Endoscopic repair of CSF leak
I have started the original work on the literature review (more than 10,000 words)
Need to add 5000 words to the work focusing on comparing endoscopic repair of CSF leak in the trauma and the spontaneous group (example like the recurrence of leaks after repair, is the method of repair different, i
LITERATURE REVIEW:
Endoscopic repair of CSF leak
TABLE OF CONTENTS
Preliminary Instructions from the client: i
Table of contents iii
1 Introduction 1
2 Overview of CSF leaks 1
2.1 Causes of CSF leaks 1
2.1.1 Traumatic causes of CSF leaks 2
2.1.2 Non-traumatic causes of CSF leaks 2
2.1.3 Spontaneous CSF leaks 3
2.2 Anatomical detail of CSF leaks 4
2.3 Dangers of CSF leaks 5
2.4 Historical overview of CSF leak repair 5
2.5 Detection of CSF leaks 6
2.5.1 Intrathecal fluorescein 7
2.5.2 MRI and CT Cisternography 7
2.5.3 Pre-operative assessment 8
3 Treatment of CSF leak 9
4 Types of approaches to the skull base 9
4.1 Intracranial procedures 10
4.2 Extracranial procedures 11
4.2.1 Endoscopic approaches 12
4.2.2 Open transcranial versus endoscopic endonasal approaches 12
5 Material used for CSF leak repair 14
5.1 Grafting materials 14
5.2 Intraoperative instruments 15
6 Repair of CSF leaks by Endoscopic Endonasal Surgery 15
6.1 Onlay or overlay technique 16
6.2 Underlay technique 17
6.3 Combined technique 18
6.4 Obliteration technique 19
7 Challenges to CSF leak repair 19
7.1 Recurrence of CSF leak 21
8 Conclusion 21
References 22
1 INTRODUCTION
Cerebrospinal fluid leaks (CSF) are caused by an abnormal communication between the extracranial space and the subarachnoid space (46). Leakage of spinal fluid into either the ear or nose is termed CSF otorrhea or rhinorrhea, respectively (25). CSF leaks were first characterised as a pathologic entity in 1899 by St Clair Thompson(1,25). Rhinorrhea, or the seeping of fluid through the nose, manifests in roughly 90% of CSF leaks that occur at the anterior skull base, which can become a life-threatening condition (46). When conservative treatments are not successful, surgical intervention is advised (19).
This review presents a comparison between traumatic and spontaneous CSF leak and the advantage that endoscopic repair has over open craniotomy surgery. It also presents the difference between the spontaneous and traumatic forms of CSF leaks, from presentation, to their causes, modes of treatment, and their recurrence after treatment. The review begins, next, with an overview of CSF leaks.
2 OVERVIEW OF CSF LEAKS
2.1 Causes of CSF leaks
CSF leaks are classified within two etiologies: traumatic or non-traumatic (2,46), and the system of classification as developed by Ommaya in 1960, is the most widely accepted classification system today (25,53). Ommanya’s etiological classification divides CSF rhinorrhea into two categories: traumatic andnon-traumatic, with non-traumatic being further subdivided into non-traumatic with CSFhypertension and non-traumatic with normal pressure (53). A third category — spontaneous leaks, or primary CSF rhinorrhea — has been recently defined, which describes leaks in patients with no prior history of trauma, or with no other predispositionto CSF leaks (25). Spontaneous, or primary CSF rhinorrhea is thus classified as a non-traumatic form of CSF leak (39). Bedrosian et al., (3) make the classification distinction that CSF-leaks are either iatrogenic, or non-iatrogenic, and non-iatrogenic CSF leaks (or those not caused by surgical trauma) can be largely classified into three groups or categories: traumatic, tumour-related, and spontaneous.
CSF flow is higher in the non-traumatic etiologies, and anosmia, which is common in traumaticcases (53), is rare among the non-traumatic forms; although headaches arecommon in the non-traumatic form.
2.1.1 Traumatic causes of CSF leaks
The more common of the etiologies of CSF leaks is the traumatic form, which may be divided into iatrogenic, and noniatrogenic leaks (3). Between 81% and 90% of the cases of CSF leaks are caused by trauma (7), while noniatrogenic traumatic CSF leaks are usually caused by accidental trauma, which is the cause of 70% to 80% of cases (3). The most common types of trauma observed in CSF leak cases are blunt traumas such as from industrial or motor vehicle accidents; penetrating injuries, such as from gunshot wounds; or from intracranial or extracranial surgical trauma (iatrogenic reasons) (7,39).CSF leak occurs among approximately 2% of all cranial injuries (7).Traumatic CSF leaks show little relationship to gender, unlike the non-traumatic etiology, which affects predominantly adults over 30 years of age, and affects women twice as often as men (53). Posttraumatic CSF leaks are, however, less common in children than in adults, occurring in between 0.2% and 0.3% of childhood head traumas. Ibrahim et al. (18) attribute this to the greater flexibility of children’s skull bones, which can respond better to the impact of traumatic shock. Anosmia is observed in 78% of traumatic cases, although CSF flow is typically higher in the non-traumatic etiologies (53).
In more than 50% of traumatic cases, rhinorrhea stops within one week; and the remainder of leaks heal within six months(53).
The most common causes of iatrogenic CSF leaks are due to the resection of transsphenoidal pituitary tumours, with an incidence of between 0.5% and 15% (3); while acoustic neuroma surgery and functional endoscopic sinus surgeries also account for between 7% and 11%, and between 0.5% and 3% of cases respectively (21). Iatrogenic injury most frequently occurs from an inadvertent violation of the cribriform plate or the roof of the posterior ethmoid sinus during endoscopic sinus surgery (EES). Half of iatrogenic leaks present intraoperatively, or immediately following surgery, while the remaining 50% only present between one week and one month postoperatively. Theories for the delay in presentation are postoperative increase in ICP, resolving cerebral edema, wound contraction, or flap devascularisation (21).
2.1.2 Non-traumatic causes of CSF leaks
The less common, non-traumatic etiologies of CSF leakare typically a result of erosion or increased intracranial pressure, and are caused by leaks that can arise due to infections such as osteomyelitis of the skull and tuberculosis, congenital defects, meningoceles, encephaloceles, intracranial tumours such as osteomas and angiofibromas that destroy the bones of the skull base (26),intracranial pressure (ICP), or hydrocephalus(2,7,37,39,48). Meningoencephaloceles or meningoceles may, however, occur in both non-traumatic and traumatic cases (39).
Intracranial tumors can cause CSF leaks by obstructing CSF reabsorption, which results in increased ICP leading to high pressure leaks (3). Otherwise, extracranial or intracranial tumour growth can cause an indirect erosion of the skull base (3).
Another more common cause of non-traumatic CSF leaks is congenital encephaloceles,which occurs in cases of open neural tube defects whereby herniations of the meninges and brain matter protrude through structural defects in the cranium (27). The incidence of congenital CSF leak with encephalocele has been reported in approximately one in every 4000-5000 live births (18,55), often existing at birth in affected individuals. It is, however, typically only diagnosed once the patient presents symptoms of meningitis, CSF leak, a nasal obstruction, or a facial deformity (55).
2.1.3 Spontaneous CSF leaks
Spontaneous, or primary CSF fistulas are classified as a separate etiological entity, since it describes patients that have “no other discernible etiology for their CSF leak”(25, p.727), for example, such as a tumour or congenital abnormality, or any history of trauma. They are therefore classified as having originated from other idiopathic reasons (25,28).
According to current understanding, spontaneous or primary CSF leaks are typically associated with increased ICP, which is likely caused by benign intracranial hypertension (BIH) (3). This is due to the finding that 70% of spontaneous CSF leak patients are diagnosed with BIH (51). Lopatin et al. (26) have also listed obesity, an overpneumatised sphenoid, and empty sella syndrome as other etiological factors in the spontaneous generation of CSF fistulas. Spontaneous leaks are also usually associated with the formation of encephaloceles, whereby Bedrosian et al. (3) suggest that increased ICP may result in the formation of quite large encephaloceles that herniate through pre-existing skull base defects; pushing the brain contents through these small skull-base defects.
Spontaneous CSF leaks are most commonly observed in obese middle-aged women (3,25); and although spontaneous leaks are reported rarely, it is believed that that they may be more common than previously thought (25).
2.2 Anatomical detail of CSF leaks
In the case of CSF rhinorrhea, CSF leaks into the paranasal sinuses from the subarachnoid space and into the sinonasal tract (19,39). Leaks into the nasal cavity can occur directly from the anterior cranial fossa, namely the frontal sinus or the cribriform plate, or as a result of defects in the cranial fossa, namely the sphenoid sinus (22). Ultimately, defects leading to CSF rhinorrhea can occur at any point along the ventral skull base, including the cribriform plate, fovea ethmoidalis, sphenoid bone, temporal bone, or the posterior table of the frontal sinus (32,39), as shown inFigure 1 (3). Although uncommon, CSF that enters into the nose indirectly through the eustachian tube via the mastoid air cell system, such as the middle and posterior fossa, is specifically referred to as CSF otorhinorrhea (22,34).
Figure 1. Illustration of the sagittal view of the skull base, depicting the locations of possible skull base defects, with defects shown at the cribriform region (posterior),and the foramen cecum (anterior). The inset also depicts the fovea ethmoidalis, a frequent site for iatrogenic skull-base violation.
Source: Bedrosian et al. (3)
During spinal surgery, CSF fistulas may also occur which are attributed to inadvertent dural tears (DTs), or deliberate dural opening such as for marsupialisation of cysts, performing shunts or resecting intradural tumours or lesions (Epstein, 2013). DTs can arise inadvertently during primary spinal surgery, but are observed more often during revision spinal surgery as a result of epidural scarring. CSF fistulas or DTs may also be caused by resection of ossification of the posterior longitudinal ligament (OPLL), ossification of the yellow ligament (OYL), or epidural steroid injections (Epstein, 2013). Due to the extracranial localisation of most CSF fistulas and dural tears occurring during spinal surgery, they will not be considered in more detail for this review.
2.3 Dangers of CSF leaks
Defects that remain untreated expose patients to the risk of pneumocephalus, intracranial abscess, and meningitis (2,46). Meningitis, which is a primary hazard in the traumatic form, is far more common than in the non-traumatic varieties (53).
Surgical repair of skull base defects is also performed to prevent nasal obstruction, feeding difficulties, and problems with oral breathing that may be caused by the growth of defects in children (55).
2.4 Historical overview of CSF leak repair
When conservative treatments are not successful, surgical intervention is advised (19). Early attempts at repairing CSF leaks were performed by Grant (15) and Dandy (8) in 1923 and 1926 respectively, the latter of whom closed cranionasal fistulas through a frontal craniotomy (7,19,39).
Fascia lata was first used to repair CSF fistula through a transcranialextradural repair in 1937 by Cairns (5); however, the transnasal approach was limited to cauterisation until 1948, when the transnasal-transethmoid approach was described(11) by sealing off the cribriform plate leak with a septal and middle turbinate (MT) flap (53). The first reported extracranial repair of a CSF rhinorrhea was also performed by Dohlman in 1948 (11), using a naso-orbital incision (22,52). Subsequently, various endonasal approaches were developed using turbinate or septal flaps to repair the fistula site. In 1981, Wigand performed the first successful endoscopic endonasal repair of a CSF fistula, using a rod lens rigid endoscope (49).
Current advancements in surgical techniques and medical instrumentation have made endoscopic repair of anterior skull base CSF leaks a standard in otolaryngological care, and endoscopic sinus surgery (EES) has become a common procedure in the field of otolaryngology (46). More than 90% of cases are treated successfully using this technique (2).
2.5 Detection of CSF leaks
Clinical confirmation of CSF rhinorrhea involves nasal inspection and laboratory testing for CSF markers (7,46). During nasal inspection, the common presenting symptom observed in patients with CSF rhinorrhea is the seeping of a clear fluid from one side of the nose (7).
The CSF has a low specific gravity, high sugar (higher than 30mg/dL, or 1.7 mmol/L), and low protein content (26,53). Measurement of the sugar content is performed on the nasal fluid using glucose oxidase test papers to provide preliminary confirmation of the presence of CSF (7).Drops of CSF from a leak, which are placed on absorbentfilter paper, also typically form a “double-ring” pattern, due to a central ring of blood, and a perimeter ring of CSF (53, p.157).
CSF markers that are used nowadays to confirm CSF rhinorrhea include ß2-transferrin and ß-trace protein. ß2-transferrin is a protein that is only found in CSF, aqueous humour, and perilymph; thus, testing the nasal secretions for the presence of ß2-transferrin represents a far more specific test than the glucose oxidase test (7). ß-trace protein markers are economical and have a high specificity and sensitivity, while ß2-transferrin markers have a high specificity and sensitivity; but are less economical than ß-trace protein markers (45,46).
It should be noted that while the ß2-transferrin assay is usually more specific for CSF than other methods, in the case of associated orbital injuries it can be unreliable since ß2-transferrin also exists in the vitreoushumour (46).
Confirmation of CSF leaks is accurate in more than 90% of cases (2); however, in some cases, the accurate localisation is difficult to discern (28). While the afore-mentioned tests are non-invasive and accurately diagnose the leakage of CSF, they offer little information on the actual location of the leak (7). Accurately identifying the location of a CSF fistula is important for planning the surgical treatment (28). Various studies have listed the identification of the site, size and etiology of CSF leaks as being the most important factors in determining the success of any corrective surgery (46).
Detection of the leak site is usually performed either through nasoendoscopy with intrathecal fluorescein, magnetic resonance imaging (MRI), or computed tomography (CT) scan. Radiolabeled cisternogram or CT/MRI cisternograms are performed less frequently intraoperatively (2).
2.5.1 Intrathecal fluorescein
If the location of the defect is unknown, or less apparent following an MRI or CT (or in the case of spontaneous or multiple defects), a lumbar puncture is performed, and one hour before surgery, a 10% fluorescein in 10ml CSF mixture is slowly injectedover more than one minute (53). The patient is then laid in a trendelenburg position to aid the fluorescein in reaching the intracranial compartment. Intrathecal fluorescein is, however, not always used, as in the case of iatrogenic injury, where the defect is clearly visible on MRI or CT, and the location is known. Its use is also much debated in the literature (19,46,53). In the case of concurrent leaks, or multiple defect sites, many researchers argue that it is especially important that intrathecal fluorescein is used (2). CSF is observed, and thus the location of a leak may be visualised, when fluorescein-stained CSF isseen seeping as a bright yellow-greenfluid that emanates from the defect site (39,53).
Martin-Martin et al. (46) argue that intrathecal fluorescein should not be used during surgery, due to its possible complications. Instead, they recommend observing the leak during surgeryby a Valsalva manoeuvre,thereby increasing intracranial pressure by pressing on the abdomen, and locating the leak as a stream of transparent fluid. Sharma et al. (53) also suggest that there are risks of allergic reactions and transverse myelitis with fluorescein. Fluorescein is neurotoxic in commercial doses, however, Javadi et al. (19) maintain that, based on the results of their study, diluted fluorescein is safe in the low doses administered during endoscopic repair of CSF rhinorrhea. Numerous authors have also suggested that identification of the fistula is one of the most difficult challenges in CSF leak repair, and successful identification is central to the success of any operation (3,25). The risks are therefore often weighed by the advantages of using intrathecal fluorescein.
Other methods of CSF observation have also been employed in the past, including dyes such as phenolsulfonphthalein, indigo carmine and methylene blue, which were introduced intranasally or into the subarachnoid spaces prior to surgery; however, these dyes are no longer in use since they can cause chemical meningitis, and carry a significant risk of morbidity (53).
2.5.2 MRI and CTCisternography
For over a decade, the standard for CSF leak location detection has been CT cisternography, since it has been observed to render an accuracy of 92% in active leaks, and 40% in inactive leaks (28,44). A shortfall of CT cisternography, however, is that it is time-consuming, invasive, uncomfortable for the patient, and can carry the risk of headaches and infections (28). It is also contraindicated in patients with elevated ICP, or meningitis (28).
Unlike CSF leak detection following trauma, CT is not sufficient in the case of spontaneous CSF rhinorrhea, since patients with spontaneous CSF rhinorrhea naturally lack skull fracture sites that can be detected by high resolution CT in traumatic patients (28). CT only provides indirect evidence for CSF leaks, through abnormalities such as bone defects, or a fluid in the paranasal sinus, or pneumocephalus. Spontaneous leak patients are also often associated with encephalocele formation (between 50 and 100%), and large meningoencephaloceles often herniate through relatively small bony defects, which may be mistaken on CT to be small bony defects or secretions of the paranasal sinus, perhaps not actively leaking CSF (28,41).
False positives have also been observed in CT scans during spontaneous CSF leaks, whereby dehiscence or thinning of the skull base, which would be observed under high-resolution CT, could mimic small bone defects at a glance (4).
In some cases, MRI has advantages over CT in CSF leak detection (28). Firstly, MRI complements high-resolution CT, with an accuracy of 89%, sensitivity of 87% and specificity of 100%, in demonstrating the extracranial extension of the CSF column (41). MRI is also more effective in evaluating the leak point when the accurate evaluation of the CSF leak site(s) may be precluded by fibrous tissue or hematoma in the paranasal sinuses; or when there are multiple fractures of the skull base (28).
2.5.3 Pre-operative assessment
Patients are typically referred for neurosurgical evaluation prior to undergoing operative repair, which is ultimately determined by the location and size of the area for repair. The surgical approach will depend where the defect is located, though most often the defect is located in the cribriform region or ethmoid roof, as well as in the sphenoid sinus (37).In the case of iatrogenic injury, the most common location of CSF leak is at the ethmoid roof and the lateral lamella, as shown in Figure 2.
Figure 2 CT scan of an iatrogenic leak in the lateral lamella (left), and coronal CT of a spontaneous leak in the ethmoid roof (right)
Sources: Anstead and Liu (2) (Left); Martin-Martin et al. (46) (Right)
3 TREATMENT OF CSF LEAK
Most CSF leaks that result from iatrogenic or accidental causes, heal over the course of seven to ten days, following the implementation of conservative measures (39). Leaks that are less likely to spontaneously heal are those in which CSF rhinorrhea develops a few days or weeks after a trauma,leaks that are caused by gunshot wounds, large leaks that occur immediately after surgery, or in the event of normal-pressure CSF leaks (39).
The preliminary means of treatment includes bed rest with an elevated head, avoiding straining activities such as coughing, sneezingnose blowing, and the application of stool softeners. Surgery is indicated if no resolution is detected within one-to-two weeks (39). The etiology of the leak also affects the risk of recurrence of CSF leaks, and therefore the method of repair of the defect, since the etiology would typically have a bearing on the location, size, degree of dural involvement, the probability of raised ICP, and the likelihood of meningoencephalocele protrusion (46).
4 TYPES OF APPROACHES TO THE SKULL BASE
Multiple approaches have been described for reaching defects at the base of the skull, including transsphenoidal, transethmoidal, transpterygoid, transcribiform, transplanum, and transclival; each depending on the site of injury (14,35,42). Three core approaches exist, however, for reaching CSF fistulas: Intracranial, extracranial, and endoscopic (53). Surgical repair of CSF leak defects may be achieved extracranially through a frontal sinusotomy or external ethmoidectomy, transcranially through a bifrontal craniotomy, or transnasally through visualisation with endoscopic or microscopic instruments (52). Conventionally, fistulas that persist, or those that do not respond to conservative treatment have beenmanaged by a frontal craniotomy (52).
In the case of defects of the ethmoid roof or cribriform, a direct paraseptal approach may be recommended (34). To create adequate exposure, a complete ethmoidectomy and maxillary sinusotomy are often required, while frontal sinusotomies, middle-superior turbinectomies, and sphenoidotomies mayalso be required to provide added exposure.
In a study by Kirtane et al. (22, p.208) on 267 CSF leak repairs, the authors suggested that in the event of defects in the medial lamella of the cribriform plate, the preferred approach to the defect was between the septum and the middle turbinate, thereby allowing the defect to be localised and sealed, without “sacrificing the turbinate.”
4.1 Intracranial procedures
Originally described by Grant (15) and Dandy (8), intracranial procedures are still prescribed for most traumatic and non-traumaticcerebral fistulas. The critical element for surgical treatment is for the meningeal defect to be adequately closed (53), with careful patching of the fistula site typically accomplished using a fat graft — with or without fascia lata as a free graft, and often using the patient’s own fat.
Although highly invasive, various advantages of the transcranial approach exist (52). These include the ability to directly visualise the dural tear, the ability to treat any adjacent brain injuries that may exist, or the treatment of intracranial bleeding, especially in the case of trauma-related CSF leaks. Another advantage is the opportunity to use a pericranial vascularised flapto cover the anterior skull base, which is not possible during endonasal endoscopic approaches (EEA) (52).
The primary disadvantages of intracranial approaches are edema that is related to brain retraction, anosmia, and intracranial haemorrhaging (43). The success rate for transcranial repairs is only generally considered to be between 60% and 80% (23,24,52) with Sharma et al. (53) suggesting that success rate from the first attempt is only around 60%.Invasive techniques such as open transcranial repair, which traverse neurovascular structures, account for a substantial morbidity, and renders this type of repair a high-risk surgery (17). Reasons for the morbidity associated with the transcranial approaches for repair of CSF rhinorrhea include intracranial haemorrhage, venous infarction, cerebral contusion, bifrontal retraction injury, cerebral edema from frontal lobe retraction, pneumocephalus, anosmia from trauma to the cribriform plate and the olfactory bulb area, and bone flap infection (13,39,52).
Aside from increased risks of morbidity, other complications associated with the open transcranial approach are loss of smell and memory deficits (1,55).In transcranial approaches to the skull base, extensive bone drilling, nerve manipulation and brain retraction is required to expose the underlying pathology in the skull base (38). Transcranial surgery is a difficult operation that typically causes damage to the olfactory nerve fibres traversing the cribriform plate (28), since it requires mobilisation of one or both of the frontal lobes (18). It also carries the need for a large external incision, resulting in a large surgical wound (23,52). Various transcranial procedures have also been suggested for repairing anterior skull base defects in children; however, Ibrahim et al. (18) suggest that these approaches can potentially upset the growth centres in the craniofacial skeleton, causing facial asymmetry.
In many circumstances, however, intracranial approaches are the only possible option, such as in many of the traumatic etiologies, and often in the case of tumours (38). In spite of recent progress in microsurgical techniques, the location of lesions, and their contiguity to vital neurovascular structures can at times make surgical resection difficult. In the case of ventral midline tumours, transcranial approaches that use microscopic equipment need large bone openings to be made, that facilitate the passage of adequate light to the lateral extents of the lesion sites (38). This can require any of a range of open-skull base techniques to allow the surgeon to pass either sub-frontally or laterally, thereby providing a convoluted pathway to the lesion site. As alluded to previously, these techniques typically require large regions of bone to be removed, retraction of the brain to some degree, and manipulation of the cranial nerves across the operative trajectory between the surgeon and the lesion (38).
4.2 Extracranial procedures
Recommended by Aboulker et al. in 1966 (53), the extracranial approach toCSF leaks involves access to the defectthrough the frontal and ethmoidal sinus. Sharma et al. (53, p.159) assert that leaks occurring through thesphenoid sinus and sella turcica are best approached via the “microneurosurgical trans-sphenoid” route.
The primary advantages of the extracranial approach are higher rates of success than the intracranial approaches, lower rates of morbidity, and far less risk of anosmia (6,10,29,33). These approaches also offer the best exposure of the parasellar, sphenoid, and posterior ethmoid regions, and allow superior visualisation of fistulas in the cribriform plate, fovea ethamoidalis, and the posterior wall of the frontal sinus (30,53).
4.2.1 Endoscopic approaches
The endoscopic approach to CSF fistulas is a “subset” of the extradural, extracranial, approaches to CSF leaks (53, p.159). As noted previously, since the first performance of an endoscopic treatment of CSF rhinorrhea by Wigand (49), the technique has become popular, globally, due to its various benefits, including shortened operation time, good visualisation, and precise graft placement successes (47).
The endoscope-assisted ventral endonasal approaches utilise less-invasive means, since they take advantage of natural anatomic corridors that exist, in order to reach the defects of the midline skull base, while providing maximal preservation of the anatomic structures. Other prime advantages of the transnasal, or endoscopic endonasal approach (EEA) are that it minimises the intranasal trauma to the patient while preserving the bony framework that supports the frontal recess and other critical regions of the face (53,54). EEAs also offer higher efficacy of repair, and lower incidences of complications relative to the traditional cranial base techniques (38).
Since they provide an accessible trajectory to reaching the anterior skull base through the ethmoid and sphenoid sinuses, EEA can be used either as an adjunct to the microscope for reaching more lateral components of the target, or the sole means of illumination in accessing the ventral and midline regions (38).
Since the first successful repair of a CSF leak performed by Wigand in 1981 (49), minimally invasive endoscopic endonasal surgery (EES) for repair of CSF rhinorrhea has almost completely replaced the more invasive open transcranial approaches to the skull base (7,39).
4.2.2 Open transcranial versus endoscopic endonasal approaches
Endoscopic endonasal approaches allow excellent exposure of the nasal cavity roof, and improved access, which in turn offer the opportunity to reach and treat defects highly efficiently (31,46). Numerous other advantages of EEA exist over open transcranial and extracranial interventions (46). These are summarised as follows:
• EES is a minimally invasive surgical technique, as compared to open transcranial repair, as it provides a “direct short-cut access” to the anterior and middle skull base, without the need for traversing any important neurovascular structures;
• EES provides an excellent, panoramic view of the surgical field (53);
• EES does not require specific material or instruments for performing the procedure, aside from a rod lens rigid endoscope;
• Nasal endoscopes are available with different angled lenses, which can clearly expose the roof of the sinonasal tract, and facilitate the precise localisation of CSF fistulas (52);
• There is no minimum age limit for children or infants to undergo EES; and
• EES may be performed in a shorter surgery time than transcranial procedures (53).
Defects that are smaller than 1.5 cm in size, and located within the cribriform, sphenoid, ethmoid, and frontal sinuses, which are most easily accessed transnasally, are best repaired by EES (34). Increased success rates for the EEStypes of treatment have also been cited, whereby the success rate for leak closure of endoscopic CSF leak repairs was observed in a systematic review (28) to be 90.6% after the first attempt, and as high as 96.6% following a second attempt; with very little chance of complications (0.03%). Additionally, in a study by Martin-Martin et al. (46), the success rate of 30 patients who underwent CSF leak repair surgery by EES was even higher, at 93.4%, and none of the patients that required a second procedure required a craniotomy for closure.
As described above, there appears to be no minimum age limit for EES (55), and in a study by Di Rocco et al. (9), the youngest reported CSF leak repair patient was 1.5 months old. Similarly, in a study by Ma et al. (55), the youngest patient was 3 months old, while a large number of the study’s patients were younger than 1 year of age.
It should be noted that EES is not an option in all cases, and as described previously, in the event that fistulas occur in the posterior wall of the frontal sinus, open transcranial techniques are still the only option (46). Situations where a craniotomy are still required include oncologic procedures, as described previously, frontal sinus defects with lateral extensions; defects that are greater than 1.5cm in size, or defects of the posterior wall of the frontal sinus where an open technique best addresses the primary lesion site (32,34).
Furthermore, Cukurova et al. (7) assert that while a leak in the ethmoid roof or cribriform plate can be treated with standard EES, a full endoscopic ethmoidectomy is often required to provide suitable exposure of a skull-base defect and leak; and at times, a frontal sinusotomy, sphenoidotomy, and middlesuperior turbinectomy may be needed if additional exposure is required.
5 MATERIAL USED FOR CSF LEAK REPAIR
Various materials are used for CSF leak repair (52). The ultimate purpose of surgical intervention is to insert a seal or blockage to the CSF fistula, thereby stemming the flow of CSF. For this purpose, numerous grafting materials, and intraoperative instruments have been prescribed (12,56).
5.1 Grafting materials
Grafting materials used for CSF repair are most often cartilage, fascia, fat, local pedicle tissue, cadaveric fascia or dermis, mucoperichondrium, turbinate, septal mucosa, free mucosal grafts, or composite grafts (34). In high-flow or large skull base defects, pedicle nasoseptal flaps (PNSFs) have been widely used since their inception in 2006 (12,16,20). Zweig et al. (52) categorise the materials used for grafting as either autologous, homologous, or allografts:
• Autologous materials include septal mucosa, abdominal fat, turbinate bone, or temporalis fascia;
• Homologous materials include fascia lata, or cadaveric pericardium; and
• Allografts include materials such as hydroxyapatite cement or other artificially produced medical devices.
Often, surgeons recommend obtaining grafts of the nasal passages, and specifically from the nasal septum, turbinates or the nose floor. The temporalis fascia is also considered appropriate (40). Each Fistula should be treated uniquely, though, and Martin-Martin et al. (46, p.4) recommend that a surgeon should “know the different options” available, in order to “solve the problem”.
Saafan et al. (39) suggest that in the event that the patient has increased CSF pressures, a rigid underlay graft should be used, such as bone. Conversely, in the event of leaks that have normal intracranial pressures, soft tissue grafts are often suitable, and rigid grafts are typically not necessary (39).
Material that can be used for rigid grafts includes bone grafts from the mastoid, turbinates or septum; while soft tissue materials for overlay or underlay grafts can include fascia lata, temporalis fascia, free mucosal or mucoperichondrial grafts, or cadaveric dermis or fascia (39,50). These may be used overlay, such as over the nasal side of the defect, or underlay — between the skull base bone and dura — to seal the affected region (39).
Zweig et al. (52, p.139) argue that, regardless of the choice of material and the specific technique performed in the repair, “if the surgical technique is sound”, the endoscopic repair of CSF leaks should still be “highly successful”.
5.2 Intraoperative instruments
Instruments used in the endonasal endoscopic surgical (EES) repair of CSF rhinorrhea include various endoscopic nasal instruments, such as 0-, 30-, and 45-degree rigid nasal endoscopes. In the event that fluorescein is to be used for the purposes of the CSF leak, a yellow light filter is applied for the endoscope, and a blue light filter is used for identifying the leak site (34).
Although its use is disputed (56), a perioperative lumbar drain is often used to regulate ICP, administer intrathecal fluorescein, and aid in reducing encephaloceles (34). The drain typically remains in situ, postoperatively, for between 24 and 72 hours (34). A low rate (5 mL/h) lumbar drain for a short duration postoperatively also assists in avoiding pooling at the defect reconstruction site following placement of the graft, thereby allowing any sealant to fully harden with a watertight seal (32).
6 REPAIR OF CSF LEAKS BY ENDOSCOPIC ENDONASAL SURGERY
The team involved in an EES repair of a CSF rhinorrhea typically involves an otolaryngologist and neurosurgeon. General anaesthesia isalmost always induced (19,23), and a topical decongestion of the nose is achieved using cottonoids soaked in phenylephrine, oxymetazoline, or 4% cocaine (32). The nasal mucosa is typically treated with epinephrine to achieve a complete contraction of the blood vessels, and the nasal cavity is also disinfected with iodoform (23). The patient is then usually placed in a supine position with their head elevated by 15?(19,23).
A lumbar drain is typically placed; and prior to the injection of fluorescein, the patient should receive a dose ofdiphenhydramine and dexamethasone (32).Standard procedure then dictates the slowinjection of 0.2 ml of 10% fluorescein,intrathecally, diluted in 10 mL CSF, up to one hour before surgery (2). A blue light filter positioned on the endoscopic light source enhances the fluorescein dye, and helps to locate the CSF leak (32,34). In the event that the defect location is known, such as in the case of iatrogenic or traumatic injuries, or if the defect is clearly visible on MRI or CT, intrathecal fluorescein is not necessarily used (2).
In the first phase of the surgical procedure, adequate exposure of the entire bony defect must be obtained, which may necessitate an extended approach to allow visualisation of the skull base defect (32). In the case of lateral sphenoid defects, a transmaxillary, transpterygoidal approach may be required as an adjunct to the standard transsphenoidal, transethmoidal approach. Furthermore, in the case of cribriform plate defects, a partial or total resection of the middle turbinate (MT) may be required in order to access the defect (32). Thus, while one school of thought is that the middle turbinate should be excised, another belief is that the operation should simply lateralise the middle turbinate (53).
Surgery can be performed with or without the use of a nasal speculum; however, a nasal speculum can obviate the need for a middle turbinectomy, thereby widening the nasal passage to facilitate the placement of the telescope and other instruments (53). A middle turbinectomy also prevents accidentalknocking of the telescope against the turbinate (53).
Once the defect has been located, the mucosa must be entirely stripped away from the defect site, and a bed fashioned in preparation for a graft (34).Curettes or a diamond burr are often used for this purpose (18). Awide exposure of the defect site will assist graftplacement and improve the rate of success of closure (32).
In preparation of the site, any encephaloceles or dural protrusions must be resected or reduced into the intracranial cavity — for example, by bipolar elecrocautery at the stalk — to prevent them from retracting into, and haemorrhaging within the skull (32,18). Careful use of a microdebrider, or otherwise thru-cut forceps can be used to reduce or resect the herniated dura (32). In the case of any encephaloceles, herniated brain tissue within the nasal cavity is seldom functional, and is deemed a source of intracranial infection if not resected (57). It is also important to ensure that any contact between the prolapsed brain and the bony defect is severed (32).
A graft is then placed over the site to cover the defect (34).Closure of the grafted repair site is performed using either an overlay, underlay, combined, or obliteration technique, depending on the nature and size of the defect (34).
6.1 Onlay or overlay technique
The onlay or overlay technique is generally recommended in small leaks less than 10 mm, or in cases where the underlay technique is not possible (32,46). In the overlay technique, the graft is placed extrinsically, or on the nasal side of the defect, as shown in Figure 3.
Figure 3 Photograph of the overlay technique, with fascia being grafted into a defect of the sphenoid roof (LEFT), and a schematic sagittal diagram of a defect being plugged by soft tissue using a seeker probe (RIGHT)
Source: Paul and Upadhyay (34) (LEFT); Nyquist et al.(32) (RIGHT)
Small defects are usually sealed by placing an inlay of graft material, or simply by “plugging” tissue into thedefect using a seeker probe, as shown inFigure 3. The bony defect is transcended by the graft with both a sinonasal and an intracranial component, which circles the defect with a surrounding, watertightseal (32). Materials that are commonly used for the onlay graft include fascia lata, fat, and medical device products such as Alloderm by LifeCell Corporation in Branchburg, New Jersey, or DuraGuard by Biovascular Corporation in Minneapolis (32). Often, a tissue sealant such as Duraseal by Covidien in Mansfield, Massachusetts, can be used to secure the graft in place (32).
6.2 Underlay technique
In the underlay technique, the graft material is placed between the dura and the bone of the skull base, as shown in Figure 4. Various CSF leakage repair treatments have been described that used an underlay technique, and it is widely accepted that the preferred method of treatment for large defects is through the underlay technique (46). In this method, fistulas are closed by placing mucoperichondrium, which is combined with a grafting of cartilage, and sealed with fibrin glue into the fistula site (34).
Figure 4 Photograph of the underlay technique, with conchal cartilage being grafted into a defect of the medial lamella
Source: Paul and Upadhyay (34)
6.3 Combined technique
In combined techniques of CSF leak repair, the graft is placed below the dura, between dura and bone, while anextracranial overlay is also used (34). Otherwise described as the ‘sandwich-grafting technique’, this technique often incorporates two layers of facia lata (underlay and overlay), interposed with a layer of conchal bone or septal cartilage in-between (39). Saafan et al. (39) argue that using a three-layered sandwich-grafting technique of facia lata provides added security to the sealing of CSF leaks, and enhances the chances of success of the surgery.
Various other authors also describe multilayer techniques (18,32). The method used by Ibrahim et al. (18), for example, consists of the following five layers:
1. Layer one is an intracranial intradural underlay fat graft harvested from the anterior aspect of the thigh;
2. Layer two is an intracranial extradural layer of fascia lata slippedunderneath the bony edge of the defect;
3. Layer three is an intracranial extradural layer of bone to close the bone defect, harvested from the bonyseptum or MT;
4. Layer four is an extracranial overlay graft of fascia lata over the defect; and
5. Layer five is a free mucoperiosteal graftfrom the MT in the event a middle turbinectomy has been performed, or otherwise an extracranial vascularised nasoseptal rotational flap.
In many larger defects, and for those along the ventral skull base, a multi-layered gasket seal is often favoured, which consists of a soft tissue graft of fascia lata centred over the defect, and with the surrounding edges of thegraft circumferentially surpassing the bony defect (32). A rigid graft is often shaped to roughly the size of the bony defect, and surgeons such as Nyquist et al. (32) recommend vomer bone, or medical devices such as Medpor by PorexSurgical in Newnan for this purpose. Approximately 5 mm of excess soft tissue is left around the rigid graft, which is gently countersunk into thebony defect to form a watertight seal, or gasket seal. The gasket seal is then covered by a vascularised flap, which is adhered to the surrounding bony skull base aroundthe gasket seal with a tissue sealant, as shown in Figure 5.
Figure 5 Schematic diagram of the coronal view of a defect being plugged by both an onlay, and an underlay graft
Source: Nyquist et al. (32)
In some clinical situations, such as after the removal of large intracranial tumours, dead space should first be eliminated with a filling of fat before placement of the gasket seal; unless communication exists between the defect and the third ventricle, whereby fat may migrate and cause an obstructive hydrocephalus (32).
6.4 Obliteration technique
When repairing a CSF leak with obliteration, firstly the mucosa is completely stripped, before a graft of abdominal fat is inserted into the defect graft bed. Fibrin glue is then often used to assist in wound healing by facilitating the contact of the graft to the recipient site (34).
7 CHALLENGES TO CSF LEAK REPAIR
In many cases, CSF leaks are completely repaired through a minimally invasive endoscopic endonasal surgery, though this requires a complete and accurate preoperative determination of the leak site to be performed (28). Javadi et al. (19) assert that identifying and locating the dural defects and CSF leaks are a significant challenge, since CSF is translucent, and the operative field is typically obscured with mucosal secretions or blood.
As noted previously, various studies have listed the identification of the site, size and etiology of CSF leaks as being the most important factor in determining the success of any surgery (46). However, CSF leaks that occur in the anterior skull base form one of the more difficult of the endonasal endoscopic surgeries, due to the location, which is technically demanding to access, and anatomically complicated (46).
Another significant challenge exists when recreating the barrier between the nasal cavity and the cranial vault to eliminate the CSF leak, and in turn, protect the brain from exposure to infection (46).
Ma et al. (55) assert that in the case of paediatric CSF leak repair, such as in infants and small children, diagnosis and surgical intervention is challenging. Furthermore, according to Ma et al. (55, p.2), “the general principles and results of endoscopic transnasal surgery in adults cannot be directly extrapolated to infants and children.” Endoscopic procedures are known to be more challenging in children because of their narrow nasal fossae, which require a higher surgical experience to navigate successfully (18).
Bedrosian et al. (3, p.87) argue that “in many ways, spontaneous CSF leaks are the most difficult to treat”. They assert that this is because the small, slow leaks that are typical of spontaneous CSF leaks can often be difficult to locate, while the broad attenuation of the skull-base bones makes the complete watertight sealing of leaks difficult. Furthermore, associated meningoencephaloceles or encephaloceles are observed in between 50% and 100% of patients, with rates of postoperative recurrence being generally higher than any of the other causes (between 25% and 87% in many cases). While repair techniques are similar to the other etiologies, postoperative management of spontaneous leak patients is “critical” (3, p.87).
A debate exists over the use of fixators for CSF leak repair. These include compounds such as fibrin glue and/or packing, as well as postoperative adjunctive management, such as the use of perioperative antibiotics and lumbar drains (39). Upon placement of the graft, a sealant such as fibrin glue can be applied to secure the graft in place. Absorbable nasal packing, or gel-foam, is also usually applied for between five and seven days postoperatively, directly on the mucosal edge of the graft to improve support. This is followed by a non-absorbable packing that provides additional support and hemostasis, and these packs are typically removed after between five and seven days (36).
A controversy also exists in which technique of graft placement to use. Depending on the size of the leak, either the onlay technique or the underlay technique is used. Authors such as Martin-Martin et al. (46) use curettes of different sizes to determine the size of the fistula. Sizes of defects vary greatly, and a study by Ma et al. (55) observed defect sizes with expanses of between 4 and 150mm2 in size.
Bacterial meningitis may also be caused following surgery when a repair has not healed sufficiently,or when a lumbar drain still remains after the procedure, or if prophylactic antibiotics have been administered that promote the growth of bacterial resistance and infection (46).
7.1 Recurrence of CSF leak
Traditionally, defects that have been managed via lateral rhinotomy or craniotomy have been associated with considerable recurrence rates, with studies reporting up to 40% recurrence rates following these techniques (1,55).
Endoscopic endonasal repair of CSF leak has been shown to be effective, and minimises morbidity. However, general principles of adequate bridgement of the surrounding mucosa should be ensured, and suitable postoperative care should also be followed (2). Recurrence of CSF leak has been seen, though it is typically associated with benign intracranial hypertension, and high-flow CSF leaks. In such patients, postoperative acetazolamide, ventriculoperitoneal shunts, or lumbar drains may be indicated (2).
Persistent leaks that require a second operation occur in between five and ten percent of endoscopic repairs. A second EES increases the rate of success to 97%. Rates of persistent leaks that do not respond even after a second EES include the following (34):
• Frontal lobe abscess (0.9%);
• Anosmia (0.6%);
• Pneumocephalus (0.6);
• Meningitis (0.3%);
• Intracranial haemorrhage or hematoma (0.3%); and
• Chronic headache (0.3%).
8 CONCLUSION
Numerous differences exist between traumatic and spontaneous CSF leakfrom presentation, to their causes, modes of treatment, and their recurrence after treatment. Endoscopic endonasal approaches to repair haveseveral advantages over open craniotomy surgery; however, it is not always possible to perform EES. Therefore, each of the primary forms of surgery are still prevalent, and research is needed to continue to improve them.
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