Bongianni M et al. 2017, Diagnosis of human prion disease using real-time quaking-induced conversion testing of olfactory mucosa and cerebrospinal fluid samples (JAMA Neurol 74(2):155-162, PMID 27942718, doi 10.1001/jamaneurol.2016.4614)

A case-control study from the University of Verona with NIAID Rocky Mountain Laboratories and Italian partners that tested RT-QuIC on cerebrospinal fluid (CSF) and on nasal olfactory mucosa samples from people with suspected Creutzfeldt-Jakob disease (CJD). It reported 100 percent sensitivity and specificity for sporadic CJD when the two sample types were combined, and proposed a stepwise algorithm: improved CSF testing first, olfactory mucosa testing when CSF is negative. It also showed that a soft flocked swab can replace the earlier brush for sampling. Published online 12 December 2016 and in print in February 2017. Information only, not medical advice; the figures come from one study with a modest sample.

Key facts

  • Citation verified: JAMA Neurol 2017;74(2):155-162, doi 10.1001/jamaneurol.2016.4614, PMID 27942718, 26 authors, first author Matilde Bongianni and senior author Gianluigi Zanusso, both at the University of Verona.
  • Design: a case-control study of 86 patients with probable (51), possible (24) or suspected (11) CJD plus 104 negative control samples (54 CSF, 50 olfactory mucosa), with data collected between 1 January and 30 June 2015.
  • All 61 sporadic CJD patients were positive on olfactory mucosa, CSF or both, giving 100 percent sensitivity (95 percent CI 93 to 100).
  • All non-prion-disease samples (71 CSF and 67 olfactory) were negative: 100 percent specificity (95 percent CI 94 to 100).
  • Among 8 symptomatic patients with genetic CJD or Gerstmann-Straussler-Scheinker syndrome, 6 were positive: 75 percent sensitivity with a wide interval (CI 36 to 96).
  • CSF alone was 95 percent sensitive for sporadic CJD (54 of 57) using the improved CSF conditions the authors introduced.
  • The flocked swab collected olfactory neurons as well as the cytobrush with less nasal abrasion and discomfort, though the brush yielded more red blood cells.
  • The proposed algorithm starts with improved CSF RT-QuIC and adds olfactory mucosa testing if CSF is negative.
  • A stated limitation: every CJD patient was symptomatic, so performance before symptoms is unknown.
  • A 2022 review lists the olfactory mucosa sensitivity from this paper as 90 to 95 percent in 61 sporadic CJD (depending on brush type), with 100 percent specificity in 50 controls, and notes the method is limited to a few specialised laboratories with confirmatory studies lacking.
  • In a 2020 six-laboratory ring trial including Verona and RML, olfactory samples showed 98 percent overall concordance (165 of 168 results), supporting reproducibility.
  • The PubMed/Europe PMC record shows the paper is not open access, not in PMC, and had a cited-by count of 155 at the time of fetch.

Timeline

  1. 2015to 2015-06 Sample and data collection period for the study.
  2. 2016Published online 12 December 2016.
  3. 2017Print publication in JAMA Neurology volume 74, issue 2, pages 155-162.
  4. 2020Six-laboratory ring trial published, citing the paper and confirming olfactory sample reproducibility.
  5. 2022Review lists the paper's figures among olfactory RT-QuIC studies.

Last checked 1 November 2026

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