CSF Leak - Beta-2 Transferrin


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

Clinical Background

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
Test Name and Number Recommended Use Limitations Follow Up
Beta-2 Transferrin 0050047
Method: Qualitative Immunofixation Electrophoresis
Detect presence of CSF leak

Only use on CSF specimen; low sensitivity