Diagnostic accuracy of cerebrospinal fluid biomarkers for the differential diagnosis of sporadic Creutzfeldt-Jakob disease: a (network) meta-analysis
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Diagnostic accuracy of cerebrospinal fluid biomarkers for the differential diagnosis of sporadic Creutzfeldt-Jakob disease: a (network) meta-analysis. / Rübsamen, Nicole; Pape, Stephanie; Konigorski, Stefan; Zapf, Antonia; Rücker, Gerta; Karch, André.
In: EUR J NEUROL, Vol. 29, No. 5, 05.2022, p. 1366-1376.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Diagnostic accuracy of cerebrospinal fluid biomarkers for the differential diagnosis of sporadic Creutzfeldt-Jakob disease: a (network) meta-analysis
AU - Rübsamen, Nicole
AU - Pape, Stephanie
AU - Konigorski, Stefan
AU - Zapf, Antonia
AU - Rücker, Gerta
AU - Karch, André
N1 - © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
PY - 2022/5
Y1 - 2022/5
N2 - 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.
AB - 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.
U2 - 10.1111/ene.15258
DO - 10.1111/ene.15258
M3 - SCORING: Journal article
C2 - 35075751
VL - 29
SP - 1366
EP - 1376
JO - EUR J NEUROL
JF - EUR J NEUROL
SN - 1351-5101
IS - 5
ER -