AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Defects in the floor of the anterior cranial fossa can lead to the leakage of CSF into the nasal cavity. Because of the microbiologic nature of the nasal cavity and its continuity with the rest of the upper aerodigestive tract, communication with the intracranial contents can lead to meningitis and other intracranial complications, including serious and sometimes lethal medical problems.

With increased performance of endoscopic procedures of the anterior skull base and given the nature of trauma to this area, the number of patients with CSF rhinorrhea has increased. This article discusses the various etiologies of CSF leaks, diagnostic tests and how they should be used, and, the management of the problem after it occurs.

Problem

The underlying defect responsible for CSF leaks, regardless of the etiology, is the same: disruption in the arachnoid and dura mater coupled with an osseus defect and a CSF pressure gradient that is continuously or intermittently greater than the tensile strength of the disrupted tissue.

Frequency

See Etiology.

Etiology

The classification of CSF leaks is based on the etiology; however, the anatomic site, the age of patient, and the underlying intracranial pressure all affect the clinical presentation. Trauma causes 90% of all cases of CSF rhinorrhea; the incidence in closed head injury is 1-3%. Trauma, both surgical and other, can lead to transient or permanent CSF leaks.

The onset of nonsurgical traumatic rhinorrhea is variable. It can be classified as immediate (within 48 h) or delayed. Of patients with delayed CSF leaks, 95% present within 3 months after the insult. Most patients with CSF leaks secondary to nonsurgical trauma (eg, motor vehicle accidents) present immediately. In contrast, only 50% of patients with iatrogenic CSF leaks present within the first week.

Surgical trauma represents a distinct type of trauma in regards to CSF leaks. Differences associated with surgical trauma include the size of the bony defect, the extent of dural damage, and the associated damage to the brain parenchyma. Iatrogenic defects can cause defects ranging from several millimeters to centimeters, extensive dural tears, and clinically significant parenchymal disruption. Of note, revision endoscopic sinus surgery increases the risk of iatrogenic CSF leak for a variety of reasons, and transsphenoidal hypophysectomy is the most common etiology of a CSF leak from a neurosurgical procedure.

Nontraumatic CSF rhinorrhea occurs relatively infrequently. In approximately one half of all nontraumatic CSF leaks, increased CSF pressure occurs because of a tumor or hydrocephalus. This entity is termed secondary nontraumatic CSF rhinorrhea. Cases of CSF leak with normal CSF pressure are termed primary nontraumatic CSF leaks. This is a poorly understood entity and extremely rare. Some postulate that congenital defects in the floor of the anterior cranial fossa are the cause.

Pathophysiology

In cases of an immediate leak, a dural tear and a bony defect or fracture has occurred. Possible causes of a delayed traumatic leak are a previously intact dural layer that has slowly become herniated through a bony defect, finally tearing the dura and causing the leak. According to another theory, the tear and bony defect are present from the time of the original injury, but the leak occurs only after the masking hematoma dissolves.

Spontaneous CSF rhinorrhea usually manifests in adulthood, coinciding with a developmental rise in CSF pressures with maturity. The dura of the anterior cranial base is subject to wide variations in CSF pressure because of several factors, including normal arterial and respiratory fluctuations. Other stresses on the dura include Valsalva-like actions during nose blowing. This stress can lead to dural injury in areas of abnormalities of the bony floor.

Increased intracranial pressure is not necessary for nontraumatic CSF leaks to occur. Theories for primary nontraumatic CSF leaks include focal atrophy, rupture of arachnoid projections that accompany the fibers of the olfactory nerve, and persistence of an embryonic olfactory lumen.

Clinical

History

A thorough history is the first step toward accurate diagnosis. The typical history of a CSF leak is that of clear, watery discharge, usually unilateral. Diagnosis is made more easily in patients with recent trauma or surgery than in others. Delayed fistulas are difficult to diagnose and can occur years after the trauma or operation. These cases often lead to a misdiagnosis of allergic and vasomotor rhinitis. On occasion, the patient has a history of headache relieved by drainage of CSF. Drainage may be intermittent as the fluid accumulates in 1 of the paranasal sinuses and drains externally with changes in head position (ie, reservoir sign).

A history of headache and visual disturbances suggests increased intracranial pressure. Sometimes, associated symptoms can assist in localizing the leak. For example, anosmia (present in 60% of individuals with posttraumatic rhinorrhea), indicates an injury in the olfactory area and anterior fossa, especially when it is unilateral. Interference with function of the optic nerve suggests a lesion in the region of tuberculum sellae, sphenoid sinus, or posterior ethmoid cells. Patients with recurrent meningitis, especially pneumococcal meningitis, should be evaluated for a defect that exposes the intracranial space to the upper airway regardless of the presence or absence of CSF rhinorrhea.

Physical

Physical examination should include complete rhinologic (including endoscopic), otologic, head and neck, and neurologic evaluations. Endoscopy may reveal pathology, such as an encephalocele or meningocele. Drainage of CSF can often be elicited on endoscopy by having the patient perform a Valsalva maneuver or by compressing both jugular veins (Queckenstedt-Stookey test). A change in head position can elicit a reservoir sign.

In patients with head trauma, a mixture of blood and CSF may make the diagnosis difficult. CSF separates from blood when it is placed on filter paper, and it produces a clinically detectable sign: ring sign, double-ring sign, or halo sign. However, the presence of a ring sign is not exclusive to CSF and can lead to false-positive results. In contrast to unilateral rhinorrhea, bilateral rhinorrhea gives no clue of the laterality of the defect. However, even in this situation, exceptions can occur. Paradoxical rhinorrhea occurs when midline structures that act as separating barriers (eg, crista galli, vomer) are dislocated. This dislocation allows CSF to flow to the opposite side and manifest at the contralateral naris. The clinical findings most frequently associated with CSF rhinorrhea are meningitis (30%) and pneumocephalus (30%).

INDICATIONS

Section 3 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Surgical repair is recommended in patients with large high-volume fistulas, nontraumatic leaks, prolonged leaks regardless of etiology, and recurrent leaks. Immediate surgical exploration and closure of dural fistulas are indicated in patients with open wounds that are connected to the dural defect. Other situations that warrant immediate repair are closed head injuries with intracranial complications and fistulas caused by and detected at operation, either intracranial or nasal. Surgical intervention is also warranted for a CSF leak associated with intracranial complications, such as meningitis. Regardless of which surgical technique is used, conservative management methods are used for the initial postoperative period.

RELEVANT ANATOMY

Section 4 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

The most common anatomic sites of CSF leaks are the areas of congenital weakness of the anterior cranial fossa and areas related to the type of surgery performed. According to data from 53 patients with different causes of CSF rhinorrhea, 39% of leaks occurred in the region of the cribriform plate and air cells of the ethmoid sinus; in 15% of leaks, the fistula extended to the frontal sinus; and in another 15%, the leak was in the area of the sella turcica and sphenoid sinus. Common sites of injury secondary to endoscopic sinus surgery include the lateral lamella of the cribriform plate and the posterior ethmoid roof near the anterior and medial sphenoid wall. In the rare situation, the leak can originate in the middle or posterior cranial fossa and can reach the nasal cavity by way of the middle ear and eustachian tube.

CONTRAINDICATIONS

Section 5 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

The management of CSF rhinorrhea depends on the cause, location, and severity of the leak. When trauma is the cause, the interval between trauma and leak is important. The natural history of CSF leak depends on the etiology. Traumatic leaks often stop spontaneously. The leakage stops within 1 week in 70% of patients, within 3 months in 20-30%, and within 6 months in most patients; leakage rarely recurs. The opposite is true for nontraumatic leaks; only one third stop spontaneously, and they tend to persist for several years, with intermittent leakage.

WORKUP

Section 6 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Lab Studies

• A rapid but highly unreliable test is glucose-content determination with the use of glucose oxidase paper.
• • 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.
  • Despite these drawbacks, glucose testing can be used as a first-line diagnostic test in a patient with a history of craniofacial injury. However, all positive results should be confirmed with the beta2-transferrin test, which is more reliable than the glucose test.
• Immunoelectrophoretic identification of CSF-specific marker proteins is the current standard for identifying CSF.
• • At present, the beta2-transferrin assay is the most widely used test and is considered the criterion standard for diagnosis of CSF rhinorrhea.
  • Beta2-transferrin is a protein that is highly specific for human CSF. It may also be found in the serum of newborns, in vitreous humor, and in patients with liver disease.
  • The assay has a high sensitivity and specificity, it is performed rapidly, and it is noninvasive.
  • 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.
• Total protein analysis, a test of specific gravity, and salt-content tests are no longer performed because other tests provide better results.

Imaging Studies

• Plain radiography
• • Plain radiographs can demonstrate a fracture of the skull, an air-fluid level in the sinus, or an aerocele in the cranial vault.
  • Air in the subarachnoid space on a plain radiograph is an almost pathognomonic sign of dural injury. It is usually the result of a large tear in the dural envelope.
  • In the absence of a history of trauma, plain radiographs are of little value.
• CT scanning
• • CT scans can reveal the fracture site that underlies a traumatic leak, reveal an underlying anatomic or developmental abnormality in the case of nontraumatic leak, and provide information on the brain parenchyma in the vicinity of the leak. At present, it is the criterion standard in the evaluation of craniofacial trauma.
  • Especially helpful are thin-section (1-mm) coronal CT scan. These thin sections can depict small defects of the cranial base that are not visible on standard CT scans or reconstructed images.
  • In some circumstances, an air-fluid level is present in the sphenoid sinus. This could mean that the leak is in the sphenoid sinus; however, a leak in the area of the posterior cribriform plate or posterior fovea ethmoidalis can drain into the sphenoid sinus by way of its ostium.
  • Pneumocephalus on a scan suggests a large dural tear.
  • 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.
  • A modified technique known as digital subtraction cisternography may be useful if CT cisternography does not reveal the leakage site.
• Omnipaque CT cisternography or metrizamide CT cisternography
• • The diagnostic yield of CT scan is improved by injecting metrizamide, a water-soluble nonionic tri-iodinated contrast agent. Another option involves the use of iohexol (Omnipaque). These agents are injected intrathecally.
  • Omnipaque CT cisternography or metrizamide CT cisternography (MCTC) depicts the precise location of CSF leakage in most patients with active leaks. Intermittent or slow leaks may not be identifiable.
  • This procedure has a low morbidity rate, it is most useful in the presence of severe leakage, and it provides high contrast with the air in the paranasal sinus. Although the morbidity is low, nausea, headaches, and acute organic psychosyndromes have been reported. Severe toxicities have been reported in patients undergoing myelography, which requires a dose of contrast agent higher than that used for routine MCTC.
  • Some controversy exists regarding the usefulness of MCTC in accurately delineating the site of leak. One study demonstrated positive localization by means of MCTC in 76% of cases examined; 87% of active fistulas were identified. However, none of the inactive fistulas were identified.
• • In patients with intermittent or slow leaks who are poor candidates for MCTC, a repeat study can be performed after the intracranial pressure (ICP) is increased by intrathecally infusing isotonic sodium chloride solution just before imaging to activate the leak. Some have reported a good result by using the Valsalva maneuver or coughing to increase ICP.
• Pneumoencephalography
• • This is an obsolete procedure that is also uncomfortable because patients are required to be in a head-hanging position.
  • This study provides poor contrast with the paranasal sinuses and nasal airway.
• Magnetic resonance imaging
• • MRI typically is not recommended in the evaluation of a CSF leak because it does not demonstrate bony defects very well. However, a heavy T2-weighted image can reveal a brisk CSF leak.
  • This modality also can be useful when trying to determine the extent of an encephalocele.
• Nuclear medicine studies
• • Radioactive isotopes can be introduced into the CSF by means of lumbar or suboccipital puncture. The distribution of these agents then can be determined by using serial scanning or scintiphotography. Another option is to introduce 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, and ^99mTc pertechnetate, can be used. Despite their relative safety, studies based on these tracers have several limitations: (1) They do not help in precisely identifying the location of the leak. (2) The isotope is absorbed into the circulatory system and can contaminate extracranial tissue. (3) Patient positioning can cause distal pledgets to incorrectly take up the isotope. (4) Readings of radioactivity should be high to determine a true leak; borderline readings are not reliable. False-positive results are present in as many as 33% patients.
• Overpressure radionuclide cisternography
• • An undetected fistula can be elicited by increasing ICP.
  • One group compared overpressure radionuclide cisternography (ORNC) with MCTC. ORNC was more sensitive than MCTC at confirming the diagnosis of a leak, but MCTC was more helpful for localizing the site of the leak.

Diagnostic Procedures

• The intrathecal injection of nonradiographic dyes and their recovery on cottonoids inserted inside the nasal cavity are of historic interest. Use of indigo carmine, methylene blue, and Evans blue dye has been abandoned because of neurologic toxicity (Paraplegia has been reported.) and poor localization of the leak.
• Fluorescein (0.1-0.2 mL of 5% solution mixed with 5-10 mL of CSF) injected intrathecally is the most accurate method of localizing the site of the leak. This method can be used preoperatively and intraoperatively to localize and repair the causative defect. Transient neurologic complications have been reported with this technique, and the US Food and Drug Administration (FDA) has not approved the intrathecal administration of fluorescein.
• Nasal endoscopy performed 20-30 minutes after an intrathecal injection of fluorescein is optimal in finding a leak. The observer should look for fluorescent CSF that is visible with the light of the endoscope. No additional ultraviolet light is necessary, but a blue-light filter on the endoscope can enhance visualization.
• Routine otologic examination can reveal fluorescence medial to the tympanic membrane, as can examination of the oral cavity and posterior pharyngeal wall. One also can place pledgets in the nasal cavity and look for absorption of the contrast agent. Precise location of the stained pledget can point to the leak. This technique is typically useful in situations in which MCTC is not helpful and surgery is being considered.

TREATMENT

Section 7 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Medical therapy

Conservative management consists of a 1- to 2-week trial of bed rest with the patient in a head-up position. Coughing, sneezing, nose blowing, and heavy lifting should be avoided as much as possible. Stool softeners or laxatives can be used to decrease the strain and increased ICP associated with bowel movements. A lumbar drain or repeated lumbar puncture can be used to decrease ICP even further; a rough guideline is the removal of 150 mL of CSF per day. A theoretical possibility of increased risk of meningitis with this treatment exists, probably because the decreased outflow of CSF may allow bacteria to enter the basal cisterns. Lumbar puncture should not be performed in patients with cerebral edema or increased ICP.

Acetazolamide is a diuretic that has also been used as an adjunct therapy for CSF leaks. This diuretic decreases CSF production by as much as 48%. When increased ICP is problematic and contributes to the CSF leak, acetazolamide can play an adjunctive role.

The issue of prophylactic antibiotics is controversial. To the authors' knowledge, no prospective controlled study has been conducted to resolve this question. The overall impression is that the routine use of prophylactic antibiotics is not indicated and that this practice may select out resistant organisms. However, in some high-risk groups, antibiotic therapy may be justifiable. Patients with previous sinus operations or preexisting sinusitis are in one such group. Use of steroids and diuretics can be considered, but they probably have a relatively small effect on the overall outcome. An obvious disadvantage with the conservative approach is the risk of meningitis and brain abscess.

Surgical therapy

Surgical options for repair of CSF leaks arising from the anterior skull base can be divided into intracranial and extracranial approaches.

Intracranial repair

Until recently, intracranial repair has been the standard method of repair. Leaks arising from an anterior defect can be approached from a frontal anterior fossa craniotomy. In rare situations, a middle fossa craniotomy or posterior fossa craniotomy is required for leaks arising in those areas. Different repair techniques have been used, including the use of free or pedicled periosteal or dural flaps, muscle plugs, mobilized portions of the falx cerebri, fascia grafts, and flaps in conjunction with fibrin glue. Leaks arising from the sphenoid sinus are difficult to reach by means of an intracranial approach.

Advantages of the intracranial approach include the ability to inspect the adjacent cerebral cortex, direct visualization of the dural defect, and better ability to seal a leak in the presence of increased ICP. When preoperative localization attempts fail to reveal the site of a leak, intracranial approach with blind repair has been successful. In these situations, the cribriform and the sphenoid area, if necessary, are covered with the repair material.

Disadvantages of the intracranial approach include increased morbidity, increased risk of permanent anosmia, trauma related to brain retraction (hematoma, cognitive dysfunction, seizures, edema, hemorrhage), and prolonged hospital stays. Failure rates for this approach are 40% for the first attempt and 10% overall.

Extracranial repair

Extracranial repair can be divided into external approaches and endoscopic techniques.

External approach

External approaches include the use of an anterior osteoplastic flap through a bicoronal or eyebrow incision, external ethmoidectomy, transethmoidal sphenoidotomy, transseptal sphenoidotomy, and the transantral approach. Choices of graft material include the fascia lata, temporalis fascia, septal or turbinate mucosa, muscle, fat, and septal cartilage. All of these materials can be placed by using the endoscopic technique as well. These external approaches are alternatives to the less invasive, and probably equally effective, endoscopic techniques. For cribriform or fovea ethmoidalis leaks, a transnasal ethmoidectomy is performed, and for sphenoidal leaks, sphenoidotomy is performed as well; graft material is placed over the fistula. If possible, the graft is placed superior to the bony skull base inferior to the dural defect.

Success rates for the extracranial or external approach are 86-100%. Disadvantages include the inability to treat concomitant intracranial abnormality, difficulty with frontal and sphenoid repair with prominent lateral extensions, and the relative ineffectiveness of repairing high-pressure leaks from below. Despite these disadvantages, primary surgical repair of CSF rhinorrhea is usually extracranial unless exploring intracranially is necessary to repair other damage.

Endoscopic techniques

Compared with external techniques, endoscopic techniques have several advantages, including better field of vision with enhanced illumination and magnified-angle visualization. Other advantages include the ability to clean the mucosa off the adjacent bone without increasing the size of the defect and accurate positioning of the graft. McMains et al reported a highly successful case series of 92 patients with long-term follow-up, solidifying the role of endoscopic control of CSF rhinorrhea. To the authors' knowledge, no prospective comparative analysis of extracranial and intracranial techniques has been performed. Despite this lack, the advantages are apparent: improved visualization, lowered morbidity, and no anosmia. An overall success rate of 90-95% has been reported with endoscopic repair of CSF leaks.

Adjunctive therapy

Adjuncts to extracranial endoscopic repair include a variety of therapies. Coupling repair with postoperative conservative care, such as bed rest, lumbar-drain placement, and/or acetazolamide therapy, can increase success rates for CSF leak repair. The intraoperative techniques of free mucosal transfer, either from the middle turbinate or from the anterior sphenoid wall, can additionally support the classically described overlay or underlay repair techniques. To the authors' knowledge, no randomized control studies have demonstrated that use of any particular tissue adhesive and/or fibrin sealant increases success rates. In terms of postrepair packing, many packing materials have been used, with no clear benefit from any particular product.

COMPLICATIONS

Section 8 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

Knowing the natural course of this condition is important before one examines the results of the various interventions. Meningitis is the most frequent and severe complication of a CSF leak; Streptococcus pneumoniae and Haemophilus influenzae are the most common pathogens. The risk of meningitis during the first 3 weeks after trauma is estimated to be 10%. The rate is 40% in nontraumatic rhinorrhea.

Meningitis caused by a persistent CSF leak is associated with a high mortality rate. Because of the relatively low rate of spontaneous closure, a conservative approach for these indications is not recommended. Spontaneous closure rates vary with the etiology; the recurrence rate after spontaneous closure was 7% in 1 study. The surgical mortality rate is 1-3% for intracranial procedures and is negligible for external procedures. The morbidity for intracranial approaches is clinically significant, with anosmia being the most common complication (10-25% of patients).

OUTCOME AND PROGNOSIS

Section 9 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

See individual surgical techniques in Surgical therapy.

FUTURE AND CONTROVERSIES

Section 10 of 11  

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

CSF rhinorrhea can occur as a result of craniofacial injury, iatrogenic surgical trauma, or spontaneous causes. Several diagnostic tools are available to aid in diagnosis. In the case of early-onset traumatic fistula, a conservative approach can be used. Other causes require a more aggressive intervention. Endoscopic and external techniques have replaced invasive craniotomy. Because of these techniques, the otolaryngologist plays a key role in diagnosing and managing this problem.

With the growing popularity of computer-assisted, image-guided surgical techniques, the ability to precisely locate areas of CSF leakage is enhanced. This advance may improve the accuracy and precision of closing the defects, with a resulting increase in success rates. In addition, the use of synthetic graft material to repair these defects is another option that has recently become available.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Indications
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Future And Controversies
• References

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Article Last Updated: Sep 8, 2006