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

Peckeu, Laurène; Delasnerie-Lauprêtre, N; Brandel, Jean‐Philippe; Salomon, Dominique; Sazdovitch, Véronique; Laplanche, Jean‐Louis; Duyckaerts, Charles; Seilhean, Danielle; Haı̈k, Stéphane; Hauw, Jean‐Jacques

doi:10.2807/1560-7917.es.2017.22.41.16-00715

Cited by 26 publications

(25 citation statements)

References 29 publications

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“…These findings are similar to findings by Torres et al (2012) where 14-3-3 protein levels were inconsistent in longitudinal samples and did not track with advancing disease in CJD patients [43]. Furthermore, use of 14-3-3 detection in the diagnosis of CJD has led to an increase in over diagnosis of sporadic CJD and misdiagnosis of potentially treatable diseases [46,47]. Our data indicates a lack of prognostic utility for 14-3-3 and NSE for prion infection and questions the utility of these biomarkers for clinical diagnosis in the context of improved imaging and development of direct detection of PrP CJD by RT QuIC.…”

Section: Discussionsupporting

confidence: 86%

14-3-3 and enolase abundances in the CSF of Prion diseased rats

Gushue

Herbst

Sim

et al. 2018

Prion

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Creutzfeldt-Jakob disease (CJD) is characterized by an extended asymptomatic preclinical phase followed by rapid neurodegeneration. There are no effective treatments. CJD diagnosis is initially suspected based upon the clinical presentation of the disease and the exclusion of other etiologies. Neurologic symptoms are assessed in combination with results from cerebrospinal fluid (CSF) biomarker abundances, electroencephalography (EEG), magnetic resonance imaging (MRI), and in some countries, real-time quaking-induced conversion (RT-QuIC). Inconsistencies in sensitivities and specificities of prion disease biomarker abundance in CSF have been described, which can affect diagnostic certainty, but the utility of biomarkers for prognosis has not been fully explored. The clinical presentation of CJD is variable, and factors such as prion protein polymorphic variants, prion strain, and other genetic or environmental contributions may affect the disease progression, confounding the appearance or abundance of biomarkers in the CSF. These same factors may also affect the appearance or abundance of biomarkers, further confounding diagnosis. In this study, we controlled for many of these variables through the analysis of serial samples of CSF from prion-infected and control rats. Prion disease in laboratory rodents follows a defined disease course as the infection route and time, prion strain, genotype, and environmental conditions are all controlled. We measured the relative abundance of 14-3-3 and neuron-specific enolase (NSE) in CSF during the course of prion infection in rats. Even when disease-related, environmental and genetic variables were controlled, CSF 14-3-3 and NSE abundances were variable. Our study emphasizes the considerable diagnostic and prognostic limitations of these prion biomarkers.

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Section: Discussionsupporting

confidence: 86%

14-3-3 and enolase abundances in the CSF of Prion diseased rats

Gushue

Herbst

Sim

et al. 2018

Prion

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“…However, the specificity of this test has been questioned. In one study, a false positive rate of approximately 30% was found in a population with 14-3-3 protein detected in the CSF who also met diagnostic criteria for probable sCJD 4. Only 59% of this population were found to have sCJD and, interestingly, none were found to have CBD pathology 4.…”

Section: Discussionmentioning

confidence: 99%

“…In one study, a false positive rate of approximately 30% was found in a population with 14-3-3 protein detected in the CSF who also met diagnostic criteria for probable sCJD 4. Only 59% of this population were found to have sCJD and, interestingly, none were found to have CBD pathology 4. A diagnostic test such real-time quaking induced conversion (RT-QuIC), with a similar sensitivity to 14-3-3 CSF analysis but a specificity rate of 98%–100%5 6 would have been a more useful test for the diagnosis of CJD before the patient’s death.…”

Section: Discussionmentioning

confidence: 99%

Rare histotype of sporadic Creutzfeldt-Jakob disease, clinically suspected as corticobasal degeneration

Tilley¹,

Smith

Pavese

et al. 2019

BMJ Case Rep

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Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disease that can mimic other neurological disorders. We present a case of sCJD in a 64-year-old man that presented with corticobasal syndrome and survived for 3 years. He presented initially with dementia, hemiparkinsonism and alien limb phenomenon and was diagnosed with corticobasal degeneration, ultimately progressing to immobility and akinetic mutism. With a normal MRI 1 year before onset, his neuroimaging 1 year later revealed abnormal DaTscan, cortical and hippocampal atrophy with ventricular dilatation on MRI, and diffusion-weighted cortical ribboning and thalamic hyperintensity. Postmortem, the patient’s brain was collected by the Parkinson’s UK Tissue Bank. Prion protein immunohistochemistry revealed widespread diffuse microvacuolar staining without kuru-type plaques. Hyperphosphorylated tau was only found in the entorhinal cortex and hippocampus. This case highlights the clinical heterogeneity of sCJD presentation and the important inclusion of CJD in the differential diagnosis of atypical presentations of neurodegenerative disease.

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“…Lumbar puncture and extraction of CSF is a usual procedure in patients showing neurological signs and especially in those presenting rapidly progressive dementias. Since the quantification of 14-3-3 protein levels is one of the standardized diagnostic criteria [91], this body fluid is available for most of the patients suspected of a TSE. Since the first human CSF-adapted RT-QuIC was reported in 2011, in which from 48 CSF samples of sCJD, iCJD and from other neurodegenerative pathologies they achieved about 80% sensitivity and 100% specificity [92], improvements mainly in the recombinant PrP used as substrate have allowed to increase the sensitivity and to screen for other TSEs apart from sCJD and iCJD [42,93].…”

Section: Prp Sc In Csf In Human Prion Diseasesmentioning

confidence: 99%

Detection of Pathognomonic Biomarker PrPSc and the Contribution of Cell Free-Amplification Techniques to the Diagnosis of Prion Diseases

et al. 2020

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Transmissible spongiform encephalopathies or prion diseases are rapidly progressive neurodegenerative diseases, the clinical manifestation of which can resemble other promptly evolving neurological maladies. Therefore, the unequivocal ante-mortem diagnosis is highly challenging and was only possible by histopathological and immunohistochemical analysis of the brain at necropsy. Although surrogate biomarkers of neurological damage have become invaluable to complement clinical data and provide more accurate diagnostics at early stages, other neurodegenerative diseases show similar alterations hindering the differential diagnosis. To solve that, the detection of the pathognomonic biomarker of disease, PrP Sc , the aberrantly folded isoform of the prion protein, could be used. However, the amounts in easily accessible tissues or body fluids at pre-clinical or early clinical stages are extremely low for the standard detection methods. The solution comes from the recent development of in vitro prion propagation techniques, such as Protein Misfolding Cyclic Amplification (PMCA) and Real Time-Quaking Induced Conversion (RT-QuIC), which have been already applied to detect minute amounts of PrP Sc in different matrixes and make early diagnosis of prion diseases feasible in a near future. Herein, the most relevant tissues and body fluids in which PrP Sc has been detected in animals and humans are being reviewed, especially those in which cell-free prion propagation systems have been used with diagnostic purposes.

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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

Cited by 26 publications

References 29 publications

14-3-3 and enolase abundances in the CSF of Prion diseased rats

14-3-3 and enolase abundances in the CSF of Prion diseased rats

Rare histotype of sporadic Creutzfeldt-Jakob disease, clinically suspected as corticobasal degeneration

Detection of Pathognomonic Biomarker PrPSc and the Contribution of Cell Free-Amplification Techniques to the Diagnosis of Prion Diseases

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