Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt–Jakob disease
Article first published online: 27 AUG 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 72, Issue 2, pages 278–285, August 2012
How to Cite
McGuire, L. I., Peden, A. H., Orrú, C. D., Wilham, J. M., Appleford, N. E., Mallinson, G., Andrews, M., Head, M. W., Caughey, B., Will, R. G., Knight, R. S. G. and Green, A. J. E. (2012), Real time quaking-induced conversion analysis of cerebrospinal fluid in sporadic Creutzfeldt–Jakob disease. Ann Neurol., 72: 278–285. doi: 10.1002/ana.23589
- Issue published online: 27 AUG 2012
- Article first published online: 27 AUG 2012
- Accepted manuscript online: 15 MAR 2012 11:52PM EST
- Manuscript Accepted: 9 MAR 2012
- Manuscript Revised: 24 FEB 2012
- Manuscript Received: 30 MAY 2011
Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt–Jakob disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14-3-3, which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real time quaking-induced conversion (RT-QuIC). The objective of this study is to investigate whether CSF RT-QuIC analysis could be used as a diagnostic test in sCJD.
An exploratory study was undertaken that analyzed 108 CSF samples from patients with neuropathologically confirmed sCJD or from control patients. Of the 108 CSF samples, 56 were from sCJD patients (30 female, 26 male; aged 31–84 years; mean age, 62.3 ± 13.5 years), and 52 were from control patients (26 female, 26 male; aged 43–84 years; mean age, 67.8 ± 10.4 years). A confirmatory group of 118 patients was subsequently examined that consisted of 67 cases of neuropathologically confirmed sCJD (33 female, 34 male; aged 39–82 years; mean age, 67.5 ± 9.0 years) and 51 control cases (26 female, 25 male; aged 36–87 years; mean age, 63.5 ± 11.6 years).
The exploratory study showed that RT-QuIC analysis had a sensitivity of 91% and a specificity of 98% for the diagnosis of sCJD. These results were confirmed in the confirmatory study, which showed that CSF RT-QuIC analysis had a sensitivity and specificity of 87% and 100%, respectively.
This study shows that CSF RT-QuIC analysis has the potential to be a more specific diagnostic test for sCJD than current CSF tests. ANN NEUROL 2012;72:278–285.