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Diagnostic accuracy of cerebrospinal fluid biomarkers for the differential diagnosis of sporadic Creutzfeldt–Jakob disease: a (network) meta‐analysis
Author(s) -
Rübsamen Nicole,
Pape Stephanie,
Konigorski Stefan,
Zapf Antonia,
Rücker Gerta,
Karch André
Publication year - 2022
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.15258
Subject(s) - medicine , meta analysis , biomarker , cochrane library , cerebrospinal fluid , diagnostic accuracy , pathology , population , oncology , biochemistry , chemistry , environmental health
Background There are no systematic reviews of cerebrospinal fluid and blood biomarkers for sporadic Creutzfeldt–Jakob disease (sCJD) in specialized 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 generalized 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 Of 2976 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.