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Olfactory Mucosa Brushings Accurate for Use in Creutzfeldt- Jakob Disease Testing

by Amy Eckner • November 4, 2014

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How well does real-time quaking-induced conversion (RT-QuIC) analysis of olfactory mucosa brushings discriminate between patients with sporadic Creutzfeldt–Jakob disease (CJD) and controls who do not have the disease?

Background: A test detecting the specific marker for CJD, the prion protein, through RT-QuIC testing of cerebrospinal fluid, has a sensitivity of 80% to 90% for sporadic CJD diagnosis. It has been difficult to identify a prion protein assay and a procedure for obtaining a tissue specimen that are sufficiently sensitive, noninvasive, and practical for use in patients. A much safer and less invasive nasal-brushing procedure may be a viable choice.

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November 2014

Study design: Controlled case study of olfactory epithelium brushings and cerebrospinal fluid samples from patients with and those without sporadic CJD.

Setting: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy; Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; Clinica Otorinolaringoiatrica, Policlinico G.B. Rossi, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.

Synopsis: An olfactory mucosa sample spiking from a patient without CJD combined with brain homogenate from a patient with sporadic CJD induced strong ThT fluorescence, indicating amyloid fibril formation. All four replicate reactions from a patient with sporadic CJD, seeded with dilutions of the olfactory mucosa pellet, gave strong ThT positivity within 30 hours. Blinded sample sets comprising 74 olfactory mucosa samples from patients with definite (15 samples), probable (14), or inherited (2) CJD, and from negative controls without CJD, were tested. Positive RT-QuIC reactions were observed in 1:250 dilutions of olfactory mucosa samples from 15 of 15 patients with definite sporadic CJD, 13 of 14 with probable sporadic CJD, and two of two with inherited CJD. Olfactory mucosa samples from all 43 control patients were RT-QuIC-negative at the same dilution. RT-QuIC analysis of cerebrospinal fluid samples had a sensitivity of 77%, with 23 RT-QuIC-positive reactions in 30 samples from sporadic CJD patients and a specificity of 100% with 46 RT-QuIC-negative reactions in 46 samples from patients without CJD. Limitations included a need for further validation of both tests to fully establish their relative diagnostic sensitivities in clinical settings.

Bottom line: RT-QuIC testing of olfactory epithelium samples obtained from nasal brushings was accurate in diagnosing CJD and indicated substantial prion seeding activity lining the nasal vault.

Citation: Orrú CD, Bongianni M, Tonoli G, et al. A test for Creutzfeldt–Jakob disease using nasal brushings. N Engl J Med. 2014;371:519-529.

Pages: 1 2 | Single Page

Filed Under: Literature Reviews, Practice Focus, Rhinology, Rhinology Tagged With: rhinologyIssue: November 2014

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  • Olfactory Impairment and Disease Etiology are Linked
  • MRIs Not Cost Effective for Evaluating Idiopathic Olfactory Loss
  • ESS Improves CRS-Related Subjective Olfactory Dysfunction
  • Olfactory Recovery Is Possible Following Post-Infectious Olfactory Loss

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