant to human health. However, propagating these strains in mice expressing human or bovine prion protein has been difficult because of prolonged incubation periods or inefficient transmission. Here, we show that transgenic mice expressing guinea pig prion protein are fully susceptible to vCJD and BSE prions but not to sporadic CJD prions. Our results suggest that the guinea pig prion protein is a better, more rapid substrate than either bovine or human prion protein for propagating BSE and vCJD prions.

scholarly journals Sensitive and specific detection of sporadic Creutzfeldt–Jakob disease brain prion protein using real-time quaking-induced conversion

2012 ◽  
Vol 93 (2) ◽  
pp. 438-449 ◽  
Author(s):  
Alexander H. Peden ◽  
Lynne I. McGuire ◽  
Nigel E. J. Appleford ◽  
Gary Mallinson ◽  
Jason M. Wilham ◽  
...  
Keyword(s):  
Real Time ◽  
Prion Protein ◽  
Protein Misfolding ◽  
Conformational Transition ◽  
Specific Test ◽  
Related Sequence ◽  
Jakob Disease ◽  
Scrapie Strains ◽  
Codon 129 ◽  
Sheep Scrapie

Real-time quaking-induced conversion (RT-QuIC) is an assay in which disease-associated prion protein (PrP) initiates a rapid conformational transition in recombinant PrP (recPrP), resulting in the formation of amyloid that can be monitored in real time using the dye thioflavin T. It therefore has potential advantages over analogous cell-free PrP conversion assays such as protein misfolding cyclic amplification (PMCA). The QuIC assay and the related amyloid seeding assay have been developed largely using rodent-passaged sheep scrapie strains. Given the potential RT-QuIC has for Creutzfeldt–Jakob disease (CJD) research and human prion test development, this study characterized the behaviour of a range of CJD brain specimens with hamster and human recPrP in the RT-QuIC assay. The results showed that RT-QuIC is a rapid, sensitive and specific test for the form of abnormal PrP found in the most commonly occurring forms of sporadic CJD. The assay appeared to be largely independent of species-related sequence differences between human and hamster recPrP and of the methionine/valine polymorphism at codon 129 of the human PrP gene. However, with the same conditions and substrate, the assay was less efficient in detecting the abnormal PrP that characterizes variant CJD brain. Comparison of these QuIC results with those previously obtained using PMCA suggested that these two seemingly similar assays differ in important respects.

scholarly journals Human variant Creutzfeldt-Jakob disease and sheep scrapie PrPres detection using seeded conversion of recombinant prion protein

2009 ◽  
Vol 22 (8) ◽  
pp. 515-521 ◽  
Author(s):  
C. D. Orru ◽  
J. M. Wilham ◽  
A. G. Hughson ◽  
L. D. Raymond ◽  
K. L. McNally ◽  
...  
Keyword(s):  
Prion Protein ◽  
Jakob Disease ◽  
Recombinant Prion Protein ◽  
Sheep Scrapie
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