CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.
OBJECTIVE
To analyze the diagnostic sensitivity and specificity of various brain-derived proteins (14-3-3, Tau, neuron specific enolase [NSE], and S100b) in the CSF of patients with Creutzfeldt-Jakob disease (CJD) and to analyze biologic factors that modify these parameters.


METHODS
CSF was tested for 14-3-3, Tau, NSE, and S100b in 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD, and in 1,117 controls.


RESULTS
The highest sensitivity was achieved for 14-3-3 and Tau in sporadic CJD (85% and 86%), and a combined determination of 14-3-3 and Tau, S100b, or NSE increased the sensitivity to over 93%. A multivariate analysis showed that the sensitivity of all tests was highest in patients with the shortest disease duration, age at onset >40 years, and homozygosity at codon 129 of the prion protein gene. In a group of patients with repeated lumbar punctures, a second test also increased the diagnostic sensitivity.


CONCLUSIONS
The detection of elevated levels of brain-derived proteins in the CSF in patients with suspected Creutzfeldt-Jakob disease is a valuable diagnostic test. A second lumbar puncture may be of value in patients with atypical clinical course in whom the first test was negative.
Sanchez-Juan
P
P
Department of Epidemiology &s Biostatistics, Erasmus University Medical Center Rotterdam, The Netherlands.
Green
A
A
Ladogana
A
A
Cuadrado-Corrales
N
N
Sáanchez-Valle
R
R
Mitrováa
E
E
Stoeck
K
K
Sklaviadis
T
T
Kulczycki
J
J
Hess
K
K
Bodemer
M
M
Slivarichová
D
D
Saiz
A
A
Calero
M
M
Ingrosso
L
L
Knight
R
R
Janssens
A C J W
AC
van Duijn
C M
CM
Zerr
I
I
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000453:epidemiology; D003937:Diagnosis, Differential; D005060:Europe / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D048948:14-3-3 Proteins; D015415:Biomarkers; D009419:Nerve Tissue Proteins