CSF Rhinorrhea

Cerebrospinal fluid (CSF) rhinorrhea is a rare but potentially devastating condition that can lead to significant morbidity and mortality for the patient. Disruption of the barriers between the sinonasal cavity and the anterior and middle cranial fossae is the underlying factor leading to the discharge of CSF into the nasal cavity. The resulting communication with the central nervous system (CNS) can result in a multitude of infectious complications that impart significant morbidity and potentially disastrous long-term deficits for the patient. While some forms of CSF rhinorrhea resolve with conservative therapy, many patients require surgical treatment to prevent intracranial complications. High-resolution computed tomography (CT) scanning is the imaging modality of choice for identifying a skull base defect associated with CSF rhinorrhea.

Workup in CSF rhinorrhea

The beta-2 transferrin assay is currently the 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.

Another technique, the injection of intrathecal fluorescein, has been used not only to diagnose CSF rhinorrhea but also to localize the site(s) where it occurs. However, the US Food and Drug Administration (FDA) has not approved the use of fluorescein for these purposes.

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.

Management of CSF rhinorrhea

Conservative treatment has been advocated in cases of immediate-onset CSF rhinorrhea following accidental trauma, given the high likelihood of spontaneous resolution of the leak. Conservative management consists of a 5- to 7-day trial of bed rest, with the head of the bed elevated approximately 15-30°.

Several surgical options exist for the repair of CSF leaks arising from the anterior skull base. Intracranial repair was frequently used (and is still used in select cases) for the routine repair of anterior cranial fossa CSF leaks. These leaks were typically approached via a frontal craniotomy.

Defects in the posterior table of the frontal sinus may be approached externally via a coronal incision and osteoplastic flap. The osteoplastic flap provides the surgeon with a view of the entire posterior table of the frontal sinus and is especially useful for defects more than 2 cm above the floor and lateral to the lamina papyracea.

Compared with external techniques, endoscopic techniques have several advantages, including better field visualization with enhanced illumination and magnified as well as angled visualization. Another advantage is the ability to more accurately position underlay or overlay grafts. Multiple studies have demonstrated a 90-95% success rate with closure of skull base defects using the endoscopic approach. ^{[, , , , , ]}

CSF leaks are generally classified as traumatic, iatrogenic, or spontaneous/idiopathic. Traumatic causes include both blunt and penetrating facial injuries. Iatrogenic causes include neurosurgical and otolaryngologic approaches to neoplastic disease, as well as functional endoscopic sinus surgery (FESS). Most spontaneous, or primary, causes of CSF rhinorrhea are now thought actually to be secondary to elevations in intracranial pressure (ICP) that might be seen in patients with idiopathic intracranial hypertension (IIH). Congenital skull base defects and certain tumors can also lead to CSF rhinorrhea. ^[]

A literature review by Lobo et al indicated that in addition to increased ICP, risk factors for spontaneous CSF leaks include obesity, female gender, and obstructive sleep apnea. In the study, about 72% of patients with spontaneous CSF leaks were female, and about 45% had obstructive sleep apnea. ^[]

Traumatic CSF rhinorrhea

Penetrating and closed-head trauma are responsible for 90% of all cases of CSF leaks. CSF rhinorrhea following a traumatic injury is classified as immediate (within 48 hours) or delayed. The majority of patients with a CSF leak due to accidental trauma (eg, motor vehicle accident) present immediately. Most of the patients (95%) with a delayed CSF leak present within 3 months after the injury.

Iatrogenic CSF rhinorrhea

In contrast to traumatic leaks, only 50% of patients with iatrogenic CSF leaks present within the first week after the insult. In most cases, the patient will have been discharged when the leak presents itself. Hence, educating the patient regarding the common symptoms associated with a CSF leak such as salty or metallic taste is of paramount importance.

Any surgical manipulation near the skull base can result in an iatrogenic CSF leak. Skull base injuries can vary from simple cracks in the bony architecture to large (>1 cm) defects with disruption of the dura and, potentially, the brain parenchyma.

Otolaryngology procedures, including FESS and septoplasty, can lead to a skull base defect and CSF rhinorrhea. Certain neurosurgical procedures such as craniotomy and transsphenoidal pituitary resections are most commonly associated with an increased risk of CSF rhinorrhea.

In patients undergoing endoscopic sinus surgery, the site of injury is most frequently the lateral lamella of the cribriform plate, where the bone of the anterior skull base is thinnest. Other common locations include the posterior fovea ethmoidalis and the posterior aspect of the frontal recess.

A study by the CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) Consortium found that in patients who underwent the transsphenoidal approach for sellar tumors or the expanded endonasal approach for skull base tumors, the rate of postoperative CSF rhinorrhea was low whether obesity was present or not. Among the transsphenoidal surgery patients, 5% of those with obesity had postoperative CSF rhinorrhea, compared with 3% of those without obesity, a non-statistically significant difference. Among the expanded endonasal approach patients, the rate of CSF rhinorrhea was 7% both for those with and for those without obesity. Because the rates of CSF rhinorrhea were extremely low, the investigators "were unable to fully exclude a minor contribution of obesity towards the development of" these leaks. ^[]

Tumor-related CSF rhinorrhea

The growth of benign tumors does not commonly result in CSF rhinorrhea. However, locally aggressive lesions such as inverted papilloma and malignant neoplasms can erode the bone of the anterior cranial fossa. The enzymatic breakdown or destruction of the bony architecture results in inflammation and potential violation of the dura. Even if the tumor itself does not lead to CSF rhinorrhea, the resection typically causes immediate leakage. Hence, the surgical team should be prepared to repair the resulting CSF leak at the time of the resection, either transcranially or endoscopically.

Congenital CSF rhinorrhea

Defects in the closure of the anterior neuropore can cause herniation of central nervous tissue through the anterior cranial fossa. These defects are infrequently associated with CSF rhinorrhea. The embryologic defect is typically a patent fonticulus frontalis or foramen cecum. Meningoencephaloceles usually present in childhood as an intranasal/extranasal mass that transilluminates and expands with crying (Furstenberg sign). A high index of suspicion should be maintained with all pediatric intranasal masses, particularly those occurring at the midline. A biopsy should never be obtained unless a complete imaging workup has been conducted.

Spontaneous CSF rhinorrhea

Spontaneous CSF rhinorrhea occurs in patients without antecedent causes. This terminology seems to imply that spontaneous CSF leaks are idiopathic in nature; however, evidence has led to the realization that spontaneous CSF rhinorrhea may in reality be secondary to an intracranial process, namely elevated intracranial pressure (ICP). There are several causes of elevated ICP; however, the proposed mechanism underlying spontaneous CSF rhinorrhea is idiopathic intracranial hypertension (IIH). Obstructive sleep apnea (OSA) has also been linked to elevated ICP. ^[]

Despite the multifactorial causes of elevated ICP, once this problem ensues, the pressure exerted on areas of the anterior skull base such as the lateral lamella of the cribriform or lateral recess of the sphenoid sinus results in bone remodeling and thinning. Ultimately, a defect is formed. At this point, the dura herniates through the defect (meningocele). If the defect is large, brain parenchyma may also herniate through the defect (encephalocele).

Immediate traumatic leaks result from a bony defect or fracture in conjunction with a dural tear. A possible cause of a delayed traumatic leak is a previously intact dural layer that has slowly herniated through a bony defect, finally tearing and allowing the CSF to 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 pressure 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 include Valsalva-like maneuvers during nose blowing or straining. This can lead to dural tears in areas of abnormalities of the bony floor.

A study by Lieberman et al found evidence of a significant incidence of multiple simultaneous skull base defects in cases of spontaneous CSF rhinorrhea, reporting the existence of such defects in eight out of 44 patients (18.2%) in the study. The investigators suggested that intracranial hypertension may put patients at risk for developing these defects. ^[]

However, increased intracranial pressure is not always present in the case of spontaneous CSF rhinorrhea. Other proposed mechanisms for 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.

Iatrogenic CSF rhinorrhea results from surgical disruption of the skull base and dura, as previously discussed.

CSF consists of a mixture of water, electrolytes (Na⁺, K⁺, Mg²⁺, Ca²⁺, Cl^-, and HCO₃^-), glucose (60-80% of blood glucose), amino acids, and various proteins (22-38 mg/dL). CSF is colorless, clear, and typically devoid of cells such as polymorphonuclear cells and mononuclear cells (< 5/μL).

The primary site of CSF production is the choroid plexus, which is responsible for 50-80% of its daily production. Other sites of production include the ependymal surface layer (up to 30%), while capillary ultrafiltration is responsible for up to 20% of production. CSF represents the end product of the ultrafiltration of plasma across epithelial cells in the choroid plexus lining the ventricles of the brain. A basal layer Na⁺/K⁺ adenosine triphosphatase (ATPase) is responsible for actively transporting Na⁺ into epithelial cells, after which water follows across this gradient. Carbonic anhydrase catalyzes the formation of bicarbonate inside the epithelial cell. Another Na⁺/K⁺ ATPase lining the ventricular side of the epithelium extrudes Na⁺ into the ventricle, with water following across this ionic gradient. The resulting fluid is CSF.

CSF is produced at a rate of approximately 20 mL/h for a total of approximately 500 mL daily. At any given time, approximately 90-150 mL of CSF is circulating throughout the CNS. CSF produced at the choroid plexus typically circulates from the lateral ventricles to the third ventricle via the aqueduct of Sylvius. From the third ventricle, the fluid circulates into the fourth ventricle and out into the subarachnoid space via the foramina of Magendie and Luschka. After circulating through the subarachnoid space, CSF is reabsorbed via the arachnoid villi.

Circulation of CSF is maintained by the hydrostatic differences between its rate of production and its rate of absorption. Normal CSF pressure is approximately 10-15 mm Hg, and elevated pressure constitutes an intracranial pressure (ICP) greater than 20 mm Hg.

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

The most common anatomic sites of spontaneous CSF leaks are the areas of congenital weakness of the anterior cranial fossa and areas related to the type of surgery performed. The lateral lamella of the cribriform plate appears to be involved in approximately 40% of the cases, whereas a defect in the region of the frontal sinus is detected 15% of the time. The sella turcica and sphenoid sinus are involved in 15% of the cases as well.

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 walls. Rarely, 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. These patients typically present with aural fullness due to a serous middle ear effusion.

It has long been known that the shape and configuration of the skull base correlate with injury during endoscopic sinus surgery. The author personally reviewed five features of skull base anatomy that are believed to increase the risk of inadvertent skull base injury. The height of the skull base (Keros classification) was reviewed preoperatively. In one series of the author's patients (unpublished data), 129 individuals (56.7%) had type II or III anatomy. Low skull base configuration has been associated with injury during endoscopic sinus surgery. Additionally, an asymmetrical skull base has been linked to increased complications. In the author's series, asymmetrical skull bases occurred more frequently than Keros type III skull bases (14.3% vs 6.2%, respectively), making recognition of asymmetry vitally important prior to skull base dissection. The ethmoid and sphenoid roofs were dehiscent in 8.6% and 3.3% of patients, respectively; these were identified preoperatively and carefully encountered during surgery.