CSF Leak - Beta-2 Transferrin

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Presence of otorrhea or rhinorrhea
  • Patient with recurrent episodes of meningitis

Laboratory Testing

  • Chemical analysis (eg, Glucostix) of the fluid for glucose and protein – unreliable in determining the presence of CSF fluid
  • Presence of beta-2 transferrin indicates CSF leakage (high specificity) – 0.5 cc fluid required to perform test
    • If positive, perform high resolution CT (HRCT) to identify area of leak
    • If negative but strong suspicion, perform HRCT, followed by MRI cisternogram
    • False positives suggest chronic liver disease or inborn errors of glycoprotein metabolism

Imaging Studies

  • HRCT – initial study of choice
  • MRI or MRI  cisternogram – cisternogram is the procedure of choice
  • Cisternogram by CT
  • Radiographic studies, with or without intrathecal injection of dye or radioisotope – not always successful in demonstrating small or delayed CSF leaks

The leakage of cerebrospinal fluid (CSF) into nasal, oral, or ear cavities, or leakage from a dermal sinus and its subsequent drainage from these cavities, may be the result of trauma, intracranial surgical procedures, infection, hydrocephalus, congenital malformations, or neoplasms. The most severe consequence of a CSF leak is microorganism contamination and the development of meningitis.


  • Prevalence – 70-80% are related to accidental trauma
    • 2-4% of head injuries result in CSF leaks
  • Age – middle age for spontaneous leaks; newborn for dermal sinus leakage
  • Sex – M<F for spontaneous leaks


  • Trauma
  • Nontraumatic
    • Surgery – usually spinal or neurosurgery
      • Postoperative defect
    • Infection
    • Tumor obstruction
    • Congenital defects at the base of the skull or at the end of the spinal cord
    • Hydrocephalus
    • Spontaneous – no known defect or trauma


  • Beta-2 transferrin, a protein produced by neuraminidase activity in the brain – uniquely found in CSF and perilymph fluid
  • Interruption of the anterior cranial fossa floor allows leaks of CSF through the cribriform plate
  • 80% of posttraumatic leaks occur ≤48 hours posttrauma
  • Presence of beta-2 transferrin in nasal or ear fluid highly suggestive of CSF leak

Clinical Presentation

  • CSF leakage most commonly presents as otorrhea or rhinorrhea
  • Patient may complain of salty or sweet taste
  • Intermittent clear nasal discharge exacerbated by Valsalva maneuver
    • Most often unilateral drainage
  • Presence of halo sign on used tissues or bed linen

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Beta-2 Transferrin 0050047
Method: Qualitative Immunofixation Electrophoresis


Only use on CSF specimen; low sensitivity

General References

Abuabara A. Cerebrospinal fluid rhinorrhoea: diagnosis and management. Med Oral Patol Oral Cir Bucal. 2007; 12(5): E397-400. PubMed

Bullock R, Soares D. Current imaging of cerebrospinal fluid leaks. West Indian Med J. 2009; 58(4): 362-6. PubMed

Görögh T, Rudolph P, Meyer J, Werner J, Lippert B, Maune S. Separation of beta2-transferrin by denaturing gel electrophoresis to detect cerebrospinal fluid in ear and nasal fluids. Clin Chem. 2005; 51(9): 1704-10. PubMed

Kerr J, Chu F, Bayles S. Cerebrospinal fluid rhinorrhea: diagnosis and management. Otolaryngol Clin North Am. 2005; 38(4): 597-611. PubMed

Lloyd K, DelGaudio J, Hudgins P. Imaging of skull base cerebrospinal fluid leaks in adults. Radiology. 2008; 248(3): 725-36. PubMed

Wise S, Schlosser R. Evaluation of spontaneous nasal cerebrospinal fluid leaks. Curr Opin Otolaryngol Head Neck Surg. 2007; 15(1): 28-34. PubMed

Medical Reviewers

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Last Update: December 2015