Application of real-time quaking-induced conversion in Creutzfeldt-Jakob disease surveillance

TY - JOUR

T1 - Application of real-time quaking-induced conversion in Creutzfeldt-Jakob disease surveillance

AU - Hermann, Peter

AU - Schmitz, Matthias

AU - Cramm, Maria

AU - Goebel, Stefan

AU - Bunck, Timothy

AU - Schütte-Schmidt, Julia

AU - Schulz-Schaeffer, Walter

AU - Stadelmann, Christine

AU - Matschke, Jakob

AU - Glatzel, Markus

AU - Zerr, Inga

N1 - © 2023. The Author(s).

PY - 2023/4

Y1 - 2023/4

N2 - BACKGROUND: Evaluation of the application of CSF real-time quaking-induced conversion in Creutzfeldt-Jakob disease surveillance to investigate test accuracy, influencing factors, and associations with disease incidence.METHODS: In a prospective surveillance study, CSF real-time quaking-induced conversion was performed in patients with clinical suspicion of prion disease (2014-2022). Clinically or histochemically characterized patients with sporadic Creutzfeldt-Jakob disease (n = 888) and patients with final diagnosis of non-prion disease (n = 371) were included for accuracy and association studies.RESULTS: The overall test sensitivity for sporadic Creutzfeldt-Jakob disease was 90% and the specificity 99%. Lower sensitivity was associated with early disease stage (p = 0.029) and longer survival (p < 0.001). The frequency of false positives was significantly higher in patients with inflammatory CNS diseases (3.7%) than in other diagnoses (0.4%, p = 0.027). The incidence increased from 1.7 per million person-years (2006-2017) to 2.0 after the test was added to diagnostic the criteria (2018-2021).CONCLUSION: We validated high diagnostic accuracy of CSF real-time quaking-induced conversion but identified inflammatory brain disease as a potential source of (rare) false-positive results, indicating thorough consideration of this condition in the differential diagnosis of Creutzfeldt-Jakob disease. The surveillance improved after amendment of the diagnostic criteria, whereas the incidence showed no suggestive alterations during the COVID-19 pandemic.

AB - BACKGROUND: Evaluation of the application of CSF real-time quaking-induced conversion in Creutzfeldt-Jakob disease surveillance to investigate test accuracy, influencing factors, and associations with disease incidence.METHODS: In a prospective surveillance study, CSF real-time quaking-induced conversion was performed in patients with clinical suspicion of prion disease (2014-2022). Clinically or histochemically characterized patients with sporadic Creutzfeldt-Jakob disease (n = 888) and patients with final diagnosis of non-prion disease (n = 371) were included for accuracy and association studies.RESULTS: The overall test sensitivity for sporadic Creutzfeldt-Jakob disease was 90% and the specificity 99%. Lower sensitivity was associated with early disease stage (p = 0.029) and longer survival (p < 0.001). The frequency of false positives was significantly higher in patients with inflammatory CNS diseases (3.7%) than in other diagnoses (0.4%, p = 0.027). The incidence increased from 1.7 per million person-years (2006-2017) to 2.0 after the test was added to diagnostic the criteria (2018-2021).CONCLUSION: We validated high diagnostic accuracy of CSF real-time quaking-induced conversion but identified inflammatory brain disease as a potential source of (rare) false-positive results, indicating thorough consideration of this condition in the differential diagnosis of Creutzfeldt-Jakob disease. The surveillance improved after amendment of the diagnostic criteria, whereas the incidence showed no suggestive alterations during the COVID-19 pandemic.

U2 - 10.1007/s00415-022-11549-2

DO - 10.1007/s00415-022-11549-2

M3 - SCORING: Journal article

C2 - 36624183

VL - 270

SP - 2149

EP - 2161

JO - J NEUROL

JF - J NEUROL

SN - 0340-5354

IS - 4

ER -