Test Catalog

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

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 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.

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 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 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

Do not interpret neuron-specific enolase (NSE) levels in spinal fluid as absolute evidence for the presence or absence of malignant disease. Results must be used in conjunction with information from the clinical evaluation of the patient and other diagnostic procedures.


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-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.


NSE 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, as well as by false-high results in the presence of heterophile antibodies.

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;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