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Neuron – specific enolase (NSE)

SI UNITS (recommended)

CONVENTIONAL UNITS

Synonyms

  • NSE
  • γ-enolase
  • Neuron-specific γ-enolase
  • Neural enolase
  • Neuroendocrine enolase
  • Enolase 2 (ENO2)

Units of Measurement

  • ng/mL
  • ng/dL
  • ng/100 mL
  • ng%
  • ng/L
  • µg/L

Molecular Weight

78–82 kDa (dimeric enzyme)

Unit Conversions

Direct Mass Units

1 ng/mL=100 ng/dL1\ \text{ng/mL} = 100\ \text{ng/dL}1 ng/mL=100 ng/dL 1 ng/mL=1 µg/L1\ \text{ng/mL} = 1\ \text{µg/L}1 ng/mL=1 µg/L 1 ng/L=0.001 ng/mL1\ \text{ng/L} = 0.001\ \text{ng/mL}1 ng/L=0.001 ng/mL

ng% / ng/100mL

\text{ng%} = \text{ng/dL} = \frac{\text{ng/mL}}{100}

Description

Neuron-Specific Enolase (NSE) is the neuron- and neuroendocrine-restricted isoenzyme of the glycolytic enzyme enolase. It is present in:

  • Neurons
  • Neuroendocrine cells
  • Neuroblastoma cells
  • Small-cell lung carcinoma (SCLC) cells
  • Chromaffin cells

NSE is released into blood when:

  • Neuroendocrine tumors proliferate
  • Neuronal injury occurs
  • Cell lysis happens (hemolysis, sample handling errors)

NSE is used as:

  • Tumor marker
  • Neurological injury marker
  • Prognostic indicator after cardiac arrest

Physiological Role

Although an enzyme in glycolysis, NSE in clinical medicine is a biomarker for damaged or proliferating neural/neuroendocrine tissue.

Clinical Significance

HIGH NSE

1. Small-Cell Lung Carcinoma (SCLC)

Most important indication.

  • 60–80% of SCLC patients show elevated NSE
  • Useful for:
    • Diagnosis
    • Staging
    • Monitoring chemotherapy response
    • Detecting relapse

2. Neuroblastoma

Used in:

  • Diagnosis
  • Tumor burden assessment
  • Monitoring treatment

3. Other Neuroendocrine Tumors

  • Pheochromocytoma
  • Medullary thyroid carcinoma
  • Pancreatic neuroendocrine tumors
  • Carcinoid tumors

4. Neuronal Injury

Raised in:

  • Traumatic brain injury (TBI)
  • Hypoxic brain injury
  • Stroke
  • Cardiac arrest (prognostication)
  • Seizures
  • CNS infections

5. Hemolysis

Red blood cells contain NSE.
Even slight hemolysis causes false elevation
(NSE is extremely hemolysis-sensitive)

LOW NSE

Not clinically significant.
Used mainly to confirm:

  • Successful tumor response
  • Absence of neuronal injury

Reference Intervals

Adults

  • < 12.5 ng/mL

Children

  • Similar to adults
  • Neuroblastoma patients often show markedly elevated levels

Interpretation Thresholds

  • < 12.5 ng/mL → Normal
  • 12.5–20 ng/mL → Slight elevation (repeat & rule-out hemolysis)
  • > 20 ng/mL → Suggestive of neuroendocrine tumor
  • > 100 ng/mL → Strongly indicative of aggressive disease
  • > 200 ng/mL → High tumor burden or extensive metastatic disease

Diagnostic Uses

1. Small-Cell Lung Carcinoma (SCLC)

  • Diagnose
  • Monitor chemotherapy response
  • Detect relapse (rising NSE precedes imaging changes)
  • Prognostic marker

2. Neuroblastoma

  • Baseline marker
  • Treatment monitoring
  • Prognosis assessment

3. Cardiac Arrest Prognostication

In post–cardiac arrest patients cooled with TTM:

  • High NSE at 24–72 hours = poor neurological outcome

4. Traumatic Brain Injury & Stroke

Reflects acute neuronal cell damage.

5. Pheochromocytoma & Neuroendocrine Tumors

Additional marker along with chromogranin A, metanephrines.

Analytical Notes

  • Most hemolysis-sensitive tumor marker
    → Even minimal hemolysis invalidates results
  • Preferred sample: serum
  • Refrigerate if not processed immediately
  • Half-life: 24 hours
  • Not specific alone; interpret with clinical and imaging findings
  • Useful in serial measurements (trend > single value)

Clinical Pearls

  • In SCLC, falling NSE after chemotherapy indicates good response.
  • In cardiac arrest patients, NSE > 60–90 ng/mL at 48–72 hrs predicts poor neurologic recovery.
  • Always repeat NSE if sample shows hemolysis.
  • Neuroblastoma often produces extremely high NSE levels (hundreds to thousands).
  • NSE is not recommended as a stand-alone diagnostic test; must be correlated clinically.

Interesting Fact

NSE was first discovered in neurons, but is now known to be highly expressed in neuroendocrine tumors, making it one of the earliest and most important neuro-oncology biomarkers.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Tumor Markers
  2. NCCN Guidelines - Small Cell Lung Cancer
  3. Mayo Clinic Laboratories - NSE
  4. ARUP Consult - Neuroendocrine Tumor Markers
  5. AHA/Neurology Guidelines - Post–Cardiac Arrest Prognostication
  6. MedlinePlus / NIH — NSE Test

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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