CSF Rhinorrhea Workup

Updated: May 08, 2020
  • Author: Kevin C Welch, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
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Laboratory Studies

Glucose content

A rapid but highly unreliable test is glucose-content determination with the use of glucose oxidase paper. This method of detecting cerebrospinal fluid (CSF) rhinorrhea is not recommended as a screening or confirmatory laboratory test to detect the presence of CSF in the nasal cavity for the following reasons:

  • Reducing substances present in the lacrimal-gland secretions and nasal mucus may cause false-positive results.

  • Glucose, at a concentration of 5 mg/dL, can lead to a positive result with this test.

  • Active meningitis can lower the glucose level in the CSF and may lead to false-negative readings.

  • This test is not specific for the side or site of leak.

Beta-trace protein [12]

Also known as prostaglandin D synthase, this protein is synthesized primarily in arachnoid cells, oligodendrocytes, and the choroids plexus within the CNS. Beta-trace protein is also present in the human testes, heart, and serum. It is altered by the presence of renal failure, multiple sclerosis, cerebral infarction, and certain CNS tumors. This test has been used to diagnose CSF rhinorrhea in multiple studies, with a sensitivity of 92% and specificity of 100%. This test is not specific for side or site of leak and can be difficult to collect if the leak is intermittent.


Beta2-transferrin is produced by neuraminidase activity within the central nervous system. Therefore, beta2-transferrin is located only within the CSF, perilymph, and aqueous humor.

The assay has a high sensitivity and specificity, it is performed rapidly, and it is noninvasive. [13] A minimum of 0.5 mL of fluid is necessary for electrophoresis, but difficulties in collection of this fluid have been noted, especially in intermittent, low-volume leaks.

Beta2-transferrin is stable at room temperature for approximately 4 hours; therefore, immediate refrigeration following collection is recommended. Specimens should not be frozen.

This is currently single best laboratory test for identifying the presence of CSF in sinonasal fluid. It should be kept in mind, however, that this test does not provide information regarding the site or laterality of the defect. Not all centers are capable of testing fluid for beta2-transferrin; therefore, sending the laboratory specimen out for processing may delay diagnosis.


Imaging Studies

Computed tomography (CT) scanning

High-resolution CT scanning is the imaging modality of choice for identifying a skull base defect associated with CSF rhinorrhea. CT scans may demonstrate skull base defects resulting from accidental or iatrogenic trauma, an underlying anatomic or developmental abnormality, or an erosive lesion such as a neoplasm.

CT scans should be performed in the axial plane with 1 mm (or less) slice thickness and reformatted into coronal and sagittal planes. The evaluation of congenital defects or spontaneous defects may be aided by 3-dimensional reconstruction of the bone to permit in-depth analysis of the floor of the anterior or middle cranial fossa.

Pneumocephalus on a CT scan may indicate a dural tear. A deviated crista galli is a radiologic sign in patients presenting with primary CSF rhinorrhea; this finding supports a congenital bony dehiscence as the etiologic basis for this condition. In some circumstances, an air-fluid level is present in one or more of the sinuses. This is not diagnostic of CSF and may be the result of acute or chronic inflammation.

High-resolution CT imaging may reveal defects in the skull base that do not leak or are not sites of active leaking, making the diagnosis more difficult.

CT cisternography [14]

CT cisternography improves the diagnostic yield of plain CT by injecting intrathecal contrast to better localize the site of the CSF leak. As opposed to conventional CT imaging, only one study is typically necessary. CT cisternography depicts the precise location of CSF rhinorrhea in most patients with active leaks. Patients with intermittent CSF rhinorrhea may have false-negative CT cisternograms. Another disadvantage of this technique is that it may miss cribriform or ethmoid sinus defects.

This is an invasive procedure and is not very frequently used. Despite its low morbidity, it can be associated with nausea, headaches, and acute organic psychosyndromes.

Magnetic resonance imaging (MRI)

MRI typically is not recommended as a first-line imaging modality in the evaluation of CSF rhinorrhea unless an encephalocele is demonstrated on examination or is suspected. Unlike CT imaging, MRI does not delineate well bony defects within the anterior or middle cranial fossa. In addition, MRI is more costly and more time consuming. In many instances, the injection of a contrast agent may be necessary. Similar to CT imaging, MRI may not be localizing.

MR cisternography [15]

Avoidance of intrathecal injection of contrast is a key benefit of MR cisternography. T2-weighted imaging can be used to detect the presence of CSF in the sinonasal cavity without the invasiveness of contrast injection. Pulse sequences performed during MRI can be designed so as to enhance the probability of detecting CSF within the sinonasal cavity. As with CT cisternography, false-negative studies may result when CSF rhinorrhea is intermittent.

Nuclear medicine studies

Radioactive isotopes can be introduced into the CSF by means of a lumbar or suboccipital puncture. Serial scanning or scintiphotography can then be used to determine the distribution of these agents.

A commonly used adjunct is the placement of nasal pledgets in various high-risk areas. These pledgets then can be analyzed for the presence of the tracer. Different tracers, including radioactive iodine-131, radioactive iodinated serum albumin (RISA), ytterbium-169, diethylenetriamine pentaacetic acid (DTPA), indium-111 DTPA, technetium-99m human serum albumin, and99m Tc pertechnetate can be used. Despite their relative safety, studies based on these tracers have several limitations, including the following:

  • Precise localization of the defect site is difficult

  • The isotope is absorbed into the circulatory system and can contaminate extracranial tissue.

  • Patient positioning can cause distal pledgets to incorrectly absorb the isotope.

  • False-positive results are present in as many as 33% patients.

  • Borderline readings are not reliable. A high reading of radioactivity is necessary to diagnose a true leak.

For further information, please see Cerebrospinal Fluid Leak Imaging in the Radiology section.


Diagnostic Procedures

The injection of intrathecal fluorescein has been used to diagnose and localize the site(s) of cerebrospinal fluid (CSF) rhinorrhea.

The injection of intrathecal fluorescein is commonly used to diagnose and localize the site(s) of CSF rhinorrhea. However, the US Food and Drug Administration has not approved the use of fluorescein for this purpose.

A lumbar puncture and/or placement of a subarachnoid lumbar drain is used to facilitate the injection. After puncture or drain placement, 10 mL of CSF is withdrawn in a sterile fashion. Precisely 0.1 mL of 10% nonophthalmic fluorescein solution is diluted in the 10 mL of CSF. The mixture is then reinjected into the subarachnoid space over a period of 10 minutes. The use of this dilution and the slow injection technique help minimize central potential complications (eg, seizures) that have been previously reported with intrathecal fluorescein.

In most instances, fluorescein is visible with standard xenon light sources used during endoscopic sinus surgery. However, minute amounts of fluorescein resulting from small bony defects may be difficulty to detect using a rigid endoscope.

Since the peak absorption of fluorescein occurs at 494 nm, a blue-light filter (440-490 nm wavelength) can help enhance visualization. This is particularly useful when fluorescein is filling an encephalocele or in cases of very small leaks that cannot be observed with standard xenon light sources. See the image below.

After intrathecal fluorescein is administered, an After intrathecal fluorescein is administered, an exposed frontal recess encephalocele is seen.