2012 4 Focus1244

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 potentially fatal condition that still presents a major
challenge in terms of its diagnosis and management. It is estimated that meningitis develops in approximately 10%25% of patients with this disorder, and 10%
of them die as a result. Approximately 80% of all cases of
CSF rhinorrhea are caused by head injuries that are associated with cranial fractures.118 The estimated incidence
of basilar skull fracture from nonpenetrating head trauma
varies between 7% and 15.8% of all skull fractures, with
associated CSF leakage occurring in 10%30% of these
patients.95,118 The leak can occur wherever the dura mater
is lacerated during injury and there is a communication
between the intracranial and nasal cavities.
Despite many advances, it is still difficult to critically
interpret the literature with regard to the optimal management of CSF leakage following craniomaxillofacial
trauma. Most published articles, while documenting the
efficacy of endoscopic surgery to repair CSF leaks, have
failed to separate patients into distinct etiological groups
when reporting outcome. In addition, no authors have
consistently analyzed the success of nonsurgical treatment modalities, such as bed rest and CSF diversion, and
still little is known about the incidence and natural history of this disease entity, the need for antibiotics, and the
surgical indications for and timing of intervention.10
Abbreviations used in this paper: bTP = b trace protein; CTC

= CT cisternography; EVD = external ventricular drain; GCS
= Glasgow Coma Scale; GdMRC = MRC with intrathecal Gdenhancing contrast; HRCT = high-resolution CT; ICP = intracranial
pressure; MRC = MR cisternography.
Neurosurg Focus / Volume 32 / June 2012
Furthermore, the issues related to CSF leak caused

by traumatic injury are complex and multiple. Having
conducted a thorough review of existing literature, we
discuss here the pathophysiology, diagnosis, and management of CSF rhinorrhea relevant to traumatic anterior
skull base injuries and attempt to identify areas in which
further research is needed.
Methods
For this review, primary and secondary neurosurgery,

otorhinolaryngology, craniofacial surgery, and general
surgery literature in the English language and published
in the period from 1926 to 2009 was searched on Medline. The key words used for our search included anterior skull base fracture, skull base endoscopy, surgical
treatment of skull fractures, head trauma, and CSF
rhinorrhea. All publications referring to CSF rhinorrhea
not of traumatic origin were excluded from our analysis,
and only those referring to the CSF rhinorrhea following traumatic anterior skull base fractures were included.
We also excluded publications that classified postsurgical
CSF rhinorrhea as posttraumatic. Furthermore, we excluded all publications referring to patients younger than
18 years of age.
We focused our review on the methods of clinical,
chemical, and imaging diagnosis of CSF rhinorrhea following traumatic injury. We reviewed the literature on
nonsurgical and intracranial and extracranial surgical
treatment of posttraumatic CSF rhinorrhea.
Regarding the extracranial endoscopic repair of posttraumatic CSF leakage, we reviewed the English literature
1
M. Ziu, J. G. Savage, and D. F. Jimenez

published in the period from 1980 to 2009. We found 37
articles that discussed patients with posttraumatic CSF rhinorrhea (Table 1). We were unable to find any articles that
reported studies exclusively on accidental posttraumatic
CSF rhinorrhea. We excluded those studies in which the
number of leaks, rather than the number of patients, were
reported.121
Results
A Historical Overview
In 1745 Bidloo the Elder was the first to describe CSF

rhinorrhea after a traumatic skull fracture and correlate
them.29 It was not until the advent of radiographic techniques that the presence of a communication between the
TABLE 1: Literature review of studies on endoscopic transnasal repair of CSF rhinorrhea*

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

cranial and nasal cavities was diagnosed in a live patient.
Luckett73 was the first, in 1913, to publish this event by describing the presence of an intracranial aerocele. In 1937
Cairns,19 a British neurosurgeon, was the first to propose
a classification of CSF rhinorrhea. He divided them into
acute traumatic, postoperative, delayed traumatic, and
spontaneous. Ommaya91 and then Vrabec and Hallberg114
later refined this classification. In his series, Ommaya reported a 2% incidence of CSF leaks in all head injuries.
The incidence increased to 5% when considering only patients with skull base fractures. In addition, he noted that
90% of CSF leaks were caused by traumatic events.
In 1926 Dandy31 described the first successful intradural closure of a CSF fistula by suturing autologous
fascia lata behind the posterior wall of the frontal sinus.
In 1937 Cairns19 demonstrated that CSF leaks could also
be repaired with the extradural application of fascia lata.
Nevertheless, reports that spontaneous cessation of
a CSF leak was possible led some to think that surgical
intervention was unnecessary and unproven.21,54 Calvert
and Cairns,20 in a discussion of war injuries to the frontal
and ethmoidal sinuses, described a number of cases in
which CSF rhinorrhea healed spontaneously.54
Other treatment modalities were advocated as well.
In his paper published in 1944, Schroeder105 described a
patient with CSF rhinorrhea who recovered after treatment with sulfonamides and a lumbar puncture. Also in
1944 Dandy32 advocated the surgical repair of any CSF
leak within 2 weeks of its onset to prevent meningitis. The
review of Lewin69,70 of the British combat experience and
a large series of skull fractures built the case for adopting
more aggressive operative management of CSF leaks as
the standard of care.29 In 1948 Dohlman36 performed the
first extracranial repair of spontaneous CSF rhinorrhea
via a naso-orbital incision. In 1981 Wigand116 was the first
to use an endoscope for the extracranial repair of a CSF
leak. It appears that Mattox and Kennedy,81 in 1990, were
the first to use an endoscope for the diagnosis and transnasal repair of CSF rhinorrhea in a series of patients with
accidental craniofacial fractures. Over the last 30 years,
the transnasal endoscopic approach has become a very
important part of the armamentarium for repairing most
cases of CSF rhinorrhea, with reported success rates of
approximately 90% (Table 1).
Classification of Anterior Skull Base Fractures and CSF
Rhinorrhea
Cerebrospinal fluid rhinorrhea can be classified

based on etiology, anatomical location, age of the patient,
or extent of bony defect. The most frequently used type
of classification is based on the etiology of the CSF fistula. Several such classifications have been proposed, and
the main difference among them is in grouping CSF rhinorrhea due to accidental trauma and postsurgical CSF
rhinorrhea together under the posttraumatic category
(Fig. 1). Because of the different types of defects created,
diagnosis, time of presentation, underlying brain pathology, and speed of injury impact, we prefer to consider
the postsurgical CSF fistula and postaccidental traumatic
CSF leak in separate categories (Fig. 1 upper). The type
of classification used should consider the timing of the
diagnosis, type and extent of skull defect, and duration

of symptomatology and suggest the possible timing and
type of repair to be undertaken.
The most favorable groups of patients to treat appear
to be those who suffer head injuries resulting in a narrow
fracture of the skull base. In contrast, those groups that
suffer multiple or large fractures and a broad or multifocal injury, as well as those that are victims of penetrating
injury with significant comminuting fractures of the skull
base, represent the most difficult groups to treat.102
The relationship between skull fractures and CSF
leaks is well described throughout the literature, and we
know that given the close relationship of the meninges
and the skull, these fractures can cause CSF fistulas and
leaks. Identifying the types of skull fractures that would
suggest an increased risk for persistent CSF leaks and/or
meningitis and those refractory to conservative management is crucial in determining appropriate management.
Anterior skull base fractures include a significant number
of injuries resulting in rhinorrhea from a CSF fistula.104
Friedman and colleagues46 reported that CSF fistulas in
84% of 51 patients were attributable to skull fractures
most commonly involving the frontal sinus, followed by
the orbital and petrous bones.
The anterior cranial base consists of a number of segments that vary significantly in rigidity and orientation
relative to the horizontal plane and in their proximity to
different compartments and constructs of subarachnoid
spaces, and as a consequence is exposed to different local CSF flow pressures and velocities.100 Building on
these principles, multiple groups have suggested classifications that allow more precise localization and a better understanding of the relationship between specific
fracture types and the risk of subsequent CSF fistula. In
an effort to find a relationship between the location and
size of cranial base fractures and intracranial infection,
Sakas et al.100 classified anterior cranial base fractures
into 4 types: Type I, cribriform, a linear fracture through
the cribriform plate without involvement of the ethmoid
or frontal sinuses; Type II, frontoethmoidal, fracture that
extends through the medial portion of the anterior cranial
fossa floor where it directly involves the ethmoid sinuses
and/or walls of the medial frontal sinus; Type III, lateral
frontal, fracture that extends through the lateral frontal
sinus (superomedial wall of the orbit) and may involve the
superior or inferior walls of the lateral frontal sinus; and
Type IV, complex, any combination of the prior types. Using this classification scheme, Sakas and colleagues concluded that Type I cribriform fractures have the highest
risk for infection at 60%, with Type II frontoethmoidal
fractures a close second at 43%. This finding was probably attributable to a higher incidence of larger fracture
sizes and CSF rhinorrhea in these groups. The authors
concluded that after an anterior skull base fracture, patients with Type I and II fractures (fractures close to midline), fracture displacement > 1 cm, and prolonged rhinorrhea (> 8 days) have an increased risk of posttraumatic
meningitis.
Using this classification scheme, Madhusudan and
colleagues76 developed an expanded nomenclature of
frontobasal fractures to include the frontobasal region in3
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 otolaryngology literature, iatrogenic postsurgical and accidental posttraumatic CSF rhinorrhea are grouped together as posttraumatic.
volved, the associated midfacial injury, and the mode of

injury. In this scheme, the frontobasal region is divided
into frontal, basal, and combined frontobasal regions,
with the basal region described as the floor of the anterior fossa formed by the bony ethmoid labyrinth, planum
sphenoidale, and lateral orbital walls. These regions are
then subdivided sagittally into central, lateral, and combined areas. The authors results revealed that the frontobasal type is the most common skull fracture. They reported that the incidence of a CSF leak was significantly
higher in impure types of frontobasal fractures, defined
as the presence of a midface fracture.
While anterior skull base fractures appear to be the
most common types of fractures resulting in rhinorrhea,
Brodie and Thompson16 indicated that CSF rhinorrhea
can also result from temporal bone fractures. In their
study of 820 temporal bone fractures, these authors found
that 72% of patients with temporal bone fractures and
CSF fistulas presented with CSF rhinorrhea.
When evaluating traumatic CSF leaks involving the
anterior skull base, one must also take into account the
possibility of paradoxical rhinorrhea. Simply stated, para4
doxical rhinorrhea is rhinorrhea from the naris contralateral to the site of CSF leakage. It can occur with displaced
fractures of the midline structures, the crista galli and
vomer, and can also be seen in the setting of mucocele
formation obstructing the ipsilateral naris.12 Paradoxical
rhinorrhea should also be considered after temporal bone
fractures when the temporal dura is torn and CSF travels
from the origin of the leak, down the eustachian tube into
the nasopharynx, and ultimately to the site where CSF
exits the naris.12 The majority of paradoxical CSF leaks
have been managed conservatively with good success.30
Pathophysiology and Anatomy of Posttraumatic CSF
Rhinorrhea
Accidental trauma can lead to a variety of skull base

defects, and thus accidental traumatic CSF leaks are associated with a heterogeneous group of injuries needing
highly individualized care. To this purpose, understanding basic CSF physiology and ICP changes will be helpful
when developing treatment plans for patients with CSF
leaks.
Cerebrospinal fluid is formed by the choroid plexNeurosurg Focus / Volume 32 / June 2012

uses as capillary ultrafiltrate during various metabolic
processes at a rate of 0.35 ml/minute (350500 ml/day).
The total volume of CSF in an adult at any given time
is approximately 90150 ml. The cycle of continual production and absorption results in the total volume of CSF
being turned over 35 times/day. Arachnoid villi are the
anatomical structures where CSF absorption occurs. A
pressure gradient of 1.57 cm of water is required to drive
CSF through these structures.102
Cerebrospinal fluid rhinorrhea refers to CSF leakage
through the nose. For this to occur, both a communication
between the intracranial space and the nasal cavity and
a breach in the dura mater should be present. Traumatic
CSF leaks usually begin within 48 hours of injury, and
95% of them manifest within 3 months.102 More than 85%
of traumatic CSF rhinorrhea cases cease with observation or nonsurgical treatment, such as bed rest and CSF
flow diversion. It has been suggested that leaks that close
without surgical repair are probably covered by a layer of
fibrous tissue or regenerated nasal mucosa since dura mater does not regenerate.102 In some instances, the presence
of an encephalocele or a meningocele through the bony
defect may disallow the healing process. Furthermore,
the size of the defect is an important factor in predicting
the possibility of spontaneous cessation of the leak.99,100
Hence, treatment approaches must be individualized,
especially when considering patients with closed-head
injuries and small fractures versus those with large and
comminuted fractures or those with penetrating injury to
the skull base.99,102
Another important factor in determining the appropriate treatment for CSF leakage is the anatomy of the
dura at the location of the fracture. In other words, the
native dural integrity and its relation to the skull base
play a role in the formation of a CSF fistula. As discussed
above, a large portion of CSF leaks and subsequent cases
of meningitis appear to be more common in instances of
frontobasal fractures. Sakas and colleagues100 remind us
that the cribriform plate is thin and fragile, covered only
by the arachnoid layer, and is missing a true dural investment. Without protection from the dura mater, the delicate
arachnoid layer is easily violated by even a small fracture.
Additionally, since the cribriform plate is located in the
midline of the anterior fossa, at the bottom of a slight
medial slope of the skull base floor, CSF may gravitate to
this area. If a small portion of the brain cannot herniate
through the defect and create an effective seal, spontaneous resolution and nonoperative management may prove
difficult.100
Presentation of CSF Rhinorrhea
Cerebrospinal fluid rhinorrhea in the acute phase after trauma has been reported in as many as 39% of the
patients with skull base fractures.104 Patients present with
a variety of symptoms depending on the acuteness of the
event. In the acute phase following the traumatic event,
patients may present with epistaxis, nasal discharge, periorbital ecchymosis, chemosis, oculomotor impairment,
anosmia, motor deficit, open-head injury with CSF leakage, loss of vision, cranial nerve deficits (most frequently,
firstthird and fifthseventh cranial nerve injuries), men-
ingitis, and pneumocephalus.104,118 In the chronic phase,

patients may present with recurrent meningitis, intermittent nasal discharge, headaches, salty or sweet taste in the
retropharyngeal space, 59 hyposmia,23 and brain abscess.
The risk of recurrent meningitis after posttraumatic
CSF leakage has been reported to range from 12.5% to
50%, with a 29.4% neurological complication rate.43 Eljamel and Foy42,43 have reported an overall 30.6% risk of
meningitis before surgical repair and a risk of 1.3% per
day in the first 2 weeks after injury, 7.4% per week in the
1st month after injury, and a cumulative risk of 85% at the
10-year follow-up. Infection is the most feared complication because of its association with increased mortality
and morbidity. As such, its prevention, in parallel with
management of the primary injury, is critical to optimizing outcome.2
Diagnosis of CSF Rhinorrhea
Differentiating CSF rhinorrhea from other types of

nasal secretions is the cornerstone in diagnosing the CSF
fistula. In patients with profuse posttraumatic CSF leakage, the diagnosis is obvious and needs only to be confirmed.115 However, in the acute posttraumatic phase and
especially in obtunded patients, the diagnosis could be
complicated by the presence of sanguineous fluids exiting
from the nasal cavities as the result of other existing facial
fractures. Furthermore, it is not rare for CSF rhinorrhea
to be intermittent and sometimes start even years after a
traumatic event, when that event has been forgotten. It is
in these cases that the diagnosis of CSF leakage could be
challenging and frustrating.115
The reservoir sign, which is the ability of a patient
to leak CSF by flexing the head, is taken to be specific
for a fistula, although the sign is not always positive even
when the leak exists. Target sign refers to the ability of
CSF to migrate further, creating a bulls-eye stain with
blood in the center, on a filter paper or gauze. This has
been reported as a very unreliable sign since watery nasal
secretions and blood are mixed, and the same pseudochromatographic patterns can occur.28
Chemical Diagnosis. Chemical analysis of the discharge is the oldest method of diagnosing CSF leaks.
Chemical examination of the nasal fluid became the standard of care after Sir St. Clair Thomson published his book
The Cerebrospinal Fluid in 1899. In it he described in detail the chemical and physical characteristics that distinguish CSF fluid and nasal secretions based on differences
in glucose concentrations.54 The concentration of glucose
in CSF exceeds 50% of the serum concentration except
during meningitis, subarachnoid hemorrhage, or some other unusual circumstance.28 The glucose concentration in
nasal secretions is 10 mg/dl or less. Nonetheless, a glucose
test is not definitive because the glucose oxidase assays
used nowadays are too sensitive, turning positive even at
low values of glucose; therefore, even normal nasal secretions can elicit false-positive reactions.52,60,63 As a result, the
glucose test for CSF rhinorrhea has become obsolete.
The asialo form of transferrin, b2-transferrin is produced by neuraminidase activity in the brain and found
abundantly in CSF. It occurs in lower concentrations in
5

the perilymph of the cochlea and the aqueous and vitreous humor of the eye.103,115 Since it is not normally contained in nasal secretions, its detection allows indirect diagnosis of CSF rhinorrhea. Samples of suspected CSF are
obtained by direct drip collection or via the placement of
intranasal sponges. The samples are sent to the laboratory
with a serum sample, and b2-transferrin is detected by
immunoblotting or immunofixation and silver stain in the
majority of large diagnostic laboratories.103,115 Since its
introduction in 1979,87 b2-transferrin detection has been
widely used for the diagnosis of extracranial CSF leakage, with a reported sensitivity and specificity up to 99%
and 97%, respectively.115 Nevertheless, multiple disadvantages have been cited for this test, the most important being the highly intensive work and length of time required
to perform the assays (12 days) and the need for high
expertise in the interpretation of the results (Table 2).85
Another protein proposed as a potential marker for
the diagnosis of CSF rhinorrhea is b-trace protein, or
bTP.4,45,8385,98,103,112 It is the second most abundant protein
in human CSF following albumin83 and is mainly produced in the epithelial cells of the choroid plexus and in
the leptomeninges in the CNS.83,103 The CSF concentration of bTP is approximately 35-fold higher than in plasma.103 It is found in nasal secretions and other body fluids
as well, but in very low concentrations.83 The rationale for
the bTP test relies on the large concentration difference
between CSF and nasal secretions and an easy-to-use serum/CSF concentration gradient.112 By utilizing a highly
sensitive nephelometric measurement, this immunological test can even detect very low amounts of CSF in nasal
secretions.83 bTP is identical to prostaglandin-D synthase
and is thought to be important for maturation and maintenance of the CNS.83,86 bTP has been identified by rocket
immunoelectrophoresis with a reported sensitivity of
91%.7 An immunonephelometric bTP assay has been proposed for routine use in clinical practice for the diagnosis
of CSF rhinorrhea.98 The overall accuracy of this method
in diagnosing CSF leaks has been reported to approach
0.974, with a negative predictive value of 0.971 and a
positive predictive value of 1.8 The advantages of using
bTP rather than b2-transferrin as a marker for CSF rhinorrhea have been described by Meco and colleagues85 as
less time consuming, less labor intensive (< 15 minutes),
and less expensive. Furthermore, the bTP test carries all
the advantages of the b2-transferrin test: noninvasive,
repeatable, same sample collection methods, and high
sensitivity and specificity. The wide use of bTP for this
purpose has been slow because the test is not suitable in
patients with bacterial meningitis or those with reduced
glomerular filtration because of variation in the levels of
this protein.85,113 Furthermore, at concentrations between
1.31 and 1.69 mg/L in the nasal secretions, there is an
overlap of individuals with and without CSF leakage.85,103
For these patients, other tests are required to confirm the
pathological condition (Fig. 2).
Intrathecal injection of a sodium fluorescein solution
following a thorough endoscopic examination has been
used to establish the diagnosis of CSF rhinorrhea. However, its ability to precisely localize the leak is limited.
Nonetheless, the accuracy of the test has been reported102
6
to be around 96%. The usefulness of this test depends on

the extent of the dural defect, rate of leakage, timing of
the intrathecal injection, and rate of CSF turnover that
could dilute or disperse the fluorescein. Reported complications of the solutions injection, and thus limitations
to its use, have ranged from mild tinnitus, headache, nausea and vomiting, transient pulmonary edema, confusion,
seizures, and coma, to death. Keerl et al.58 analyzed 420
administrations of fluorescein solution and their complications as reported in Europe and the US. The reasons for
the complications were found in the method of administration, formulation of the solution, idiopathic reactions,
and concentration or dose of fluorescein. 58 Other authors
have come to the same conclusions.89,117 At concentrations
of 5% or lower, side effects are transient. Schlosser and
Bolger102 recommend the use of 0.1 ml of 10% fluorescein
diluted in 10 ml of the patients CSF with slow injection
over 1015 minutes. They reported no complications with
this method of injection. Keerl and colleagues58 reported
that the intraoperative use of a maximum dose of 1 ml
(50 mg of fluorescein) or 0.1 ml per 10 kg of body weight
in Germany, and 0.52 ml (2.510 mg) of the more diluted or hypodense 0.5% solution in the US, was without
any complications. Informed consent and a comprehensive discussion with the patient regarding the advantages
of using fluorescein in detecting the CSF leak, reported
risks of fluorescein intrathecal injection, and information
about the lack of FDA approval are recommended.58,102
Imaging Diagnosis. After confirming the presence of

CSF rhinorrhea, the next step in its management is localization of the leakage site. Localizing this site assists in
surgical planning and increases the chance for a successful repair. Imaging studies play a very important role in
this step.
High-resolution CT examination with axial, coronal,
and sagittal reconstructions has replaced plain radiography of the skull in diagnosing skull fractures. Very few
studies have been done exclusively to assess the accuracy
of HRCT in posttraumatic CSF leaks. In a retrospective
review of 47 cases of traumatic and nontraumatic CSF
leaks visualized on HRCT, Zapalac and colleagues119 reported a sensitivity and an accuracy of 87% each. Yilmazlar and colleagues118 reviewed 81 patients who were
treated for CSF leakage due to skull base fractures. They
found that coronal bone window HRCT scans are important in identifying the site of CSF leakage, whereas axial
images are important in demonstrating fractures of the
posterior wall of the frontal sinus. Lund and associates75
suggested that HRCT can accurately demonstrate the position of the fracture as well as the size of the defect. Nevertheless, HRCT scans show the bony fracture, but the
presence of a fracture is not always correlated with the
presence of a CSF leak.
Computed tomography cisternography is useful when
there is an active leak at the time of intrathecal contrast administration or when the leak can be induced by Valsalva
maneuver or bending down. Schlosser and Bolger102 reported that the greatest utility of CTC is in frontal or sphenoid sinus leaks because these sinuses act as reservoirs of
the contrast material. They also asserted that in cribriform
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

into the pharynx and never collect to a volume substantial
enough to be detectable on imaging.102 If the leak is not
active, CTC is not more useful than noncontrast HRCT.
Moreover, CTC can provide further proof of the presence
of a leak but not its precise location.74 Cisternography with
radioactive isotope injected intrathecally has been used in
cases of intermittent low-flow CSF rhinorrhea. This technique requires endoscopic transnasal placement of pledgets
at the anterior cribriform plate, middle meatus, or sphenoethmoidal recess. Although detection of radioactivity in
the pledgets indicates a leak, this technique does not provide information about the precise location of the fistula.
Note that the sensitivity ranges from 62% to 76% and that
false readings occur in up to 33% of cases.33 The success
rate for preoperative localization of CSF fistulas has been
reported as 62.5% with radioisotope cisternography and
95.7% with CTC.44
Magnetic resonance imaging has been suggested as
a very valuable technique for localizing CSF fistulas because CSF gives a hyperintense signal on T2-weighted
imaging and because, in general, this imaging technique
can demonstrate cranial anatomy in detail and in multiple
planes.44 Magnetic resonance imaging without contrast
medium has been used with an accuracy of 60%94%,
but high false-positive rates up to 40% have been reported (reviewed in the study by Goel et al.48). These falsepositive rates have been attributed to the difficulty in differentiating CSF from mucosal thickening and fluid that
can be seen within a sinus. Some authors have reported
very high sensitivity in localizing the side of the leak in
patients with intermittent CSF rhinorrhea based on demonstrations of brain hernia or the presence of a high signal that is continuous and similar to that for CSF in the
basal cisterns through the cribriform plate or paranasal
sinuses.44 When interpreting the literature, one must pay
attention to the nomenclature, because some authors use
the term MR cisternography to describe routine MRI
studies that rely primarily on T2-weighted sequences to
highlight CSF rather than on those in which intrathecal contrast medium is used.102 Nowadays, MRI for CSF
leak detection refers to a technique that uses a fast spin
echo sequence with fat suppression and image reversal.102
Some authors have reported good results using this technique to detect intermittent CSF leaks, with an accuracy
up to 89%, 85%92% sensitivity, and 100% specificity.102
Another diagnostic methodology is MRC performed
with the intrathecal injection of Gd-enhancing contrast
medium (GdMRC), first described in monkeys in 1985 by
Di Chiro and colleagues34 and in humans in 1994 by el
Gammal and Brooks.38 Few reports have been published
on this method and its accuracy in the diagnosis of CSF
leakage. The method still requires the performance of
lumbar puncture with injection of contrast medium. Behavioral, neurological (focal seizures, ataxia, and delayed
tremor), and histological changes (loss of oligodendroglia,
hypertrophy of astrocytes, and formation of eosinophilic
granules) have been described in animal studies.96,97 In
human studies, no gross behavioral changes, neurological
alterations, or seizure activity at any time after the procedure has been reported.5,6,109,120 Symptoms, such as postural
postlumbar puncture headache, nausea, and episodes of
7

vomiting, were documented, but all resolved within the
first 24 hours of the lumbar puncture with conservative bed
rest.109 In a prospective pilot trial in 20 patients, Aydin and
colleagues5 used a total volume of 0.51.0 ml of intrathecal
contrast medium without any significant gross neurological, CSF, electroencephalography, or MRI changes related
to the medium on the initial follow-up examination.120 In
this trial, the estimated intrathecal dose used per gram of
brain was much less than that used in animal experiments
(0.070.36 mmol/g brain vs 2.515 mmol/g brain).5 The authors reported successful CSF localization with positive
MRC studies and confirmation at the time of surgery in 14
patients and with positive MRC studies in 2 other patients
who did not undergo the surgical procedure. Since there
were no false positives in the surgically treated patients,
they reported 100% accuracy of GdMRC in this group.
In a later publication, Aydin and colleagues6 reported the
use of GdMRC in 51 patients with CSF rhinorrhea; in 59%
of these patients, the etiology was accidental trauma. The
GdMRC studies were positive for CSF rhinorrhea in 44 of
the 51 patients, and in 43 of them the leak was confirmed
during surgical repair, for an accuracy of 98%. None of
the patients demonstrated any acute adverse reaction that
could be attributed to the procedure.6 Furthermore, none of
them exhibited any neurological symptoms or signs caused
by the intrathecal Gd injection during a mean follow-up
of 4.12 years.6 Unfortunately, as in many other studies, the
authors did not report the specific accuracy, specificity,
and sensitivity exclusively for the posttraumatic patients.
Of note, Aydin and colleagues5,6 have suggested the use of
GdMRC with fat suppression sequences to enhance the accuracy of CSF leak detection. The sensitivity of this method for all CSF rhinorrheas is 84%87%, and the accuracy
ranges from 78% to 100%.6,39 It is believed that GdMRC is
more sensitive and more accurate than CTC because the
high viscosity of the contrast agents used in the latter contributes to a difficulty in being distributed to the entire subarachnoid space and in penetrating the small dural tears in
some patients. However, even for GdMRC, the patient must
have an active leak at the time of imaging for the diagnosis
to be revealed. Furthermore, GdMRC is more expensive
than CTC.
In conclusion, GdMRC is another safe imaging method with good accuracy and sensitivity that is part of the
surgeons armamentarium in localizing CSF leaks during
preoperative planning (Table 2). No clear criteria have been
defined for when to use GdMRC versus CTC. El Gammel
and colleagues39 suggest using HRCT in combination with
GdMRC for an optimal imaging approach in the diagnosis of CSF rhinorrhea. While the diagnosis of acute CSF
rhinorrhea caused by comminuted and complex skull base
fractures appears easy, that of intermittent and chronic
leakage is more challenging. In Fig. 2, we show a modified
version of the algorithm provided by Zapalac et al.,119 integrating all the new chemical and imaging tools that would
be more suitable and cost effective for the diagnosis of
posttraumatic CSF fistulas. Unfortunately, the diagnosis of
an occult fistula in a patient who presents with meningitis
and without CSF rhinorrhea becomes more difficult, and
all effort should be made to find the fistula by using all the
imaging studies deemed necessary.
8
Nonsurgical Management
Nonsurgical therapy begins with bed rest, head elevation (to prevent a negative gradient between intracranial
and paranasal sinus cavities that would allow an ascending
path for the bacteria intracranially), and strict CSF rhinorrhea precautions (avoid nose blowing, Valsalva maneuvers,
the use of straws, the use of an incentive spirometer, and so
forth). In a retrospective study of 735 craniofacial traumas,
with 34 patients presenting with CSF rhinorrhea (9 patients) and CSF otorrhea (25 patients), Bell and colleagues10
reported that these nonsurgical measures alone provided
resolution in 85% of the 34 cases. Only 3 (33%) of the 9 patients with posttraumatic CSF rhinorrhea did not respond
to any of the nonsurgical measures and required surgical
intervention to close the CSF leak. Mincy88 reported that
spontaneous closure occurs in 68% of posttraumatic CSF
fistulas within 48 hours of injury and 85% within 1 week.
If bed rest, head elevation, and strict CSF rhinorrhea precautions fail, then CSF diversion has been advocated.10,61 In the majority of cases, lumbar draining is
the method of choice for CSF diversion. External ventriculostomy draining is another method that provides
CSF diversion. The use of an EVD for this purpose has
not been explored in the literature, most likely because
it is considered to be more invasive than a lumbar drain.
Yilmazlar and colleagues118 reported on 81 patients with
CSF leakage due to traumatic skull fractures and divided
the patients into 2 groups based on their GCS scores at
presentation. While lumbar drains were used in patients
with a GCS score > 8, there was no mention of the CSF
diversion method in patients with a GCS score 8, for
whom the traumatic brain injury guidelines14 suggest
placement of an ICP monitor. Nevertheless, we believe
that placement of an EVD instead of a lumbar drain can
be considered in selected cases. Placing an EVD should
be considered first in patients who might benefit from an
ICP monitoring device given the severity of the traumatic
event and a low GCS score. In such cases, the EVD plays
the dual role of ICP monitor and CSF diverter. Placement
of an EVD could be preferred over a lumbar drain in patients who present with increased supratentorial pressure
due to cerebral edema, intraparenchymal contusions, or
other lesions not amenable to surgical evacuation. Evaluation of the EVD as a CSF diverter in posttraumatic CSF
rhinorrhea warrants further study.
In general, there are still some questions to be answered on CSF diversion for CSF rhinorrhea. Which patients would most benefit from CSF diversion? When is
the best time to proceed with lumbar or ventricular drain
placement? How long should one wait before deciding
that CSF diversion has failed and proceed to surgical
management? Knowing that 85% of posttraumatic CSF
fistulas close spontaneously (within 48 hours in 68% of
cases and within 1 week in 85%),88 that the meningitis
risk is 0.62% in the first 24 hours after injury, and that the
cumulative meningitis risk is 9.12% at the end of the 1st
week and 18.82% at the end of the 2nd week after injury,42
some have suggested a waiting period of 72 hours1 week
before attempting any invasive treatment for acute posttraumatic CSF rhinorrhea.71,118 In contrast, surgical intervention has been advocated as the first line of treatment

TABLE 2: Advantages and disadvantages of the most commonly used diagnostic tests for the diagnosis of CSF rhinorrhea
Diagnostic Test
chemical
b2-transferrin
bTP
Advantages
Disadvantages
noninvasive
repeatable
sensitivity up to 99%
specificity up to 97%
protein detectable only in CSF, perilymph, & aqueous humor
noninvasive
repeatable
sensitivity 91%100%
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
ternography
HRCT
CTC
MRI
MRC
intrathecal sodium
fluorescein
noninvasive
valuable for localizing fistula
anatomy in 3 planes
accuracy 60%94%
increased specificity to 92% & sensitivity to 100% (in intermittent
leaks) if using fast spin echo w/ fat suppression sequences
contrast less viscous than CT contrast & better penetrates
small fractures or tears
sensitivity 85%92%
specificity up to 100%
increased accuracy if fat suppression sequences used
may detect leak
possibility of repairing leak when test performed
not suitable in patient w/ bacterial meningitis or low glomerular

filtration rate
values 1.311.69 mg/L need other confirmatory test
invasive, requiring intranasal endoscopic procedure & intrathe cal injection of radioactive material
no details on site of leak
sensitivity 62%76%
fracture not always correlated w/ presence of leak
risks of radiation
diagnose site of fracture

diagnose size of defect
noninvasive
sensitivity >87%
accuracy approximately 87%
diagnose site of fracture
diagnose size of defect
possibility of correlating site of fracture w/ leak
sensitivity 48%96%
95% success rate in diagnosis
for delayed posttraumatic CSF rhinorrhea.46,99,102 We think

that there is a need to further study this argument and
evaluate whether even those patients with delayed CSF
rhinorrhea could benefit from a trial of nonsurgical management. The duration of nonsurgical management with
leak precautions and diversion of CSF has ranged from 7
days to 6 weeks.61,99,100,118 Unfortunately, it is unknown61
whether there is any difference in the rate of closure of
a CSF fistula between 7 days and 6 weeks of nonsurgical trials. Nevertheless, one could argue that with a 7.4%
labor intensive & time consuming

requires high expertise for interpretation & performance
performed in only a few specialized laboratories
invasive
intrathecal injection of contrast material
active leak must be present at time of CT scan
high viscosity of contrast material reduces its penetration in
small fractures or defects
risks of radiation
high false-positive rate (40%)
not every patient can undergo MRI
expensive
invasive w/ intrathecal injection of contrast material

very few studies done so far
severe complications reported in animal studies
active leak must be present at time of study
expensive
limited ability to localize leak
depends on timing & rate of leak, timing of injection, rate of
CSF circulation & turnover
reported complications such as coma, seizures, death
meningitis risk per week within the 1st month, surgical

management should be considered within the 2nd week
after CSF rhinorrhea fails to resolve with conservative
management, as first suggested by Dandy32 in 1944.
As stated above, meningitis is the most frequent complication of posttraumatic CSF rhinorrhea. Although 11%
38% of patients with CSF rhinorrhea become infected,57
the use of prophylactic antibiotics continues to be a controversial issue. The incidence of meningitis after posttraumatic CSF rhinorrhea is higher in the 1st few weeks,50 and
9

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.27,37,4042 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 Society 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 eradicate 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 57 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
of prophylactic antibiotics following traumatic skull base
fractures. Eljamel41 retrospectively reviewed 215 patients
with a definitive diagnosis of posttraumatic CSF fistula,
106 of whom were treated with antibiotics prophylactically and 109 who were not. They did not find a significant
difference in the risk of meningitis between the 2 groups.
They concluded that it is ethically justifiable to withhold
antibiotic prophylaxis in patients with CSF fistulas until
a prospective controlled double-blind trial has settled the
question.41
Surgical Management
Surgery is reserved for the treatment of CSF leaks

that do not spontaneously close or respond to conservative management with CSF diversion.118 Furthermore, early surgical intervention has been recommended in cases
in which the intracranial pathology requires acute intervention (Fig. 3) or the anatomy of the skull fracture suggests that spontaneous closure would be impossible, such
as in a large depressed skull base fracture, a fracture accompanied by complications (for example, cranial nerve
deficits), or tension pneumocephalus.104,118 Two types of
approaches for the repair of a posttraumatic dural defect
and a consequent CSF leak have been described in the lit10
Fig. 3. High-resolution CT scans (AD) obtained in a patient who

presented after a fall from a 30-foot building. Multiple comminuted
craniofacial fractures involved the cribriform-ethmoid, maxillary, and
frontal sinus. Head CT scans (E and F) showing a large right frontal
intraparenchymal hematoma with midline shift. The patient underwent
emergent surgical intervention for evacuation of the hematoma, reduction of nasofrontal fractures, cranialization of frontal sinus, and dural
repair with autologous pericranium graft. An EVD was placed on arrival
because of a low GCS score and was kept in place for 10 days. No CSF
leak was noted at the 6-month follow-up.
erature: transcranial approach and extracranial approach.

Transcranial approaches were first described by Dandy31
in 1926, as he reported the first successful dural defect repair. Extracranial approaches have improved over recent
years with the advancement in endoscopic sinus surgery
and the transnasal endoscopic route, which has been used
successfully for the closure of posttraumatic CSF fistulas
in properly selected patients (Fig. 4).
Eljamel and Foy43 conducted a long-term analysis of
160 patients with acute posttraumatic CSF fistula; 149
patients underwent surgical dural repair. Forty-seven patients had a first episode of meningitis before the surgical
repair. The overall risk of meningitis was reduced from
30.6% before surgery to 4% after surgery, and the cumulative risk at the 10-year follow-up was reduced to 7%
Fig. 4.Coronal (A and B) and axial (C and D) HRCT scans obtained

in a patient who presented with clear rhinorrhea 5 months after a traumatic event, showing no fractures. Note that the b2-transferrin test was
positive. Air-fluid level as an indication of CSF leakage was noted on the
left sphenoid sinus. A lumbar drain was placed and fluorescein dye was
injected. A leak was noted on endoscopic transnasal exploration and
was successfully repaired via an extracranial endoscopic approach.
after surgical repair from more than 85% prior to repair.

The recurrence rate of CSF leakage after the first dural
repair was reported as 17% in this series, with an operative mortality of 1.3%, regardless of whether a bicoronal
or unilateral approach was used. At the end of this retrospective study, the authors43 concluded that surgical repair seems to be the only durable long-term prophylaxis
against the development of meningitis in patients with
posttraumatic rhinorrhea and therefore should be undertaken as soon as the patient is fit for surgery.
Friedman and colleagues46 published a study of posttraumatic CSF leaks in 101 patients. Spontaneous resolution of the CSF leaks occurred over an average of 4.8 days
in 26 (60%) of the 43 patients with clinically evident leaks.
Twenty-four patients (47%) were surgically treated, and the
median time from the initial traumatic event to surgery was
45 days among them all. A variety of surgical approaches
were used, including intracranial, extracranial, and combined intracranial-extracranial. Of the 24 surgically treated patients, 3 (12.5%) experienced further CSF leakage requiring reoperation. No patient suffered recurrent leakage
after a reoperation. Lumbar drainage was used in only a
few patients in this series, and no meaningful conclusions
could be drawn regarding its efficacy. However, the authors
did conclude that the rate of surgical repair may have been
lower had they more aggressively pursued lumbar drainage
and conservative management.46
Rocchi and colleagues99 reported their experience
with 58 patients who had posttraumatic CSF rhinorrhea,
36 of whom underwent surgical repair according to speNeurosurg Focus / Volume 32 / June 2012
cific criteria that have been reported100 to increase the longterm 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 fracturessuch
as compound, comminuted, depressed, or craniofacial
fractures larger than 1 cm, fractures close to the midline,
or those involving the cribriform platerequire 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
Yilmazlar and colleagues118 described a series of 81
patients with persistent CSF otorrhea and rhinorrhea for
more than 24 hours after the traumatic event. Conservative measures for 72 hours were undertaken in all patients
except those who required emergent surgical treatment
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
suggested a treatment algorithm in which bed rest measures were applied for 72 hours7 days, and if that failed,
a CSF external drain was placed for 710 days. Surgical
intervention was undertaken after conservative measures
failed. Thirty-two patients underwent surgical repair: 12
of them within 3 days, 10 within 1030 days, and 10 others at 3 months22 years after the traumatic event. The
authors observed that patients with GCS scores 8 at
presentation had a poorer disease prognosis and a high
risk of meningitis regardless of the method of treatment
for the CSF leak, as compared with patients with GCS
scores > 8.
The type of transcranial approach undertaken for
closure of rhinorrhea depends on the fistula location and
the type and size of the fracture. Several surgical techniques have been described in the literature, ranging from
the classic frontal craniotomy, which can be bilateral or
unilateral, to the suprasinus transfrontal approach with
lateral extension.10,43,46,70,99,100,104 If primary repair of the
dura is not feasible, dural substitutes, such as pericranial graft, fascia lata, temporalis muscle fascia, or other
autologous (preferably) or nonautologous grafts, can be
used. Each fracture associated with a CSF leak is unique,
and the type of approach used to repair the leak depends
on the specific situation and cannot be organized in an
algorithmic form. The same can be said about the use of
graft materials. The type of graft material depends on the
location and size of the defect, extent of dural laceration,
and availability of the graft. Until clinical trials evaluate
the superiority of one surgical approach over another and
11

one type of graft over another, the choice will depend on
the situation and the surgeons choice. The mortality rate
for surgical exploration and repair has ranged from 0% to
6% in the literature.19,43,46,70,99,104 In cases in which one or
more sinuses are involved in the fracture, obliteration of
the sinuses is crucial not only to stop the CSF fistula but
also to prevent the occurrence of a mucocele and delayed
infection. For fractures involving the frontal sinus, for
example, obliteration is accomplished first by meticulous
stripping of sinus mucosa, removing the posterior table of
the sinus, and then packing the communication between
the frontal sinus and the nasal cavity with autogenous fat
or muscle.46,66 The risk of a recurrent leak after transcranial repair of traumatic CSF rhinorrhea has been reported
to be 6%32%.10,43,46,66,68,69,99,104,118
Extracranial repairs can be achieved through different types of approaches. The most frequently used has
been the transnasal approach, first described by Hirsch54
in 1952.
Since 1981 when Wigand116 first described the successful extracranial repair of a CSF leak, the endoscopic
approach has progressively become preferred.104 Although this technique has a high rate of success and a
lower rate of morbidity, limitations do exist. It may be
most appropriate for specific cases, such as for a leak due
to a precisely located small tear or in the absence of associated brain injuries requiring surgical treatment.99
McMains and colleagues82 reported an overall success
rate of 94% in CSF leak repair via the endoscopic extracranial approach in 92 patients. Only 18 of these patients
had suffered accidental trauma. The authors noted that in
patients in whom the endoscopic repair had failed, the defects were larger than 1.5 cm. The specific success rate in
the accidental trauma subgroup was not reported. Banks
and colleagues9 described their 21-year experience with
endoscopic CSF leak repair in 193 cases, with an overall
success rate of 98%. They included 109 posttraumatic CSF
leaks in their study, 15% of which had occurred after accidental craniofacial trauma. Recurrence of the leak was
reported to occur within an average of 4 months after
endoscopic repair.9 Cassano and Felippu23 documented a
series of 125 patients at 2 different institutions who underwent endoscopic endonasal repair of CSF leaks. The duration of CSF rhinorrhea prior to surgical repair ranged from
fewer than 7 days (32 patients) to more than 30 days (29
patients). Accidental trauma was the etiological factor in 41
patients (32.8%). These authors reported an initial overall
success rate of 94.4% and a success rate of 100% in the
posttraumatic patients.23 Kirtane and colleagues61 have described their experience with 267 patients who underwent
endoscopic transnasal repair, and a posttraumatic CSF
leak was diagnosed in 119. These latter patients were first
treated conservatively for 46 weeks in the form of complete bed rest, acetazolamide, broad-spectrum antibiotic
prophylaxis, and the avoidance of straining. Cerebrospinal
fluid drainage via repeated lumbar punctures was preferred
rather than leaving a lumbar drain. The authors reported a
success rate of 96.6%, with 9 patients having a postoperative recurrence of the CSF leak. Six of these patients underwent successful repair via an endoscopic approach and
2 via a transcranial approach, with an overall success rate
12
of 98.8%; 1 patient was lost to follow-up. The authors did

not mention how many of these 9 patients were in the accidental trauma group. They did recommend performing the
transcranial approach in all patients with frontal sinus fractures and CSF leakage, as well as considering the transnasal endoscopic approach only in patients with sphenoid,
cribriform, and ethmoid roof fractures. In their publication,
they described only those patients in whom conservative
management failed; hence, it is difficult to discern how
many CSF leaks resolved with 46 weeks of conservative
management. In the series of Locatelli et al.72 of 135 patients with CSF rhinorrhea, 39 cases were the result of accidental traumatic injury. These patients underwent surgical
treatment after 2 weeks of conservative management had
failed. The authors recommended conservative management first for acute posttraumatic CSF rhinorrhea and then
surgical exploration and repair only if the first option fails.
In contrast, for delayed posttraumatic CSF rhinorrhea, surgical treatment was recommended without a first trial of
conservative management.72
Although numerous, most of the reports published
on the extracranial endoscopic repair of CSF rhinorrhea
include patients with different etiological backgrounds,
making it difficult to discern the specific success rate of
this technique for posttraumatic leaks (Table 1). Furthermore, several authors group together in 1 category (Fig.
1 lower) the accidental traumatic leaks and the postsurgical ones. In addition, very few reports have addressed the
utility of endoscopic treatment in the acute setting.61
The techniques used for endoscopic transnasal repair
of CSF rhinorrhea depend on the location of the leak, the
size of the defect, and surgeon preference. A direct paraseptal approach with or without opening of the ethmoidal
cells, an anteroposterior ethmoidotomy with preservation
of the middle turbinate, and an ethmoidosphenoidotomy
with complete removal of ethmoidal turbinates have been
used for an olfactory groove defect.72,80 A sphenoidotomy with a direct paraseptal endonasal approach limiting
enlargement of the natural ostium of the sphenoid and a
transethmoid-pterygosphenoidal approach have been used
for a sphenoid bone defect, depending on the anatomy of
the sphenoid sinuses.72,80 Various authors have successfully used different types of autologous and nonautologous
grafts, such as a mucoperiosteal flap from the middle turbinate or septum or mucoperichondrial, osseous, cartilaginous, fat, muscular fascia, middle turbinate, or septum pedunculated graft, or any combination of these grafts.1,3,11,
13,15,22,2426,28,35,47,51,55,56,64,65,67,77,79,90,101,108
Another widely discussed issue in endoscopic transnasal repair is whether
the grafts used for repair should be placed above (inlay)
or beneath (onlay) the skull base defects. In a meta-analysis, Hegazy et al.53 found that both techniques yielded
similar results. Nevertheless, there are no data on whether
there is any difference in these techniques.
Still unsettled in the literature is the issue of placing
a lumbar drain after endoscopic repair of CSF rhinorrhea.
Indications for lumbar drain placement are not clear, and
most surgeons insert them based on their past anecdotal
results.22 Some authors report that there is no difference
in CSF rhinorrhea repair with or without postoperative
lumbar drain insertion.9,22,55,83,102 Furthermore, none of

these authors specify the need for a lumbar drain in posttraumatic CSF rhinorrhea (Table 1).
There is a multitude of articles describing the success
rates of endoscopic repair of CSF leaks, but none exclusively document the outcome in patients with traumatic
fractures. In these articles, 1585 patients underwent endoscopic repair of a CSF leak with a reported initial success rate range of 75%100%. Four hundred twenty-five
of these patients presented with CSF rhinorrhea following
accidental trauma. More than 13 studies with 255 patients
with posttraumatic CSF leaks did not specify the recurrence rate in this group. In 170 posttraumatic patients, the
success rate ranged from 50% to 100%, with failure of
the first transnasal endoscopic repair in only 12 patients
(7.05%).1,9,11,13,15,18,2326,28,35,47,51,55,56,59,61,62,64,65,67,71,72,74,7779,
81,82,90,93,101,107,108,111
After conducting a questionnaire survey
of 72 otorhinolaryngologists who regularly performed this
procedure, Senior and colleagues106 reported a complication rate of 2.5% for transnasal endoscopic repair among
a sample of 650 patients of different CSF rhinorrhea etiological groups. The complications after endoscopic repair
of a CSF leak were seizure, meningitis, cavernous sinus
thrombosis, temporary visual problems, sinusitis, intracranial hypertension, and death. In a meta-analysis of
studies published after 1990, Hegazy et al.53 reported an
incidence of less than 1% of major complications, such
as meningitis, subdural hematoma, and intracranial abscesses, after endoscopic repair of CSF rhinorrhea.
Summary
Although the first report of the successful surgical

treatment of CSF rhinorrhea due to posttraumatic anterior cranial injury dates back to 1926,31 many controversies regarding its optimal management still exist today.
Diagnosis should start with a clinical suspicion, continue
with chemical investigation to confirm its presence, and
hopefully end with imaging studies to define the location
and size of the fistula (Fig. 2). Starting with the simplest
diagnostic tool and progressing to the most complex ap-
pears to be the most efficient and cost-effective route

(Table 2).119
While embarking on the treatment of these fistulas,
we must remember that 85% of CSF rhinorrhea cases resulting from head trauma stop spontaneously and that the
risk of meningitis is 0.68% in the first 24 hours after injury and increases up to 18.87% in the first 2 weeks after
injury.42,88 Published reviews have not shown that prophylactic treatment with antibiotics makes a difference, and
therefore such therapy should be discouraged.40,41,49,57
It has been suggested that patients who need emergent surgical treatment for intracranial pathology should
undergo intracranial repair of the fistula in the same setting.99,104,118 Nevertheless, this decision must be made while
taking into consideration the amount of cerebral edema
and the hemodynamic stability of the patient.46,99 In some
instances, treating the intracranial pathology first and then
repairing the CSF fistula later, when the patients vegetative
parameters allow, may be wiser (Figs. 5 and 6).46,99,104,118
While there appears to be some consensus that the majority of patients should first undergo nonsurgical management
with bed rest, head-of-bed elevation, and CSF external diversion to allow spontaneous healing to occur, there remains some controversy regarding the length of time such
treatment should be pursued. While some authors suggest
72 hours7 days of bed rest and then a 7- to 10-day trial of
CSF diversion maneuvers,118 others recommend pursuing
surgical treatment after the failure of 8 days of nonsurgical management.99,100 We found no randomized controlled
studies that evaluated these treatment strategies, however.
The surgical management of posttraumatic CSF fistula depends on the impact of the trauma, the location
of the fistula, and the temporal relationship between the
leak and the traumatic event. It has been suggested that
a CSF fistula located closer to the midline and associated with fractures > 1.5 cm, frontal sinus fractures, and
meningoceles or encephaloceles inside the fistula will not
heal spontaneously and therefore almost always require
surgical repair.99,104 Nevertheless, other authors have recommended 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 afterward without signs of meningitis or CSF rhinorrhea.
13
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

traumatic intracranial pathology (Fig. 6). No studies have
indicated which specific type of craniotomy or intracranial approach works best for each type of fracture. The
same can be said of the type of tissue adhesive to use in
these situations, because no scientific studies have been
conducted for this purpose. We believe that until these
studies appear in the literature, each skull defect and CSF
leak should be considered unique and that the choice of
intracranial approach depends on surgeon preference.
The surgical repair of CSF fistulas caused by traumatic anterior skull base fractures has been performed
through intracranial intradural or extradural repair. With
the advancement of endoscopic technology, transnasal repair has been widely used with good results. Reported
failure rates for intracranial repair of rhinorrhea range
from 6% to 27%,118 and the corresponding range for extracranial endoscopic repair is 2%50% (Table 1). A direct
comparison between the transcranial and the endoscopic
extracranial techniques is difficult without data from randomized clinical trials. Furthermore, the results of endoscopic repairs of CSF rhinorrhea have been reported
without etiological differences, and very few reports have
provided the specific success rate in the posttraumatic
cases. Further research is needed to define the criteria for
and which patients would benefit from endoscopic extracranial approaches versus the transcranial approach and
14
to determine the time to treatment as well as more specific technical issues of endoscopic intervention in this
population, such as those pertaining to the type of graft,
the overlay versus inlay technique, or postoperative lumbar drain placement. In conclusion, we believe that intracranial and extracranial approaches for posttraumatic
CSF rhinorrhea closure should be complementary instead
of competing procedures.
Disclosure
The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this
paper.
Author contributions to the study and manuscript preparation include the following. Conception and design: Ziu, Jimenez.
Acquisition of data: Ziu, Savage. Analysis and interpretation of
data: all authors. Drafting the article: Ziu, Savage. Critically revising
the article: all authors. Reviewed submitted version of manuscript:
all authors. Approved the final version of the manuscript on behalf
of all authors: Ziu. Administrative/technical/material support: Ziu,
Jimenez. Study supervision: Ziu, Jimenez.
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Manuscript submitted January 30, 2012.

Accepted April 5, 2012.
Please include this information when citing this paper: DOI:
10.3171/2012.4.FOCUS1244.
Address correspondence to: Mateo Ziu, M.D., Department of
Neurosurgery, University of Texas Health Science Center at San
Antonio, 7703 Floyd Curl Drive (MC 7843), San Antonio, Texas
78229-3900. email: ziu@uthscsa.edu.
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Neurosurg Focus 32 (6):E3, 2012

Diagnosis and treatment of cerebrospinal fluid rhinorrhea

Key Words craniomaxillofacial trauma head trauma

Abbreviations used in this paper: bTP = b trace protein; CTC

Neurosurg Focus / Volume 32 / June 2012

Furthermore, the issues related to CSF leak caused

For this review, primary and secondary neurosurgery,

M. Ziu, J. G. Savage, and D. F. Jimenez

In 1745 Bidloo the Elder was the first to describe CSF

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

Patients w/ Accidental Trauma

Neurosurg Focus / Volume 32 / June 2012

Cerebrospinal fluid rhinorrhea after anterior skull base trauma

Cerebrospinal fluid rhinorrhea can be classified

Neurosurg Focus / Volume 32 / June 2012

diagnosis, type and extent of skull defect, and duration

M. Ziu, J. G. Savage, and D. F. Jimenez

volved, the associated midfacial injury, and the mode of

Accidental trauma can lead to a variety of skull base

Cerebrospinal fluid rhinorrhea after anterior skull base trauma

Neurosurg Focus / Volume 32 / June 2012

ingitis, and pneumocephalus.104,118 In the chronic phase,

Differentiating CSF rhinorrhea from other types of

M. Ziu, J. G. Savage, and D. F. Jimenez

to be around 96%. The usefulness of this test depends on

Imaging Diagnosis. After confirming the presence of

Cerebrospinal fluid rhinorrhea after anterior skull base trauma

plate olfactory groove defects, contrast material can drain

M. Ziu, J. G. Savage, and D. F. Jimenez

Cerebrospinal fluid rhinorrhea after anterior skull base trauma

Neurosurg Focus / Volume 32 / June 2012

not suitable in patient w/ bacterial meningitis or low glomerular

diagnose site of fracture

for delayed posttraumatic CSF rhinorrhea.46,99,102 We think

labor intensive & time consuming

invasive w/ intrathecal injection of contrast material

meningitis risk per week within the 1st month, surgical

M. Ziu, J. G. Savage, and D. F. Jimenez

Surgery is reserved for the treatment of CSF leaks

Fig. 3. High-resolution CT scans (AD) obtained in a patient who

erature: transcranial approach and extracranial approach.

Cerebrospinal fluid rhinorrhea after anterior skull base trauma

Fig. 4.Coronal (A and B) and axial (C and D) HRCT scans obtained

after surgical repair from more than 85% prior to repair.

M. Ziu, J. G. Savage, and D. F. Jimenez

of 98.8%; 1 patient was lost to follow-up. The authors did

Cerebrospinal fluid rhinorrhea after anterior skull base trauma

Although the first report of the successful surgical

pears to be the most efficient and cost-effective route

Neurosurg Focus / Volume 32 / June 2012

M. Ziu, J. G. Savage, and D. F. Jimenez

tients who do not need emergent surgical treatment for

Neurosurg Focus / Volume 32 / June 2012

Cerebrospinal fluid rhinorrhea after anterior skull base trauma

Neurosurg Focus / Volume 32 / June 2012

doscopic repair of cerebrospinal fluid rhinorrhea. Rhinology

M. Ziu, J. G. Savage, and D. F. Jimenez

72. Locatelli D, Rampa F, Acchiardi I, Bignami M, De Bernardi

Neurosurg Focus / Volume 32 / June 2012

Cerebrospinal fluid rhinorrhea after anterior skull base trauma

Neurosurg Focus / Volume 32 / June 2012

110. Tos M: Course of and sequelae to 248 petrosal fractures. Acta

Manuscript submitted January 30, 2012.