- Author: Kevin C Welch, MD; Chief Editor: Arlen D Meyers, MD, MBA more...
Cerebrospinal fluid (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%) and capillary ultrafiltration (up to 20%). 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+ 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 termed cerebrospinal fluid.
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 forth 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.
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 CNS can result in a multitude of infectious complications that impart significant morbidity and potentially disastrous long-term deficits for the patient.
This article discusses current concepts in the etiology, diagnosis, and treatment of CSF rhinorrhea, as well as long-term management of patients following successful treatment.
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History Of The Procedure
From the first intracranial repair in the 1900s to the use of endoscopes and image-guidance systems, the management of cerebrospinal fluid (CSF) rhinorrhea has greatly evolved. Dandy is credited with the first surgical repair of a CSF leak via a frontal craniotomy approach in 1926. Various other authors, including Dohlman (1948), Hirsch (1952), and Hallberg (1964), subsequently reported successful repair of CSF rhinorrhea through different external approaches. In 1981, Wigand reported on the use of the endoscope to assist with the repair of a skull base defect. Since then, endoscopic repair has become the preferred method of addressing CSF rhinorrhea, given the high success rate of 90-95% and the decreased morbidity associated with this approach.
The underlying defect responsible for cerebrospinal fluid (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 frequency of cerebrospinal fluid (CSF) rhinorrhea is determined by the underlying etiology. Please refer to Etiology for further details.
Cerebrospinal fluid (CSF) leaks are generally classified as traumatic, iatrogenic, and 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.
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 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.
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 results in 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 result in the herniation of central nervous tissue through anterior cranial fossa. These 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, recent evidence has led us to realize 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 cerebrospinal fluid (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.
A thorough history is the first step toward accurate diagnosis. The typical history of a cerebropsinal fluid (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 one 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 post-traumatic rhinorrhea), indicates an injury in the olfactory area and anterior fossa, especially when it is unilateral. Optic nerve deficits suggest 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 examination should include complete rhinologic (including endoscopic), otologic, head and neck, and neurologic evaluations. Endoscopy may reveal an encephalocele or meningocele. Drainage of CSF in some cases may often be elicited on endoscopy by having the patient perform a Valsalva maneuver or by compressing both jugular veins (Queckenstedt-Stookey test). However, most of the time physical examination is unrevealing, especially in patients with intermittent CSF rhinorrhea.
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: the 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%).
Unless medical or surgical contraindications exist, surgical repair is recommended in all patients with spontaneous or iatrogenic cerebropsinal fluid (CSF) rhinorrhea in order to prevent ascending meningitis.
In patients with nonsurgical trauma, waiting a period of 5-7 days to allow conservative measures (bed rest, stool softeners, and lumbar drainage) to assist with secondary closure of the traumatic defect is reasonable. However, if CSF rhinorrhea persists beyond this point, or if a large skull base defect is observed at the time of injury, surgical repair is warranted.
If an iatrogenic leak is detected intraoperatively, it should be repaired at the time of the original surgery. In most cases of iatrogenic injury presenting in a delayed fashion, surgical repair is necessary. A lumbar drain placed at the time of repair has not been shown to decrease recurrence of the CSF leak.
The most common anatomic sites of spontaneous cerebrospinal fluid (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 fontal 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 wall. 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.
Surgical repair of skull base defects resulting in cerebrospinal fluid (CSF) rhinorrhea is contraindicated in any patient who is not medically stable to undergo a general anesthetic or comply with postoperative care.
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 the onset of the leak is important. The natural history of CSF rhinorrhea is highly dependant on the underlying etiology.
Traumatic leaks stop spontaneously in the majority of cases, thus a conservative approach is best. The leakage stops within 1 week in 70% of patients, within 3 months in 20-30%, and within 6 months in most patients. The leak almost never recurs. The opposite is true for nontraumatic leaks, as only one third stop spontaneously. Intermittent leakage over several years is characteristic.
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