NR AXMZ
AU Geschwind,M.D.; Haman,A.; Torres-Chae,C.; Raudabaugh,B.J.; Devereux,G.; Miller,B.L.
TI Diagnostic Utility of CSF Biomarkers and General CSF Findings in a U.S Sporadic CJD Cohort
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Epidemiology, Risk Assessment and Transmission P04.33
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: The diagnostic utility of CSF biomarkers, including 14-3-3 protein, neuron-specific enolase (NSE), AB42, total Tau (T-Tau), and phosphorylated Tau (P-
Tau)/T-Tau ratio are often are used for sporadic CJD (sCJD) diagnosis is controversial. We have previously reported the CSF 14-3-3 protein to have poor sensitivity for CJD diagnosis. In this study, now report the sensitivity and specificity of several CSF biomarkers and general characteristics in a U.S. cohort of sCJD and non-prion rapidly progressive dementia (RPD) controls (Non-CJD cohort) subjects.
Design/Methods: Clinical diagnoses are made through review of medical records, clinical evaluation, and in many cases pathology. Data is stored in a secure clinical relational database, which was queried for various CSF findings, including cell count, protein, IgG index, oligoclonal bands (OCBs), 14-3-3, NSE, T-Tau in patients with probable or definite sporadic CJD and non-prion rapidly progressive dementias (RPD), most of whom were referred to our center with a potential diagnosis of CJD. For probable sCJD diagnosis, we used UCSF criteria that are modified from WHO to substitute MRI for 14-3-3. T-Tau and NSE were considered positive if > 1300 pg/ml and > 35 ng/ml, respectively. For this analysis, ambiguous 14-3-3 results were considered as negative.
Results: 14-3-3 protein (n=149) sensitivity was only 48% (47% for definite; 50% for probable sCJD). NSE (n=49) sensitivity was 63% (66% for definite; 59% for probable sCJD). T-Tau (n=28) was the most sensitive at 68% (69% for definite; 67% for probable sCJD). The specificity of these biomarkers among our CJD and RPD controls (n=72) was 66% for 14-3-3 (n=47), 81% for NSE (n=21), and 100% for T-Tau (n=7). The 14-33 had the lowest sensitivity and specificity. Mildly elevated CSF protein (<100 mg/dl) is common in sCJD; High WBC; >20, is uncommon in sCJD.
Conclusions/Relevance: In a cohort from a major U.S. CJD referral center, the 14-3-3 is neither sensitive nor specific for sCJD. NSE and T-Tau also show poor sensitivity for sCJD. T-Tau may be more specific than 14-3-3 and NSE, but our "n" is small. WHO sCJD criteria should be revised; by eliminating 14-3-3 and including brain MRI into the criteria. We are currently analyzing the effects of disease duration and codon 129 polymorphism on these CSF biomarker results.
AD M.D. Geschwind, A. Haman, C. Torres-Chae, B.J. Raudabaugh, G. Devereux, B.L. Miller, University of California, San Francisco, USA
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren: M.D. Geschwind, D.Y. Johnson, J. Goldman, A. Haman, G. Devereux, B.J. Raudabaugh, C. Torres-Chae, B.L. Miller; Postertitel: Diagnosing Genetic Prion Disease)