Cerebrospinal Fluid (CSF) Leak

Cerebrospinal fluid (CSF) leaks, also referred to as CSF fistulas, result from dura mater defects that allow CSF to escape from the intracranial space and into outer areas such as nasal and auricular cavities.  The majority of CSF leaks result from traumatic injury, such as facial or skull fractures, but CSF leaks can also occur due to infection, hydrocephalus, congenital malformations, or neoplasms.  They can be a complication of surgical procedures, especially those involving the ear, sinuses, or skull base, or can be spontaneous.  The most severe consequences of a CSF leak are brain abscess or bacterial meningitis due to the passage of bacteria from nasal and paranasal areas into the intracranial space. Early diagnosis and intervention are critical to prevent these outcomes.   Diagnosis can be challenging in outpatient and postsurgical contexts, in part because a CSF leak can be difficult to distinguish from chronic rhinitis. Beta (β)-2-transferrin testing is the preferred laboratory approach to assess patients for CSF leaks and can be especially helpful in these settings.   Neuroimaging is used to confirm the diagnosis and to ascertain the location of the leakage.  

Quick Answers for Clinicians

How do cerebrospinal fluid leaks present clinically?

Presenting signs of a cerebrospinal fluid (CSF) leak include persistent headaches; discharge of clear, watery, and sometimes bloody fluid from the ear and nose, which is affected by bodily position; and postnasal drip with a salty taste.  Other possible signs include a sensation of ear fullness and difficulty hearing, and the presence of a “halo” or “double ring” sign on bedsheets or on tissue used to collect fluid draining from the nose or ear.  However, the double ring sign is not specific for a CSF leak; this sign can appear when blood is mixed with fluids other than CSF. 

Should glucose oxidase testing be used for the diagnosis of cerebrospinal fluid leaks?

Traditional assessment for cerebrospinal fluid (CSF) leaks involved testing nasal discharge with glucose oxidase strips (Glucostix). However, this testing is no longer recommended due to its inadequate sensitivity and specificity for CSF leak diagnosis.   Bacterial contamination can cause false-negative results, and patients with diabetes may have false-positive results.  Glucose testing is also discouraged to confirm diagnosis. 

What is the connection between cerebrospinal fluid leaks and connective tissue disorders?

Spontaneous cerebrospinal fluid (CSF) leaks have been reported in association with heritable connective tissue disorders such as Marfan syndrome and Ehlers-Danlos syndrome, and can be the first presenting sign of the disease. CSF leaks may occur because of the fragility of connective tissue in these disorders.  Some investigators suggest that all patients with spontaneous CSF leaks be evaluated for connective tissue and vascular anomalies. 

Indications for Testing

Testing for a CSF leak is appropriate in patients with otorrhea or rhinorrhea, particularly following trauma or surgery. 

Laboratory Testing


Biochemical Markers

Beta-2 Transferrin

β-2 transferrin is a protein found in CSF, but not in nasal secretions or adjacent tissue.  Testing fluid from the ear or nose for β-2 transferrin is the recommended method to assess patients for a CSF leak because this approach is noninvasive as well as highly sensitive and specific.    Immunofixation electrophoresis (IFE) is the method typically used.  However, because β-2 transferrin is also a component of the vitreous humor, patients with eye ruptures can test positive for β-2 transferrin in the absence of a CSF leak.  Rare allelic variants of transferrin may also cause false-positive results in the detection of CSF leakage.  Patients with prolonged alcohol consumption can show increased concentrations of a carbohydrate-deficient transferrin isoform.  Simultaneous analysis of serum and CSF from the same individual is suggested to rule out these rare false-positive results. 

In patients with negative β-2 transferrin results but high clinical suspicion for a CSF leak, imaging is recommended. See Other Tests.

Other Tests

Imaging is used to detect the location of the leak to guide intervention.  Recommended imaging techniques include high-resolution computed tomography (HRCT), magnetic resonance cisternography, or magnetic resonance imaging (MRI) with intrathecal contrast.  

Although radionucleotide cisternography may be helpful to assess patients with possible intermittent or low volume CSF leaks, it is not recommended as a routine approach to diagnose or confirm CSF leaks because of its higher cost, lower accuracy, and invasive nature compared with β-2 transferrin testing. 

ARUP Laboratory Tests

Aid in diagnosis of CSF leak

Medical Experts



Julio Delgado, MD, MS
Executive Vice President, ARUP Laboratories
Division Chief of Clinical Pathology, University of Utah and ARUP Laboratories
Professor of Clinical Pathology, University of Utah
Medical Director, Protein Immunology and Immunologic Flow Laboratories, ARUP Laboratories


Additional Resources