Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples

Early and accurate in vivo diagnosis of Creutzfeldt-Jakob disease (CJD) is necessary for quickly distinguishing treatable from untreatable rapidly progressive dementias and for future therapeutic trials. This early diagnosis is becoming possible using the real-time quaking-induced conversion (RT-QuI...

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Published in:JAMA neurology Vol. 74; no. 2; p. 155
Main Authors: Bongianni, Matilde, Orrù, Christina, Groveman, Bradley R, Sacchetto, Luca, Fiorini, Michele, Tonoli, Giovanni, Triva, Giorgio, Capaldi, Stefano, Testi, Silvia, Ferrari, Sergio, Cagnin, Annachiara, Ladogana, Anna, Poleggi, Anna, Colaizzo, Elisa, Tiple, Dorina, Vaianella, Luana, Castriciano, Santina, Marchioni, Daniele, Hughson, Andrew G, Imperiale, Daniele, Cattaruzza, Tatiana, Fabrizi, Gian Maria, Pocchiari, Maurizio, Monaco, Salvatore, Caughey, Byron, Zanusso, Gianluigi
Format: Journal Article
Language:English
Published: United States 01.02.2017
Subjects:
Aged
Algorithms
Case-Control Studies
Creutzfeldt-Jakob Syndrome - cerebrospinal fluid
Creutzfeldt-Jakob Syndrome - diagnosis
Creutzfeldt-Jakob Syndrome - pathology
Female
Humans
Italy
Male
Middle Aged
Olfactory Mucosa - metabolism
Olfactory Mucosa - pathology
Prions - cerebrospinal fluid
Sensitivity and Specificity
ISSN:2168-6157, 2168-6157
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Summary:Early and accurate in vivo diagnosis of Creutzfeldt-Jakob disease (CJD) is necessary for quickly distinguishing treatable from untreatable rapidly progressive dementias and for future therapeutic trials. This early diagnosis is becoming possible using the real-time quaking-induced conversion (RT-QuIC) seeding assay, which detects minute amounts of the disease-specific pathologic prion protein in cerebrospinal fluid (CSF) or olfactory mucosa (OM) samples. To develop an algorithm for accurate and early diagnosis of CJD by using the RT-QuIC assay on CSF samples, OM samples, or both. In this case-control study, samples of CSF and OM were collected from 86 patients with a clinical diagnosis of probable (n = 51), possible (n = 24), or suspected (n = 11) CJD and 104 negative control samples (54 CSF and 50 OM). The CSF and OM samples were analyzed using conventional RT-QuIC. The CSF samples underwent further testing using improved RT-QuIC conditions. In addition, the diagnostic performance of a novel, easy-to-use, gentle flocked swab for sampling of OM was evaluated. Data were collected from January 1 to June 30, 2015. Correlations between RT-QuIC results and the final diagnosis of recruited patients. Among the 86 patients (37 men [43%] and 49 women [57%]; mean [SD] age, 65.7 [11.5] years) included for analysis, all 61 patients with sporadic CJD had positive RT-QuIC findings using OM or CSF samples or both for an overall RT-QuIC diagnostic sensitivity of 100% (95% CI, 93%-100%). All patients with a final diagnosis of non-prion disease (71 CSF and 67 OM samples) had negative RT-QuIC findings for 100% specificity (95% CI, 94%-100%). Of 8 symptomatic patients with various mutations causing CJD or Gerstmann-Sträussler-Scheinker syndrome, 6 had positive and 2 had negative RT-QuIC findings for a sensitivity of 75% (95% CI, 36%-96%). A proposed diagnostic algorithm for sporadic CJD combines CSF and OM RT-QuIC testing to provide virtually 100% diagnostic sensitivity and specificity in the clinical phase of the disease.
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ISSN:2168-6157
2168-6157
DOI:10.1001/jamaneurol.2016.4614