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Test ID: NSESF Neuron-Specific Enolase (NSE), Spinal Fluid

Reporting Name

Neuron Specific Enolase, CSF

Useful For

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

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 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, in particular when caused by hypoxic insult.

Interpretation

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.

Analytic Time

1 day

Day(s) and Time(s) Performed

Monday through Friday; 8 a.m.-2 p.m.

Saturday; 8 a.m.-1 p.m.

Clinical Reference

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

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, et al: The prognostic value of serum neuron-specific enolase in traumatic brain injury: systematic review andmeta-analysis. PLoS One. 2014 Sep 4;9(9): e106680

Method Name

Homogeneous Time-Resolved Fluorescence

Specimen Type

CSF


Specimen Required


Container/Tube: Sterile vial

Specimen Volume: 0.5 mL


Specimen Minimum Volume

0.3 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
CSF Refrigerated (preferred) 15 days
  Ambient  72 hours

Reference Values

Normal: ≤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 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.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

83520

LOINC Code Information

Test ID Test Order Name Order LOINC Value
NSESF Neuron Specific Enolase, CSF 44802-7

 

Result ID Test Result Name Result LOINC Value
NSESF Neuron Specific Enolase, CSF 44802-7

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Behavioral, mml-Pediatric