Diagnosis and Treatment of Cerebrospinal Fluid Rhinorrhea Following Accidental Traumatic Anterior Skull Base Fractures

Neurosurg Focus 32 (6):E3, 2012

Diagnosis and treatment of cerebrospinal fluid rhinorrhea following accidental traumatic anterior skull base fractures

Mateo Ziu, M.D., Jennifer Gentry Savage, M.D., and David F. Jimenez, M.D. Department of Neurosurgery, University of Texas Health Science Center at San Antonio, Texas

Cerebrospinal fluid rhinorrhea is a serious and potentially fatal condition because of an increased risk of meningitis and brain abscess. Approximately 80% of all cases occur in patients with head injuries and craniofacial fractures. Despite technical advances in the diagnosis and management of CSF rhinorrhea caused by craniofacial injury through the introduction of MRI and endoscopic extracranial surgical approaches, difficulties remain. The authors review here the pathophysiology, diagnosis, and management of CSF rhinorrhea relevant exclusively to traumatic anterior skull base injuries and attempt to identify areas in which further work is needed. (http://thejns.org/doi/abs/10.3171/2012.4.FOCUS1244)

Key Words • craniomaxillofacial trauma • head trauma • cerebrospinal fluid rhinorrhea • meningitis • dural repair • endoscopic surgery • skull base fracture

erebrospinal fluid rhinorrhea is a serious and po- Furthermore, the issues related to CSF leak caused tentially fatal condition that still presents a major by traumatic injury are complex and multiple. Having challenge in terms of its diagnosis and manage- conducted a thorough review of existing literature, we ment.C It is estimated that meningitis develops in approxi- discuss here the pathophysiology, diagnosis, and man- mately 10%–25% of patients with this disorder, and 10% agement of CSF rhinorrhea relevant to traumatic anterior of them die as a result. Approximately 80% of all cases of skull base injuries and attempt to identify areas in which CSF rhinorrhea are caused by head injuries that are asso- further research is needed. ciated with cranial fractures.118 The estimated incidence of basilar skull fracture from nonpenetrating head trauma Methods varies between 7% and 15.8% of all skull fractures, with associated CSF leakage occurring in 10%–30% of these For this review, primary and secondary neurosurgery, patients.95,118 The leak can occur wherever the dura mater otorhinolaryngology, craniofacial surgery, and general is lacerated during injury and there is a communication surgery literature in the English language and published between the intracranial and nasal cavities. in the period from 1926 to 2009 was searched on Med- Despite many advances, it is still difficult to critically line. The key words used for our search included “anteri- interpret the literature with regard to the optimal man- or skull base fracture,” “skull base endoscopy,” “surgical agement of CSF leakage following craniomaxillofacial treatment of skull fractures,” “head trauma,” and “CSF trauma. Most published articles, while documenting the rhinorrhea.” All publications referring to CSF rhinorrhea efficacy of endoscopic surgery to repair CSF leaks, have not of traumatic origin were excluded from our analysis, failed to separate patients into distinct etiological groups and only those referring to the CSF rhinorrhea follow- when reporting outcome. In addition, no authors have ing traumatic anterior skull base fractures were included. consistently analyzed the success of nonsurgical treat- We also excluded publications that classified postsurgical ment modalities, such as bed rest and CSF diversion, and CSF rhinorrhea as posttraumatic. Furthermore, we ex- still little is known about the incidence and natural his- cluded all publications referring to patients younger than tory of this disease entity, the need for antibiotics, and the 18 years of age. surgical indications for and timing of intervention.10 We focused our review on the methods of clinical, chemical, and imaging diagnosis of CSF rhinorrhea fol- Abbreviations used in this paper: bTP = b trace protein; CTC lowing traumatic injury. We reviewed the literature on = CT cisternography; EVD = external ventricular drain; GCS nonsurgical and intracranial and extracranial surgical = Glasgow Coma Scale; GdMRC = MRC with intrathecal Gd- treatment of posttraumatic CSF rhinorrhea. enhancing contrast; HRCT = high-resolution CT; ICP = intracranial Regarding the extracranial endoscopic repair of post- pressure; MRC = MR cisternography. traumatic CSF leakage, we reviewed the English literature

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Unauthenticated | Downloaded 10/01/21 02:35 AM UTC M. Ziu, J. G. Savage, and D. F. Jimenez published in the period from 1980 to 2009. We found 37 Results articles that discussed patients with posttraumatic CSF rhi- A Historical Overview norrhea (Table 1). We were unable to find any articles that reported studies exclusively on accidental posttraumatic In 1745 Bidloo the Elder was the first to describe CSF CSF rhinorrhea. We excluded those studies in which the rhinorrhea after a traumatic skull fracture and correlate number of leaks, rather than the number of patients, were them.29 It was not until the advent of radiographic tech- reported.121 niques that the presence of a communication between the

TABLE 1: Literature review of studies on endoscopic transnasal repair of CSF rhinorrhea*

All Patients Reported† Patients w/ Accidental Trauma‡ No. of Initial Success No. of Patients No. of Initial Success No. of Patients Authors & Year Patients Rate (%) w/ Recurrence Patients Rate (%) w/ Recurrence Mattox & Kennedy, 1990 5 100 0 2 100 0 Dodson et al., 1994 29 76 7 3 100 0 Anand et al., 1995 12 92 1 3 100 0 Burns et al., 1996 42 83 7 5 100 0 Sethi et al., 1996 5 100 0 1 100 0 Lanza et al., 1996 36 94 2 4 100 0 Hao, 1996 6 100 0 2 100 0 Schick et al., 1997 23 95 1 20 NS NS Hughes et al., 1997 17 94 1 2 100 0 Klotch et al., 1998 12 75 3 6 83 1 Castillo et al., 1999 27 82 5 4 75 1 Marks, 1998 18 94 1 2 100 0 Casiano & Jassir, 1999 33 97 1 2 100 0 Nachtigal et al., 1999 12 83 2 3 NS NS Bibas et al., 2000 4 75 3 2 50 1 Mao et al., 2000 20 86 3 3 NS NS Marshall et al., 2001 53 90 6 9 NS NS Castelnuovo et al., 2001 31 87 4 13 85 2 Lund, 2002 34 85 5 9 NS NS Husain et al., 2003 9 89 1 6 83 1 Chin & Rice, 2003 37 89 4 3 NS NS Lee et al., 2004 39 92 3 20 NS NS Lindstrom et al., 2004 36 89 4 6 100 0 McMains et al., 2004 92 85 14 18 NS NS Landeiro et al., 2004 10 90 1 7 100 0 Briggs & Wormald, 2004 52 90 5 13 NS NS Tosun et al., 2005 10 100 0 3 100 0 Kirtane et al., 2005 267 97 9 119 NS NS Araujo et al., 2005 44 80 9 8 NS NS Gendeh et al., 2005 16 87 2 3 100 0 Bernal-Sprekelsen et al., 2005 39 98 1 14 NS NS Locatelli et al., 2006 123 93 9 27 85 4 Silva et al., 2006 19 100 0 8 100 0 Cukurova et al., 2008 3 100 0 2 100 0 Banks et al., 2009 193 91 17 16 NS NS Cassano & Felippu, 2009 125 94 8 41 100 0 Presutti et al., 2009 52 88.5 6 16 87.5 2

* NS = not specified; that is, did not specify the rate of success for postaccidental trauma repairs. † Total number of cases reported with the initial success rate. ‡ Patients with postaccidental traumatic CSF rhinorrhea extrapolated from all patients reported.

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Unauthenticated | Downloaded 10/01/21 02:35 AM UTC Cerebrospinal fluid rhinorrhea after anterior skull base trauma cranial and nasal cavities was diagnosed in a live patient. diagnosis, type and extent of skull defect, and duration Luckett73 was the first, in 1913, to publish this event by de- of symptomatology and suggest the possible timing and scribing the presence of an intracranial aerocele. In 1937 type of repair to be undertaken. Cairns,19 a British neurosurgeon, was the first to propose The most favorable groups of patients to treat appear a classification of CSF rhinorrhea. He divided them into to be those who suffer head injuries resulting in a narrow acute traumatic, postoperative, delayed traumatic, and fracture of the skull base. In contrast, those groups that spontaneous. Ommaya91 and then Vrabec and Hallberg114 suffer multiple or large fractures and a broad or multifo- later refined this classification. In his series, Ommaya re- cal injury, as well as those that are victims of penetrating ported a 2% incidence of CSF leaks in all head injuries. injury with significant comminuting fractures of the skull The incidence increased to 5% when considering only pa- base, represent the most difficult groups to treat.102 tients with skull base fractures. In addition, he noted that The relationship between skull fractures and CSF 90% of CSF leaks were caused by traumatic events. leaks is well described throughout the literature, and we In 1926 Dandy31 described the first successful in- know that given the close relationship of the meninges tradural closure of a CSF fistula by suturing autologous and the skull, these fractures can cause CSF fistulas and fascia lata behind the posterior wall of the frontal sinus. leaks. Identifying the types of skull fractures that would In 1937 Cairns19 demonstrated that CSF leaks could also suggest an increased risk for persistent CSF leaks and/or be repaired with the extradural application of fascia lata. meningitis and those refractory to conservative manage- Nevertheless, reports that spontaneous cessation of ment is crucial in determining appropriate management. a CSF leak was possible led some to think that surgical Anterior skull base fractures include a significant number intervention was unnecessary and unproven.21,54 Calvert of injuries resulting in rhinorrhea from a CSF fistula.104 and Cairns,20 in a discussion of war injuries to the frontal Friedman and colleagues46 reported that CSF fistulas in and ethmoidal sinuses, described a number of cases in 84% of 51 patients were attributable to skull fractures which CSF rhinorrhea healed spontaneously.54 most commonly involving the frontal sinus, followed by Other treatment modalities were advocated as well. the orbital and petrous bones. In his paper published in 1944, Schroeder105 described a The anterior cranial base consists of a number of seg- patient with CSF rhinorrhea who recovered after treat- ments that vary significantly in rigidity and orientation ment with sulfonamides and a lumbar puncture. Also in relative to the horizontal plane and in their proximity to 1944 Dandy32 advocated the surgical repair of any CSF different compartments and constructs of subarachnoid leak within 2 weeks of its onset to prevent meningitis. The spaces, and as a consequence is exposed to different “lo- review of Lewin69,70 of the British combat experience and cal” CSF flow pressures and velocities.100 Building on a large series of skull fractures built the case for adopting these principles, multiple groups have suggested classi- more aggressive operative management of CSF leaks as fications that allow more precise localization and a bet- the standard of care.29 In 1948 Dohlman36 performed the ter understanding of the relationship between specific first extracranial repair of spontaneous CSF rhinorrhea fracture types and the risk of subsequent CSF fistula. In via a naso-orbital incision. In 1981 Wigand116 was the first an effort to find a relationship between the location and to use an endoscope for the extracranial repair of a CSF size of cranial base fractures and intracranial infection, leak. It appears that Mattox and Kennedy,81 in 1990, were Sakas et al.100 classified anterior cranial base fractures the first to use an endoscope for the diagnosis and trans- into 4 types: Type I, cribriform, a linear fracture through nasal repair of CSF rhinorrhea in a series of patients with the cribriform plate without involvement of the ethmoid accidental craniofacial fractures. Over the last 30 years, or frontal sinuses; Type II, frontoethmoidal, fracture that the transnasal endoscopic approach has become a very extends through the medial portion of the anterior cranial important part of the armamentarium for repairing most fossa floor where it directly involves the ethmoid sinuses cases of CSF rhinorrhea, with reported success rates of and/or walls of the medial frontal sinus; Type III, lateral approximately 90% (Table 1). frontal, fracture that extends through the lateral frontal sinus (superomedial wall of the orbit) and may involve the Classification of Anterior Skull Base Fractures and CSF superior or inferior walls of the lateral frontal sinus; and Rhinorrhea Type IV, complex, any combination of the prior types. Us- Cerebrospinal fluid rhinorrhea can be classified ing this classification scheme, Sakas and colleagues con- based on etiology, anatomical location, age of the patient, cluded that Type I cribriform fractures have the highest or extent of bony defect. The most frequently used type risk for infection at 60%, with Type II frontoethmoidal of classification is based on the etiology of the CSF fis- fractures a close second at 43%. This finding was prob- tula. Several such classifications have been proposed, and ably attributable to a higher incidence of larger fracture the main difference among them is in grouping CSF rhi- sizes and CSF rhinorrhea in these groups. The authors norrhea due to accidental trauma and postsurgical CSF concluded that after an anterior skull base fracture, pa- rhinorrhea together under the posttraumatic category tients with Type I and II fractures (fractures close to mid- (Fig. 1). Because of the different types of defects created, line), fracture displacement > 1 cm, and prolonged rhi- diagnosis, time of presentation, underlying brain pathol- norrhea (> 8 days) have an increased risk of posttraumatic ogy, and speed of injury impact, we prefer to consider meningitis. the postsurgical CSF fistula and postaccidental traumatic Using this classification scheme, Madhusudan and CSF leak in separate categories (Fig. 1 upper). The type colleagues76 developed an expanded nomenclature of of classification used should consider the timing of the frontobasal fractures to include the frontobasal region in-

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Fig. 1. Two types of classifications of CSF rhinorrhea most frequently used in the literature. Upper: Classification that considers postaccidental trauma and iatrogenic postsurgical CSF rhinorrhea as different entities. Lower: In some of the otolar- yngology literature, iatrogenic postsurgical and accidental posttraumatic CSF rhinorrhea are grouped together as posttraumatic. volved, the associated midfacial injury, and the mode of doxical rhinorrhea is rhinorrhea from the naris contralat- injury. In this scheme, the frontobasal region is divided eral to the site of CSF leakage. It can occur with displaced into frontal, basal, and combined frontobasal regions, fractures of the midline structures, the crista galli and with the basal region described as the floor of the ante- vomer, and can also be seen in the setting of mucocele rior fossa formed by the bony ethmoid labyrinth, planum formation obstructing the ipsilateral naris.12 Paradoxical sphenoidale, and lateral orbital walls. These regions are rhinorrhea should also be considered after temporal bone then subdivided sagittally into central, lateral, and com- fractures when the temporal dura is torn and CSF travels bined areas. The authors’ results revealed that the fronto- from the origin of the leak, down the eustachian tube into basal type is the most common skull fracture. They re- the nasopharynx, and ultimately to the site where CSF ported that the incidence of a CSF leak was significantly exits the naris.12 The majority of paradoxical CSF leaks higher in impure types of frontobasal fractures, defined have been managed conservatively with good success.30 as the presence of a midface fracture. While anterior skull base fractures appear to be the Pathophysiology and Anatomy of Posttraumatic CSF most common types of fractures resulting in rhinorrhea, Rhinorrhea Brodie and Thompson16 indicated that CSF rhinorrhea Accidental trauma can lead to a variety of skull base can also result from temporal bone fractures. In their defects, and thus accidental traumatic CSF leaks are as- study of 820 temporal bone fractures, these authors found sociated with a heterogeneous group of injuries needing that 72% of patients with temporal bone fractures and highly individualized care. To this purpose, understand- CSF fistulas presented with CSF rhinorrhea. ing basic CSF physiology and ICP changes will be helpful When evaluating traumatic CSF leaks involving the when developing treatment plans for patients with CSF anterior skull base, one must also take into account the leaks. possibility of paradoxical rhinorrhea. Simply stated, para- Cerebrospinal fluid is formed by the choroid plex-

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Unauthenticated | Downloaded 10/01/21 02:35 AM UTC Cerebrospinal fluid rhinorrhea after anterior skull base trauma uses as capillary ultrafiltrate during various metabolic ingitis, and pneumocephalus.104,118 In the chronic phase, processes at a rate of 0.35 ml/minute (350–500 ml/day). patients may present with recurrent meningitis, intermit- The total volume of CSF in an adult at any given time tent nasal discharge, headaches, salty or sweet taste in the is approximately 90–150 ml. The cycle of continual pro- retropharyngeal space,59 hyposmia,23 and brain abscess. duction and absorption results in the total volume of CSF The risk of recurrent meningitis after posttraumatic being turned over 3–5 times/day. Arachnoid villi are the CSF leakage has been reported to range from 12.5% to anatomical structures where CSF absorption occurs. A 50%, with a 29.4% neurological complication rate.43 El- pressure gradient of 1.5–7 cm of water is required to drive jamel and Foy42,43 have reported an overall 30.6% risk of CSF through these structures.102 meningitis before surgical repair and a risk of 1.3% per Cerebrospinal fluid rhinorrhea refers to CSF leakage day in the first 2 weeks after injury, 7.4% per week in the through the nose. For this to occur, both a communication 1st month after injury, and a cumulative risk of 85% at the between the intracranial space and the nasal cavity and 10-year follow-up. Infection is the most feared complica- a breach in the dura mater should be present. Traumatic tion because of its association with increased mortality CSF leaks usually begin within 48 hours of injury, and and morbidity. As such, its prevention, in parallel with 95% of them manifest within 3 months.102 More than 85% management of the primary injury, is critical to optimiz- of traumatic CSF rhinorrhea cases cease with observa- ing outcome.2 tion or nonsurgical treatment, such as bed rest and CSF flow diversion. It has been suggested that leaks that close Diagnosis of CSF Rhinorrhea without surgical repair are probably covered by a layer of Differentiating CSF rhinorrhea from other types of fibrous tissue or regenerated nasal mucosa since dura ma- 102 nasal secretions is the cornerstone in diagnosing the CSF ter does not regenerate. In some instances, the presence fistula. In patients with profuse posttraumatic CSF leak- of an encephalocele or a meningocele through the bony age, the diagnosis is obvious and needs only to be con- defect may disallow the healing process. Furthermore, firmed.115 However, in the acute posttraumatic phase and the size of the defect is an important factor in predicting 99,100 especially in obtunded patients, the diagnosis could be the possibility of spontaneous cessation of the leak. complicated by the presence of sanguineous fluids exiting Hence, treatment approaches must be individualized, from the nasal cavities as the result of other existing facial especially when considering patients with closed-head fractures. Furthermore, it is not rare for CSF rhinorrhea injuries and small fractures versus those with large and to be intermittent and sometimes start even years after a comminuted fractures or those with penetrating injury to traumatic event, when that event has been forgotten. It is the skull base.99,102 in these cases that the diagnosis of CSF leakage could be Another important factor in determining the appro- challenging and frustrating.115 priate treatment for CSF leakage is the anatomy of the The “reservoir sign,” which is the ability of a patient dura at the location of the fracture. In other words, the to leak CSF by flexing the head, is taken to be specific native dural integrity and its relation to the skull base play a role in the formation of a CSF fistula. As discussed for a fistula, although the sign is not always positive even above, a large portion of CSF leaks and subsequent cases when the leak exists. “Target sign” refers to the ability of of meningitis appear to be more common in instances of CSF to migrate further, creating a bull’s-eye stain with frontobasal fractures. Sakas and colleagues100 remind us blood in the center, on a filter paper or gauze. This has that the cribriform plate is thin and fragile, covered only been reported as a very unreliable sign since watery nasal secretions and blood are mixed, and the same pseudo- by the arachnoid layer, and is missing a true dural invest- 28 ment. Without protection from the dura mater, the delicate chromatographic patterns can occur. arachnoid layer is easily violated by even a small fracture. Chemical Diagnosis. Chemical analysis of the dis- Additionally, since the cribriform plate is located in the charge is the oldest method of diagnosing CSF leaks. midline of the anterior fossa, at the bottom of a slight Chemical examination of the nasal fluid became the stan- medial slope of the skull base floor, CSF may gravitate to dard of care after Sir St. Clair Thomson published his book this area. If a small portion of the brain cannot herniate The Cerebrospinal Fluid in 1899. In it he described in de- through the defect and create an effective seal, spontane- tail the chemical and physical characteristics that distin- ous resolution and nonoperative management may prove guish CSF fluid and nasal secretions based on differences difficult.100 in glucose concentrations.54 The concentration of glucose in CSF exceeds 50% of the serum concentration except Presentation of CSF Rhinorrhea during meningitis, subarachnoid hemorrhage, or some oth- Cerebrospinal fluid rhinorrhea in the acute phase af- er unusual circumstance.28 The glucose concentration in ter trauma has been reported in as many as 39% of the nasal secretions is 10 mg/dl or less. Nonetheless, a glucose patients with skull base fractures.104 Patients present with test is not definitive because the glucose oxidase assays a variety of symptoms depending on the acuteness of the used nowadays are too sensitive, turning positive even at event. In the acute phase following the traumatic event, low values of glucose; therefore, even normal nasal secre- patients may present with epistaxis, nasal discharge, peri- tions can elicit false-positive reactions.52,60,63 As a result, the orbital ecchymosis, chemosis, oculomotor impairment, glucose test for CSF rhinorrhea has become obsolete. anosmia, motor deficit, open-head injury with CSF leak- The asialo form of transferrin, b2-transferrin is pro- age, loss of vision, cranial nerve deficits (most frequently, duced by neuraminidase activity in the brain and found first–third and fifth–seventh cranial nerve injuries), men- abundantly in CSF. It occurs in lower concentrations in

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Unauthenticated | Downloaded 10/01/21 02:35 AM UTC M. Ziu, J. G. Savage, and D. F. Jimenez the perilymph of the cochlea and the aqueous and vitre- to be around 96%. The usefulness of this test depends on ous humor of the eye.103,115 Since it is not normally con- the extent of the dural defect, rate of leakage, timing of tained in nasal secretions, its detection allows indirect di- the intrathecal injection, and rate of CSF turnover that agnosis of CSF rhinorrhea. Samples of suspected CSF are could dilute or disperse the fluorescein. Reported com- obtained by direct drip collection or via the placement of plications of the solution’s injection, and thus limitations intranasal sponges. The samples are sent to the laboratory to its use, have ranged from mild tinnitus, headache, nau- with a serum sample, and b2-transferrin is detected by sea and vomiting, transient pulmonary edema, confusion, immunoblotting or immunofixation and silver stain in the seizures, and coma, to death. Keerl et al.58 analyzed 420 majority of large diagnostic laboratories.103,115 Since its administrations of fluorescein solution and their compli- introduction in 1979,87 b2-transferrin detection has been cations as reported in Europe and the US. The reasons for widely used for the diagnosis of extracranial CSF leak- the complications were found in the method of adminis- age, with a reported sensitivity and specificity up to 99% tration, formulation of the solution, idiopathic reactions, and 97%, respectively.115 Nevertheless, multiple disadvan- and concentration or dose of fluorescein.58 Other authors tages have been cited for this test, the most important be- have come to the same conclusions.89,117 At concentrations ing the highly intensive work and length of time required of 5% or lower, side effects are transient. Schlosser and to perform the assays (1–2 days) and the need for high Bolger102 recommend the use of 0.1 ml of 10% fluorescein expertise in the interpretation of the results (Table 2).85 diluted in 10 ml of the patient’s CSF with slow injection Another protein proposed as a potential marker for over 10–15 minutes. They reported no complications with the diagnosis of CSF rhinorrhea is b-trace protein, or this method of injection. Keerl and colleagues58 reported bT P. 4,45,83–85,98,103,112 It is the second most abundant protein that the intraoperative use of a maximum dose of 1 ml in human CSF following albumin83 and is mainly pro- (50 mg of fluorescein) or 0.1 ml per 10 kg of body weight duced in the epithelial cells of the choroid plexus and in in Germany, and 0.5–2 ml (2.5–10 mg) of the more di- the leptomeninges in the CNS.83,103 The CSF concentra- luted or hypodense 0.5% solution in the US, was without tion of bTP is approximately 35-fold higher than in plas- any complications. Informed consent and a comprehen- ma.103 It is found in nasal secretions and other body fluids sive discussion with the patient regarding the advantages as well, but in very low concentrations.83 The rationale for of using fluorescein in detecting the CSF leak, reported the bTP test relies on the large concentration difference risks of fluorescein intrathecal injection, and information between CSF and nasal secretions and an easy-to-use se- about the lack of FDA approval are recommended.58,102 rum/CSF concentration gradient.112 By utilizing a highly sensitive nephelometric measurement, this immunologi- Imaging Diagnosis. After confirming the presence of cal test can even detect very low amounts of CSF in nasal CSF rhinorrhea, the next step in its management is local- secretions.83 bTP is identical to prostaglandin-D synthase ization of the leakage site. Localizing this site assists in and is thought to be important for maturation and main- surgical planning and increases the chance for a success- tenance of the CNS.83,86 bTP has been identified by rocket ful repair. Imaging studies play a very important role in immunoelectrophoresis with a reported sensitivity of this step. 91%.7 An immunonephelometric bTP assay has been pro- High-resolution CT examination with axial, coronal, posed for routine use in clinical practice for the diagnosis and sagittal reconstructions has replaced plain radiogra- of CSF rhinorrhea.98 The overall accuracy of this method phy of the skull in diagnosing skull fractures. Very few in diagnosing CSF leaks has been reported to approach studies have been done exclusively to assess the accuracy 0.974, with a negative predictive value of 0.971 and a of HRCT in posttraumatic CSF leaks. In a retrospective positive predictive value of 1.8 The advantages of using review of 47 cases of traumatic and nontraumatic CSF bTP rather than b2-transferrin as a marker for CSF rhi- leaks visualized on HRCT, Zapalac and colleagues119 re- norrhea have been described by Meco and colleagues85 as ported a sensitivity and an accuracy of 87% each. Yilma- less time consuming, less labor intensive (< 15 minutes), zlar and colleagues118 reviewed 81 patients who were and less expensive. Furthermore, the bTP test carries all treated for CSF leakage due to skull base fractures. They the advantages of the b2-transferrin test: noninvasive, found that coronal bone window HRCT scans are impor- repeatable, same sample collection methods, and high tant in identifying the site of CSF leakage, whereas axial sensitivity and specificity. The wide use of bTP for this images are important in demonstrating fractures of the purpose has been slow because the test is not suitable in posterior wall of the frontal sinus. Lund and associates75 patients with bacterial meningitis or those with reduced suggested that HRCT can accurately demonstrate the po- glomerular filtration because of variation in the levels of sition of the fracture as well as the size of the defect. Nev- this protein.85,113 Furthermore, at concentrations between ertheless, HRCT scans show the bony fracture, but the 1.31 and 1.69 mg/L in the nasal secretions, there is an presence of a fracture is not always correlated with the overlap of individuals with and without CSF leakage.85,103 presence of a CSF leak. For these patients, other tests are required to confirm the Computed tomography cisternography is useful when pathological condition (Fig. 2). there is an active leak at the time of intrathecal contrast ad- Intrathecal injection of a sodium fluorescein solution ministration or when the leak can be induced by Valsalva following a thorough endoscopic examination has been maneuver or bending down. Schlosser and Bolger102 re- used to establish the diagnosis of CSF rhinorrhea. How- ported that the greatest utility of CTC is in frontal or sphe- ever, its ability to precisely localize the leak is limited. noid sinus leaks because these sinuses act as reservoirs of Nonetheless, the accuracy of the test has been reported102 the contrast material. They also asserted that in cribriform

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Fig. 2. Modified algorithm for the diagnosis of posttraumatic CSF rhinorrhea in a stepwise fashion by first confirming the leak and then localizing the side of the fistula. + = positive results; - = negative results; +/- = indeterminate values of bTP to make a diagnosis. Modified and reprinted with permission from Sage Publications, Inc. (Zapalac et al.119). plate olfactory groove defects, contrast material can drain patients with intermittent CSF rhinorrhea based on dem- into the pharynx and never collect to a volume substantial onstrations of brain hernia or the presence of a high sig- enough to be detectable on imaging.102 If the leak is not nal that is continuous and similar to that for CSF in the active, CTC is not more useful than noncontrast HRCT. basal cisterns through the cribriform plate or paranasal Moreover, CTC can provide further proof of the presence sinuses.44 When interpreting the literature, one must pay of a leak but not its precise location.74 Cisternography with attention to the nomenclature, because some authors use radioactive isotope injected intrathecally has been used in the term “MR cisternography” to describe routine MRI cases of intermittent low-flow CSF rhinorrhea. This tech- studies that rely primarily on T2-weighted sequences to nique requires endoscopic transnasal placement of pledgets highlight CSF rather than on those in which intrathe- at the anterior cribriform plate, middle meatus, or spheno- cal contrast medium is used.102 Nowadays, MRI for CSF ethmoidal recess. Although detection of radioactivity in leak detection refers to a technique that uses a fast spin the pledgets indicates a leak, this technique does not pro- echo sequence with fat suppression and image reversal.102 vide information about the precise location of the fistula. Some authors have reported good results using this tech- Note that the sensitivity ranges from 62% to 76% and that nique to detect intermittent CSF leaks, with an accuracy false readings occur in up to 33% of cases.33 The success up to 89%, 85%–92% sensitivity, and 100% specificity.102 rate for preoperative localization of CSF fistulas has been Another diagnostic methodology is MRC performed reported as 62.5% with radioisotope cisternography and with the intrathecal injection of Gd-enhancing contrast 95.7% with CTC.44 medium (GdMRC), first described in monkeys in 1985 by Magnetic resonance imaging has been suggested as Di Chiro and colleagues34 and in humans in 1994 by el a very valuable technique for localizing CSF fistulas be- Gammal and Brooks.38 Few reports have been published cause CSF gives a hyperintense signal on T2-weighted on this method and its accuracy in the diagnosis of CSF imaging and because, in general, this imaging technique leakage. The method still requires the performance of can demonstrate cranial anatomy in detail and in multiple lumbar puncture with injection of contrast medium. Be- planes.44 Magnetic resonance imaging without contrast havioral, neurological (focal seizures, ataxia, and delayed medium has been used with an accuracy of 60%–94%, tremor), and histological changes (loss of oligodendroglia, but high false-positive rates up to 40% have been report- hypertrophy of astrocytes, and formation of eosinophilic ed (reviewed in the study by Goel et al.48). These false- granules) have been described in animal studies.96,97 In positive rates have been attributed to the difficulty in dif- human studies, no gross behavioral changes, neurological ferentiating CSF from mucosal thickening and fluid that alterations, or seizure activity at any time after the proce- can be seen within a sinus. Some authors have reported dure has been reported.5,6,109,120 Symptoms, such as postural very high sensitivity in localizing the side of the leak in post–lumbar puncture headache, nausea, and episodes of

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Unauthenticated | Downloaded 10/01/21 02:35 AM UTC M. Ziu, J. G. Savage, and D. F. Jimenez vomiting, were documented, but all resolved within the Nonsurgical Management first 24 hours of the lumbar puncture with conservative bed Nonsurgical therapy begins with bed rest, head eleva- rest.109 In a prospective pilot trial in 20 patients, Aydin and 5 tion (to prevent a negative gradient between intracranial colleagues used a total volume of 0.5–1.0 ml of intrathecal and paranasal sinus cavities that would allow an ascending contrast medium without any significant gross neurologi- path for the bacteria intracranially), and strict CSF rhinor- cal, CSF, electroencephalography, or MRI changes related 120 rhea precautions (avoid nose blowing, Valsalva maneuvers, to the medium on the initial follow-up examination. In the use of straws, the use of an incentive spirometer, and so this trial, the estimated intrathecal dose used per gram of forth). In a retrospective study of 735 craniofacial traumas, brain was much less than that used in animal experiments with 34 patients presenting with CSF rhinorrhea (9 pa- m m 5 (0.07–0.36 mol/g brain vs 2.5–15 mol/g brain). The au- tients) and CSF otorrhea (25 patients), Bell and colleagues10 thors reported successful CSF localization with positive reported that these nonsurgical measures alone provided MRC studies and confirmation at the time of surgery in 14 resolution in 85% of the 34 cases. Only 3 (33%) of the 9 pa- patients and with positive MRC studies in 2 other patients tients with posttraumatic CSF rhinorrhea did not respond who did not undergo the surgical procedure. Since there to any of the nonsurgical measures and required surgical were no false positives in the surgically treated patients, intervention to close the CSF leak. Mincy88 reported that they reported 100% accuracy of GdMRC in this group. 6 spontaneous closure occurs in 68% of posttraumatic CSF In a later publication, Aydin and colleagues reported the fistulas within 48 hours of injury and 85% within 1 week. use of GdMRC in 51 patients with CSF rhinorrhea; in 59% If bed rest, head elevation, and strict CSF rhinor- of these patients, the etiology was accidental trauma. The rhea precautions fail, then CSF diversion has been ad- GdMRC studies were positive for CSF rhinorrhea in 44 of vocated.10,61 In the majority of cases, lumbar draining is the 51 patients, and in 43 of them the leak was confirmed the method of choice for CSF diversion. External ven- during surgical repair, for an accuracy of 98%. None of triculostomy draining is another method that provides the patients demonstrated any acute adverse reaction that 6 CSF diversion. The use of an EVD for this purpose has could be attributed to the procedure. Furthermore, none of not been explored in the literature, most likely because them exhibited any neurological symptoms or signs caused it is considered to be more invasive than a lumbar drain. by the intrathecal Gd injection during a mean follow-up Yilmazlar and colleagues118 reported on 81 patients with 6 of 4.12 years. Unfortunately, as in many other studies, the CSF leakage due to traumatic skull fractures and divided authors did not report the specific accuracy, specificity, the patients into 2 groups based on their GCS scores at and sensitivity exclusively for the posttraumatic patients. presentation. While lumbar drains were used in patients Of note, Aydin and colleagues5,6 have suggested the use of with a GCS score > 8, there was no mention of the CSF GdMRC with fat suppression sequences to enhance the ac- diversion method in patients with a GCS score ≤ 8, for curacy of CSF leak detection. The sensitivity of this meth- whom the traumatic brain injury guidelines14 suggest od for all CSF rhinorrheas is 84%–87%, and the accuracy placement of an ICP monitor. Nevertheless, we believe ranges from 78% to 100%.6,39 It is believed that GdMRC is that placement of an EVD instead of a lumbar drain can more sensitive and more accurate than CTC because the be considered in selected cases. Placing an EVD should high viscosity of the contrast agents used in the latter con- be considered first in patients who might benefit from an tributes to a difficulty in being distributed to the entire sub- ICP monitoring device given the severity of the traumatic arachnoid space and in penetrating the small dural tears in event and a low GCS score. In such cases, the EVD plays some patients. However, even for GdMRC, the patient must the dual role of ICP monitor and CSF diverter. Placement have an active leak at the time of imaging for the diagnosis of an EVD could be preferred over a lumbar drain in pa- to be revealed. Furthermore, GdMRC is more expensive tients who present with increased supratentorial pressure than CTC. due to cerebral edema, intraparenchymal contusions, or In conclusion, GdMRC is another safe imaging meth- other lesions not amenable to surgical evacuation. Evalu- od with good accuracy and sensitivity that is part of the ation of the EVD as a CSF diverter in posttraumatic CSF surgeon’s armamentarium in localizing CSF leaks during rhinorrhea warrants further study. preoperative planning (Table 2). No clear criteria have been In general, there are still some questions to be an- defined for when to use GdMRC versus CTC. El Gammel swered on CSF diversion for CSF rhinorrhea. Which pa- and colleagues39 suggest using HRCT in combination with tients would most benefit from CSF diversion? When is GdMRC for an optimal imaging approach in the diagno- the best time to proceed with lumbar or ventricular drain sis of CSF rhinorrhea. While the diagnosis of acute CSF placement? How long should one wait before deciding rhinorrhea caused by comminuted and complex skull base that CSF diversion has failed and proceed to surgical fractures appears easy, that of intermittent and chronic management? Knowing that 85% of posttraumatic CSF leakage is more challenging. In Fig. 2, we show a modified fistulas close spontaneously (within 48 hours in 68% of version of the algorithm provided by Zapalac et al.,119 inte- cases and within 1 week in 85%),88 that the meningitis grating all the new chemical and imaging tools that would risk is 0.62% in the first 24 hours after injury, and that the be more suitable and cost effective for the diagnosis of cumulative meningitis risk is 9.12% at the end of the 1st posttraumatic CSF fistulas. Unfortunately, the diagnosis of week and 18.82% at the end of the 2nd week after injury,42 an occult fistula in a patient who presents with meningitis some have suggested a waiting period of 72 hours–1 week and without CSF rhinorrhea becomes more difficult, and before attempting any invasive treatment for acute post- all effort should be made to find the fistula by using all the traumatic CSF rhinorrhea.71,118 In contrast, surgical inter- imaging studies deemed necessary. vention has been advocated as the first line of treatment

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TABLE 2: Advantages and disadvantages of the most commonly used diagnostic tests for the diagnosis of CSF rhinorrhea

Diagnostic Test Advantages Disadvantages chemical b2-transferrin noninvasive labor intensive & time consuming repeatable requires high expertise for interpretation & performance sensitivity up to 99% performed in only a few specialized laboratories specificity up to 97% protein detectable only in CSF, perilymph, & aqueous humor bTP noninvasive not suitable in patient w/ bacterial meningitis or low glomerular repeatable filtration rate sensitivity 91%–100% values 1.31–1.69 mg/L need other confirmatory test specificity 86%–100% not labor intensive & less time consuming not expensive protein is second most abundant protein in CSF imaging radioisotope cis- may detect presence of CSF leak even if intermittent invasive, requiring intranasal endoscopic procedure & intrathe- ternography cal injection of radioactive material no details on site of leak sensitivity 62%–76% HRCT diagnose site of fracture fracture not always correlated w/ presence of leak diagnose size of defect risks of radiation noninvasive sensitivity >87% accuracy approximately 87% CTC diagnose site of fracture invasive diagnose size of defect intrathecal injection of contrast material possibility of correlating site of fracture w/ leak active leak must be present at time of CT scan sensitivity 48%–96% high viscosity of contrast material reduces its penetration in 95% success rate in diagnosis small fractures or defects risks of radiation MRI noninvasive high false-positive rate (40%) valuable for localizing fistula not every patient can undergo MRI anatomy in 3 planes expensive accuracy 60%–94% increased specificity to 92% & sensitivity to 100% (in intermittent leaks) if using fast spin echo w/ fat suppression sequences MRC contrast less viscous than CT contrast & better penetrates invasive w/ intrathecal injection of contrast material small fractures or tears very few studies done so far sensitivity 85%–92% severe complications reported in animal studies specificity up to 100% active leak must be present at time of study increased accuracy if fat suppression sequences used expensive intrathecal sodium may detect leak limited ability to localize leak fluorescein possibility of repairing leak when test performed depends on timing & rate of leak, timing of injection, rate of CSF circulation & turnover reported complications such as coma, seizures, death for delayed posttraumatic CSF rhinorrhea.46,99,102 We think meningitis risk per week within the 1st month, surgical that there is a need to further study this argument and management should be considered within the 2nd week evaluate whether even those patients with delayed CSF after CSF rhinorrhea fails to resolve with conservative rhinorrhea could benefit from a trial of nonsurgical man- management, as first suggested by Dandy32 in 1944. agement. The duration of nonsurgical management with As stated above, meningitis is the most frequent com- leak precautions and diversion of CSF has ranged from 7 plication of posttraumatic CSF rhinorrhea. Although 11%– days to 6 weeks.61,99,100,118 Unfortunately, it is unknown61 38% of patients with CSF rhinorrhea become infected,57 whether there is any difference in the rate of closure of the use of prophylactic antibiotics continues to be a con- a CSF fistula between 7 days and 6 weeks of nonsurgi- troversial issue. The incidence of meningitis after posttrau- cal trials. Nevertheless, one could argue that with a 7.4% matic CSF rhinorrhea is higher in the 1st few weeks,50 and

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Unauthenticated | Downloaded 10/01/21 02:35 AM UTC M. Ziu, J. G. Savage, and D. F. Jimenez the cumulative risk increases with persistence of the leak.42 That is why early reports recommended the use of prophylactic antibiotics for at least 7 days from the time of injury in all patients who presented with a CSF leak or pneumocephalus.17,57,68 Conversely, more recent retrospective and prospective controlled studies have discouraged the use of prophylactic antibiotics in this situation.27,37,40 – 42 Choi and Spann27 retrospectively reviewed 293 patients with posttraumatic skull base fractures, and a CSF leak was diagnosed in 115. The authors found that the use of prophylactic antibiotics increased the risk of infection when considering all patients with skull fractures. They did not find a significant difference in the occurrence of meningitis even when they considered only those patients with clinical evidence of a CSF leak. Interestingly, they found that there was an increase in the rate of meningitis soon after the antibiotics were stopped. This finding strengthened the argument against the prophylactic use of antibiotics in these situations.92,94,110 A working group of the British Soci- ety for Antimicrobial Chemotherapy,2 after reviewing the current available studies on this matter, argued against the routine use of prophylactic antibiotic treatment following traumatic skull base fractures: first, because the commonly used antibiotics poorly penetrate the noninflamed meninges, and second, because antibiotics are unlikely to eradi- cate potential pathogens, such as pneumococci from the upper respiratory tract. Additionally, treatment may lead to colonization with strains that are resistant to antibiotics, complicating the management of any future episodes of meningitis.49 It can be further argued that the prophylactic administration of antibiotics for an arbitrary period of 5–7 days does not reduce the risk of later meningitis, especially when the CSF leak frequently persists beyond 7 days and sometimes even years.57 Ratilal and colleagues95 performed a meta-analysis of all the published randomized controlled trials on this matter and concluded that given the current data, it is not possible to recommend the use Fig. 3. High-resolution CT scans (A–D) obtained in a patient who of prophylactic antibiotics following traumatic skull base presented after a fall from a 30-foot building. Multiple comminuted fractures. Eljamel41 retrospectively reviewed 215 patients craniofacial fractures involved the cribriform-ethmoid, maxillary, and with a definitive diagnosis of posttraumatic CSF fistula, frontal sinus. Head CT scans (E and F) showing a large right frontal 106 of whom were treated with antibiotics prophylacti- intraparenchymal hematoma with midline shift. The patient underwent emergent surgical intervention for evacuation of the hematoma, reduc- cally and 109 who were not. They did not find a significant tion of nasofrontal fractures, cranialization of frontal sinus, and dural difference in the risk of meningitis between the 2 groups. repair with autologous pericranium graft. An EVD was placed on arrival They concluded that it is ethically justifiable to withhold because of a low GCS score and was kept in place for 10 days. No CSF antibiotic prophylaxis in patients with CSF fistulas until leak was noted at the 6-month follow-up. a prospective controlled double-blind trial has settled the question.41 erature: transcranial approach and extracranial approach. Transcranial approaches were first described by Dandy31 Surgical Management in 1926, as he reported the first successful dural defect re- Surgery is reserved for the treatment of CSF leaks pair. Extracranial approaches have improved over recent that do not spontaneously close or respond to conserva- years with the advancement in endoscopic sinus surgery tive management with CSF diversion.118 Furthermore, ear- and the transnasal endoscopic route, which has been used ly surgical intervention has been recommended in cases successfully for the closure of posttraumatic CSF fistulas in which the intracranial pathology requires acute inter- in properly selected patients (Fig. 4). vention (Fig. 3) or the anatomy of the skull fracture sug- Eljamel and Foy43 conducted a long-term analysis of gests that spontaneous closure would be impossible, such 160 patients with acute posttraumatic CSF fistula; 149 as in a large depressed skull base fracture, a fracture ac- patients underwent surgical dural repair. Forty-seven pa- companied by complications (for example, cranial nerve tients had a first episode of meningitis before the surgical deficits), or tension pneumocephalus.104,118 Two types of repair. The overall risk of meningitis was reduced from approaches for the repair of a posttraumatic dural defect 30.6% before surgery to 4% after surgery, and the cumu- and a consequent CSF leak have been described in the lit- lative risk at the 10-year follow-up was reduced to 7%

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cific criteria that have been reported100 to increase the long- term risk of infection. Early surgery was performed in 18 patients with compressive hematoma, open trauma, severe bone derangement, and severe CSF discharge.99 Delayed surgery was undertaken in 10 patients after conservative treatment failed and in 8 patients after stabilization of the vegetative parameters and regression of the cerebral edema. There was no mention of what conservative measures were attempted to stop the CSF leak in these 8 patients while waiting for stabilization. The leak ceased within 1 week in the 22 patients who were treated conservatively. Five of these 22 patients returned later with a recurrent leak and/or meningitis. Dural defects were closed using vascularized pericranium and fibrin glue. The authors further suggested that some types of cranial fractures—such as compound, comminuted, depressed, or craniofacial fractures larger than 1 cm, fractures close to the midline, or those involving the cribriform plate—require surgical intervention since they do not heal spontaneously. In addition, surgical repair was suggested in cases with an encephalocele or meningocele in the fracture crease, since they would not heal spontaneously, and in cases in which conservative treatment fails after 8 days.99,100 118 Fig. 4. Coronal (A and B) and axial (C and D) HRCT scans obtained Yilmazlar and colleagues described a series of 81 in a patient who presented with clear rhinorrhea 5 months after a trau- patients with persistent CSF otorrhea and rhinorrhea for matic event, showing no fractures. Note that the b2-transferrin test was more than 24 hours after the traumatic event. Conserva- positive. Air-fluid level as an indication of CSF leakage was noted on the tive measures for 72 hours were undertaken in all patients left sphenoid sinus. A lumbar drain was placed and fluorescein dye was injected. A leak was noted on endoscopic transnasal exploration and except those who required emergent surgical treatment was successfully repaired via an extracranial endoscopic approach. due to intracranial pathology, open fractures, and cranial nerve compression. Overall, spontaneous cessation of the leak was achieved in 39.5% of the patients. The authors after surgical repair from more than 85% prior to repair. suggested a treatment algorithm in which bed rest mea- The recurrence rate of CSF leakage after the first dural sures were applied for 72 hours–7 days, and if that failed, repair was reported as 17% in this series, with an opera- a CSF external drain was placed for 7–10 days. Surgical tive mortality of 1.3%, regardless of whether a bicoronal intervention was undertaken after conservative measures or unilateral approach was used. At the end of this retro- failed. Thirty-two patients underwent surgical repair: 12 spective study, the authors43 concluded that surgical re- of them within 3 days, 10 within 10–30 days, and 10 oth- pair seems to be the only durable long-term prophylaxis ers at 3 months–22 years after the traumatic event. The against the development of meningitis in patients with authors observed that patients with GCS scores ≤ 8 at posttraumatic rhinorrhea and therefore should be under- presentation had a poorer disease prognosis and a high taken as soon as the patient is fit for surgery. risk of meningitis regardless of the method of treatment Friedman and colleagues46 published a study of post- for the CSF leak, as compared with patients with GCS traumatic CSF leaks in 101 patients. Spontaneous resolu- scores > 8. tion of the CSF leaks occurred over an average of 4.8 days The type of transcranial approach undertaken for in 26 (60%) of the 43 patients with clinically evident leaks. closure of rhinorrhea depends on the fistula location and Twenty-four patients (47%) were surgically treated, and the the type and size of the fracture. Several surgical tech- median time from the initial traumatic event to surgery was niques have been described in the literature, ranging from 45 days among them all. A variety of surgical approaches the classic frontal craniotomy, which can be bilateral or were used, including intracranial, extracranial, and com- unilateral, to the suprasinus transfrontal approach with bined intracranial-extracranial. Of the 24 surgically treat- lateral extension.10,43,46,70,99,100,104 If primary repair of the ed patients, 3 (12.5%) experienced further CSF leakage re- dura is not feasible, dural substitutes, such as pericra- quiring reoperation. No patient suffered recurrent leakage nial graft, fascia lata, temporalis muscle fascia, or other after a reoperation. Lumbar drainage was used in only a autologous (preferably) or nonautologous grafts, can be few patients in this series, and no meaningful conclusions used. Each fracture associated with a CSF leak is unique, could be drawn regarding its efficacy. However, the authors and the type of approach used to repair the leak depends did conclude that the rate of surgical repair may have been on the specific situation and cannot be organized in an lower had they more aggressively pursued lumbar drainage algorithmic form. The same can be said about the use of and conservative management.46 graft materials. The type of graft material depends on the Rocchi and colleagues99 reported their experience location and size of the defect, extent of dural laceration, with 58 patients who had posttraumatic CSF rhinorrhea, and availability of the graft. Until clinical trials evaluate 36 of whom underwent surgical repair according to spe- the superiority of one surgical approach over another and

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Unauthenticated | Downloaded 10/01/21 02:35 AM UTC M. Ziu, J. G. Savage, and D. F. Jimenez one type of graft over another, the choice will depend on of 98.8%; 1 patient was lost to follow-up. The authors did the situation and the surgeon’s choice. The mortality rate not mention how many of these 9 patients were in the acci- for surgical exploration and repair has ranged from 0% to dental trauma group. They did recommend performing the 6% in the literature.19,43,46,70,99,104 In cases in which one or transcranial approach in all patients with frontal sinus frac- more sinuses are involved in the fracture, obliteration of tures and CSF leakage, as well as considering the trans- the sinuses is crucial not only to stop the CSF fistula but nasal endoscopic approach only in patients with sphenoid, also to prevent the occurrence of a mucocele and delayed cribriform, and ethmoid roof fractures. In their publication, infection. For fractures involving the frontal sinus, for they described only those patients in whom conservative example, obliteration is accomplished first by meticulous management failed; hence, it is difficult to discern how stripping of sinus mucosa, removing the posterior table of many CSF leaks resolved with 4–6 weeks of conservative the sinus, and then packing the communication between management. In the series of Locatelli et al.72 of 135 pa- the frontal sinus and the nasal cavity with autogenous fat tients with CSF rhinorrhea, 39 cases were the result of acci- or muscle.46,66 The risk of a recurrent leak after transcra- dental traumatic injury. These patients underwent surgical nial repair of traumatic CSF rhinorrhea has been reported treatment after 2 weeks of conservative management had to be 6%–32%.10,43,46,66,68,69,99,104,118 failed. The authors recommended conservative manage- Extracranial repairs can be achieved through differ- ment first for acute posttraumatic CSF rhinorrhea and then ent types of approaches. The most frequently used has surgical exploration and repair only if the first option fails. been the transnasal approach, first described by Hirsch54 In contrast, for delayed posttraumatic CSF rhinorrhea, sur- in 1952. gical treatment was recommended without a first trial of Since 1981 when Wigand116 first described the suc- conservative management.72 cessful extracranial repair of a CSF leak, the endoscopic Although numerous, most of the reports published approach has progressively become preferred.104 Al- on the extracranial endoscopic repair of CSF rhinorrhea though this technique has a high rate of success and a include patients with different etiological backgrounds, lower rate of morbidity, limitations do exist. It may be making it difficult to discern the specific success rate of most appropriate for specific cases, such as for a leak due this technique for posttraumatic leaks (Table 1). Further- to a precisely located small tear or in the absence of as- more, several authors group together in 1 category (Fig. sociated brain injuries requiring surgical treatment.99 1 lower) the accidental traumatic leaks and the postsurgi- McMains and colleagues82 reported an overall success cal ones. In addition, very few reports have addressed the rate of 94% in CSF leak repair via the endoscopic extra- utility of endoscopic treatment in the acute setting.61 cranial approach in 92 patients. Only 18 of these patients The techniques used for endoscopic transnasal repair had suffered accidental trauma. The authors noted that in of CSF rhinorrhea depend on the location of the leak, the patients in whom the endoscopic repair had failed, the de- size of the defect, and surgeon preference. A direct para- fects were larger than 1.5 cm. The specific success rate in septal approach with or without opening of the ethmoidal the accidental trauma subgroup was not reported. Banks cells, an anteroposterior ethmoidotomy with preservation and colleagues9 described their 21-year experience with of the middle turbinate, and an ethmoidosphenoidotomy endoscopic CSF leak repair in 193 cases, with an overall with complete removal of ethmoidal turbinates have been success rate of 98%. They included 109 posttraumatic CSF used for an olfactory groove defect.72,80 A sphenoidoto- leaks in their study, 15% of which had occurred after ac- my with a direct paraseptal endonasal approach limiting cidental craniofacial trauma. Recurrence of the leak was enlargement of the natural ostium of the sphenoid and a reported to occur within an average of 4 months after transethmoid-pterygosphenoidal approach have been used endoscopic repair.9 Cassano and Felippu23 documented a for a sphenoid bone defect, depending on the anatomy of series of 125 patients at 2 different institutions who under- the sphenoid sinuses.72,80 Various authors have successful- went endoscopic endonasal repair of CSF leaks. The dura- ly used different types of autologous and nonautologous tion of CSF rhinorrhea prior to surgical repair ranged from grafts, such as a mucoperiosteal flap from the middle tur- fewer than 7 days (32 patients) to more than 30 days (29 binate or septum or mucoperichondrial, osseous, cartilag- patients). Accidental trauma was the etiological factor in 41 inous, fat, muscular fascia, middle turbinate, or septum pe- patients (32.8%). These authors reported an initial overall dunculated graft, or any combination of these grafts.1,3,11, success rate of 94.4% and a success rate of 100% in the 13,15,22,24–26,28,35,47,51,55,56,64,65,67,77,79,90,101,108 Another widely dis- posttraumatic patients.23 Kirtane and colleagues61 have de- cussed issue in endoscopic transnasal repair is whether scribed their experience with 267 patients who underwent the grafts used for repair should be placed above (inlay) endoscopic transnasal repair, and a posttraumatic CSF or beneath (onlay) the skull base defects. In a meta-anal- leak was diagnosed in 119. These latter patients were first ysis, Hegazy et al.53 found that both techniques yielded treated conservatively for 4–6 weeks in the form of com- similar results. Nevertheless, there are no data on whether plete bed rest, acetazolamide, broad-spectrum antibiotic there is any difference in these techniques. prophylaxis, and the avoidance of straining. Cerebrospinal Still unsettled in the literature is the issue of placing fluid drainage via repeated lumbar punctures was preferred a lumbar drain after endoscopic repair of CSF rhinorrhea. rather than leaving a lumbar drain. The authors reported a Indications for lumbar drain placement are not clear, and success rate of 96.6%, with 9 patients having a postopera- most surgeons insert them based on their past anecdotal tive recurrence of the CSF leak. Six of these patients un- results.22 Some authors report that there is no difference derwent successful repair via an endoscopic approach and in CSF rhinorrhea repair with or without postoperative 2 via a transcranial approach, with an overall success rate lumbar drain insertion.9,22,55,83,102 Furthermore, none of

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Unauthenticated | Downloaded 10/01/21 02:35 AM UTC Cerebrospinal fluid rhinorrhea after anterior skull base trauma these authors specify the need for a lumbar drain in post- pears to be the most efficient and cost-effective route traumatic CSF rhinorrhea (Table 1). (Table 2).119 There is a multitude of articles describing the success While embarking on the treatment of these fistulas, rates of endoscopic repair of CSF leaks, but none exclu- we must remember that 85% of CSF rhinorrhea cases re- sively document the outcome in patients with traumatic sulting from head trauma stop spontaneously and that the fractures. In these articles, 1585 patients underwent en- risk of meningitis is 0.68% in the first 24 hours after in- doscopic repair of a CSF leak with a reported initial suc- jury and increases up to 18.87% in the first 2 weeks after cess rate range of 75%–100%. Four hundred twenty-five injury. 42,88 Published reviews have not shown that prophy- of these patients presented with CSF rhinorrhea following lactic treatment with antibiotics makes a difference, and accidental trauma. More than 13 studies with 255 patients therefore such therapy should be discouraged.40,41,49,57 with posttraumatic CSF leaks did not specify the recur- It has been suggested that patients who need emer- rence rate in this group. In 170 posttraumatic patients, the gent surgical treatment for intracranial pathology should success rate ranged from 50% to 100%, with failure of undergo intracranial repair of the fistula in the same set- the first transnasal endoscopic repair in only 12 patients ting.99,104,118 Nevertheless, this decision must be made while (7.05%).1,9,11,13,15,18,23–26,28,35,47,51,55,56,59,61,62,64,65,67,71,72,74,77–79, taking into consideration the amount of cerebral edema 81,82,90,93,101,107,108,111 After conducting a questionnaire survey and the hemodynamic stability of the patient.46,99 In some of 72 otorhinolaryngologists who regularly performed this instances, treating the intracranial pathology first and then procedure, Senior and colleagues106 reported a complica- repairing the CSF fistula later, when the patient’s vegetative tion rate of 2.5% for transnasal endoscopic repair among parameters allow, may be wiser (Figs. 5 and 6).46,99,104,118 a sample of 650 patients of different CSF rhinorrhea etio- While there appears to be some consensus that the majori- logical groups. The complications after endoscopic repair ty of patients should first undergo nonsurgical management of a CSF leak were seizure, meningitis, cavernous sinus with bed rest, head-of-bed elevation, and CSF external di- thrombosis, temporary visual problems, sinusitis, intra- version to allow spontaneous healing to occur, there re- cranial hypertension, and death. In a meta-analysis of mains some controversy regarding the length of time such studies published after 1990, Hegazy et al.53 reported an treatment should be pursued. While some authors suggest incidence of less than 1% of major complications, such 72 hours–7 days of bed rest and then a 7- to 10-day trial of as meningitis, subdural hematoma, and intracranial ab- CSF diversion maneuvers,118 others recommend pursuing scesses, after endoscopic repair of CSF rhinorrhea. surgical treatment after the failure of 8 days of nonsurgical management.99,100 We found no randomized controlled Summary studies that evaluated these treatment strategies, however. The surgical management of posttraumatic CSF fis- Although the first report of the successful surgical tula depends on the impact of the trauma, the location treatment of CSF rhinorrhea due to posttraumatic ante- of the fistula, and the temporal relationship between the rior cranial injury dates back to 1926,31 many controver- leak and the traumatic event. It has been suggested that sies regarding its optimal management still exist today. a CSF fistula located closer to the midline and associ- Diagnosis should start with a clinical suspicion, continue ated with fractures > 1.5 cm, frontal sinus fractures, and with chemical investigation to confirm its presence, and meningoceles or encephaloceles inside the fistula will not hopefully end with imaging studies to define the location heal spontaneously and therefore almost always require and size of the fistula (Fig. 2). Starting with the simplest surgical repair.99,104 Nevertheless, other authors have rec- diagnostic tool and progressing to the most complex ap- ommended a trial of nonsurgical management in all pa-

Fig. 5. High-resolution CT scans obtained in a patient with severe craniomaxillofacial fractures after a motor vehicle accident, showing involvement of the frontal sinus and bone, the ethmoid and sphenoid sinus (A and B), and a large left epidural hematoma (C). The patient underwent emergent craniotomy for evacuation of the hematoma. Because of hemodynamic instability, the reduction of his fractures was postponed. The next day CSF rhinorrhea was noted. In a combined approach performed by neurosurgeons and oromaxillofacial surgical specialists, the patient underwent bifrontal craniotomy for repair of craniomaxillary fractures as well as intracranial dural repair with autologous pericranial graft. The patient was discharged home a few days after- ward without signs of meningitis or CSF rhinorrhea.

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Fig. 6. Proposed algorithm for the management of posttraumatic anterior skull base CSF fistulas. LD = lumbar drain. tients who do not need emergent surgical treatment for to determine the time to treatment as well as more spe- traumatic intracranial pathology (Fig. 6). No studies have cific technical issues of endoscopic intervention in this indicated which specific type of craniotomy or intracra- population, such as those pertaining to the type of graft, nial approach works best for each type of fracture. The the overlay versus inlay technique, or postoperative lum- same can be said of the type of tissue adhesive to use in bar drain placement. In conclusion, we believe that in- these situations, because no scientific studies have been tracranial and extracranial approaches for posttraumatic conducted for this purpose. We believe that until these CSF rhinorrhea closure should be complementary instead studies appear in the literature, each skull defect and CSF of competing procedures. leak should be considered unique and that the choice of intracranial approach depends on surgeon preference. Disclosure The surgical repair of CSF fistulas caused by trau- The authors report no conflict of interest concerning the mate- matic anterior skull base fractures has been performed rials or methods used in this study or the findings specified in this through intracranial intradural or extradural repair. With paper. the advancement of endoscopic technology, transnasal re- Author contributions to the study and manuscript prepara- pair has been widely used with good results. Reported tion include the following. Conception and design: Ziu, Jimenez. failure rates for intracranial repair of rhinorrhea range Acquisition of data: Ziu, Savage. Analysis and interpretation of from 6% to 27%,118 and the corresponding range for extra- data: all authors. Drafting the article: Ziu, Savage. Critically revising the article: all authors. Reviewed submitted version of manuscript: cranial endoscopic repair is 2%–50% (Table 1). A direct all authors. Approved the final version of the manuscript on behalf comparison between the transcranial and the endoscopic of all authors: Ziu. Administrative/technical/material support: Ziu, extracranial techniques is difficult without data from ran- Jimenez. Study supervision: Ziu, Jimenez. domized clinical trials. Furthermore, the results of endoscopic repairs of CSF rhinorrhea have been reported References without etiological differences, and very few reports have 1. Anand VK, Murali RK, Glasgold MJ: Surgical decisions in provided the specific success rate in the posttraumatic the management of cerebrospinal fluid rhinorrhoea. Rhinol- cases. Further research is needed to define the criteria for ogy 33:212–218, 1995 and which patients would benefit from endoscopic extra- 2. Anonymous: Management of cerebrospinal fluid leaks. J cranial approaches versus the transcranial approach and Trauma 51 (2 Suppl):S29–S33, 2001

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3. Araujo Filho BC, Butugan O, Pádua FG, Voegels RL: Endo- doscopic repair of cerebrospinal fluid rhinorrhea. Rhinology scopic repair of CSF rhinorrhea: experience of 44 cases. Braz 37:33–36, 1999 J Otorhinolaryngol 71:472–476, 2005 26. Chin GY, Rice DH: Transnasal endoscopic closure of cerebro- 4. Arrer E, Meco C, Oberascher G, Piotrowski W, Albegger K, spinal fluid leaks. Laryngoscope 113:136–138, 2003 Patsch W: beta-Trace protein as a marker for cerebrospinal 27. Choi D, Spann R: Traumatic cerebrospinal fluid leakage: risk fluid rhinorrhea. Clin Chem 48:939–941, 2002 factors and the use of prophylactic antibiotics. Br J Neuro- 5. Aydin K, Guven K, Sencer S, Jinkins JR, Minareci O: MRI surg 10:571–575, 1996 cisternography with gadolinium-containing contrast medium: 28. Cukurova I, Cetinkaya EA, Aslan IB, Ozkul D: Endonasal en- its role, advantages and limitations in the investigation of rhi- doscopic repair of ethmoid roof cerebrospinal fluid fistula by norrhoea. 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kar JJ, Rose D, et al: Intrathecal gadolinium-enhanced magnet- 72. Locatelli D, Rampa F, Acchiardi I, Bignami M, De Bernardi ic resonance cisternography in cerebrospinal fluid rhinorrhea: F, Castelnuovo P: Endoscopic endonasal approaches for repair road ahead? J Neurotrauma 24:1570–1575, 2007 of cerebrospinal fluid leaks: nine-year experience. Neurosur- 49. Greig JR: Antibiotic prophylaxis after CSF leaks lacks evi- gery 58 (4 Suppl 2):ONS-246–ONS-257, 2006 dence base. BMJ 325:1037, 2002 73. Luckett WH: Air in the ventricle of the brain following frac- 50. Hand WL, Sanford JP: Posttraumatic bacterial meningitis. ture of the skull. Surg Gynecol Obstet 17:237–240, 1913 Ann Intern Med 72:869–874, 1970 74. Lund VJ: Endoscopic management of cerebrospinal fluid 51. Hao SP: Transnasal endoscopic repair of cerebrospinal fluid rhi- leaks. Am J Rhinol 16:17–23, 2002 norrhea: an interposition technique. Laryngoscope 106:501– 75. 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96. Ray DE, Cavanagh JB, Nolan CC, Williams SC: Neurotoxic 110. Tos M: Course of and sequelae to 248 petrosal fractures. Acta effects of gadopentetate dimeglumine: behavioral disturbance Otolaryngol 75:353–354, 1973 and morphology after intracerebroventricular injection in rats. 111. Tosun F, Gonul E, Yetiser S, Gerek M: Analysis of different AJNR Am J Neuroradiol 17:365–373, 1996 surgical approaches for the treatment of cerebrospinal fluid 97. Ray DE, Holton JL, Nolan CC, Cavanagh JB, Harpur ES: rhinorrhea. Minim Invasive Neurosurg 48:355–360, 2005 Neurotoxic potential of gadodiamide after injection into the 112. Tumani H, Nau R, Felgenhauer K: Beta-trace protein in lateral cerebral ventricle of rats. AJNR Am J Neuroradiol cerebrospinal fluid: a blood-CSF barrier-related evaluation in 19:1455–1462, 1998 neurological diseases. Ann Neurol 44:882–889, 1998 98. Reiber H, Walther K, Althaus H: Beta-trace protein as sensi- 113. 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Neurosurgery 62:463–471, 2008 gadolinium-enhanced MR myelography and cisternography: 105. Schroeder MC: Meningitis due to posttraumatic cerebro-spinal a pilot study in human patients. AJR Am J Roentgenol 173: rhinorrhea. Arch Otolaryngol 40:206–207, 1944 1109–1115, 1999 106. Senior BA, Jafri K, Benninger M: Safety and efficacy of endo- 121. Zweig JL, Carrau RL, Celin SE, Schaitkin BM, Pollice PA, scopic repair of CSF leaks and encephaloceles: a survey of the Snyderman CH, et al: Endoscopic repair of cerebrospinal fluid members of the American Rhinologic Society. Am J Rhinol leaks to the sinonasal tract: predictors of success. Otolaryngol 15:21–25, 2001 Head Neck Surg 123:195–201, 2000 107. Sethi DS, Chan C, Pillay PK: Endoscopic management of cerebrospinal fluid fistulae and traumatic cephalocoele. Ann Acad Med Singapore 25:724–727, 1996 108. Silva LR, Santos RP, Zymberg ST: Endoscopic endonasal Manuscript submitted January 30, 2012. approach for cerebrospinal fluid fistulae. Minim Invasive Accepted April 5, 2012. Neurosurg 49:88–92, 2006 Please include this information when citing this paper: DOI: 109. Tali ET, Ercan N, Krumina G, Rudwan M, Mironov A, Zeng 10.3171/2012.4.FOCUS1244. QY, et al: Intrathecal gadolinium (gadopentetate dimeglu- Address correspondence to: Mateo Ziu, M.D., Department of mine) enhanced magnetic resonance myelography and cister- Neurosurgery, University of Texas Health Science Center at San nography: results of a multicenter study. Invest Radiol 37: Antonio, 7703 Floyd Curl Drive (MC 7843), San Antonio, Texas 152–159, 2002 78229-3900. email: [email protected].

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