The Generative Brain

Olfactory mucosa (nasal brushing) RT-QuIC

RT-QuIC on a nasal brushing (olfactory mucosa) is a minimally invasive prion test: 97 percent sensitive and 100 percent specific in a 2014 NEJM study, more sensitive than CSF in the same patients, and combined with CSF testing it approached 100 percent in 2017. It carries biosafety implications because brushings hold many prion seeds.

Key facts

  • Included with CSF in the six-laboratory ring trial (98 to 100 percent concordance).
  • Around 96 percent sensitivity and close to 100 percent specificity reported for CSF and olfactory mucosa.
  • Limits: Needs trained sampling and a reference laboratory.
  • What it asks of the person: Brushing of the nasal cavity.
  • A 2014 NEJM study (Orru et al.) found nasal brushing RT-QuIC positive in 30 of 31 CJD patients (15 of 15 definite sporadic, 13 of 14 probable sporadic, 2 of 2 inherited) and negative in 43 of 43 controls: 97 percent sensitivity and 100 percent specificity.
  • In the same patients CSF RT-QuIC was 77 percent sensitive and 100 percent specific and took twice as long to obtain.
  • Brushings contained more prion seeds than CSF, which raises biosafety questions about nasal secretions and instruments.
  • A 2017 JAMA Neurology study combining CSF and olfactory mucosa RT-QuIC reported virtually 100 percent sensitivity and specificity in the clinical phase, with all 71 CSF and 67 olfactory samples from non-prion patients negative.
  • The authors propose that a positive CSF result suffices and olfactory sampling is needed when CSF is negative or lumbar puncture is not feasible, using a soft flocked swab instead of the earlier cytobrush.
  • A 2022 review reports about 96 percent sensitivity and close to 100 percent specificity in CSF and olfactory mucosa and sees peripheral-tissue RT-QuIC as a path to preclinical diagnosis in people at genetic risk.

Timeline

  1. 2014NEJM nasal brushing study published.
  2. 2017JAMA Neurology two-test algorithm published (print issue 74(2)).
  3. 2022Review of RT-QuIC for human prion disease published.
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