Correspondence
Case 28-1999: Creutzfeldt–Jakob Disease
N Engl J Med 2000; 342:292-293January 27, 2000
- Article
To the Editor:
In Dr. Shinobu's discussion of Creutzfeldt–Jakob disease in the September 16 Case Records,1 he implies that cerebrospinal fluid markers have little diagnostic value. In fact, a positive test for 14-3-3 protein in cerebrospinal fluid has now been shown to be an accurate predictor of the disease. Traditionally, the most useful noninvasive study for the diagnosis of sporadic Creutzfeldt–Jakob disease has been electroencephalography, with a characteristic tracing of periodic sharp-wave complexes reported to have a sensitivity of 67 percent and a specificity of 86 percent. However, the test for the 14-3-3 protein in cerebrospinal fluid has a sensitivity of 92 to 96 percent and a specificity of 93 to 100 percent.2-4 The accuracy of this test led the World Health Organization and the European Union's Biomed 2 surveillance program for Creutzfeldt–Jakob disease to revise their clinical criteria for the diagnosis of sporadic Creutzfeldt–Jakob disease. A positive cerebrospinal fluid test for the protein 14-3-3 is now given a diagnostic weight similar to that of characteristic findings on an electroencephalogram (Table 1Table 1
World Health Organization's Clinical Criteria for the Diagnosis of Sporadic Creutzfeldt–Jakob Disease.).5 The 14-3-3 protein can be detected in the cerebrospinal fluid in other conditions,2-4 but they are usually easy to distinguish from Creutzfeldt–Jakob disease. The protein has been shown to be stable at room temperature for prolonged periods, and specimens can therefore be sent by mail to special centers for testing; analysis can be completed in a few days. Many laboratories throughout the world are now routinely testing cerebrospinal fluid specimens from patients suspected of having Creutzfeldt–Jakob disease.
5 ReferencesMartin Zeidler, B.M., M.R.C.P.
Western General Hospital, Edinburgh EH4 2XU, United KingdomAlison J.E. Green, M.Sc.
National Hospital for Neurology and Neurosurgery, London WC1 3BG, United KingdomInga Zerr, M.D.
Georg-August-Universität Göttingen, D-37075 Göttingen, Germany1
Case Records of the Massachusetts General Hospital (Case 28-1999)
Full Text | Web of Science | Medline2
Hsich G ,Kenney K ,Gibbs CJ Jr ,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;335:924-930
Full Text | Web of Science | Medline3
Brandel J-P ,Beaudry P ,Delasnerie-Laupretre N ,Laplanche J-L . Maladie de Creutzfeldt-Jakob: valeur diagnostique de la détection de la protéine 14-3-3 et du dosage de la NSE dans le liquide céphalo-rachidien. Rev Neurol 1999;155:148-151
Web of Science | Medline4
Zerr I ,Bodemer M ,Gefeller O , et al. Detection of 14-3-3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt-Jakob disease. Ann Neurol 1998;43:32-40
CrossRef | Web of Science | Medline5
Human transmissible spongiform encephalopathies Wkly Epidemiol Rec 1998;73:361-365
Medline
Author/Editor Response
Dr. Shinobu replies:
To the Editor: The comments by Zeidler et al. convey several important points made in the original discussion, which was shortened for publication. Elevations in the cerebrospinal fluid protein levels of lactic acid, A beta-protein, tau, ubiquitin, protein S-100, and neuron-specific enolase all have some demonstrated usefulness in differentiating cases of Creutzfeldt–Jakob disease from other neurodegenerative diseases, when there is a high a priori clinical suspicion of the disease.1-5 Nonetheless, detection of the 14-3-3 protein in the cerebrospinal fluid, in the appropriate clinical context, deserves special attention. The current criteria of the World Health Organization underscore the consensus on the usefulness of this marker. Analysis of data being collected by the National Prion Disease Pathology Surveillance Center (which, among other things, tests frozen brain tissue and blood for the gene for prion protein and tests cerebrospinal fluid for the 14-3-3 protein) should help determine the incidence and specific characteristics of selected cases in which tests for the 14-3-3 protein are currently considered to have false negative results.
5 ReferencesLeslie A. Shinobu, M.D., Ph.D.
Massachusetts General Hospital, Boston, MA 021141
Kropp K ,Zerr I ,Schulz-Schaeffer WJ , et al. Increase of neuron-specific enolase in patients with Creutzfeldt-Jakob disease. Neurosci Lett 1999;261:124-126
CrossRef | Web of Science | Medline2
Nooijen PT ,Schoonderwaldt HC ,Wevers RA ,Hommes OR ,Lamers KJ . Neuron-specific enolase, S-100 protein, myelin basic protein and lactate in CSF in dementia. Dement Geriatr Cogn Disord 1997;8:169-173
CrossRef | Web of Science | Medline3
Otto M ,Wiltfang J ,Tumani H , et al. Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurosci Lett 1997;225:210-212
CrossRef | Web of Science | Medline4
Otto M ,Stein H ,Szudra A , et al. S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. J Neurol 1997;244:566-570
CrossRef | Web of Science | Medline5
Manaka H ,Kato T ,Kurita K , et al. Marked increase in cerebrospinal fluid ubiquitin in Creutzfeldt-Jakob disease. Neurosci Lett 1992;139:47-49
CrossRef | Web of Science | Medline
- Citing Articles (3)
Citing Articles
1
Diego Franciotta, Carlo Avolio, Elisabetta Capello, Francesco Lolli. (2005) Consensus recommendations of the Italian Association for Neuroimmunology for immunochemical cerebrospinal fluid examination. Journal of the Neurological Sciences 237:1-2, 5-11
CrossRef2
Richard B. Thomson, Heidi Bertram. (2001) LABORATORY DIAGNOSIS OF CENTRAL NERVOUS SYSTEM INFECTIONS. Infectious Disease Clinics of North America 15:4, 1047-1071
CrossRef3
Inga Zerr, Walter J. Schulz-Schaeffer, Armin Giese, Monika Bodemer, Andreas Schr
ter, Karsten Henkel, Henriette J. Tschampa, Otto Windl, Annette Pfahlberg, Bernhard J. Steinhoff, Olaf Gefeller, Hans A. Kretzschmar, Sigrid Poser. (2000) Current clinical diagnosis in Creutzfeldt-Jakob disease: Identification of uncommon variants. Annals of Neurology 48:3, 323-329
CrossRef
