Cerebrospinal Fluid (CSF) Leak - Beta-2 Transferrin

A cerebrospinal fluid (CSF) leak occurs when CSF leaks into nasal, oral, or ear cavities, or when leakage from a dermal sinus drains from these cavities. CSF leaks may be the result of trauma, intracranial surgical procedures, infection, hydrocephalus, congenital malformations, or neoplasms. The most severe consequence of a CSF leak is the development of meningitis caused by microorganism contamination.

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Presence of otorrhea or rhinorrhea – particularly following trauma
  • Recurrent episodes of meningitis

Laboratory Testing

  • Chemical analysis (eg, Glucostix) of fluid for glucose and protein – unreliable in determining presence of cerebrospinal fluid (CSF)
  • Beta-2 transferrin (CSF)
    • 0.5 cc fluid required to perform test – may not have this volume in low volume or intermittent CSF leaks
    • Highly sensitive and specific for CSF leak
    • Results
      • If positive, perform high resolution CT (HRCT) to identify area of leak
      • If negative but strong suspicion, perform HRCT, followed by magnetic resonance imaging (MRI) cisternogram
      • False positive suggests chronic liver disease or inborn error of glycoprotein metabolism

Imaging Studies

  • HRCT – initial study of choice
  • MRI or MRI cisternogram – cisternogram is 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


  • 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


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


  • 80% of posttraumatic leaks occur ≤48 hours posttrauma – interruption of anterior cranial fossa floor allows leaks of CSF through cribriform plate
  • Beta-2 transferrin is produced by neuraminidase activity in the brain
    • Uniquely found in CSF and perilymph fluid
    • Presence of beta-2 transferrin in nasal or ear fluid highly sensitive and specific for 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
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

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 JE, Werner JA, Lippert BM, 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 JT, Chu FW, Bayles SW. Cerebrospinal fluid rhinorrhea: diagnosis and management. Otolaryngol Clin North Am. 2005; 38(4): 597-611. PubMed

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

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

Medical Reviewers

Last Update: October 2017