Evidence-based guideline: Diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease

Abstract

Objective: 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). Methods: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?" Results: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. Recommendation:For patients who have rapidly progressive dementia and are strongly suspected of having sCJD and for whom diagnosis remains uncertain (pretest probability ϳ20%-90%), clinicians should order CSF 14-3-3 assays to reduce the uncertainty of the diagnosis (Level B). Neurology ® 2012;79:1499-1506 GLOSSARY CI ϭ confidence interval; CJD ϭ Creutzfeldt-Jakob disease; DWI ϭ diffusion-weighted imaging; FLAIR ϭ fluid-attenuated inversion recovery; NSE ϭ neuron-specific enolase; PSWC ϭ periodic sharp and slow wave complexes; ROC ϭ receiver operator characteristic; sCJD ϭ sporadic Creutzfeldt-Jakob disease; WB ϭ Western blot.

Dysregulation of 14‐3‐3 proteins in neurodegenerative diseases with Lewy body or Alzheimer pathology

“…Measurement of 14‐3‐3s in CSF has been used clinically as a diagnostic biomarker for Creutzfeldt‐Jakob Disease (CJD), although recent studies have demonstrated that the specificity for CJD is lower than initially thought 48, 49, 50, 51. However, this body of research has demonstrated that 14‐3‐3 measurements in CSF are reliable and stable in patients, and can help with diagnosis in the right clinical context 48, 49. Further evaluation of 14‐3‐3 phosphorylation in CSF and plasma is indicated for these disorders.…”

Two Forms of Presentation of Confirmed Sporadic Creutzfeldt-Jakob Disease

“…Similar findings in the NMR and EEG also appear in metabolic and toxic encephalopathies, viral encephalomyelitis (HIV and herpes virus) and paraneoplastic syndromes [5]. The positive identification of 14-3-3 protein in cerebrospinal fluid (sensitivity 92%, specificity 80%) is one of the most frequently used analytical methods for the diagnosis [6]. Mean survival usually ranges from six months to a year [7].…”

A rare case of rapidly progressive dementia with elevated RT-QuIC and negative 14-3-3 and tau proteins

“…For the longest time, detection of 14-3-3 protein in the CSF was regarded as a highly specific test for diagnosing sCJD. 1 However, false positive elevations in CSF 14-3-3 have recently been reported in herpes simplex encephalitis, hypoxic encephalopathy, cerebral metastases, paraneoplastic disease, and metabolic encephalopathies. 2 A variety of other CSF diagnostic tests have been reported in small series, including the S100 protein, neuron specific enolase, thymosin b4, and tau protein.…”