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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
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.
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.
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.
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.
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