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      Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease: report of the guideline development subcommittee of the American Academy of Neurology.


      14-3-3 Proteins, cerebrospinal fluid, Academies and Institutes, standards, Creutzfeldt-Jakob Syndrome, Databases, Factual, statistics & numerical data, Evidence-Based Medicine, Female, Guidelines as Topic, Humans, Male, Neurology, Sensitivity and Specificity

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          To assess the available evidence for the diagnostic accuracy of CSF testing for protein 14-3-3 in patients with suspected sporadic Creutzfeldt-Jakob disease (sCJD). The authors performed a systematic review of the available literature from 1995 to January 1, 2011, to identify articles involving patients who were suspected of having sCJD and who had CSF analysis for protein 14-3-3. Studies were rated according to the American Academy of Neurology classification of evidence scheme for diagnostic studies, and recommendations were linked to the strength of the evidence. A pooled estimate of sensitivity and specificity was obtained for all studies rated Class II or higher. The question asked is "Does CSF 14-3-3 protein accurately identify Creutzfeldt-Jakob disease (CJD) in patients with sCJD?" The analysis was conducted on the basis of samples of 1,849 patients with suspected sCJD from 9 Class II studies. Assays for CSF 14-3-3 protein are probably moderately accurate in diagnosing sCJD: sensitivity 92% (95% confidence interval [CI] 89.8-93.6), specificity 80% (95% CI 77.4-83.0), likelihood ratio of 4.7, and negative likelihood ratio of 0.10. For patients who have rapidly progressive dementia and are strongly suspected of having sCJD and for whom diagnosis remains uncertain (pretest probability ∼20%-90%), clinicians should order CSF 14-3-3 assays to reduce the uncertainty of the diagnosis (Level B).

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