NR AHDR
AU Lee,K.H.; Harrington,M.G.
TI Premortem diagnosis of Creutzfeldt-Jakob disease by cerebrospinal fluid analysis
QU Lancet 1996 Sep 28; 348(9031): 887
KI Lancet. 1996 Sep 28;348(9031):835. PMID: 8826801
PT letter
VT
Sir - The new variant of Creutzfeldt-Jakob disease (CJD)[1] is remarkable because it affects younger individuals, presents with different symptoms, and has different pathological findings to sporadic CJD. There is a need to determine the epidemiology of this disease with a specific and sensitive premortem diagnostic test.
Among tests available for the premortem diagnosis of CJD is determination of the presence of two low-abundance proteins, 130/131, reported to discriminate CJD from other causes of dementia when detected in the cerebrospinal fluid (CSF).[2] In that previous report, all 21 patients with CJD had CSF proteins (p) 130/131, which were not present in the CSF of any of the 87 patients with other causes of dementia. This test for p 130/131 has not come into use in clinical laboratories because of its technical complexity. However, in collaboration with researchers at the National Institutes of Health, we have developed a simplified test based on the characterisation of these proteins[3] that should lead to widespread use of these marker proteins in the routine diagnosis of CJD. Since our publication in 1986, we have studied over 500 samples from patients with dementia referred to us by clinicians. After p 130/131 testing, we were able to determine the necropsy diagnosis in 260 of these patients. Only two of the 260 patients had a misdiagnosis based on the p 130/131 test: one with primary central nervous system lymphoma was p 130/131 positive and one patient with CJD pathological findings had no p 130/131 detected at the time of examination. Of the remaining 258 patients, 48 were positive for p 130/131 and for CJD pathological findings and 210 were negative for p 130/131 and had no evidence of CJD. If we combine these previously unpublished results with those from the original publication,[2] the p 130/131 test has a more than 98% sensitivity for CJD with a more than 99% specificity (table).
No of patients with dementia
Studied Sensitivity Specificity
1986 report 129 100% (21/21) 100% (87/87)
This report 260 >97% (48/49) >99% (210/211)
Total 389 >98% (69/70) >99% (297/298)
Table: Sensitivity and specificity of 130/131 test for CJD
We are currently investigating at which stage of the disease the p 130/131 marker test becomes positive, the use of this marker in diagnosing new variant CJD, and for diagnosing transmissible spongiform encephalopathy in animals.
1 Will GR, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347: 921-25.
2 Harrington MG, Merril CR, Asher DM, Gajdusek DC. Abnormal proteins in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. N Engl J Med 1986; 315: 279-83.
3 Hsich G, Kennedy K, Gibbs CJ, Lee KH, Harrington MG. The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 1996; 335: 924-30.
IN Die Autoren berichten, dass sie mit ihrem Test, der die Proteine 130 und 131 in Rückenmarksflüssigkeit nachweist, 48 von 49 CJK-Patienten, aber nur 1 von 211 nicht an Creutzfeldt-Jakob erkrankten Menschen fälschlich erkannt haben.
ZR 3
MH Cerebrospinal Fluid Proteins/*analysis; Creutzfeldt-Jakob Syndrome/cerebrospinal fluid/*diagnosis; Human; Sensitivity and Specificity
AD Kelvin H Lee, *Michael G Harrington, Biology 139-74, California Institute of Technology, Pasadena, CA 91125, USA
SP englisch
PO England