COMPLICATION

Brain Herniation After Endoscopic Transnasal

Resection of Anterior Skull Base Malignancies
Paolo Battaglia, MD*
Mario Turri-Zanoni, MD*
Paolo Castelnuovo, MD*
Daniel M. Prevedello, MD‡
Ricardo L. Carrau, MD§
*Division of Otorhinolaryngology, De-
partment of Biotechnology and Life
Sciences, University of Insubria, Varese,
Italy; ‡Department of Neurological
Surgery, The Ohio State University,
Columbus, Ohio; §Department of Oto-
laryngology, Head and Neck Surgery, The
Ohio State University, Columbus, Ohio
Correspondence:
Mario Turri-Zanoni, MD,
Division of Otorhinolaryngology,
Department of Biotechnology
and Life Sciences,
University of Insubria,
Varese, Italy, Via Guicciardini 9,
Varese, Italy.
E-mail: tzmario@inwind.it
Received, March 1, 2015.
Accepted, May 21, 2015.
Published Online, June 24, 2015.
Copyright © 2015 by the
Congress of Neurological Surgeons.
BACKGROUND: Endoscopic endonasal approaches, when appropriate, allow a less
invasive method to remove anterior skull base cancer than traditional external trans-
facial/craniofacial approaches. The resultant skull base defect can be significantly large,
potentially extending from the posterior table of the frontal sinus to the tuberculum
sellae in the sagittal plane, and from one lamina papyracea to the other in the coronal
plane. However, frontal lobe herniation after such expanded endoscopic resection has
been considered more of a theoretical than a practical occurrence.
OBJECTIVE: To report the occurrence of frontal lobe herniation into the sinonasal
cavity after expanded endonasal approaches, and to analyze causes and pathogenetic
mechanisms of this unusual complication, proposing how it could have been pre-
vented.
METHODS: Two cases have been observed in 2 different skull base referral centers in
the United States and Italy. Surgical and perioperative complications, postoperative
course, and need for revisions were analyzed.
RESULTS: Available data support the hypothesis that this complication is not attrib-
utable to the size of the anterior skull base defect, to the surgical technique, or to the
materials used for the reconstruction. We found that 1 possible contributing factor may
be the presence of increased intracranial pressure associated with obesity and
obstructive sleep apnea, observed in both patients.
CONCLUSION: Frontal lobe herniation must be considered as a possible, albeit rare,
complication of expanded endoscopic anterior skull base resection. Preoperative in-
vestigations concerning the presence of obstructive sleep symptoms as well as proper
identification of neuroimaging signs of intracranial hypertension are recommended for
such cases.
KEY WORDS: Brain herniation, Endoscopic endonasal, Intracranial hypertension, Sinonasal cancer, Skull base,
Sleep apnea syndrome

Operative Neurosurgery 11:457–462, 2015 DOI: 10.1227/NEU.0000000000000859

D
uring the past two decades, significant
advances in endoscopic skull base surgery
have allowed the extirpation of tumors
involving the anterior skull base by the use of
a pure endonasal approach. This technique has
shown promising oncologic outcomes that are
comparable to those obtained with external
approaches and that have been reproduced
among various skull base centers worldwide.
Therefore, these data suggest that endoscopic
endonasal resection, when properly planned, and
ABBREVIATION: BMI, body mass index
performed by experienced surgeons, is an accept-
able treatment for select skull base malignancies.1
Major advantages of endoscopic over external
approaches include the absence of facial incisions
or osteotomies, less brain manipulation,
decreased hospitalization time, improved visual-
ization of tumor borders, and reduced morbidity
and mortality rates.2 Furthermore, retraction on
the frontal lobes, with the ensuing associated
complications, is avoided.
Endoscopic endonasal techniques afford a less
invasive approach to remove lesions encroaching
the skull base than traditional external transfacial/
craniofacial approaches.3 However, the resultant
skull base defect can be significant, potentially

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BATTAGLIA ET AL
extending from the posterior table of the frontal sinus to the
tuberculum sellae in the sagittal plane, and from one lamina
papyracea to the other in the coronal plane. Therefore, failure of
transnasal reconstruction with a resultant postoperative cerebro-
spinal fluid (CSF) leak is considered a significant caveat.
Moreover, the extent of the disease often requires resection of
the dura mater, which further increases the likelihood of
a postoperative CSF leak.
In recent years, technical refinements in skull base reconstruc-
tion, including the use of a multilayer technique and the adoption
of pedicled flaps, have significantly reduced the rate of post-
operative CSF leaks.4 Frontal lobe sagging after reconstruction of
these large anterior skull base defects has not been considered to
be a significant complication. In fact, frontal lobe herniation, as
a complication of an expanded endoscopic resection of the
anterior skull base, has not been reported in the literature
regardless of the technique and material used for the
reconstruction.5
This report analyzes 2 unusual cases of frontal lobe herniation
after endoscopic endonasal resection of a sinonasal malignancy. Its
pathophysiology and management are discussed within the
confines of our experience and a pertinent literature review.
METHODS
We retrospectively reviewed the combined experience of more than 500
cases of endoscopic endonasal anterior skull base reconstruction after
malignant tumor resection performed in 2 skull base referral centers in the
United States and Italy from 1998 to 2014, reporting 2 cases of brain
parenchyma herniation into the sinonasal cavity. Parameters including
clinical data, preoperative imaging studies, surgical and perioperative
complications, length of postoperative stay, and the need for surgical
revisions were analyzed. The present study was conducted according to
policies approved by the local institutional review boards. Informed
consent was obtained from all patients involved in this survey.
RESULTS
Patient 1
A 72-year-old man with an occupational history of woodwork-
ing was referred for an intestinal-type adenocarcinoma of the left
ethmoid sinuses (Figures 1A and 1B). Clinical comorbidities
included a history of a previous myocardial infarction treated with
percutaneous transluminal coronary angioplasty (10 years
before), arterial hypertension, obesity (body mass index [BMI],
36.2 kg/m2), and obstructive sleep apnea syndrome.
The patient underwent an endoscopic resection with transnasal
craniectomy, following a previously described surgical technique.6
Given the biology of this lesion, the entire ethmoid sinuses
(bilateral) were included in the resection (ie, carcinogenic
exposure to wood dust renders the mucosa of the nasoethmoidal
complex vulnerable to developing multiple foci of adenocarci-
noma).7 A nasal septectomy was required as part of the oncologic
resection, therefore, precluding the use of a pedicled nasoseptal
flap for the reconstruction. The resulting dural defect extended
458 | VOLUME 11 | NUMBER 3 | SEPTEMBER 2015
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from the posterior wall of the frontal sinus back to the planum
sphenoidale and from orbit to orbit. It was repaired by using
a multilayer closure technique comprising 3 layers of autologous
iliotibial tract (first layer, subdural; second layer, intracranial
epidural; third layer, extracranial). Finally, oxidized methylcel-
lulose was placed around the edges of the extracranial layer to
secure it to the adjacent bone, and the surgical cavity was packed
with expandable sponge nasal packing (Merocel, Medtronic
Xomed; Jacksonville, Florida) covered with bacitracin ointment.
Postoperatively, the patient was kept on bed rest with the head
of the bed elevated to 30°, under the coverage of a third-
generation cephalosporin and stool softeners. Two days later, the
nasal packing was removed under endoscopic control and
a scheduled brain computed tomography (CT) scan ruled out
any intracranial complication (Figures 1C and 1D). At the fifth
postoperative day, an endoscopic examination showed the
presence of a CSF leak with brain exposure due to the
displacement of the duraplasty. A head CT scan surprisingly
revealed a herniation of the frontal lobe through the surgical
anterior skull base defect (Figures 1E and 1F). Remarkably, the
patient was asymptomatic, maintaining an alert and oriented
mental state, without localizing neurological findings.
This situation required an urgent endoscopic surgical revision of
the duraplasty to prevent tension pneumocephalus and intracra-
nial infections, such as ascending bacterial meningitis or abscess.
Intraoperatively, the herniated brain parenchyma could not be
reduced, because it extended well below the bony margins of the
defect; therefore, the exposed brain was covered with fascia lata,
and autologous free fat was grafted to eliminate the dead space and
to flatten the residual denuded anterior skull base. A final overlay
layer was made of a large iliotibial tract free graft, fixed with fibrin
glue and buttressed with gelatin foam pledgets (Gelfoam;
Pharmacia, Kalamazoo, Michigan). Moreover, a lumbar spinal
drain was placed for 5 days to reduce intracranial pressure,
therefore helping the healing and consolidation of the anterior
skull base reconstruction.
The patient was discharged home 10 days after the surgical
revision with clear instructions to avoid nose blowing and any
activity that could raise intracranial pressure (ie, straining).
Considering the low grade (G1 adenocarcinoma) and limited
stage (pT2, American Joint Committee on Cancer staging
system, 7th edition, 2010) of the tumor on the final histological
analysis and the radical resection with tumor-free margins, no
adjuvant radiotherapy was recommended. One year after
surgery, the patient continues to be completely asymptomatic,
and a contrasted MR scan demonstrated a stable frontal lobe
herniation (Figures 1G and 1H).
Patient 2
A 64-year-old man was referred with a biopsy-proven esthesio-
neuroblastoma that had initially presented with left nasal bleeding
and obstruction. The tumor extended bilaterally into the nasal
cavities, ethmoid sinuses, and nasal septum, and invaded the left
anterior cranial fossa (Figures 2A and 2B). Clinical comorbidities
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 BRAIN HERNIATION AFTER EXPANDED ENDONASAL APPROACHES

FIGURE 1. Preoperative contrast-enhanced MRI in coronal (A) and sagittal (B) view, showing a left ethmoidal intestinal-type
adenocarcinoma, involving the nasal septum and encroaching the left anterior skull base. Although an early postoperative CT scan looks
normal (C, D), the fifth postoperative day CT scan reveals a herniation of the frontal lobe through the surgical anterior skull base defect
(E, F). The postoperative MRI performed 1 year after the surgical revision demonstrated a stable frontal lobe herniation (G, H).

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BATTAGLIA ET AL

FIGURE 2. Pre-operative contrast-enhanced coronal MRI (A) and CT scan (B) showing a left esthesioneuroblastoma (T), involving the nasal septum, right ethmoid sinuses and
anterior cranial fossa (white arrow in A). Postoperative coronal MRI (C) and CT scan (D) within 24 hours of the resection reveal an adequate resection and no brain sagging
(white arrows). Subsequent coronal MRI (E) and CT scan (F) show significant sagging of the frontal lobe, marked by the white arrows (B, brain). Radionecrosis of the
reconstructive flap led to significant brain herniation (BH) demonstrated By sagittal (G) and coronal (H) MRI views (white arrows indicate the brain herniation). A Lactasorb
plate and fascia lata were required to maintain the reduction of the brain herniation as shown by sagittal (I) and coronal (J) MRI views (white arrows point out the successful skull
base reconstruction). K and L demonstrate progressive parenchymal radionecrosis (white arrows). T, tumor; FB, Foley Balloon catheter; B, brain; BH, brain herniation.

included a history of arterial hypertension, obesity (BMI, 38.8
kg/m2), and obstructive sleep apnea syndrome.
The patient underwent an endoscopic resection with transnasal
craniectomy, following a previously described technique.8 Given
the biology and extent of this lesion, the entire ethmoid labyrinth
(bilaterally), lamina papyraceae, septum, dura, and olfactory
bulbs were included in the resection. Sacrifice of the nasal septum
precluded the use of a pedicled nasoseptal flap for the skull base
reconstruction. Therefore, the resulting skull base and dural
defect, which extended from the posterior wall of the frontal sinus
to the planum sphenoidale and from the orbit to orbit, was
repaired by using a multilayer closure technique comprising
a subdural layer of collagen matrix and an extracranial (onlay)
pericranial flap. The latter was harvested via a coronal incision
and inserted into the nasal cavity via a bone window through the
nasion (transfrontal technique). The flap was bolstered against
the defect by using Nasopore (Stryker Corporation; Kalamazoo,
Michigan) and expandable sponge nasal packing (Merocel,
Medtronic, Jacksonville, Florida).
An immediate postoperative head CT scan ruled out any
intracranial complication. Magnetic resonance imaging (MRI)
confirmed the adequacy of the resection, good enhancement of
the flap following contrast, and minimal sagging of the brain
(Figures 2C and 2D). Postoperatively, the patient continued
receiving prophylactic third-generation cephalosporin for 48 hours
and stool softeners. The patient was discharged home from the
hospital 3 days after surgery with instructions to avoid nose
blowing and any activity that could raise intracranial pressure, such
as straining. At the sixth postoperative day, the patient was
evaluated as an outpatient, the sponge packing was removed and
the lower nasal cavity was gently debrided. A slight sagging of the
flap was noted, but it looked viable and in good contact.

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Considering the extent of the tumor (pT3 University of
California, Los Angeles staging system9 or Kadish10 stage C) and
Hyams grade II histopathology, adjuvant proton radiotherapy was
recommended. A contrast-enhanced MRI performed during the
proton therapy planning revealed further herniation of the brain
(Figures 2E and 2F). Three months after completion of the proton
therapy, the patient developed changes in personality and short-
term memory loss. MRI revealed severe radiation edema of the
frontal lobes. Despite corticosteroids and hyperbaric oxygen, the
edema and mental changes persisted, although somewhat
improved. Treatment with bevacizumab (Avastin; Genentech/
Roche, San Francisco, California) resulted in a complete resolution
of the symptoms and cerebral edema (MRI proven). Seven months
after completion of the proton therapy, the patient developed clear
rhinorrhea followed by changes in mentation requiring emergent
hospitalization. He was diagnosed with bacterial meningitis
associated with exposed brain herniating into the nasal cavity
(Figures 2G and 2H). This required a surgical repair that included
debridement of the nasal cavity and endonasal repair using
2-layered epidural fascia lata graft. Nasal examination during that
surgery revealed that the pericranial flap, mucosa, and dura were
completely necrotic, and the brain had herniated though the
original skull base defect. Extensive radionecrosis was also noted
over the periorbital and sphenoid and maxillary sinuses.
This attempt failed to repair the CSF fistula (the brain herniated
into the nasal cavity); thus, it was followed by a cranioendoscopic
repair using a 2-layer epidural fascia lata graft resulting in a similar
outcome: the brain herniated into the nasal cavity again. Finally,
using a cranioendoscopic approach, we implanted an absorbable
Lorenz Lactosorb mesh (Biomet Corporation; Jacksonville,
Florida) enveloped in fascia lata to cover the defect (subdural),
and, thus, stop the brain herniation (Figures 2I and 2J). An
extracranial lateral thigh myofascial microvascular flap was
subsequently transferred to reinforce the reconstruction after
the mesh was noted to be sagging. Furthermore, an adjunctive
external ventricular device was placed to decrease the intracranial
pressure. Unfortunately, the patient developed progressive radio-
necrosis of the frontal lobe and deterioration of neurological
function (Figures 2K and 2L). Following an intensive rehabil-
itation program, repeated courses of corticosteroids and bevaci-
zumab (Avastin; Genentech/Roche, San Francisco, California),
he finally started improving. Examination of the proton planning
revealed that the patient had received unintended radiation to the
frontal lobes due to the herniation of brain through the defect.
DISCUSSION
Frontal lobe herniation through the anterior skull base defect has
been considered more of a theoretical than practical consideration, as
confirmed by the fact that we found no other reports in the English
literature. In our combined experience of more than 500 cases of
endoscopic endonasal anterior skull base reconstruction after malig-
nant tumor resection, these are the first 2 cases of brain parenchyma
herniation. To the best of our knowledge, no similar cases have been
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BRAIN HERNIATION AFTER EXPANDED ENDONASAL APPROACHES
described as yet in the English literature. We routinely perform skull
base reconstruction according to the site, extension, and the biology of
the lesion, using a multilayer technique with reliable success rates. A
retrospective report by Eloy and colleagues5 showed no significant
frontal lobe descent after endoscopic repair of large cribriform defects
utilizing a triple-layer reconstruction technique with fascia lata,
acellular dermal allograft, and pedicled nasoseptal flap. This argues
against the need of a rigid structural graft such as cartilage, bone, or
alloplastic materials (eg, titanium plate) to reinforce the repair of the
anterior skull base.
Furthermore, available data support the hypothesis that frontal
lobe herniation into the sinonasal cavities is not attributable to the
size of the anterior skull base defect, to surgical technique, or to the
materials used for the reconstruction. We believe that a factor that
could be involved in the pathogenesis of this complication may be
the presence of increased intracranial pressure associated with
obesity and obstructive sleep apnea. Preoperative and postopera-
tive neuroimaging of these patients revealed no evidence of
abnormalities of the ventricular system, and neurodiagnostic
studies were otherwise normal, although the preoperative MRI
of patient 1 showed an empty sella, lateral sinus collapse (smooth-
walled venous stenoses), and buckling of the optic nerves with
increased perineural fluid. All these are specific signs included in
the modified Dandy criteria for idiopathic intracranial hyperten-
sion.11 Moreover, no other secondary cause for intracranial
hypertension could be found in both patients herein reported.
Obesity and sleep apnea syndrome may have played a role in the
pathogenesis of the brain herniation. Several studies have docu-
mented increased intracranial pressure during apnea periods.12
Because this is a plausible mechanism to explain increased
intracranial pressure, BMI assessment and preoperative sleep
studies in patients with symptoms suggestive of obstructive sleep
apnea may be prudent. When intracranial hypertension is
suspected to be involved in the pathogenesis, lumbar spinal
puncture and drainage could be useful to both document and
reduce intracranial pressure. One should note, however, that CSF
pressure fluctuates throughout the day and, even in pathological
states, at times could be normal; thus, a single normal CSF
measurement does not exclude intracranial hypertension defini-
tively. From a clinical viewpoint, in high-risk patients, weight loss,
sodium restriction often with the addition of acetazolamide, must
be considered to minimize the long-term failure rates of an anterior
skull base reconstruction or progressive herniation. We acknowl-
edge that this strategy is empirical and may elicit controversy.
From a technical viewpoint, other reasonable considerations for the
management of this clinical situation include an external transcranial
approach to reduce the herniated frontal lobe, the surgical resection of
the herniated brain parenchyma, or permanent CSF diversion.
However, the most important consideration is to achieve separation
between the herniated frontal lobes and the sinonasal tract to avoid
ascending infections and their complications. Progressive brain
herniation and symptomatic manifestations would require more
assertive surgical maneuvers such as the ones previously mentioned.
In such challenging cases, the use of rigid structural grafts to reinforce
VOLUME 11 | NUMBER 3 | SEPTEMBER 2015 | 461
BATTAGLIA ET AL
the skull base reconstruction is controversial because of the increased
risk of chronic inflammation, infection, radionecrosis, and/or
extrusion of both autologous (cartilage or bone) and heterologous
materials.13 In light of these risks, the use of rigid grafts has been
avoided even for the reconstruction of high-flow compartments such
as the posterior cranial fossa after transclival transdural endoscopic
approaches, where the use of fat graft combined with the
vascularized nasoseptal flap is generally adopted to minimize the
risk of pontine herniation.14
Another critical issue is the planning of adjuvant radiotherapy in
case of progressive brain herniation that complicates obtaining an
accurate definition of radiation doses and volumes on the frontal
lobes. For this reason, early recognition of this complication by
repeating appropriate imaging (CT and/or MR scan) is paramount,
in order to balance the oncologic purpose of cancer treatment with
the increased risks of radiation-induced brain edema and necrosis.
To this effect, a multidisciplinary team approach with strict
cooperation between surgeons and radiation oncologists is manda-
tory for a comprehensive management of such challenging cases.
CONCLUSION
Frontal lobe herniation must be considered as a possible, albeit
rare, complication of expanded endoscopic anterior skull base
resection. Preoperative investigations concerning the presence of
obstructive sleep symptoms as well as proper identification of
neuroimaging signs of intracranial hypertension are recommended
to ascertain the risk of this rare but important complication.
Disclosure
The authors have no personal, financial, or institutional interest in any of the
drugs, materials, or devices described in this article.
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COMMENT
T
he authors present 2 cases of brain herniation through the frontal fossa
defect after extended endonasal transsphenoidal surgery for skull base
tumors. This rare, delayed complication of the extended endonasal
approach should be recognized, particularly when rigid buttresses cannot be
used to augment the closure and in patients with signs or risk factors of
elevated intracranial pressure (sleep apnea, obesity, Chiari I malformation).
When unrecognized, as seen in the second patient, the radiation therapy
planning can inadvertently include the encephalocoele in the center of the
radiation field. This may explain the severe radiation necrosis that this
patient experienced. This supports the need for an open dialogue between
the skull base surgeons and the radiation oncologists. We commend the
authors for describing this rare complication of extended endonasal surgery.
Garni Barkhoudarian
Santa Monica, California
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