Test Catalog

Test Id : CJDEI

Not Orderable

Creutzfeldt-Jakob Disease Evaluation Interpretation, Spinal Fluid

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Useful For
Suggests clinical disorders or settings where the test may be helpful

Interpretation of the Creutzfeldt-Jakob Disease Evaluation

Method Name
A short description of the method used to perform the test

Only orderable as part of a profile. For more information see CJDE / Creutzfeldt-Jakob Disease Evaluation, Spinal Fluid.

 

Medical Interpretation

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

No

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

CJD Eval Interp, CSF

Aliases
Lists additional common names for a test, as an aid in searching

CJDEI

Specimen Type
Describes the specimen type validated for testing

CSF

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
CSF Frozen (preferred) 28 days BlueTop SARSTEDT
Refrigerated 14 days BlueTop SARSTEDT
Ambient 12 hours BlueTop SARSTEDT

Useful For
Suggests clinical disorders or settings where the test may be helpful

Interpretation of the Creutzfeldt-Jakob Disease Evaluation

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

This evaluation is intended for use in patients with suspected Creutzfeldt-Jakob disease (CJD) and other human prion diseases. CJD is a rare and fatal neurodegenerative disorder that predominantly affects the brain and is caused by misfolded prion proteins (PrP[Sc]). CJD accounts for more than 90% of human prion diseases. Initial symptom onset is heterogenous but commonly includes rapidly progressive dementia, cerebellar ataxia, and myoclonus. The timeline of symptom progression and the pattern of symptom evolution can be divergent across patients and CJD subtypes, making an accurate diagnosis based on clinical presentation alone challenging. The inclusion of biomarkers with high diagnostic accuracy has improved the differentiation of CJD and related prion diseases from treatable neurological conditions with overlapping phenotypes. The real-time quaking-induced conversion (RT-QuIC) assay in cerebrospinal fluid (CSF) has been established to have strong clinical utility for early and accurate diagnosis of CJD through numerous independent studies. Furthermore, the robustness and reproducibility of the RT-QuIC assay for CJD across laboratories has been demonstrated through international ring trials. The clinical sensitivity and specificity of second-generation RT-QuIC assays in CSF have been consistently reported to be greater than or equal to 92% and greater than or equal to 99%, respectively. Despite the high diagnostic accuracy of the assay, RT-QuIC results should be interpreted in the appropriate clinical context along with other clinical and paraclinical findings. A definitive diagnosis of sporadic prion disease can be established only through neuropathological assessment of brain tissue.

 

Unexpectedly negative RT-QuIC test results should prompt careful consideration of the differential diagnosis. If there is high suspicion of prion disease, repeat RT-QuIC testing may be warranted. A small subset of cases initially negative by RT-QuIC may become positive as the disease progresses. However, RT-QuIC may be persistently negative in a small proportion of patients with definitive prion disease. False-negative RT-QuIC results are most often encountered in cases of genetic prion disease (eg, fatal familial insomnia and Gerstmann-Straussler-Scheinker disease) and in atypical sporadic prion disease subtypes (eg, MM2 cortical subtype) that have slower indolent disease progression. Other CSF biomarkers have been utilized to support the diagnosis of CJD, including 14-3-3, total Tau measurement, and the ratio of total Tau to phosphorylated Tau at threonine 181. Recent studies have indicated that the Tau ratio (total Tau to pT181-Tau or vice versa) has a very high diagnostic accuracy, which exceeds that provided by total Tau or 14-3-3 enzyme-linked immunosorbent assays (ELISA). In a cohort of probable/definite CJD cases and controls tested utilizing the Roche Total-Tau and p-Tau (threonine 181) Elecsys assays, the optimized cut-off value for total Tau (>393 ng/L) had a clinical sensitivity and specificity of 92.3% and 88.3% for CJD, respectively; and the optimized cut-off value for the total Tau to p-Tau ratio (>18) has a clinical sensitivity and specificity of 97.4% and 95.9% for CJD, respectively.

 

Importantly, total Tau or total Tau to p-Tau ratios utilize assay-dependent cut-off values, and cut-off values from one assay are not transferable to different assay platforms.

 

The National Prion Disease Pathology Surveillance Center (NPDPSC) coordinates autopsies and neuropathologic examinations on suspected prion disease cases. More information about services available at the NPDPSC may be found at https://case.edu/medicine/pathology/divisions/prion-center.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Only orderable as part of a profile. For more information see CJDE / Creutzfeldt-Jakob Disease Evaluation, Spinal Fluid.

 

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

A positive real-time quaking-induced conversion (RT-QuIC) is supportive of prion disease and, in the correct clinical context, fulfills the Centers for Disease Control and Prevention diagnostic criteria of probable prion disease.(1)

 

An elevated total Tau (t-Tau)/p-Tau (threonine 181) ratio (>18) increases the likelihood of prion disease but can be seen in patients with rapidly progressive dementia due to other causes, including autoimmune encephalitis, central nervous system malignancy, seizure disorder, stroke, and other neurodegenerative diseases.

 

Negative results do not exclude the possibility of prion disease.

 

 

Elevated t-Tau/p-Tau ratio (>18)

Normal t-Tau/p-Tau ratio (< or =18)

RT-QuIC positive

Prion disease highly likely

Prion disease likely

RT-QuIC negative or inconclusive

Prion disease possible

Prion disease unlikely

 

RT-QuIC = Real-time quaking-induced conversion

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

These test results should be interpreted in the appropriate clinical context along with other clinical and paraclinical findings. Only through neuropathological assessment of brain tissue can a definitive diagnosis of sporadic prion disease be established.

 

Some molecular subtypes of prion protein have been reported to have lower detectability by real-time quaking-induced conversion (RT-QuIC) assays.

 

Even small quantities of blood in cerebrospinal fluid (CSF) can result in false-negative RT-QuIC results.

 

The presence of fluorescent substances may interfere with testing and prevent the accurate interpretation of the RT-QuIC assay.

 

Careful consideration of the differential diagnosis is advised when RT-QuIC test results are unexpectedly negative. Repeat testing with RT-QuIC may be warranted if there is high suspicion of prion disease.  A small subset of initially negative cases by RT-QuIC may become positive as the disease progresses. However, a small proportion of patients with definitive prion disease may be persistently negative by RT-QuIC. False-negative RT-QuIC results are most often encountered in cases of genetic prion disease, such as fatal familial insomnia and Gerstmann-Straussler-Scheinker disease, and in atypical sporadic prion disease subtypes that have slower indolent disease progression.

 

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. The presence of antibodies to streptavidin or ruthenium can also rarely occur and may interfere in this assay. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Centers for Disease Control and Prevention (CDC), National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP). Diagnostic criteria: CDC’s diagnostic criteria for Creutzfeldt-Jakob disease (CJD), 2018. CDC. Updated October 18, 2021. Accessed January 15, 2024. Available at www.cdc.gov/prions/cjd/diagnostic-criteria.html

2. Hermann P, Appleby B, Brandel JP, et al. Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. Lancet Neurol. 2021;20(3):235-246

3. Orru CD, Groveman BR, Hughson AG, et al. RT-QuIC assays for prion disease detection and diagnostics. Methods Mol Biol. 2017;1658:185-203

4. Rhoads DD, Wrona A, Foutz A, et al. Diagnosis of prion diseases by RT-QuIC results in improved surveillance. Neurology. 2020;95(8):e1017-e1026

5. Hamlin C, Puoti G, Berri S, et al. A comparison of tau and 14-3-3 protein in the diagnosis of Creutzfeldt-Jakob disease. Neurology. 2012;79(6):547-552

6. Shir D, Lazar EB, Graff-Radford J, et al. Analysis of clinical features, diagnostic tests, and biomarkers in patients with suspected Creutzfeldt-Jakob disease, 2014-2021. JAMA Netw Open. 2022;5(8):e2225098

7. Skillback T, Rosen C, Asztely F, Mattsson N, Blennow K, Zetterberg H. Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in Creutzfeldt-Jakob disease: results from the Swedish Mortality Registry. JAMA Neurol. 2014;71(4):476-483

8. Hermann P, Haller P, Goebel S, et al. Total and phosphorylated cerebrospinal fluid Tau in the differential diagnosis of sporadic Creutzfeldt-Jakob disease and rapidly progressive Alzheimer's disease. Viruses. 2022;14(2):276

Method Description
Describes how the test is performed and provides a method-specific reference

A neuroimmunology expert reviews the laboratory data and an interpretive report is issued.

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 8 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

Not Applicable

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
CJDEI CJD Eval Interp, CSF No LOINC Needed
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
620375 CJD Eval Interp, CSF 69048-7

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

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Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports