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High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD

The early and accurate in vivo diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is essential in order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive of clinical CJD diagnosis include magnetic resonance imaging (MRI), electroencephalogram...

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Autores principales: Fiorini, Michele, Iselle, Giorgia, Perra, Daniela, Bongianni, Matilde, Capaldi, Stefano, Sacchetto, Luca, Ferrari, Sergio, Mombello, Aldo, Vascellari, Sarah, Testi, Silvia, Monaco, Salvatore, Zanusso, Gianluigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038328/
https://www.ncbi.nlm.nih.gov/pubmed/32019068
http://dx.doi.org/10.3390/ijms21030880
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author Fiorini, Michele
Iselle, Giorgia
Perra, Daniela
Bongianni, Matilde
Capaldi, Stefano
Sacchetto, Luca
Ferrari, Sergio
Mombello, Aldo
Vascellari, Sarah
Testi, Silvia
Monaco, Salvatore
Zanusso, Gianluigi
author_facet Fiorini, Michele
Iselle, Giorgia
Perra, Daniela
Bongianni, Matilde
Capaldi, Stefano
Sacchetto, Luca
Ferrari, Sergio
Mombello, Aldo
Vascellari, Sarah
Testi, Silvia
Monaco, Salvatore
Zanusso, Gianluigi
author_sort Fiorini, Michele
collection PubMed
description The early and accurate in vivo diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is essential in order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive of clinical CJD diagnosis include magnetic resonance imaging (MRI), electroencephalogram (EEG), 14-3-3 protein detection, and/or real-time quaking-induced conversion (RT-QuIC) assay positivity in the cerebrospinal fluid (CSF) or in other tissues. The total CSF tau protein concentration has also been used in a clinical setting for improving the CJD diagnostic sensitivity and specificity. We analyzed 182 CSF samples and 42 olfactory mucosa (OM) brushings from patients suspected of having sCJD with rapidly progressive dementia (RPD), in order to determine the diagnostic accuracy of 14-3-3, the total tau protein, and the RT-QuIC assay. A probable and definite sCJD diagnosis was assessed in 102 patients. The RT-QuIC assay on the CSF samples showed a 100% specificity and a 96% sensitivity, significantly higher compared with 14-3-3 (84% sensitivity and 46% specificity) and tau (85% sensitivity and 70% specificity); however, the combination of RT-QuIC testing of the CSF and OM samples resulted in 100% sensitivity and specificity, proving a significantly higher accuracy of RT-QuIC compared with the surrogate biomarkers in the diagnostic setting of patients with RPD. Moreover, we showed that CSF blood contamination or high protein levels might interfere with RT-QuIC seeding. In conclusion, we provided further evidence that the inclusion of an RT-QuIC assay of the CSF and OM in the diagnostic criteria for sCJD has radically changed the clinical approach towards the diagnosis.
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spelling pubmed-70383282020-03-09 High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD Fiorini, Michele Iselle, Giorgia Perra, Daniela Bongianni, Matilde Capaldi, Stefano Sacchetto, Luca Ferrari, Sergio Mombello, Aldo Vascellari, Sarah Testi, Silvia Monaco, Salvatore Zanusso, Gianluigi Int J Mol Sci Article The early and accurate in vivo diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) is essential in order to differentiate CJD from treatable rapidly progressive dementias. Diagnostic investigations supportive of clinical CJD diagnosis include magnetic resonance imaging (MRI), electroencephalogram (EEG), 14-3-3 protein detection, and/or real-time quaking-induced conversion (RT-QuIC) assay positivity in the cerebrospinal fluid (CSF) or in other tissues. The total CSF tau protein concentration has also been used in a clinical setting for improving the CJD diagnostic sensitivity and specificity. We analyzed 182 CSF samples and 42 olfactory mucosa (OM) brushings from patients suspected of having sCJD with rapidly progressive dementia (RPD), in order to determine the diagnostic accuracy of 14-3-3, the total tau protein, and the RT-QuIC assay. A probable and definite sCJD diagnosis was assessed in 102 patients. The RT-QuIC assay on the CSF samples showed a 100% specificity and a 96% sensitivity, significantly higher compared with 14-3-3 (84% sensitivity and 46% specificity) and tau (85% sensitivity and 70% specificity); however, the combination of RT-QuIC testing of the CSF and OM samples resulted in 100% sensitivity and specificity, proving a significantly higher accuracy of RT-QuIC compared with the surrogate biomarkers in the diagnostic setting of patients with RPD. Moreover, we showed that CSF blood contamination or high protein levels might interfere with RT-QuIC seeding. In conclusion, we provided further evidence that the inclusion of an RT-QuIC assay of the CSF and OM in the diagnostic criteria for sCJD has radically changed the clinical approach towards the diagnosis. MDPI 2020-01-30 /pmc/articles/PMC7038328/ /pubmed/32019068 http://dx.doi.org/10.3390/ijms21030880 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fiorini, Michele
Iselle, Giorgia
Perra, Daniela
Bongianni, Matilde
Capaldi, Stefano
Sacchetto, Luca
Ferrari, Sergio
Mombello, Aldo
Vascellari, Sarah
Testi, Silvia
Monaco, Salvatore
Zanusso, Gianluigi
High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD
title High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD
title_full High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD
title_fullStr High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD
title_full_unstemmed High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD
title_short High Diagnostic Accuracy of RT-QuIC Assay in a Prospective Study of Patients with Suspected sCJD
title_sort high diagnostic accuracy of rt-quic assay in a prospective study of patients with suspected scjd
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038328/
https://www.ncbi.nlm.nih.gov/pubmed/32019068
http://dx.doi.org/10.3390/ijms21030880
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