Cranial cerebrospinal fluid leaks

INTRODUCTION — Cranial cerebrospinal fluid (CSF) leaks occur when a dural tear or defect allows the passage of CSF from the subarachnoid space into the extracranial space. Patients with cranial leakage of CSF may present with clear rhinorrhea or otorrhea, as well as neurologic symptoms such as headaches, tinnitus, or meningitis. By contrast, patients with postural headaches and/or other neurologic symptoms from intracranial hypotension typically have a spinal source of CSF leakage.

The etiologies, clinical features, diagnosis, treatment, and prognosis of cranial CSF leaks will be reviewed here.

CSF leaks in the spinal region causing spontaneous intracranial hypotension are reviewed separately. (See "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis" and "Spontaneous intracranial hypotension: Treatment and prognosis".)

PATHOGENESIS AND ETIOLOGIES — Cranial CSF leak is a pathologic condition caused by an abnormal communication between the subarachnoid and extradural spaces. CSF flows externally down a pressure gradient to cause clear rhinorrhea or otorrhea, the leakage of CSF into the nose or ear. The condition was first described in 1899 by St Clair Thompson [1]. Extradural CSF leakage may also lead to neurologic symptoms from changes in intracranial volume and pressure. The most common causes of cranial CSF leaks are craniofacial trauma and intracranial surgical procedures. CSF leak may also be spontaneous, due to intracranial tumors, idiopathic intracranial hypertension (IIH), or congenital skull defects.

CSF leaks causing spontaneous intracranial hypotension (SIH) are typically due to a leak in the spinal canal. Causes of SIH are discussed separately. (See "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis", section on 'Pathophysiology'.)

Craniofacial trauma — Craniofacial trauma is the most common cause of CSF leak in adults, accounting for up to 90 percent of cases [2]. Posttraumatic CSF leaks most frequently present with CSF rhinorrhea from anterior skull base fractures. In case series, the most common fracture sites resulting in CSF leaks are the frontal sinus (31 percent), sphenoid sinus (11 to 31 percent), ethmoid sinus (15 to 19 percent), cribriform plate (8 percent), frontoethmoid sinus (8 percent), and sphenoethmoid sinus (8 percent) [3,4]. CSF leak has been reported as a rare complication of nasal and nasopharyngeal swab testing for coronavirus disease 2019 (COVID-19) infection [5].

Temporal bone fractures more commonly present with CSF otorrhea due to rupture of the tympanic membrane but may also cause rhinorrhea from leakage down the Eustachian tube in the setting of an intact tympanic membrane.

CSF leaks may occur immediately after trauma. More than 50 percent become apparent within the first two days, 70 percent within the first week, and almost all within the first three months [2]. Delayed leakage can be due to necrosis of the fractured bone edges, resulting in a widened pathway for leakage, resolution of the soft tissue edema that initially prevented leakage, and increases in intracranial pressure that translate into greater CSF hydrostatic forces.

Cranial surgery — CSF leaks may occur as a complication of sinus surgery and other cranial neurosurgical procedures, representing approximately 16 percent of CSF leaks [4].

CSF leaks following functional endoscopic sinus surgery (FESS) occur most commonly through defects in the ethmoid (62 percent), cribriform (18 percent), and frontal (8 percent) bones [6]. In a retrospective review of nearly 79,000 FESS cases over a three-year period from California and Florida, the incidence of CSF leak and other skull base complications was 0.13 percent [7]. The use of vascularized pedicled mucosal flaps has reduced the incidence of CSF leaks following FESS.

CSF leaks following cranial neurosurgery are more common following skull base than procedures that involve the convexities, the dural membranes overlying the cerebral hemispheres. The rates of leakage following cranial neurosurgery range from approximately 3 percent of supratentorial procedures up to 6 percent of skull base procedures [8].

Spontaneous CSF leaks — CSF leaks that occur in the absence of a traumatic or surgical inciting event are considered to be spontaneous. Spontaneous CSF leaks occur in conditions that lead to disruption of the dural membranes by direct invasion or by erosion of bone due to CSF pulsations in the setting of chronically increased intracranial pressure. Erosion of the temporal bone causes leakage of CSF into the middle ear or mastoid while erosion of the cribriform plate or bone over the paranasal sinuses causes CSF rhinorrhea. Several conditions can cause spontaneous CSF leaks.

●Idiopathic intracranial hypertension – Approximately 70 percent of cases of spontaneous CSF leak are associated with IIH [9-11]. Chronic elevation of intracranial pressure can occur in patients with IIH from reduced CSF resorption due to reduced cerebral venous return [12]. Impaired cerebral venous return can occur with reduced cardiac filling in the setting of elevated abdominal and intrapleural pressures in patients with obesity or directly with cerebral venous sinus stenosis [9]. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Epidemiology and pathogenesis", section on 'Pathogenesis'.)

●Obstructive sleep apnea – Obstructive sleep apnea (OSA) has been associated with spontaneous CSF leaks, with some studies reporting a prevalence among patients with OSA as high as 17 percent [13]. CSF leaks may result from episodes of apnea-induced hypoxia and hypercapnia in OSA that lead to increased cerebral blood flow and secondary increased intracranial pressure. (See "Sleep-related breathing disorders and stroke", section on 'Mechanisms'.)

●Intracranial tumors – Intracranial tumors may also cause spontaneous CSF leaks in a direct or delayed fashion, typically by dural invasion and breach. As examples, a pituitary adenoma can erode through the dura and sella turcica to allow CSF leakage into the sphenoid sinus. Alternatively, a durally invasive skull-based tumor that initially blocks the skull base defect it has created can lead to a CSF leak following stereotactic treatment or spontaneous necrosis [14]. (See "Overview of the clinical features and diagnosis of brain tumors in adults".)

●Other causes – Additional potential causes of spontaneous CSF leaks are congenital cranial defects that progressively expand over time, aberrant arachnoid granulations that erode the adjacent bone in response to CSF pulsations, and infections that erode through dura and adjacent bone [15].

●Idiopathic – For some patients with a CSF leak and rhinorrhea, no underlying cause is identified despite thorough evaluation [16].

EPIDEMIOLOGY — Cranial CSF leaks are uncommon, but precise estimates on prevalence are uncertain due to multiple possible underlying causes and underreporting of cases that resolve spontaneously. The incidence of CSF leaks in all head trauma patients is estimated to be 1 to 3 percent, while that following penetrating injury is almost 9 percent [3]. In patients with fractures of the skull base, comprised of the temporal and anterior frontal bones, the incidence increases to 10 to 30 percent and overall.

In a systematic review of the incidence of CSF leakage following elective cranial neurosurgical procedures, the overall rate was 3.8 percent [8].

Spontaneous CSF leaks may occur at nearly any age, but the average age at presentation is approximately 58 years, and up to 75 percent of patients are female [10].

CLINICAL PRESENTATION — The signs and symptoms of cranial CSF leaks vary widely by underlying etiology as well as by location and severity of leak. While CSF leakage from an open fracture of the skull can be obvious, delayed or spontaneous CSF leaks can also present with isolated or mild symptoms. Many patients with closed fractures of the skull base, cranial surgical sites, or spontaneous CSF leaks present with isolated rhinorrhea or otorrhea. Other patients with intermittent or slow CSF leaks may present with auricular or other brainstem symptoms or meningismus.

Rhinorrhea or otorrhea — Patients with cranial CSF leaks frequently present with isolated unilateral clear, watery rhinorrhea. Patients able to give a history will typically report a postnasal drip that has a salty or sometimes sweet taste. Symptoms may be constant or, if intermittent, induced by tipping the head forward. Patients with posttraumatic cranial CSF leaks presenting with rhinorrhea most commonly have frontobasal skull fractures, including ethmoid or sphenoid bones [4].

Patients with damage to the tympanic membrane can present with otorrhea. Otorrhea may be isolated or associated with mastoiditis [17]. Some patients with temporal bone fractures report postnasal drip or rhinorrhea when CSF leaks down the Eustachian tube.

Headache — Headaches are common in patients with cranial CSF leaks and may be related to multiple factors. Patients with idiopathic intracranial hypertension (IIH) often have chronic headaches and may develop a cranial CSF leak as a secondary complication. Other patients who develop postoperative or tumor-related CSF leaks may have headaches due to activation of dural nociceptors. Those with iatrogenic CSF leaks following endonasal endoscopic surgery typically present with headaches along with rhinorrhea due to pneumocephalus. (See 'Neuroimaging' below.)

Some patients with a skull base cranial CSF leak may report postural headaches that worsen with prolonged upright positioning. However, postural headaches due to intracranial hypotension that occur and worsen reliably with upright positioning are uncommon with isolated skull base cranial CSF leaks. Such patients are likely to have a concurrent spinal CSF leak. Patients with postural headaches should undergo evaluation for a spinal source of CSF leak [18]. (See "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis", section on 'Clinical features'.)

Auricular and other brainstem symptoms — Patients with spontaneous CSF leaks into the temporal bone commonly present with hearing loss, aural fullness, pulsatile tinnitus, and vertigo [9].

Patients with tumor-related CSF leaks can present with symptoms that are indicative of the size and location of the tumor, such as facial pain or hearing loss for skull-based tumors.

Meningitis — Patients with subacute or chronic CSF leaks can develop meningitis or meningoencephalitis and present with fevers, chills, encephalopathy, photophobia, and neck stiffness. The reported incidence of meningitis at the time of initial presentation with a cranial CSF leak varies from 6 to 58 percent [9,10].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for patients with clear rhinorrhea includes seasonal allergic, perennial nonallergic, and vasomotor rhinitis, which are more common than CSF leaks but also may be present concurrently [4]. Otorrhea may also be due to middle ear infections, effusions, or perilymphatic fistulas [19].

The differential diagnosis for patients with neurologic symptoms such as headache or tinnitus is broad; these conditions are discussed separately. (See "Evaluation of headache in adults" and "Etiology and diagnosis of tinnitus".)

DIAGNOSIS AND EVALUATION — The diagnosis of a cranial CSF leak should be considered in patients with rhinorrhea, otorrhea, or other associated neurologic symptoms that occur after craniofacial trauma or surgery or in the setting of a condition associated with spontaneous cranial CSF leaks. (See 'Spontaneous CSF leaks' above.)

The diagnosis may be confirmed by identifying CSF in watery discharge for patients with rhinorrhea or otorrhea. Neuroimaging is performed to confirm the diagnosis for patients with other symptoms and is also indicated for all patients both to evaluate for underlying causes and to help guide management.

Assess for presence of CSF in patients with rhinorrhea or otorrhea — For patients with rhinorrhea or otorrhea with a suspected skull base CSF leak, the first step is to attempt to collect the clear drainage.

Patients will often report maneuvers that provoke drainage and should be encouraged to do so and then collect the discharge in a sterile container. If direct collection of fluid drainage is not feasible, patients may use cotton swabs to collect the sample and then place the swab in a container, such as a test tube with a tight seal.

CSF-specific proteins — For patients with rhinorrhea or otorrhea, a CSF leak may be diagnosed when CSF proteins are found by analysis of a collected sample of watery discharge.

●Beta-2 transferrin – Beta-2 transferrin is a glycoprotein present in CSF that may be used to diagnose CSF leaks. Beta-2 transferrin is not found in mucous or blood. Fluid collected from nasal or otologic discharge is analyzed by immunohistochemical assays and positive results are highly specific (97 percent) and sensitive (99 percent) for CSF leak [20].

●Beta-trace protein – Beta-trace protein is another protein produced in the leptomeninges and found in CSF that may be used to diagnose a CSF leak. The assay is relatively inexpensive, may be performed in 15 minutes, and has a specificity and sensitivity similar to beta-2 transferrin assays, making it an appealing option [21,22]. However, availability is limited in the United States and other regions. In addition, the utility of the test may be somewhat limited in patients with bloody discharge or meningitis as low levels of beta-trace protein may be found in blood and meningitis may reduce beta-trace protein levels in CSF [22,23].

Other techniques not recommended — We do not diagnose cranial CSF leaks by testing for the presence of glucose in collected rhinorrhea or otorrhea, since glucose in blood may give a false-positive result. In addition, glucose may also be detected in airway secretions of patients with inflammation or hyperglycemia [24].

Patients with bloody discharge — For patients with a possible cranial CSF leak who present with bleeding from the ear or nose, such as those in an emergency department following head trauma or symptomatic postoperative patients, a bedside "halo test" can be used to help identify CSF in the discharge. A drop of fluid is placed on filter paper and the presence of CSF may be inferred if a ring of clear fluid develops around the blood. This pattern may also be seen on bedsheets. However, a positive "halo test" may also be found with admixture of blood with saliva or other clear fluids [22] and thus is considered a somewhat nonspecific finding, but it may be used to help select patients for neuroimaging to confirm a CSF leak.

Neuroimaging — Neuroimaging is required to establish the diagnosis of a cranial CSF leak for patients presenting with rhinorrhea or otorrhea when CSF is not identified on initial testing and for all patients who present with isolated neurologic symptoms suggestive of a cranial CSF leak. In addition, neuroimaging is also indicated for all patients with a cranial CSF leak to assess the location and extent of the leak, to evaluate for underlying causes, and to help guide management.

Diagnostic imaging may demonstrate direct evidence of a cranial CSF leak by showing an osseous and/or dural defect. Common imaging features suggestive of a cranial CSF leak include the following [19]:

●Fluid opacification of sinuses associated with bony defect (image 1)

●Subgaleal fluid collections associated with bony defect

●Pneumocephalus (image 2)

●Meningocele (image 3)

●Meningoencephalocele (image 4)

For patients with spontaneous CSF leaks, imaging may identify underlying causes such as an intracranial tumor or evidence of elevated intracranial pressure associated with idiopathic intracranial hypertension.

Initial noninvasive options — We suggest initial neuroimaging with either computed tomography (CT) of the anterior skull base and paranasal sinuses and/or temporal bones or high-resolution magnetic resonance imaging (MRI) of the skull base to identify a cranial CSF leak.

The selection of initial imaging modality varies by clinical scenario and suspected location of leak. We typically start with CT to identify an osseous defect for patients with suspected skull fracture or those who have undergone sinus surgery. For other patients, including those with suspected spontaneous CSF leak, we typically start with MRI-based imaging to identify a dural defect or associated soft tissue abnormalities. When either initial neuroimaging test is nondiagnostic, we perform the other test prior to considering invasive imaging options. Approximately 80 percent of cranial CSF leaks can be identified by one of these noninvasive neuroimaging techniques [25,26]. When both high-resolution MRI through the skull base and high-resolution CT are performed, the combined sensitivity, specificity, and accuracy improve to 95, 100, and 96 percent, respectively [20,21,27,28].

CT of the skull base and/or temporal bones — High-resolution multidetector CT without contrast is the preferred initial imaging study to assess the osseous integrity of the paranasal sinus, skull base, and temporal bone structures. CT of the paranasal sinuses may be performed for patients with rhinorrhea or other symptoms following facial trauma or sinus surgery. CT of the temporal bones may be performed for patients with otorrhea, trauma or skull base surgery, or vestibulocochlear symptoms. CT imaging of both sinuses and temporal bones can be performed as a single study for patients with an uncertain location of CSF leak. Additional postcontrast imaging can be performed in selected cases to evaluate any associated soft tissue abnormality involving or adjacent to the skull base.

An osseous defect with adjacent air-fluid level or opacification of the adjacent sinus or temporal bone is highly suspicious for CSF leak (image 1). Of note, the site of a dural tear may be remote from the site of bony defects or other intracranial abnormalities, such as for patients with multiple skull fractures or pneumocephalus. In addition, some apparent bony defects identified on CT may not indicate a cranial CSF leak, such as bony scalloping seen with prominent arachnoid granulations [27].

In small cross-sectional studies, the sensitivity of high-resolution CT for diagnosis of a cranial CSF leak ranged from 70 to more than 90 percent [25,27,29]. In one single-center series of 19 patients with a cranial CSF leak, high-resolution CT identified the specific site of leak in 75 percent [27].

MRI of the skull base — Brain MRI without contrast that includes high-resolution T2-weighted sequences through the skull base and region of the internal auditory canal (eg, three-dimensional constructive interference steady state [3D-CISS] or fast/turbo-spin echo sequences optimized for isotropic three-dimensional imaging) provides high spatial resolution to identify skull base CSF leaks and associated findings such as meningoceles or meningoencephaloceles (image 3 and image 4) [20]. Some institutions refer to brain MRI with 3D-CISS sequences or 3D fast- or turbo-spin echo as "MR (magnetic resonance) cisternography" however, we reserve this term for MR imaging when an intrathecal gadolinium-based contrast agent is utilized. (See 'Other invasive imaging options' below.)

The sensitivity of brain MRI in small studies ranges from 75 to more than 90 percent with sequences for the detection of CSF leaks [26,30,31].

Invasive imaging options when initial testing is nondiagnostic — For patients with a suspected cranial CSF leak not found on initial noninvasive imaging, further imaging with intrathecal contrast is typically performed to confirm a dural defect or identify the leak site. Patients may need a combination of tests to determine the site of leak. In addition, neuroimaging with intrathecal contrast is typically required for patients diagnosed with a cranial CSF defect to guide surgical planning when initial imaging does not identify the specific site of the dural defect.

Invasive neuroimaging for cranial CSF leaks involves the use of intrathecal injection of contrast material via image-guided lumbar puncture. A CSF leak may be demonstrated by the extrathecal location of intrathecally injected material. To optimize diagnostic yield, maneuvers to provoke the CSF leak or symptoms should be performed during imaging. These may include Valsalva maneuvers, Trendelenburg body position, or specific head positioning known to elicit symptoms.

Invasive imaging carries a small risk of infection, bleeding, and postdural puncture CSF leak. In addition, adverse reactions to intrathecal contrast have been reported [32,33].

CT cisternography — CT cisternography with intrathecal contrast is considered the gold standard for evaluating a cranial CSF leak. Precontrast imaging of the anterior skull base, paranasal sinuses, and temporal bones is obtained. Then, intrathecal injection of low-osmolar iodinated contrast is performed via lumbar puncture and the patient is placed in Trendelenburg positioning. Provocative maneuvers may be performed to exacerbate CSF leak and then imaging is obtained. The presence of contrast in an extradural location confirms a CSF leak. When the sinonasal cavities or temporal bone cavities demonstrate fluid prior to intrathecal contrast administration, an increase in Hounsfield units of 50 percent or more is considered positive for CSF leak (image 5) [25]. Reported sensitivities of CT cisternography are 92 percent in active leaks and approximately 40 percent in inactive leaks [28].

Other invasive imaging options — Additional invasive imaging studies are generally reserved for patients with a cranial CSF leak established by the presence of CSF in rhinorrhea/otorrhea or when a dural defect is found on initial neuroimaging, but the site is uncertain despite CT cisternography [19]. These modalities may also be used to confirm the presence a cranial CSF leak for selected patients with a suspected slow or intermittent leak not identified on other testing.

●MR cisternography – MR cisternography of the brain is performed with intrathecal administration of very dilute gadolinium-based contrast agent. Approximately 30 to 60 minutes after intrathecal contrast administration, imaging of the skull base is performed with multiplanar, high-resolution, T1 fat-suppressed sequences. It may be useful for difficult cases when leaks are not confirmed via other means [34]. This technique is performed at several academic centers; however, intrathecal use of gadolinium is not approved by the United States Food and Drug Administration.

●Radioisotope cisternography – Cisternography may also be performed using radiotracers such as technetium-99m (TC-99m) diethylenetriaminepentaacetic acid (DTPA) or indium 111 DTPA. Radionuclide cisternography has largely been supplanted by CT and MR cisternography and is reserved for occult leaks that cannot be confirmed by other methods. For optimal sensitivity, pretreatment nasal cavity and nasopharyngeal pledgets are placed endoscopically and then collected for assessment several hours later. The accumulation of radiotracer in the nasopharynx or elevated pledget to serum tracer activity generally confirms the presence of a CSF leak [22]. However, a positive result does not usually permit for precise location of the dural defect [35]. Depending on the radiotracer used, patients can be imaged multiple times over multiple hours to days to increase the sensitivity for intermittent leaks. Overall, radionuclide cisternography identifies the presence of a leak in approximately 50 percent of cases [36].

MANAGEMENT — The management of patients with cranial CSF leaks involves treatment of underlying or causal conditions, symptomatic treatment for those with headache or other neurologic symptoms, and directed treatment for the CSF leak and possible complications.

General measures for all patients

●Management of causal conditions – Patients with CSF leak due to craniofacial trauma may require emergency evaluation and management for associated intracranial or scalp bleeding, airway compromise, traumatic brain injury, or other systemic injuries. These issues are discussed in detail separately. (See "Skull fractures in adults" and "Skull fractures in children: Clinical manifestations, diagnosis, and management" and "Initial management of trauma in adults" and "Trauma management: Approach to the unstable child".)

Patients with CSF leak due to idiopathic intracranial hypertension (IIH) frequently present with chronic headaches and other neurologic symptoms such as tinnitus and vision changes. These symptoms can overlap with clinical features of cranial CSF leaks. Effective pharmacologic treatment for IIH, often with acetazolamide, is frequently used to reduce intracranial pressure and manage the component of symptoms that are due to IIH. Surveillance ophthalmologic monitoring is also warranted to help guide duration and intensity of IIH treatment. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Prognosis and treatment".)

Patients with cranial CSF leaks due to intracranial tumors may also present with headaches and other neurologic symptoms attributed to the tumor. The management of these symptoms is discussed in detail separately. (See "Brain tumor headache" and "Management of vasogenic edema in patients with primary and metastatic brain tumors" and "Overview of the management of central nervous system tumors in children".)

●Symptomatic treatment – For patients with headache or other neurologic symptoms due to cranial CSF leaks, we typically use simple analgesic medications based on efficacy for other forms of headache. Bed rest is indicated for patients with acute or severe posttraumatic or postoperative symptoms.

●Meningitis prophylaxis – For all patients with a cranial CSF leak, we recommend pneumococcal vaccination. Cranial CSF leaks are associated with an elevated risk for bacterial meningitis. (See "Pneumococcal vaccination in adults", section on 'Indications for vaccination' and "Pneumococcal vaccination in children", section on 'Target high-risk groups'.)

Initial management for all patients — The treatment for a cranial CSF leak may be nonoperative or surgical, depending on the cause and degree of leakage.

Identify patients with an indication for initial surgical management — Initial surgical repair is indicated for patients with severe or progressive symptoms and those with a leak unlikely to resolve with conservative treatment. Underlying causes of CSF leaks that may require initial surgery include:

●Open skull fracture – Patients with a penetrating injury resulting in an open fracture of the skull with leakage of CSF require early surgical repair of the dura due to severity of injury and high risk of infection.

●Skull base fracture with bony and dural defect – Skull base fractures with bony and associated dural defects are unlikely to close on their own and are generally repaired surgically.

●Spontaneous CSF leaks – CSF leaks that occur spontaneously are frequently chronic and unlikely to close without surgical intervention.

Surgical techniques for repair of a CSF leak are discussed below. (See 'Surgical management' below.)

Initial conservative measures for other patients — We suggest trial of conservative treatment for patients with a cranial CSF leak who do not have an indication for initial surgical management. Many postoperative leaks will resolve with nonsurgical treatment [37]. Posttraumatic CSF leaks amenable to initial nonsurgical treatment include those due to blunt force injury causing a closed fracture of the skull convexity in the absence of brain compression and linear skull base fractures in the absence of any brain or visual system compression by skull fragments or hematomas. In a review of 81 patients with posttraumatic CSF leaks of at least 24-hour duration, 40 percent resolved with conservative measures alone [38].

The primary goal of the conservative management of posttraumatic CSF leaks is to enable the healing and closure of the dural and bony defects by decreasing and preventing transient spikes in intracranial pressure.

●Precautions to prevent elevated intracranial pressure – Strict bed rest with the head of bed elevated 30 degrees or above is recommended unless headaches due to intracranial hypotension develop. Patients are instructed to avoid straining, coughing, sneezing, nose blowing, and drinking through a straw. Medications including stool softeners as well as antiemetic, antitussive, and antihypertensive agents are given as needed.

●Management of subgaleal fluid collections – For patients with a CSF leak contained to the subgaleal space following cranial surgery, fluid can be removed percutaneously to relieve mass effect, prevent dehiscence of the incision, and assess for evidence of infection. Additionally, the head may be wrapped with a compressive gauze, a combination treatment commonly referred to as "tap and wrap." When there is frank leakage of CSF through the incision, the scalp opening is oversewn to minimize the chances of an infection if not already present.

●No role for prophylactic antibiotics – We do not give prophylactic antibiotics to patients with CSF leaks due to basilar skull fractures. A Cochrane database systematic review initially published in 2006 and updated in 2011 and 2015 examined the results of five clinical trials that enrolled a total of 208 subjects and found no benefit with prophylactic antibiotics for reducing meningitis frequency, all-cause mortality, meningitis-related mortality, or the need for surgical intervention [39]. One study reported that patients treated with antibiotic prophylaxis were likelier to have antibiotic resistant organisms in the posterior nasopharyngeal flora.

For patients with symptoms that fail to resolve after one week of conservative therapy, we pursue additional treatment options such as lumbar drain or surgical repair. Limited evidence suggests that patients with posttraumatic CSF leaks persisting greater than seven days have an 8- to 10-fold increased risk of developing meningitis [4]. (See 'Lumbar CSF drain for patients with persisting symptoms' below and 'Surgical management' below.)

Lumbar CSF drain for patients with persisting symptoms — For patients without clear indications for surgical intervention, the failure of initial conservative therapies is generally followed by CSF diversion procedures such as lumbar drain placement or repeated lumbar punctures. In a single-center series of 81 patients with posttraumatic CSF leaks, 24 were treated with lumbar drainage for an average of seven days [38]. The success rate was 70 percent with seven patients requiring surgery to close the leak.

The risks of lumbar drainage include meningitis, for which patients should be closely monitored clinically, and CSF should be tested periodically, and over drainage, which can result in postural headaches and pneumocephalus. We typically drain patients at a rate of 10 cc/hour.

Surgical management — We suggest surgical repair of a cranial CSF leak for patients with open skull fractures or other skull base fractures with bony and dural defects, patients with spontaneous CSF leaks, and those with persistent symptoms despite conservative measures with or without lumbar CSF drainage. The surgical approach varies by underlying cause.

Risks and complications of surgery include meningitis, intracranial hemorrhage, and perioperative seizure, but the overall incidence of these events appears less than 2 percent in some series [40].

Posttraumatic leaks — Surgical repair of posttraumatic CSF leaks often requires managing infection risk and repairing displaced bone. Bone fragments, foreign bodies, or hematomas causing brain compression are removed, and potentially infectious material is washed out. The dura is then repaired either primarily or using a graft. The skull is reconstructed as needed if there are no concerns for increased intracranial pressure postoperatively, and the overlying soft tissues such as any muscles and the scalp are closed.

Skull base fractures with larger bony and associated dural defects can be performed using an open transcranial approach or an endonasal endoscopic approach. Fibrin glue or vascularized pedicled mucosal flaps may be used to support effective closure of the dura.

Postsurgical CSF leaks — Patients with postoperative CSF leaks that persist despite compression wrapping and lumbar drainage may require surgical exploration and repeat closure of the dura. Both open and endoscopic surgical repair has been used [16]. Patients who have had endonasal endoscopic surgery that merits surgical exploration with repeat closure of the dura may also need reconstruction of defects in the skull base.

We suggest preoperative brain imaging with a noncontrast head CT or brain MRI. Prolonged postoperative CSF leakage may be a sign of hydrocephalus that requires shunting. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Removal of CSF' and "Hydrocephalus in children: Management and prognosis", section on 'CSF shunt'.)

Spontaneous CSF leaks — Surgical management of spontaneous CSF leaks varies by the location of dural defect.

●Anterior skull base defects – Anterior skull base defects that result in rhinorrhea are generally repaired using endonasal endoscopic techniques given success rates that range from 70 to 100 percent with the first attempt and 86 to 100 percent with a second attempt [22]. Other advantages to this approach compared with an open craniotomy include the avoidance of a large scalp incision or the need to retract and potentially injure the brain, shorter hospital stays, and the preservation of sinus function.

●Temporal skull base defects – Spontaneous CSF leaks that occur through defects in the temporal bone can be repaired via a mastoidectomy, middle fossa craniotomy, or combined transmastoid-middle fossa approach depending on the location and size of the defect and the relationship of the defect to the ossicles. The transmastoid approach is less invasive and is generally used for smaller defects. The middle fossa approach provides a greater exposure for the repair of larger defects and is more likely to preserve hearing but may require brain retraction and a longer hospital stay. The combined approach offers partial benefits of each individual approach. A variety of materials have been used to repair bony and dural defects including temporalis fascia, bone, fibrin glue, synthetic dura, fat, hydroxyapatite cement, cartilage, muscle, and titanium plates. The use of one material over another appears to be based on surgeon preference as no trials have been conducted comparing them.

In a systematic review that included 33 studies with a total of 873 procedures, similar success rates at >95 percent were reported for transmastoid, middle fossa, or combined approaches [41]. The overall rate of minor complications was <1 percent, and the rate of major complications was 3 percent, highest for middle fossa approaches.

The use of adjunctive therapies during or after surgical repair also appears to be largely dictated by surgeon preference or experience. Postoperative lumbar drains are more commonly placed following anterior than lateral skull base procedures. A drain would theoretically decrease intracranial pressure and promote postsurgical healing of the defect, but compelling evidence to confirm this hypothesis is unavailable [42]. Acetazolamide is used in patients with IIH to decrease CSF production and preliminary data suggest this approach may be used after sinus surgery to manage intracranial pressure, but additional data are warranted to identify patients appropriate for this approach [12,43].

PROGNOSIS — Limited data suggest most patients with a cranial CSF leak improve with treatment. In a single-center study of 18 patients treated surgically for CSF rhinorrhea, endoscopic or open surgery was successful in 17 patients, with only one patient requiring a second procedure [16]. The resolution of the leak and associated symptoms appears likelier in patients with posttraumatic or postoperative CSF leaks and an identified dural defect than those with a spontaneous CSF leak such as patients with idiopathic intracranial hypertension [12]. In one study of patients undergoing surgical repair for spontaneous CSF leaks, the recurrence rate was 6 percent [40].

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SUMMARY AND RECOMMENDATIONS

●Definition and causes – Cranial CSF leak is a pathologic condition caused by an abnormal communication between the subarachnoid and extradural spaces within the cranial vault. The most common causes of cranial CSF leaks are craniofacial trauma and intracranial surgical procedures. CSF leaks may also be spontaneous, due to intracranial tumors, idiopathic intracranial hypertension, or congenital skull defects. (See 'Pathogenesis and etiologies' above.)

●Clinical features – CSF leaks from an open fracture of the skull can be obvious; however, patients can also present with isolated clear rhinorrhea or otorrhea. Other patients with intermittent or slow CSF leaks may present with neurologic symptoms such as headaches, tinnitus, or vertigo, or with symptoms due to meningitis. (See 'Clinical presentation' above.)

●Diagnostic evaluation

•Identifying CSF in rhinorrhea or otorrhea – For patients with rhinorrhea or otorrhea, we assess for CSF protein such as beta-2 transferrin or beta-trace protein in a collected sample of watery discharge to diagnosis a cranial CSF leak. (See 'Assess for presence of CSF in patients with rhinorrhea or otorrhea' above.)

•Neuroimaging – Neuroimaging is required to establish the diagnosis of a cranial CSF leak for patients presenting with rhinorrhea or otorrhea when CSF is not identified on initial testing and for all patients who present with isolated neurologic symptoms suggestive of a cranial CSF leak. Diagnostic imaging may demonstrate direct evidence of a dural defect or indirect evidence of extradural CSF (image 1 and image 3 and image 4). (See 'Neuroimaging' above.)

Neuroimaging is also indicated for all patients with a cranial CSF leak to assess the location and extent of the leak, to evaluate for underlying causes, and to help guide management.

-Initial noninvasive imaging – We suggest initial noninvasive imaging to identify a cranial CSF leak. We typically start with CT of the anterior skull base, paranasal sinuses, and/or temporal bones to identify an osseous defect for patients with suspected skull fracture or those who have undergone sinus surgery. For other patients, including those with suspected spontaneous CSF leak, we typically start with high-resolution MRI of the skull base. (See 'Initial noninvasive options' above.)

-Invasive imaging – For patients with a suspected cranial CSF not found on initial imaging, CT-cisternography with intrathecal contrast is typically performed via lumbar puncture to confirm a dural defect or identify the leak site. Cisternography is often required for patients diagnosed with a cranial CSF defect to identify the specific site of the dural defect. (See 'Invasive imaging options when initial testing is nondiagnostic' above.)

●Management

•Initial conservative treatment for most patients – We suggest a trial of conservative treatment for stable patients with postoperative or uncomplicated posttraumatic cranial CSF leaks (Grade 2C). Posttraumatic CSF leaks amenable to initial nonsurgical treatment include those due a closed fracture of the skull convexity or linear skull base fractures in the absence of any brain or visual system compression by skull fragments or hematomas. (See 'Initial conservative measures for other patients' above.)

Conservative treatment typically includes bed rest with the head of bed elevated >30 degrees. Patients are instructed to avoid straining, and medications including stool softeners as well as antiemetic, antitussive, and antihypertensive agents are given as needed.

•Surgical repair – We suggest surgical repair of a cranial CSF leak for patients with open skull fractures or other skull base fractures with bony and dural defects, patients with spontaneous CSF leaks, and those with persistent symptoms despite initial conservative therapy (Grade 2C). (See 'Surgical management' above.)

Skull base fractures with larger bony and associated dural defects can be performed using an open transcranial approach or an endonasal endoscopic approach.

•Meningitis prophylaxis – Supportive treatment consists of pneumococcal vaccination for all patients with a cranial CSF leak. Cranial CSF leaks are associated with an elevated risk for bacterial meningitis. (See 'General measures for all patients' above.)

●Prognosis – Limited data suggest most patients with a cranial CSF leak improve with treatment. The resolution of the leak and associated symptoms appears likelier in patients with posttraumatic or postoperative CSF leaks and an identified dural defect than those with a spontaneous CSF leak. (See 'Prognosis' above.)