Test Id : NSESF
Neuron-Specific Enolase (NSE), Spinal Fluid
Useful For
Suggests clinical disorders or settings where the test may be helpful
An auxiliary test in the diagnosis of Creutzfeldt-Jakob disease
An auxiliary test in the diagnosis of small cell lung carcinoma metastasis to central nervous system or leptomeninges
Method Name
A short description of the method used to perform the test
Homogeneous Time-Resolved Fluorescence
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
CJD (Creutzfeldt-Jakob disease)
Neuron Specific Enolase, CSF
NSE
Creutzfeldt-Jakob disease
Specimen Type
Describes the specimen type validated for testing
CSF
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Container/Tube: Sterile vial
Specimen Volume: 0.5 mL
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
0.3 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Gross lipemia | OK |
| Gross icterus | Reject |
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 | Refrigerated (preferred) | 15 days | |
| Ambient | 72 hours |
Useful For
Suggests clinical disorders or settings where the test may be helpful
An auxiliary test in the diagnosis of Creutzfeldt-Jakob disease
An auxiliary test in the diagnosis of small cell lung carcinoma metastasis to central nervous system or leptomeninges
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Enolase exists in the form of several tissue-specific isoenzymes, consisting of homo or heterodimers of 3 different monomer-isoforms (alpha, beta, and gamma). Neuron-specific enolase (NSE) is a 78 kDa gamma-homodimer and represents the dominant enolase-isoenzyme found in neuronal and neuroendocrine tissues. Its levels in other tissues, except erythrocytes, are negligible. The biological half-life of NSE in body fluids is approximately 24 hours.
Due to this organ specificity, concentrations of NSE in serum or, more commonly, cerebrospinal fluid (CSF) are often elevated in diseases that result in relative rapid (hours/days to weeks, rather than months to years) neuronal destruction. Measurement of NSE in serum or CSF can therefore assist in the differential diagnosis of a variety of neuron-destructive and neurodegenerative disorders. The most common application is in the differential diagnosis of dementias, where elevated CSF concentrations support the diagnosis of rapidly progressive dementias, such as Creutzfeldt-Jakob disease (CJD). NSE might also have utility as a prognostic marker in neuronal injury. For example, there is increasing evidence that elevated serum NSE levels correlate with a poor outcome in coma, particularly when caused by hypoxic insult.
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.
Normal: < or =15 ng/mL
Indeterminate: 15-30 ng/mL
Elevated: >30 ng/mL
Elevated results may indicate the need for additional workup. Possible causes may be neuron-specific enolase-secreting central nervous system/leptomeningeal tumor or rapid neuronal destruction from a variety of causes. In the context of dementia, elevated results may be suggestive of Creutzfeldt-Jakob disease.
Interpretation
Provides information to assist in interpretation of the test results
The diagnosis of Creutzfeldt-Jakob disease (CJD) is highly complex and involves clinical history and neurologic examination; detection of characteristic periodic sharp and slow wave complexes on electroencephalographs; magnetic resonance imaging (hyperintense basal ganglia); and exclusion of other possible causes of dementia, in addition to cerebrospinal fluid (CSF) examination. Consequently, patients are often diagnosed as having possible, probable, or definite CJD based upon the constellation of clinical findings. Detection of elevated CSF levels of NSE protein in these patients assists in the final diagnosis.
A CSF neuron-specific enolase (NSE) within the normal reference range makes sporadic CJD very unlikely but can be observed in less rapidly progressive forms of CJD, such as variant CJD related to infection with prions that cause bovine spongiform encephalopathy. With the previous Mayo Clinic-developed assay, in a group of carefully pre-selected patients with a probable diagnosis of CJD and an indeterminate or elevated NSE concentration in CSF, the respective diagnostic sensitivities of approximately 87% and approximately 80%, and diagnostic specificities of approximately 66% and approximately 83% were observed.
Small cell lung carcinoma central nervous system metastases, particularly if they involve the leptomeninges, will lead to, usually substantial, elevations in CSF NSE concentrations.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
All neuron-specific enolase (NSE) test results must be considered in the clinical context, and interferences or artifactual elevations should be suspected if the clinical NSE test results are at odds with the clinical picture or other tests.
Hemolysis can lead to significant artefactual NSE elevations since erythrocytes contain NSE. Hemoglobin concentrations as low as 20 mg/dL were shown to cause invalid NSE concentrations.
Proton pump inhibitor treatment, hemolytic anemia, hepatic failure, and end-stage kidney failure can also result in artefactual NSE elevations.
Other false-positive results depend on the testing context. When performing NSE testing for tumor diagnosis or follow-up, recent epileptic seizures, brain injury, encephalitis, stroke, and rapidly progressive dementia might result in false-positive results.
When NSE testing is performed to assist in the diagnosis of Creutzfeldt-Jakob disease (CJD), recent epileptic seizures, brain injury, encephalitis, stroke, and NSE-secreting tumors can cause false-positive NSE elevations in cerebrospinal fluid (CSF).
There is insufficient evidence to support CSF NSE measurements in the prognostic evaluation of coma patients. Serum NSE should be used for this application, in conjunction with clinical predictors (pupillary light responses, corneal reflexes, motor responses to pain, myoclonus, status epilepticus), electroencephalogram, sensory-evoked potentials, and imaging.
Neuron-specific enolase values can vary significantly between methods and assays. Serial follow-up should be performed with the same assay. If assays are changed, patients should have their baseline level reestablished.
This assay is an immunometric assay, and can, in rare situations, be affected by false-low results in the presence of extremely high NSE concentrations ("hooking") or autoantibodies to NSE.
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. 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. Burghuber OC, Worofka B, Schernthaner G, et al. Serum neuron-specific enolase is a useful tumor marker for small cell lung cancer. Cancer. 1990 15;65:1386-1390
2. Lamberts SW, Hofland LJ, Nobels FR. Neuroendocrine tumor markers. Front Neuroendocrinol. 2001;22(4):309-339
3. Aksamit AJ, Jr, Preissner CM, Homburger HA. Quantitation of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt-Jacob disease. Neurology. 2001;57(4):728-730
4. Riley RD, Heney D, Jones DR, et al. A systematic review of molecular and biological tumor markers in neuroblastoma. Clin Cancer Res. 2004;10(1 Pt 1):4-12
5. Portela-Gomes GM, Hacker GW, Weitgasser R. Neuroendocrine cell markers for pancreatic islets and tumors. Appl Immunohistochem Mol Morphol. 2004;12(3):183-192
6. Wijdicks EF, Hijdra A, Young GB, Bassetti CL, Wiebe S, Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;67(2):203-210
7. Huang L, Zhou JG, Yao WX, et al. Systematic review and meta-analysis of the efficacy of serum neuron-specific enolase for early small cell lung cancer screening. Oncotarget. 2017;8(38):64358–64372
8. Cheng F, Yuan Q, Yang J, Wang W, Liu H. The prognostic value of serum neuron-specific enolase in traumatic brain injury: systematic review and meta-analysis. PLoS One. 2014;9(9):e106680
9. Katayama T, Sawada J, Takahashi K, Yahara O, Hasebe N. Meta-analysis of cerebrospinal fluid neuron-specific enolase levels in Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Alzheimers Res Ther. 2021;13(1):163. Published 2021 Oct 5. doi:10.1186/s13195-021-00907-3
Method Description
Describes how the test is performed and provides a method-specific reference
Neuron specific enolase (NSE) is measured in this homogeneous automated immunofluorescent assay on the BRAHMS Kryptor. The Kryptor uses TRACE (time resolved amplified cryptate emission) technology based on a non-radioactive transfer of energy. This transfer occurs between 2 fluorescent tracers: the donor (europium cryptate) and the acceptor (XL665). In the NSE assay, 2 monoclonal antibodies are labeled, 1 with europium cryptate and 1 with XL665. NSE is sandwiched between the 2 antibodies, bringing them into close proximity. When the antigen-antibody complex is excited with a nitrogen laser at 337 nm, some fluorescent energy is emitted at 620 nm and the rest is transferred to XL665. This energy is then emitted as fluorescence at 665 nm. A ratio of the energy emitted at 665 nm to that emitted at 620 nm (internal reference) is calculated for each sample. Signal intensity is proportional to the number of antigen-antibody complexes formed, and therefore to antigen concentration.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
Monday through Saturday
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
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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.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
83520
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 |
|---|---|---|
| NSESF | Neuron Specific Enolase, CSF | 44802-7 |
| 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.
|
|---|---|---|
| NSESF | Neuron Specific Enolase, CSF | 44802-7 |