Test ID: NSESF
Neuron-Specific Enolase (NSE), Spinal Fluid
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
An auxillary test in the diagnosis of Creutzfeldt-Jakob disease
An auxillary 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
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Neuron Specific Enolase, CSF
NSE
Creutzfeld-Jakob disease
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: Sterile vial
Specimen Volume: 0.5 mL
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| CSF | Refrigerated (preferred) | 7 days |
| Ambient | 72 hours |
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 kD 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 which 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. There is, for example, increasing evidence that elevated serum NSE levels correlate with a poor outcome in coma, in particular 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 work-up. Possible causes may be NSE-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 are 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 artefactual elevations should be suspected if the clinical NSE test results are at odds with the clinical picture of other tests. The laboratory should be contacted for assistance in these situations.
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 renal failure can also result in artefactual NSE elevations.
Other false-positives 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 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.
NSE values can vary significantly between methods/assays. Serial follow-up should be performed with the same assay. If assays are changed, patients should be re-baselined.
This assay is an immunometric assay, and can therefore in rare situations be affected by false-low results in the presence of extremely high NSE concentrations ("hooking") or autoantibodies to NSE, as well as by false-high results in the presence of heterophile antibodies.
Clinical Reference Provides recommendations for further 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;65:1386-1390
2. Lamberts SW, Hofland LJ, Nobels FR: Neuroendocrine tumor markers. Front Neuroendocrinol 2001;22:309-339
3. Aksamit AJ, Preissner CM, Homburger HA: Quantitation of 14-3-3 and neuron-specific enolase proteins in CSF in Creutzfeldt-Jacob disease. Neurology 2001;57:728-730
4. Riley RD, Heney D, Jones DR, et al: A systematic review of molecular and biological tumor markers in neuroblastoma. Clin Cancer Res 2004;10:4-12
5. Portela-Gomes GM, Hacker GW, Weitgasser R: Neuroendocrine cell markers for pancreatic islets and tumors. Appl Immunohistochem Mol Morphol 2004;12:183-192
6. Wijdicks EF, Hijdra A, Young GB, et al: Practive parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review). Neurology 2006;67:203-210
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.
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Saturday; 2:30 p.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
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 The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
83520
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| NSESF | Neuron Specific Enolase, CSF | 44802-7 |
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