Foutz A et al. 2017, Diagnostic and prognostic value of human prion detection in cerebrospinal fluid (Ann Neurol 81(1):79-92, doi 10.1002/ana.24833)

This Annals of Neurology paper, published January 2017 by 18 authors led from the National Prion Disease Pathology Surveillance Center at Case Western Reserve University, with colleagues at NIAID Rocky Mountain Laboratories and CDC, tested a second-generation CSF RT-QuIC assay in 2,141 patients with rapidly progressive neurological disorders, of whom 272 had autopsy results. It reported high accuracy against autopsy and better performance than the 14-3-3 and tau surrogate markers. It also found that assay kinetics carried information on disease subtype and survival. Evidence read: PubMed, Europe PMC and Crossref records in full, and the free PMC manuscript through a page summary; no paywalled text was used. Information only, not medical advice.

Key facts

  • Bibliographic identity is confirmed: Ann Neurol 81(1):79-92, January 2017 in print and 24 January 2017 online, DOI 10.1002/ana.24833, PMID 27893164, PMCID PMC5266667, 18 authors.
  • The study applied CSF RT-QuIC to 2,141 patients with rapidly progressive neurological disorders and evaluated 272 with autopsy-based diagnosis.
  • The autopsy-checked set split into a retrospective cohort of 193 (126 prion-positive, 67 negative) and a prospective, blinded cohort of 79 (65 positive, 14 negative).
  • Retrospectively the assay showed about 98.5% specificity and 92% sensitivity; prospectively, 100% specificity and about 95% sensitivity, with a positive predictive value of 100% and a negative predictive value of about 82%.
  • The authors judged the assay superior to the 14-3-3 and tau markers; in the prospective cohort 14-3-3 specificity was about 43% and tau about 71%.
  • Samples with heavy blood contamination were excluded (58 of 2,141, or 2.7%).
  • Seeding strength and lag time let the assay separate sporadic CJD subtypes MM1 from MM2 (about 95% probability) and VV2 from VV1 (about 80%); heterozygous and mixed type 1-2 cases gave intermediate patterns.
  • Higher seeding activity went with shorter survival, which is the basis of the "prognostic" claim in the title.
  • In genetic prion disease, E200K was consistently strongly positive, GSS and FFI varied widely, and three cases (two FFI, one GSS) were negative.
  • The one retrospective false positive was a case with Lewy body pathology at autopsy; the authors raised the possibility of subclinical prion presence, which was not confirmed.
  • Funding came from CDC, NIH, the Charles S. Britton Fund, the Fondation Alliance Biosecure and the NIAID intramural program.

Timeline

  1. 2017Paper published in print in Annals of Neurology issue 81(1).
  2. 2017Online publication on 24 January 2017 per Crossref.

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Last checked 1 November 2026

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