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Fig. 38.4 (a) Coronal MRI (T2 TSE) of a non-traumatic
CSF leak associated with idiopathic intracranial hypertension in the lateral recess of the left sphenoid sinus (image
by B.Schuknecht, MRI Institute, Zurich, Switzerland). (b)
Table 38.3 Recommendations for the diagnostic use of intrathecal sodium uorescein
Intrathecal use of sodium uorescein Remarks
Informed consent Off-label use
Lumbar puncture Small needle to prevent headaches
Aspiration of 10mL CSF
0.5mL of 5% sodium uorescein suitable for
intrathecal use
Slow injection of 0.5mL 5% sodium uorescein
that is diluted with 10mL CSF
Allow colour to reach cranial portion of CSF Diffusion depends on individual situation, reliable after 4h
Endoscopy, CSF shows yellow colour Blue light lter enhances contrast
Sodium Fluorescein
CT-MRI fusion with precise delineation of the CSF leak
to the lateral recess of the left sphenoid (image by
B.Schuknecht, MRI Institute, Zurich, Switzerland )
25mg, maximal dose should not exceed 50mg
Monitor for neurological adverse effects (headaches, nausea,
numbness of lower limbs, seizures)
Trendelenburg position, as uorescein is hygroscopically denser than CSF.
Sodium uorescein stains CSF yellow-green and
injecting this intrathecally via a lumbar puncture
can greatly enhance the detection of CSF.An active
leak would be clearly seen by nasal endoscopy and
the source identied during surgical exploration,
especially in patients where the leak is difcult to
localise (Fig.38.2c, d). The uorescence and contrast of uorescein-stained CSF is greatly enhanced
by blue light lter in minimal CSF leaks (Fig.38.2e).
Once injected intrathecally, the sodium uorescein must circulate intracranially prior to
endoscopic surgical exploration. A circulation
time of 4h was recommended for reliability, but
circulation occurs much more quickly if the
patient is placed in a supine head-down reverse-
Sodium uorescein is neurotoxic, and toxicity
increases with higher concentrations. The maximum dose of sodium uorescein should not
exceed 50mg, but nowadays, it is generally recommended to use 25mg (0.5 mL of a 5% solution) of highly puried sodium uorescein,
diluted with 10mL of CSF and re-injected relatively slowly (Table38.3).
Whilst this is unlicensed and required informed
consent, it has been tried and tested over many
years [12, 13]. Complications rarely occur, but
there is a remote risk of anaphylaxis, and preoperative skin testing has been recommended.
Reported transient adverse effects of intrathecal
sodium uorescein are headaches, nausea, dizzi-
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ness, numbness of the lower limbs and seizures,
but a fatal reaction is highly unlikely [14].
The Principles ofManagement
ofCSF Rhinorrhoea
CSF rhinorrhoea may present in four broad clinical scenarios. Whilst the principles of management remain the same, there are some possible
variations in the management algorithm:
(a) The patient with an active CSF leak
(b) The patient with a suspected subclinical CSF
leak
(c) The patient with a traumatic CSF leak
(d) CSF leak as a surgical complication
The Active Leak
In active leaks, the diagnosis is typically easy and
the location identied by nasal endoscopy and
imaging. However, it is still best to conrm the
diagnosis by beta-2 transferrin/beta-trace protein
analysis, not least for medicolegal reasons. All
active CSF leaks need closure.
The Subclinical Leak
Some patients present with infrequent episodes
of a possible ‘leak’ and minimal amounts or no
provocable rhinorrhoea. These patients pose a
clinical challenge.
It is important to try and obtain a sample of the
nasal uid for beta-2 transferrin and/or beta-trace
protein analysis in patients with a suspected subclinical leak. The sample bottles can be taken
home and kept refrigerated until enough uid has
been collected (normally a minimum of 0.5mL).
An alternative technique in patients with minimal
leaks is to insert absorbent dressings within the
nasal cavities for several hours and to send these
for uid analysis.
Both HRCT and MRI should be requested and
may demonstrate a small defect or exclude signs
of intracranial hypertension.
Nasal endoscopy after intrathecal sodium uorescein should also be considered if a CSF leak
is suspected.
There may be a reasonable argument to explore
the anterior skull base endoscopically in certain
situations where a suspected CSF leak cannot be
conrmed. This is a matter of clinical judgement.
Whilst endoscopic exploration does carry a risk,
this is controlled and may be less than the risk of
meningitis at a later day. It can also carry the
advantage of conrming or excluding a CSF leak
that affects future prognosis and management.
If there is real cause for concern, such as previous episodes of meningitis, endoscopic exploration of the skull base with intrathecal uorescein
should be considered (Table 38.4). The latter is
especially true in recurrent bacterial meningitis,
even in the absence of a CSF leak.
Table 38.4 Diagnostic algorithm for suspected CSF rhinorrhoea
Nasal endoscopy
Imaging (HRCT,
History, clinical signs
of CSF rhinorrhea
Nasal endoscopy
leak not detectable
leak visible
MRI)
Indication for closure
of the CSF leak
Measurement of
beta-2 transferrin
and/or beta trace
protein
Positive
Imaging (HRCT,
MRI)
Negative
Imaging (HRCT,
MRI)
Indication for closure of the
CSF leak
Imaging suggestive for leak
Consider intrathecal sodium
fluorescein to confirm leak, if
positive, indication for closure
Imaging negative
Reevaluate diagnosis
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The Traumatic CSF Leak
CSF leaks are most likely to occur from complex
skull fractures affecting the mid-face and anterior
skull base. These fractures may include the posterior wall of the frontal sinus, ethmoidal roof
and sphenoid sinus and can be bilateral and at
multiple sites. CSF leaks can also occur following a penetrating injury.
CSF leaks following direct head injury often
resolve once the fracture sites have been reset,
especially if secured by xation plates.
Endoscopic exploration soon after trauma is
probably unnecessary and will generally be
accompanied by mucosal bleeding and an unclear
view of the skull base. Frontal sinus defects would
need an external approach, but a limited endoscopic procedure through a small external access
point is a possibility prior to proceeding with a
wider approach or an osteoplastic procedure.
The patient is best reviewed once initial healing has occurred. If there is an element of doubt
as to the integrity of the anterior skull base, or a
persistent CSF leak, then further detailed imaging and exploration should be considered.
The principles of repair are exactly the same
as those for repairing CSF leaks electively. The
bone defect should be cleared of surrounding
mucosa and the defect repaired. Small defects are
suitable for a fat plug, but larger ones may require
a composite multilayer closure.
Should the complication arise at the time of
surgery, it is recommended that the surgeon discusses the problem with an experienced colleague to plan the management and avoid
irrational decision-making.
Postoperatively, the patient should have regular neuro-observations and a CT scan of the head
should be obtained to exclude a pneumoencephalus and intracranial bleeding. Prophylactic antibiotics are recommended. Standard measures such
as avoidance of nose blowing and stool softeners
apply. The surgeon has a duty of candor in this
situation and will need to explain the injury to the
patient.
Should a defect go unrecognised or left
untreated, then there is a signicant risk of pneumoencephalus, meningitis, intracranial infection
and cerebral abscess.
CSF Leak asaSurgical Complication
A CSF leak at the time of endoscopic sinus surgery is fortunately unusual, but highly stressful
for the surgeon should this occur. The risk is
increased with revision surgery, especially with
osteoneogenesis or altered sinus anatomy. The
dural tear should be relatively small, but those
caused by avulsion or a microdebrider can be
substantial. There is also a risk of intracranial
bleeding, especially if a penetrating injury was
caused by a microdebrider.
This complication carries a signicant risk of
intracranial infection and should be recognised at
the time of surgery or very shortly afterwards.
During surgery, the surgeon should initially
inform the anaesthetist, keep the patient horizontal to prevent air-embolus and proceed to repair
the defect. If recognised after surgery, repair is
recommended as soon as possible, particularly if
a pneumoencephalus is present as well.
Prevention ofMeningitis by
Vaccination
A dangerous complication of CSF rhinorrhoea is
bacterial meningitis, especially due to Streptococci
pneumoniae. Vaccination with 13- and 23-valent
pneumococcal conjugate vaccine has been shown
to be effective in reducing the incidence of pneumococcal meningitis. It is therefore recommended
that patients with CSF leaks are vaccinated with
pneumococcal vaccine [15], especially if surgical
repair is delayed or a CSF leak is seriously suspected but impossible to prove.
Vaccination can be extended to include
Haemophilus inuenzae, but the most important
priority is to cover the risk posed by the pneumococcus serotypes.
It is also important to warn patients of the risk
of meningitis and the initial symptoms, so that
urgent medical intervention and antibiotics are not
delayed should such a complication ever occur,
thus minimising the risk of serious consequences.
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Timing ofSurgery forLong-Term
CSF Leaks
Urgent repair: In patients with active and profuse
rhinorrhoea, the leak should be closed as soon
possible to minimise the possibility of pneumocephalus or bacterial meningitis.
Repair within several weeks: In patients with
less pronounced intermittent CSF rhinorrhoea,
the risk of meningitis is relatively low but cumulative and still signicant. Elective repair should
be done as soon possible and generally within a
few weeks.
Explore within months: The timing of surgery
is less urgent in patients with minimal intermittent CSF rhinorrhoea, especially when the diagnosis and localisation cannot be easily
conrmed.
Defer repair: Should the CSF leak remain
undiagnosed, surgery is not recommended.
There are rare occasions where surgery may
carry a greater risk to health than the risk of meningitis. Should the patient have serious coexisting
comorbidities or morbid obesity, general anaesthesia may carry signicant risk to life.
Patients awaiting diagnostic conrmation
should be informed about the potentially
increased risk of meningitis as above. Decisionmaking in some of these patients is complex
and discussion with colleagues is
recommended.
Repair ofCSF Leaks
External approaches: An external extradural
approach implicates temporary removal of the
external wall of the frontal sinus and is indicated
for leaks of the frontal sinus that are far lateral
and therefore difcult to control endoscopically.
An external intradural or transcranial approach
requires a craniotomy and gives access to dural
defects from the endocranial side of the leak.
This approach allows the reconstruction of large
defects of the anterior skull base that cannot be
reconstructed reliably by an endonasal approach,
for example, after resection of extended tumours.
Further indications for this approach are leaks at
anatomical areas that are difcult to access transnasally, such as far-lateral recesses of a very
pneumatised sphenoid sinus or lateral skull base.
Transcranial approaches have a higher morbidity due to the opening of the endocranial space
and the temporary dislocation of the frontal lobe
and the olfactory bulb [16].
Endoscopic approaches: Transnasal endoscopic approaches are suitable for most of the
CSF leaks and have a high success rate, typically
above 90%, and a low ‘approach-related’ morbidity. Transnasal endoscopic approaches are
therefore the preferred technique of choice,
except for situations where the defect cannot be
controlled reliably by the endoscopic technique.
A CSF leak from a dural defect in a laterally
pneumatised sphenoid sinus (via Sternberg’s
canal) is a challenging situation, but good access
can be obtained via the posterior wall of the maxillary sinus into the pterygomaxillary fossa and
infratemporal fossa (transpterygoidal approach).
As a basic principle, every CSF leak should be
repaired. Different surgical approaches, techniques and methods of reconstruction of skull
base defects are available, according to the size
and site of the defect.
Surgical Approach
There are two principal surgical approaches to
defects of the anterior skull base – ‘external’
approaches, which can be extradural or intradural, and transnasal endoscopic approaches.
Reconstruction Material
The reconstruction of a CSF leak requires material to seal the dural defect and integrate with the
surrounding tissue. Autologous tissue, such as
nasal mucosa, fat, muscle or fascia, is preferable.
Autologous grafts and aps: Nasal mucosa
can be used as a free ap in small defects or as
vascularised pedicled ap, such as a nasoseptal
ap, in larger defects [17]. Fat is particularly suitable for reconstruction due to its plasticity and
sealing properties.
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Fat is also easily harvested from the abdominal wall, thigh or ear lobule. Ear lobe fat is more
brous and easier to manipulate.
Fascia can be harvested from the lateral thigh
(fascia lata), the rectus abdominis or temporalis
muscles. Rectus abdominis fascia is ideal for a
medium-sized defect, but the thicker fascia lata is
best for large defects (Fig.38.5a–d).
Other autologous tissue, such as cartilage
from the nasal septum or external ear, and bone,
may be used to provide greater stability.
There are various reconstruction techniques,
such as pericranial aps, available for extensive
defects after anterior skull base surgery (please
see Chap. 36).
Heterologous grafts: Various types of collagen matrix sheets are available. They can help to
achieve a watertight reconstruction and add stability in combination with autologous material.
However, heterologous material is ‘non-vital’.
Healing and integration with the surrounding tissue takes longer compared to autologous tissue.
Fig. 38.5 (a) Large defect of the anterior skull base after
resection of an olfactory neuroblastoma. (b) Defect reconstruction with fascia lata of the lateral part of the upper
thigh. The fascia is sutured to the dura to improve stabil-
ity. (c) The margins of the defect reconstruction site are
sealed with abdominal fat. (d) Anterior skull base 3years
after reconstruction with optimal integration of the reconstruction material
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Technique ofRepair
The goal of CSF leak reconstruction is to achieve
a watertight and mechanically stable closure. A
persistent CSF leak will hinder a stable, watertight fusion of tissue and may lead to failure of
the reconstruction. If the repair is watertight,
broblasts and vessels grow into the contact zone
between the margins of the defect and the reconstruction tissue within a few days, sealing the
repair. The repair then gains strength and becomes
robust over the ensuing weeks.
Whilst there are several methods of reconstruction, the optimal technique depends on the
size and location of the defect.
Small leaks: The leak can be closed by inserting fat or fascia directly into the defect, like a
‘bath plug’ [18]. Whilst fat grafts are often very
effective at sealing smaller defects, they are not
easy to position in very tiny defects. In such situations, a seal is best obtained by initially laying
fascia over the defect and pushing part of this
directly into the defect with a ne ball probe. The
repair can then be supplemented fat, fascia and/or
mucosa where appropriate.
Larger leaks: The defect is best closed by a
multilayer technique. A tissue graft is placed
through the defect as an intracranial ‘underlay’,
and a second graft is placed as an ‘overlay’ on the
nasal side of the defect.
Large defects: Large skull base defects are
best repaired with multilayer fascia lata, possibly
with cartilage grafts as well, if appropriate. The
repair should be xed and stable. Although technically demanding and not always feasible,
suturing of the fascia to the dura provides optimal
stability (Fig. 38.5b). Resorbable or nonresorbable packing provides additional stability
for the healing period (Fig.38.6a–c).
In situations where dura has herniated
through a defect, it is usually possible to reduce
the herniation after dissection and mobilisation.
Diathermy may be used to seal the defect but
should be used sparingly and with caution.
Brain tissue is likely to be present in large herniations, and if deemed non-functional, it can
be excised if reduction intracranially is not
possible.
Graft xation: Fibrin glue (concentrated
brinogen activated by thrombin and calcium
chloride) or a similar agent is used to x the
reconstruction. Intrathecal uorescein is recommended to conrm the extent of the defect, to
identify multiple defects and to provide conrmation that the repair is watertight.
Tips andTricks
For a successful closure of a dural leak, the
graft must adhere with the margins of the
defect. The graft will not adhere to mucosa that
must be cleared and the bone around the defect
exposed. The cleared margins should be wide
enough (> 2–3mm) to generate a stable zone of
fusion.
Autologous, vital reconstruction tissue has
faster healing properties compared to heterologous material. Vascularised mucosal aps offer
the best solution to achieve a fast and stable
fusion with the defect margins and are the
method of choice for larger and ‘difcult-toclose’ leaks.
If fascia lata or other tissues from the thigh
have been utilised, the fascial defect should be
repaired with a non-resorbable or even a resorbable mesh (Fig. 38.7a, b). Failure to repair a
defect in the fascia lata can lead to muscle herniation and prolonged leg soreness.
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Fig. 38.6 (a) Reconstruction of a small CSF leak with
abdominal fat as ‘bath plug’. The fat is stabilised with a
heterologous collagen matrix sheet and resorbable packing. (b) Reconstruction of a medium-sized defect with fat
and a free mucosal ap as ‘overlay’. The reconstruction is
stabilised with brin glue and resorbable packing. (c)
Reconstruction of a large defect with rectus abdominis
fascia as ‘underlay’, fat and a free (or pedicled) mucosal
ap as ‘overlay’. The reconstruction is stabilised with
brin glue and resorbable packing. (d) Reconstruction of
a large defect with fascia lata as ‘underlay’ and fat. The
reconstruction is stabilised with a collagen matrix sheet
(heterologous) and resorbable or non-resorbable packing
(see also Fig.38.5)
ab
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Fig. 38.7 (a) Harvesting fascia lata from the right thigh. (b) Reconstruction of the donor site defect with a resorbable
‘Vicryl®’ mesh
Table 38.5 Algorithm for the reconstruction of CSF leaks depending on the size and type of the defect
Endonasal
endoscopic
Defect type
Small
(>0.5cm)
Medium
(0,5cm–2cm)
Large (>2cm) X X X X X X
Extensive
skull base
resection
High-pressure,
high- volume
CSF leak
approach
X X X X X
X X X X X X
X X X X X X X
X X X X X X X
External
approach
Collagen
matrix
(heterologous)
Mucosa
free ap
Mucosa
pedicled ap Fat Fascia
Lumbar
drainage
505
An algorithm for the reconstruction of CSF
leaks depending on the size and type of the defect
is shown in Table38.5.
A lumbar drainage also carries a risk of
additional complications such as headaches,
meningitis, pneumocephalus and subdural
haemorrhage.
Lumbar Drains
Antibiotics
There is a consensus of opinion that a lumbar
drain is not recommended in the majority of
CSF leak repairs, and the potential benet is not
proven [19, 20]. However, there are occasions
where a leak will be high pressure/high ow,
and evidence suggests that a lumbar drain lowers the risk of a persistent CSF rhinorrhoea, as
may occur when the arachnoid cistern or the
third ventricle communicates directly with the
leak [21].
Preoperative antibiotics: With the risk of meningitis in an active CSF leak, antibiotic cover would
seem logical. However, the consensus is that, in
the absence of sinusitis, the risk of meningitis is
not signicantly reduced, and bacterial resistance
may be encouraged.
Antibiotics not only increase the risk of selecting resistant bacteria but also carry a risk of other
possible adverse effects such as allergy and an
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H. R. Briner and A. C. Swift
increased risk of Clostridium difcile
enterocolitis.
Preoperative antibiotics: The evidence for
prophylactic antibiotics during and after surgery
is unclear [20]. Reasonable indications for antibiotic prophylaxis include CSF leak closure in a
patient with a purulent sinus infection, repair
with free grafts rather than vascularised aps and
prolonged graft support with absorbent nasal
packing.
Miscellaneous
Acetazolamide: Acetazolamide is a diuretic drug
that decreases CSF production and lowers intracranial pressure. There is evidence that the use of
acetazolamide lowers the risk of recurrence in
CSF leak closure in patients with idiopathic
intracranial hypertension [22, 23].
Nursing care: Patients should be counselled to
avoid manoeuvres that raise intracranial pressure
such as forceful nose blowing, coughing, sneezing, abdominal straining and lifting, especially in
the rst days after CSF leak repair when the
reconstruction is not yet stable. Obstipation
(severe constipation) is quite common in the postoperative period and leads to abdominal pressing/
straining. It should be prevented by administering
stool softeners during the recovery period.
Idiopathic Intracranial
Hypertension (IIH)
Spontaneous CSF leaks may sometimes occur
with raised intracranial pressure from IIH. From
the practical point of view, the diagnosis should
always be considered, and if appropriate, the
patient should see an ophthalmologist to exclude
papilloedema and a neurologist/neurosurgeon for
additional investigation.
IIH patients are more likely to be obese and
female (body mass index >30kg/m2). Associated
symptoms include headaches, nausea, photophobia, phonophobia, visual disturbances, papilloedema, abducens nerve palsy, diplopia, pulsatile
tinnitus and neck and back pain [22, 24]. IIH
combined with a CSF leak can be extremely difcult to identify as the intracranial pressure is
intermittently released with each CSF leak and
papilloedema may well be absent (IIH without
papilloedema: IIH WOP). Reaching the diagnosis of IIH WOP often relies on more invasive
diagnostics, such as ICP monitoring.
Radiological imaging, such as high-resolution
CT and MRI including venogram, may reveal
signs suggestive of IIH such as an empty sella
turcica, transverse sinus stenosis, perioptic subarachnoid space distention and tortuous optic
nerves and attening of the posterior globe. The
skull base may be thin or dehiscent.
Once recognised, IIH can then be treated,
either medically by a combination of weight loss,
medication such as acetazolamide or headache
management, with careful monitoring of visual
function. In more severe cases where vision is
threatened, CSF diversion, frequently with a ventriculoperitoneal shunt or venous sinus stenting,
is recommended.
Areas ofControversy
There are several areas of controversy in the
management of CSF rhinorrhoea.
Surgery when the CSF leak stops spontaneously: One subject of debate is the indication for
surgical exploration and repair in patients with
post-traumatic CSF rhinorrhoea that stops spontaneously. Spontaneous healing of small posttraumatic defects is common. However, the risk
of developing meningitis is still slightly increased
and continues in a cumulative manner over many
years. Patients should be counselled about this
potential risk, especially if surgical exploration is
not performed.
Use of antibiotics: The use of antibiotic treatment in active CSF rhinorrhoea and as prophylaxis in CSF leak repair remains controversial.
There is a general recommendation against the
use of antibiotics in CSF rhinorrhoea. However,
the benet of preventing meningitis must be
weighed up against the risks of selecting resistant
bacteria and adverse effects of antibiotics in each
individual clinical situation.
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Intrathecal fluorescein: The frequency of
use of intrathecal fluorescein is another topic
for discussion. The proponents will recommend its use in the majority of surgical cases,
but others will argue to point that they can
locate and repair the leak without staining the
CSF.
Lumbar drainage: The use of lumbar drainage
as supportive treatment in CSF leak repair is a
controversial topic that always generates much
debate. Signicant complications may occur
from lumbar drainage, and the current recommendation is to use it only in ‘difcult-to-close’
CSF leaks, such as recurrences and ‘high-ow/
high-pressure’ leaks.
Key Learning Points
• In an adult human, there is a volume of
150mL of CSF protecting the brain and the
spinal cord.
• Traumatic CSF leaks are most common
(95%).
• Spontaneous CSF leaks are least common
(5%) but may be associated with idiopathic
intracranial hypertension (IIH).
• CSF leaks can cause life-threatening compli-
cations such as meningitis and pneumocepha-
lus and must be repaired.
• The diagnosis of a CSF leak must be estab-
lished by nasal endoscopy, measurement of
CSF-specic proteins (beta-2 transferrin,
beta-trace protein) and imaging (HRCT,
MRI). Intrathecal application of sodium uo-
rescein is a further diagnostic option to con-
sider, especially in difcult-to-detect CSF
leaks.
• Autologous tissue (nasal mucosa aps, fat,
fascia) is the preferred technique for repair.
• The surgical approach and technique of repair
depend on the size and location of the CSF
leak.
Conicts of Interest Hans Rudolf Briner has a relationship as a Consultant for Karl Storz GmbH, Tuttlingen,
Germany, and is the shareholder of the Swiss Rhinology
Teaching Center GmbH Company, which gives license for
a Smell Diskettes Screening Test. None of these relations
pose a conict of interest in connection with this book
chapter.
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