title: Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples.
abstract: 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.
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Bongianni
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Christina
authors.initials: C
authors.lastname: Orrù
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Groveman
authors.affiliation: Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Sacchetto
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Fiorini
authors.affiliation: Struttura Complessa di Otorinolaringoiatria, Ospedale Santa Maria della Misericordia, Rovigo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tonoli
authors.affiliation: Copan Italia SpA, Brescia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Triva
authors.affiliation: Biocrystallography Laboratory, Department of Biotechnology, University of Verona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Capaldi
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Testi
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Department of Neuroscience, University of Padova, Padova, Italy8Istituto di Ricovero e Cura a Carattere Scientifico San Camillo Hospital, Venice, Italy.
authors.forename: Annachiara
authors.initials: A
authors.lastname: Cagnin
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ladogana
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Poleggi
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Colaizzo
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Dorina
authors.initials: D
authors.lastname: Tiple
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Vaianella
authors.affiliation: Copan Italia SpA, Brescia, Italy.
authors.forename: Santina
authors.initials: S
authors.lastname: Castriciano
authors.affiliation: Department of Surgical Sciences, Dentistry, Gynecology, and Pediatrics, University of Verona, Verona, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Marchioni
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Hughson
authors.affiliation: Neurology Unit, Ospedale Maria Vittoria, Torino, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Imperiale
authors.affiliation: Neurology Unit, Ospedale Cattinara, Trieste, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Cattaruzza
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fabrizi
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pocchiari
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Monaco
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Byron
authors.initials: B
authors.lastname: Caughey
authors.affiliation: Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Policlinico G. B. Rossi, Verona, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zanusso
mesh_terms: D000368:Aged; D000465:Algorithms; D016022:Case-Control Studies; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009831:Olfactory Mucosa / Q000378:metabolism* / Q000473:pathology*; D011328:Prions / Q000134:cerebrospinal fluid*; D012680:Sensitivity and Specificity
chemical_list: D011328:Prions