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Diagnostic accuracy of cerebrospinal fluid biomarkers for the differential diagnosis of sporadic Creutzfeldt-Jakob disease: a (network) meta-analysis

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Item Type:Article
Title:Diagnostic accuracy of cerebrospinal fluid biomarkers for the differential diagnosis of sporadic Creutzfeldt-Jakob disease: a (network) meta-analysis
Creators Name:Rübsamen, N. and Pape, S. and Konigorski, S. and Zapf, A. and Rücker, G. and Karch, A.
Abstract:BACKGROUND: There are no systematic reviews of cerebrospinal fluid and blood biomarkers for sporadic Creutzfeldt-Jakob disease (sCJD) in specialised care settings that compare diagnostic accuracies in a network meta-analysis (NMA). METHODS: We searched Medline, Embase, and Cochrane Library for diagnostic studies of sCJD biomarkers. Studies had to use established diagnostic criteria for sCJD and for diseases in the non-CJD groups, which had to represent a consecutive population of patients suspected as a CJD case, as reference standard. Risk of bias was assessed with QUADAS-2. We conducted individual biomarker meta-analyses with generalised bivariate models. To investigate heterogeneity, we performed subgroup analyses based on QUADAS-2 quality and clinical criteria. For the NMA, we applied a Bayesian beta-binomial ANOVA model. The study protocol was registered at PROSPERO (CRD42019118830). RESULTS: Out of 2,976 publications screened, we included 16 studies, which investigated 14-3-3β (n=13), 14-3-3γ (n=3), neurofilament light chain (NfL, n=1), neuron specific enolase (n=1), p-tau181/t-tau ratio (n=2), RT-QuIC (n=7), S100B (n=3), t-tau (n=12), and t-tau/Aβ42 ratio (n=1). Excluded diagnostic studies had strong limitations in study design. In the NMA, RT-QuIC (0.91; 95% CI [0.83, 0.95]) and NfL (0.93 [0.78, 0.99]) were the most sensitive biomarkers for the diagnosis of definite, probable and possible sCJD cases. RT-QuIC was the most specific biomarker (0.97 [0.89, 1.00]). Heterogeneity in accuracy estimates was high between studies. CONCLUSIONS: We identified RT-QuIC as the most accurate biomarker, partially confirming currently applied diagnostic criteria. The shortcomings identified in many diagnostic studies for sCJD biomarkers need to be addressed in future studies.
Keywords:Diagnostic Tests, Network Meta-Analysis, Prion Diseases, Sensitivity, Specificity
Source:European Journal of Neurology
Page Range:1366-1376
Date:May 2022
Official Publication:https://doi.org/10.1111/ene.15258
PubMed:View item in PubMed

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