• Christina D Orrú, Matilde Bongianni, Giovanni Tonoli, Sergio Ferrari, Andrew G Hughson, Bradley R Groveman, Michele Fiorini, Maurizio Pocchiari, Salvatore Monaco, Byron Caughey, and Gianluigi Zanusso.
• From the Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Hamilton, MT (C.D.O., M.B., A.G.H., B.R.G., B.C.); and the Department of Biomedical Sciences, University of Cagliari, Cagliari (C.D.O.), the Department of Neurologic and Movement Sciences, University of Verona, Verona (M.B., S.F., M.F., S.M., G.Z.), Clinica Otorinolaringoiatrica, Policlinico G.B. Rossi, Azienda Ospedaliera Universitaria Integrata, Verona (G.T.), and the Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome (M.P.) - all in Italy.
• N. Engl. J. Med. 2014 Aug 7; 371 (6): 519-29.

BackgroundDefinite diagnosis of sporadic Creutzfeldt-Jakob disease in living patients remains a challenge. A test that detects the specific marker for Creutzfeldt-Jakob disease, the prion protein (PrP(CJD)), by means of real-time quaking-induced conversion (RT-QuIC) testing of cerebrospinal fluid has a sensitivity of 80 to 90% for the diagnosis of sporadic Creutzfeldt-Jakob disease. We have assessed the accuracy of RT-QuIC analysis of nasal brushings from olfactory epithelium in diagnosing sporadic Creutzfeldt-Jakob disease in living patients.MethodsWe collected olfactory epithelium brushings and cerebrospinal fluid samples from patients with and patients without sporadic Creutzfeldt-Jakob disease and tested them using RT-QuIC, an ultrasensitive, multiwell plate-based fluorescence assay involving PrP(CJD)-seeded polymerization of recombinant PrP into amyloid fibrils.ResultsThe RT-QuIC assays seeded with nasal brushings were positive in 30 of 31 patients with Creutzfeldt-Jakob disease (15 of 15 with definite sporadic Creutzfeldt-Jakob disease, 13 of 14 with probable sporadic Creutzfeldt-Jakob disease, and 2 of 2 with inherited Creutzfeldt-Jakob disease) but were negative in 43 of 43 patients without Creutzfeldt-Jakob disease, indicating a sensitivity of 97% (95% confidence interval [CI], 82 to 100) and specificity of 100% (95% CI, 90 to 100) for the detection of Creutzfeldt-Jakob disease. By comparison, testing of cerebrospinal fluid samples from the same group of patients had a sensitivity of 77% (95% CI, 57 to 89) and a specificity of 100% (95% CI, 90 to 100). Nasal brushings elicited stronger and faster RT-QuIC responses than cerebrospinal fluid (P<0.001 for the between-group comparison of strength of response). Individual brushings contained approximately 10(5) to 10(7) prion seeds, at concentrations several logs10 greater than in cerebrospinal fluid.ConclusionsIn this preliminary study, RT-QuIC testing of olfactory epithelium samples obtained from nasal brushings was accurate in diagnosing Creutzfeldt-Jakob disease and indicated substantial prion seeding activity lining the nasal vault. (Funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and others.).

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