10.14639/0392-100X-suppl.1-41-2021-04
The Clivus is a bone that lies in a central position of the skull base, and it is a crucial point that splits and connects different anatomical compartments at the same time. There is significant variability of diseases involving the clivus, from neoplasms to non-neoplastic, inflammatory or traumatic lesions. Each of these is rare in frequency, and this heterogeneity contributes to yield the management even more challenging. Clival pathologies can be asymptomatic or have manifestations ranging from aspecific headache to cranial nerves palsies, till life-threatening complications as cerebrospinal fluid rhinorrhoea, meningitis or brain abscess. There isn’t an univocal endorsement among experts with regard to the best approaches to manage the clivus. The paths described are many, the main division is between the transclival and transcranial lateral approaches. We performed a review of the literature, thus highlighting how authors seem to suggest that the surgical approach shouldn’t be chosen aprioristically, but based on a patient centred analysis, considering the combination of multiple surgical corridors. From diagnosis to surgery and medical therapy, clival pathologies require a team of multidisciplinary experts to ensure the best standard of treatment and higher survival rate.
application/xml
1827-675X
1685
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Marco Benazzo
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
skull base surgery
Clivus pathologies from diagnosis to surgical multidisciplinary treatment. Review of the literature
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Marco Benazzo
2021/05/14
10.14639/0392-100X-suppl.1-41-2021-04
42
Department of Otorhinolaryngology, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy; Department of Otorhinolaryngology, University of Pavia, Italy
1827-675X
skull base surgery
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Clivus pathologies from diagnosis to surgical multidisciplinary treatment. Review of the literature
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ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41(SUPPL.1):S42-S50; doi: 10.14639/0392-100X-suppl.1-41-2021-04




Clivus pathologies from diagnosis to surgical
multidisciplinary treatment. Review of the literature
Patologie del clivus dalla diagnosi al trattamento chirurgico multidisciplinare.
Revisione della letteratura
Fabio Pagella1,2, Sara Ugolini1,2, Cesare Zoia3, Elina Matti1, Paolo Carena1, Roberta Lizzio1, Marco Benazzo1,2
1
 Department of Otorhinolaryngology, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy; 2 Department of
Otorhinolaryngology, University of Pavia, Italy; 3 Neurosurgery Unit, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy


SUMMARY
The Clivus is a bone that lies in a central position of the skull base, and it is a crucial
point that splits and connects different anatomical compartments at the same time. There is
significant variability of diseases involving the clivus, from neoplasms to non-neoplastic,
inflammatory or traumatic lesions. Each of these is rare in frequency, and this heterogene-
ity contributes to yield the management even more challenging. Clival pathologies can be
asymptomatic or have manifestations ranging from aspecific headache to cranial nerves
palsies, till life-threatening complications as cerebrospinal fluid rhinorrhoea, meningitis
or brain abscess. There isn’t an univocal endorsement among experts with regard to the
best approaches to manage the clivus. The paths described are many, the main division
is between the transclival and transcranial lateral approaches. We performed a review of
the literature, thus highlighting how authors seem to suggest that the surgical approach
shouldn’t be chosen aprioristically, but based on a patient centred analysis, considering the
combination of multiple surgical corridors. From diagnosis to surgery and medical therapy,      Received: September 8, 2020
clival pathologies require a team of multidisciplinary experts to ensure the best standard of   Accepted: January 9, 2021
treatment and higher survival rate.
                                                                                                Correspondence
KEY WORDS: clivus, clival pathology, transclival approach, transcranial approach, skull         Fabio Pagella
base surgery                                                                                    Department of Otorhinolaryngology, Fondazione
                                                                                                I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
                                                                                                E-mail: tpagella@libero.it
RIASSUNTO
Il Clivus è localizzato in sede centrale nella base cranica, rappresentando uno snodo cru-
                                                                                                Funding
ciale, che separa e collega diversi comparti anatomici. Le patologie che coinvolgono il
                                                                                                None.
clivus sono eterogenee: da neoplasie a lesioni non neoplastiche, infiammatorie o trauma-
tiche. Tutte queste sono rare per insorgenza e ciò contribuisce a renderne impegnativo il
                                                                                                Conflict of interest
trattamento. Le patologie clivali possono mantenersi asintomatiche oppure manifestarsi          The Authors declare no conflict of interest.
con sintomi che vanno dalla cefalea, alla paralisi di nervi cranici, fino a complicanze po-
tenzialmente letali come, rinoliquorrea, meningite e ascessi cerebrali. Gli esperti non sono
sempre concordi riguardo al tipo di approccio chirurgico con cui trattare il clivus. Le vie       How to cite this article: Pagella F, Ugolini S,
descritte sono molteplici, principalmente distinte tra approcci transclivali e approcci tran-     Zoia C, et al. Clivus pathologies from diagno-
                                                                                                  sis to surgical multidisciplinary treatment. Re-
scranici laterali. A oggi, dopo una revisione della letteratura, si conclude che la program-
                                                                                                  view of the literature. Acta Otorhinolaryngol
mazione chirurgica non deve essere scelta a priori, ma con un accurato studio del singolo         Ital 2021;41(SUPPL.1):S42-S50. https://doi.
caso clinico, valutando la combinazione di più corridoi chirurgici, se necessario. Dalla          org/10.14639/0392-100X-suppl.1-41-2021-04
diagnosi alla chirurgia, alla terapia medica, la gestione delle patologie clivali richiede un
team multidisciplinare di esperti, tale da garantire la migliore qualità nel trattamento e il   © Società Italiana di Otorinolaringoiatria
più alto tasso di sopravvivenza.                                                                e Chirurgia Cervico-Facciale

PAROLE CHIAVE: clivus, patologia clivale, approccio transclivale, approccio
                                                                                                               OPEN ACCESS
transcranico, chirurgia del basicranio
                                                                                                This is an open access article distributed in accordance with
                                                                                                the CC-BY-NC-ND (Creative Commons Attribution-Non-
Introduction                                                                                    Commercial-NoDerivatives 4.0 International) license. The
                                                                                                article can be used by giving appropriate credit and mentio-
                                                                                                ning the license, but only for non-commercial purposes and
In the early 1990s, Samii and Knosp defined the clivus “no man’s land” due                      only in the original version. For further information: https://
to the difficulty of accessing it 1. Today we can say that the clivus would be                  creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                       Clivus pathologies from diagnosis to surgical multidisciplinary treatment




better called “res in commune multorum”, because we are             sinus petrosi inferioris. The lateral borders of the clivus are
well aware that, due to the variety and the rarity of clival        related to cranial nerves V through XII, the internal jugu-
pathologies, the key to a better outcome for the patient is         lar veins, and the inferior petrosal sinuses and the foramen
to bring together the expertise of different specialists. Each      lacerum in the anterior part 4. The posterior endocranial sur-
clinical case should be evaluated by the otorhinolaryngolo-         face is smooth and composed of cortical bone. It is covered
gist together with a multidisciplinary team. In this review         with dura mater, which is perforated by the abducens nerves,
we will focus on clival pathologies that require a surgical         coming from its cisternal portion, in the central part of the
treatment, which always foresees the collaboration between          clivus 2. The medulla oblongata and pons lie adjacent to the
otorhinolaryngologist and neurosurgeon.                             posterior surface of the clivus, but are separated by the pre-
The Clivus is indeed a crucial point that splits and connects       pontine and perimedullary cisterns 4. Several ligaments cross
different anatomical compartments at the same time. It is a         the gap between the petrous apex and the lateral margin of
bone that lies in a central position of the skull base, being       the dorsum sellae, among these the petrosphenoidal or Gru-
a boundary between endocranial structures and maxillofa-            ber’s ligament is important for the course of the abducens
cial and neck regions. One of the first scientists that under-      nerve that passes through the foramen sphenopetrosum (fi-
took studies involving the clivus was the German Johann             brosum or osseum) and is fixed with its dural sheath at the
Friedrich Blumenbach (1752-1840) that gave name to the              superior margin of the petrous pyramid. This narrow passage
bone, therefore called Clivus Blumenbachii. Other neuro-            for the abducens nerve is known as Dorello’s canal, though
anatomists that have to be mentioned are Wenzel Leopold             it is actual knowledge that it is not a real canal 5. The tecto-
Gruber (1814-1890) who observed the Grubers’s ligament,             rial membrane and superior longitudinal band of the cruciate
Primo Dorello (1872-1963) for the so-called Dorello’s ca-           ligament both attach to the posteroinferior surface of the cli-
nal and Johann Friedrich Meckel, the first that described           vus. The fibrous raphe of the pharynx (superior pharyngeal
the condylus tertius in 1815.                                       constrictor muscle), longus capitus, rectus capitus anterior,
                                                                    and the anterior atlantooccipital membrane are found in con-
Embryology and anatomy                                              nection to the inferior exocranial surface of the clivus. The
                                                                    outer surface of the clivus is covered in thick fibrous tissue
The clivus originates from the neurocranium and particu-            which is a continuation of the fibrocartilago basalis of the
larly from the chondrocranium 2, which is formed initially          foramen lacerum.
by several separate cartilages (i.e. ossification centers) that     The arterial supply of the clivus is primarily derived from
will fuse and ossify to form the skull base, after cranial          two vessels: a branch off the internal carotid artery, the
nerves and blood vessels have developed 3. The basisphe-            meningohypophyseal trunk, and a branch of the ascending
noid and basiocciput, formed from the four primary occipi-          pharyngeal artery, the posterior meningeal artery. Dorsal to
tal sclerotomes or “vertebrae” (O1-O4) 2, are separated be-         the clivus, the basilar artery and basilar venous plexus are
fore fusion by the sphenoccipital synchondrosis. Complete           found and can create faint grooves on the bone 4.
ossification of the synchondrosis takes place at the age of
13 to 18 years in males and 12 to 16 years in females 4.
The clivus (Blumenbachii) is the central element of the skull       Pathologies
base and is about 4 to 5.5 cm long and about 3 cm wide              There is great variability of diseases involving the clivus, of
at its midpoint. The midsagittal section of the clivus clearly      different nature, and each rare in frequency. This heteroge-
presents a wedge-shaped appearance with a thin posterior            neity contributes to yield the management even more chal-
and thick anterior part. Inside a spongy structure identifies       lenging (Tab. I). Clival pathologies can be asymptomatic
the content of bone marrow. The osseous slope of the cli-           or have manifestations ranging from aspecific headache
vus slants upward and forward from the anterior aspect of           to cranial nerves palsies, visual problems, endocrinopathy
the foramen magnum to the dorsum sellae and the posterior           (if the sella is involved), till life-threatening complications
clinoid processes. The sphenoid sinus pneumatization may            as cerebrospinal fluid (CSF) rhinorrhoea and episodes of
extend to the clivus with a posterior recess, and rarely this       meningitis or brain abscess.
involves the whole clivus. From a caudal view, the anterior
margin of the clivus is bordered by the vomer with its alae.
Lateral to the clivus is the petro-occipital fissure housing the
                                                                    Neoplastic pathologies
inferior petro-occipital vein, connecting the cavernous sinus       Among clival tumors, the most frequent are chordomas.
to the internal jugular vein. Cranially, the inferior petrous si-   Chordoma is a rare cancer that accounts for 1-4% of all
nus rests on the petrooccipital fissure and creates the sulcus      bone malignancies. The incidence is of 0·08 per 100.000,



                                                                                                                                          S43
F. Pagella et al.




Table I. Multidisciplinary management for clival pathologies.
 Pathology                                            Surgery                                      Multidisciplinarity                             Other specialists
                                                                                                   between surgeons                                    involved
 Fibrous dysplasia                                 Biopsy + / decompression                         ENT surgeon +/-                                        /
                                                                                                      neurosurgeon
 Neurenteric cyst                                            Removal                                ENT surgeon +/-                                        /
                                                                                                      neurosurgeon
 Ecchordosis physaliphora                                 Removal +                                  ENT surgeon +                                         /
                                                        skull base plasty                             neurosurgeon
 Epidermoid                                                 Removal                                  ENT surgeon +                                         /
                                                                                                      neurosurgeon
 Cholesterol granuloma                                  Marsupialization                            ENT surgeon +/-                                        /
                                                                                                      neurosurgeon
 Sphenoid mucocele                                      Marsupialization                            ENT surgeon +/-                                        /
                                                                                                      neurosurgeon
 Chordoma                                  Removal with ETCA / MTCA / combined                       ENT surgeon +                                  Radiotherapist
                                                                                                      neurosurgeon                                  +/- oncologist
 Chondrosarcoma                            Removal with ETCA / MTCA / combined                       ENT surgeon +                                  Radiotherapist
                                                                                                      neurosurgeon
 Meningioma                                Removal with ETCA / MTCA / combined                       ENT surgeon +                                 Radiotherapist
                                                                                                      neurosurgeon                                 +/- oncologist
 Metastasis                                                   Biopsy                                 ENT surgeon +                                 Radiotherapist
                                                                                                      neurosurgeon                                 +/- oncologist
 Tumors of adjacent compartments                            Biopsy /                                 ENT surgeon +                                 Radiotherapist
                                                         rescue surgery                               neurosurgeon                                 +/- oncologist
 Plasmocytoma                                               Biopsy /                                ENT surgeon +/-                                Radiotherapist
                                                         rescue surgery                               neurosurgeon                               +/- hematologist
 Osteomyelitis and                                        Debridement                                ENT surgeon +                         Infectious disease specialist
 Osteoradionecrosis                                                                                   neurosurgeon
 CSF leak and meningocele                               Skull base plastic                          ENT surgeon +/-                                        /
                                                                                                      neurosurgeon
 Traumatic lesion                                      Decompression + /                             ENT surgeon +                                         /
                                                        skull base plastic                          neurosurgeon +/-
                                                                                                   maxillofacial surgeon
 Craniovertebral junction disease                  Anterior odontoidectomy +                         ENT surgeon +                                         /
                                                         decompression                                neurosurgeon
ENT: ear nose throat; ETCA: endoscopic transnasal transclival approaches; MTCA: microsurgical transcranial approaches; CSF: Cerebrospinal fluid.



with predominance in men and peak incidence between                                        entities; thus, in contrast to chondrosarcomas, they tend to
50-60 years of age; chordomas rarely affect children and                                   grow from the midline, expanding posteriorly and laterally.
adolescents (< 5% of all chordoma cases) 6. These tumors                                   At CT, clival chordoma appears as a midline soft-tissue
are thought to arise from the transformed remnants of the                                  lesion with bone destruction. The margin between the tu-
notochord. Actual data suggest they are almost equally                                     mor and normal bone is usually non-sclerotic and sharp.
distributed among the three sites of the skull base, mobile                                Radiodensities are frequently present and are thought
spine, and sacrum 7. Although slow-growing and histologi-                                  to represent remaining fragments of the destroyed clivus
cally low grade, chordomas are locally invasive and have                                   rather than new matrix formation. At MRI, they are usually
a high recurrence rate, making their clinical progression                                  hypo- to isointense on T1-weighted imaging, with cystic
similar to malignant tumors 8. They are not typically meta-                                components that may contain protein or haemorrhage, giv-
static on presentation, but the often late-stage diagnosis of                              ing them a bright signal. On T2-weighted images, they are
the disease makes distant metastasis more likely. In 5% of                                 characteristically of high signal. However, poorly differ-
chordomas there are metastasis to the lungs, bone, skin,                                   entiated chordomas have low T2 signal intensity. The en-
and brain at the time of initial presentation. Because of the                              hancement pattern is variable: heterogeneous enhancement
notochordal origin of these tumors, chordomas are midline                                  is more common than a homogeneous pattern 8.



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                                                                     Clivus pathologies from diagnosis to surgical multidisciplinary treatment




The second tumor that may involve the clivus is chondro-         pointense, but hyperintense on T2. Plasmacytoma can show
sarcoma, that account for 6% of skull-base tumors. Chon-         cavernous sinus invasion, carotid encasement, sphenoid si-
drosarcomas develop from primitive mesenchymal cells in          nus invasion and suprasellar extension 16.
synchondroses of the skull base with a high predilection         Finally the clivus is prone to be involved in a variety of
for the petroclival synchondrosis. Therefore they are para-      tumors of nearby structures: the dorsal extension of an in-
median lesions that often expand not only into the clivus        vasive pituitary adenoma, trigeminal schwannomas may
and sphenoid sinus but also into the middle and posterior        extend to the clivus leading to scalloping of its laterodorsal
cranial fossae, as well as the upper cervical area. The mean     surface, even tumors arising from the jugular foramen or
age of presentation of chondrosarcoma is 40 years 8. With        cerebellopontine cistern rarely extend as far as the clivus.
their usually slow growth rate, they are capable of reaching     Nasopharyngeal carcinomas (NPC) from their origin site
sizable dimensions, promoting bone erosion and signifi-          can directly invade the adjacent basisphenoid and basioc-
cant displacement of neurovascular structures before caus-       ciput.
ing symptomatology. Despite this local aggressiveness,
these lesions often spare the dura, compressing and dis-
placing rather than transgressing it 9. Bone destruction and     Non-neoplastic pathologies
calciﬁcation occur in about 50% of chondrosarcomas and           Most of the non-neoplastic occupying-space lesions de-
low-grade tumors tend to have more extensive calciﬁcation.       velop with a clival bone resorption. One is the neurenteric
These tumors are generally low-to-intermediate signal on         cyst, a congenital lesion that may occur along the neural
T1-weighted images and high signal on ﬂuid-attenuated in-        tube, which is formed by a failure of separation between
version recovery (FLAIR), and T2-weighted images. Stip-          endoderm and ectoderm in utero. The lesion is hyperintense
pled foci of calciﬁcation, a hallmark of this tumor, may be      (relative to grey matter) on T1-weighted and iso-intense to
demonstrated as heterogeneous areas of low signal within         hypo-intense on T2-weighted MRI 10. Another one is the
the tumor.                                                       cholesterol granuloma, rarely reported in literature involv-
Meningiomas are another type of tumor that also affects          ing the clivus 17 (Fig. 1).
the clival region. They represent the most frequent prima-       Histologically, it is characterized by chronic inflammation,
ry central nervous system tumors and they are considered         fibrous tissue reaction, cholesterol crystals and foreign
benign lesions with favorable survival rates; however, on
occasion, they may have a high-grade subtype, associated
with a poor prognosis and higher risk for metastasis. Pet-
roclival meningiomas are defined as being located medial
to the exit of the trigeminal nerve. Some clival meningi-
omas are entirely dural and subdural, but others may have
a tendency to involve the extradural and osseous compart-
ments 10. A non-contrast CT scan shows that these lesions
have either a high- or low-attenuation signal compared
with the surrounding brain. Hyperostosis, increased vascu-
lar markings and calciﬁcation are characteristic ﬁndings of
meningiomas on CT; however, malignant meningiomas can
be more destructive of bony structures and more invasive of
soft tissue 11.
In the chapter of clival malignancies, it is important to men-
tion also metastatic tumors. In patients with known cancer,      Figure 1. Images of a 46 years-old man who developed headache and pho-
the probability of a mass lesion in the clivus being a metas-    tophobia due to a cholesterol granuloma. MRI revealed a sphenoid-clival grow-
tasis is high. The most common primary sites are prostate,       ing lesion, with regular margins and 45 mm of diameter. The mass was hy-
kidney, liver (HCC), thyroid, gastrointestinal tract (adeno-     perintense on T1 (A), iso-hyperintense on T2 and determined an elevation of
                                                                 the pituitary gland, with no signs of infiltrations of surrounding structures. A
carcinoma), breast, lung, melanoma and lymphoma 12,13.           basal CT confirmed the presence of osteolysis of the posterior sphenoidal wall
Metastasis may be low signal on T2 and this potentially dif-     replaced by a mass of 29 x 30 mm (B). Swelling of the nasopharyngeal roof
ferentiates them from chordomas and chondrosarcomas 14.          was seen, through nasal endoscopy. An endoscopic transsphenoidal approach
                                                                 was made to reach the posterior sphenoidal wall where the cystic lesion was
Furthermore, plasmacytoma is exceptionally reported in           drained (D, E), with no sign of CSF leak. Postoperative endoscopic view with
the clivus 15. These lesions tend to enhance homogeneously       sella and ICAs visible through the thin clival bone left (F). A CT control 24 hours
on imaging; on T1-weighted MRI they are isointense or hy-        later showed no postoperative complications (C).



                                                                                                                                              S45
F. Pagella et al.




body giant cells 18. The pathogenesis is controversial and
can be potentially explained by either the obstruction-vac-
uum theory or ex-posed marrow hypothesis 19. On CT it ap-
pears as a smoothly marginated expansile lesion isodense
with the brain tissue and non-enhancing. On MRI, distinc-
tion from petrous bone cholesteatoma is usually possible as
cholesterol granulomas show a typical hyperintense signal
on T1 20. Also, sphenoid mucocele can result in bony re-
sorption and sometimes erosion of the clivus. Mucoceles
demonstrate variable densities at CT and signal intensities
at MRI depending on their protein content and presence of
associated infection. Rim enhancement may be seen as a
hallmark of encapsulation 8.
On the contrary fibrous dysplasia rise from the clivus where
the mature bone becomes replaced with a weaker substitute
of woven bone and fibrous tissue. This is a benign skeletal
anomaly that affects one or multiple bones, with a greater
tendency to affect long bones, ribs, and craniofacial bones.   Figure 2. Images of a 36 years-old man who developed general disori-
The lesions at CT images show a ground-glass appearance,       entation, progressive tendency to drowsiness, cephalea, fever and aqueous
while at T1-weighted MRI show low signal intensity, and        rhinorrhea 26. Four years before he was treated for undifferentiated NPC with
                                                               a left-side modiﬁed radical neck dissection and elective chemo-radiothera-
T2-weighted MRI signal intensity varies from high to in-       py, then a second line stereotactic radiotherapy (Cyberknife) for local relapse.
termediate or low based on cellularity, collagen, bone, and    At the time of admission CT scan revealed the presence of massive tension
cystic content of the lesion 21.                               pneumocephalus with an erosion of infero-posterior parts of sphenoidal sinus
Another clival congenital lesion is ecchordosis physali-       and possible radionecrosis of the clivus (A). Nasal endoscopy revealed the
                                                               presence of necrotic bone in the paramedian portion of the nasopharynx and
phora. It consists of nodules of gelatinous tissue and it is   active CSF rhinorrhea. The patient underwent endoscopic endonasal debride-
considered to be an ectopic notochord remnant along the        ment of necrotic bone (B) and repair of the clival fistula with a pedunculated
craniospinal axis, at the level of the clivus and sacrum 22.   nasoseptal (Hadad) flap. Control CT and MRI cerebral scans showed progres-
Radiological typical findings are hypointensity in T1-         sive resorption of the pneumocephalus with the nasoseptal flap covering the
                                                               bony defect (C).
weighted and hyperintensity in T2-weighted MRI, and,
most crucially, ecchordosis physaliphora shows no contrast
enhancement after the administration of gadolinium 23.         cortical bone erosion and adjacent soft tissue swelling. The
Epidermoids of the central nervous system consist of epi-      MRI findings are replacement of clival fatty bone marrow
dermal and connective tissue, usually in the form of a sac,
                                                               by exudate and effacement of soft tissues, resulting in a
characterized by slow growth. They tend to expand and
                                                               marked drop of T1-weighted signal in pre-contrast images.
spread along normal cleavage planes and thus they usually
                                                               The soft tissues and bones involved are greatly enhanced
occupy more than one intracranial compartment. They have
                                                               with contrast medium 10.
irregular “scalloped” margins and also tend to envelop vi-
                                                               Osteoradionecrosis, a possibly lethal complication of radi-
tal neurovascular structures. Epidermoids may be mistaken
for arachnoid cysts. Both lesions are non-enhancing and        ation therapy (RT) 24, can develop in the skull base (Fig. 2).
are hypointense on T1-weighted and hyperintense on T2-         In addition to neoplastic cells, RT damages healthy cells
weighted images, but, unlike arachnoid cysts, epidermoids      of the vascular endothelium, this creates the pathogenet-
have a slightly hyperintense segment when compared to          ic triad of hypoxia, hypocellularity, and hypovascularity.
CSF 20.                                                        Type II diabetes mellitus, smoke and vascular diseases are
The principal inflammatory pathology that may involve          considered possible risk factors. Among head and neck ma-
the clivus is skull base osteomyelitis. Most of the times it   lignancies, RT for nasopharyngeal carcinoma is the main
follows external ear infection in diabetic, old or otherwise   responsible for osteoradionecrosis 25,26.
immunocompromised patients, mostly males and has Pseu-         It is important to mention spontaneous clival CSF leaks 27
domonas aeruginosa as the usual pathogen. Patients usually     (Fig. 3). The diagnosis is made through beta-2-transferrin
present with ear pain and otorrhea. Skull base osteomyelitis   testing, CT scan and MRI. As reported by Van Zele et al.,
is potentially life-threatening. Imaging is of paramount im-   transclival meningoceles and spontaneous CSF leaks locat-
portance in establishing the diagnosis and CT findings are     ed at the clivus are extremely rare entities 28,29.



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                                                                                       Clivus pathologies from diagnosis to surgical multidisciplinary treatment




                                                                                    of new procedures 31. These were initially described with
                                                                                    enthusiasm, they might have become widely used, but then
                                                                                    fell into disuse after reports of complications, like transcer-
                                                                                    vical and transoral approaches.
                                                                                    Endoscopic transnasal skull base surgery started in the last
                                                                                    25 years, also addressing clival pathologies, with increas-
                                                                                    ing relevance. Since then, the endoscopic transnasal tran-
                                                                                    sclival approach has been widely accepted for extradural
                                                                                    pathologies, mainly clival chordomas, but its use remains
                                                                                    highly debated for intradural lesions due to the issue of du-
                                                                                    ral and skull base reconstruction and the high rate of post-
                                                                                    operative CSF leak (Fig. 4).
                                                                                    According to Bossi Todeschini et al. the advantages that
                                                                                    make the endoscopic transclival approach a promising
Figure 3. Computed tomography (A) and T2-weighted MRI (B) in a patient              technique to treat midline posterior fossa pathologies con-
with a right clival spontaneous cerebrospinal fluid leak. Intraoperative endo-      sist in avoiding cerebral retraction, near-field magnifica-
scopic view showing a paraseptal approach: the sphenoidotomy is enlarged to         tion, better surgical field illumination, minimal manipula-
gain adequate access to the sinus, and the intersinusal septum is drilled out.
The cerebrospinal fluid leak with small meningocele can be clearly identified in    tion of neurovascular structures, and direct access to the
the posterior wall of the sphenoid. The green colouration is due to the intraop-    tumor as well as early access to its vascular supply and the
erative use of fluorescein (C). Intraoperative view of the nasoseptal flap placed   possibility of removing the involved bone and/or dura 32.
overlay within the posterior wall of the sphenoid sinus, covering the clival ar-
                                                                                    Belotti et al. published an interesting historical overview
ea (D). Endoscopic endonasal view 24 months after surgery (E) and postop-
erative axial T1-weighted MRI scan with gadolinium showing a nasoseptal flap        about transclival approaches for intradural pathologies,
covering the clival area on the right sphenoid sinus (F).                           the results showed an initial preponderance of vascular
                                                                                    pathologies, mainly posterior circulation aneurysms and
                                                                                    some cavernous malformations of the brainstem. Intradural
Fractures of the clivus are not uncommon and have been
reported in 0.2% of patients with head injuries and in 2%
                                                                                    Table II. Surgical approaches to the clivus.
of patients with skull fractures 10. They can be classified as
                                                                                            Endoscopic transnasal transclival approaches (ETCAs)
three types: sagittal (intersecting the dorsum sellae), trans-
verse (intersecting both petrous ridges) and oblique (inter-                                                     Transnasal ETCA
secting one petrous ridge). Oblique fractures are the most                                 ETCA with intradural hypophysiopexy (pituitary transposition)
common, while patients with a transverse fracture have the                                         ETCA with far-medial extension (ETCA-FM)
highest risk of death 30.                                                                Aterolateral Microsurgical Transcranial Approaches (MTCAs)
                                                                                                           Supraorbital approach (SO)
                                                                                                          Mini-pterional approach (MPT)
Surgical approaches
                                                                                                              Pterional approach (PT)
The chapter of surgical approaches to the clivus and the                                            Pterional transzygomatic approach (PTTZ)
craniovertebral junction (CVJ) is still a field of study and                                    Fronto-temporal-orbito-zygomatic approach (FTOZ)
open debate: the major certainty is that there isn’t a com-                                Lateral Microsurgical Transcranial Approaches (MTCAs)
mon and univocal endorsement among expert with regard                                                    Subtemporal approach (ST)
to the best approaches to manage the clivus yet. The paths
                                                                                                  Subtemporal transzygomatic approach (STTZ)
described to reach clival pathologies are many; the main
                                                                                        Posterolateral Microsurgical Transcranial Approaches (MTCAs)
division is between the endoscopic transnasal transclival
                                                                                                          Retrolabyrinthine approach (RL)
approaches (ETCAs) and microsurgical transcranial ap-
                                                                                                          Translabyrinthine approach (TL)
proaches (MTCAs). Below the table with all the current
                                                                                                          Transcochlear approaches (TC)
approaches to the clivus (Tab. II).
                                                                                                              Retrosigmoid approach
Surgery of the lateral skull base has developed in the last 50
                                                                                                    Infratemporal approaches (type A, B, C, D)
years, starting from the traditional transcranial microsur-
gery. At the same time, different anterior extracranial and                                        Petro-occipital transigmoid approach (POTS)
transclival approaches have been described and applied,                                                         Far-lateral approach
characterized by “waves” with a progressive rise and fall                                                    Extreme-lateral approach




                                                                                                                                                           S47
F. Pagella et al.




                                                                                     There is an increasing number of published works that give
                                                                                     growing importance to the anterior transclival approaches
                                                                                     in terms of comparable gross total resection (GTR) rates
                                                                                     compared to the transcranial approaches 33. As regards pos-
                                                                                     sible complications, CSF leak rate was higher in midline
                                                                                     approaches, in contrast to postoperative cranial nerve palsy,
                                                                                     which was higher in lateral approaches.
                                                                                     There are still some limitations to exclusive transclival
                                                                                     approaches, according to other experts opinion, like the
                                                                                     management of lesions that further extend laterally to the
                                                                                     cranial nerves plane, and midline tumors having a very lim-
                                                                                     ited inter-carotid distance with a high risk of ICA rupture
                                                                                     and inadequate lesion exposition. According to La Corte
                                                                                     et al. such cases should benefit from a combined (one or
                                                                                     multi-staged) approach or a lateral TCA to avoid tumor re-
                                                                                     moval between cranial nerves and therefore reduce the risk
                                                                                     of postoperative deficits, and to avoid working through a
                                                                                     narrow corridor between the ICAs at different segments 34.
                                                                                     Staged surgery is a viable option when using combined ap-
                                                                                     proaches, such as extensive extradural surgery followed by
                                                                                     the removal of the intradural tumor, with a view to prevent
                                                                                     the risk of CSF leak.
                                                                                     An interesting preclinical anatomical study was made by
                                                                                     Agosti et al. in order to establish possible advantages of
                                                                                     endoscopic approaches in relation to the exposure of lateral
                                                                                     structures 35. ETCAs objectively provide an advantage in
                                                                                     terms of clival exposure, when compared with MTCAs. A
Figure 4. Images of a 35-year-old man admitted with left trigeminal (V1-
V2) palsy, dizziness, left ear hearing loss. MRI revealed a large cystic lesion      statistically significant gain of exposure of the lateral ana-
of the left cerebellopontine cistern with posterior displacement of the fifth left   tomical structures and jugular tubercles was offered by ET-
cranial nerve and a possible small post-contrast impregnation of a portion of        CAs with far-medial extension (ETCA-FM), that include
the medial wall (A, B). Head CT scan showed the surgical result (C) after an         the exposure of the neurovascular pterygoid structures,
endoscopic transsphenoidal/transclival approach performed with the complete
macroscopical removal of the lesion, that presented as a large cyst with a thin      Eustachian tube transposition, drilling of the anteromedial
layer of white capsule containing soft white tissue. A dural plastic with autolo-    portion of the ipsilateral occipital condyle and the medial
gous fat, an intradural layer of fascia lata and a septal flap followed, as shown    portion of the jugular tuberculum, identifying the lower
in postoperative MRI (D). The results of the histological tests reported aspects     cranial nerves 36.
indicative of a primary squamous cell carcinoma 42 (this article is distributed
under the terms of the Creative Commons AttributionNon CommercialShare               Minghao et al. believe that ETCA-FM approach provides
Alike 4.0 License).                                                                  the greatest surgical exposure at the lower clivus, but pro-
                                                                                     vides limited lateral exposure and surgical freedom. The
                                                                                     Extreme-Lateral approach provides the greatest surgical
pathologies, including meningiomas, schwannomas, epi-                                exposure at the lower clivus among the craniotomy ap-
dermoid cysts and neurenteric cysts were reported sporadi-                           proaches but carries a greater risk of damage to neurovas-
cally in the 1990s and showed a significant increase since                           cular structures and increased operative time 37.
2005, parallel with the evolution of transnasal endoscopy.                           Despite these data, it is important to note that, as preclinical
The main boost to the widespread use of endoscopic tran-                             studies, these works did not consider the possible increase
sclival approaches was most probably the introduction of                             in working volume and anatomical distortion caused by a
this technique for the treatment of clival chordomas 31. This                        space-occupying lesion nor the position of relevant vascu-
rise has gone together with the refinement of skull base                             lar and neural structures in relation to the mass. For such
reconstruction techniques and materials from autologous                              reasons, no surgical approach can be recommended over
flaps, fat, fascia, cartilage and bone, to synthetic materials                       another based on a preclinical study alone 35.
as fibrin glue, lyodura, collagen matrix, oxidized cellulose                         Recent studies of cadaveric dissection are testing new com-
and gelatin sponge.                                                                  bined and hybrid approaches, that are more in the field



S48
                                                                                Clivus pathologies from diagnosis to surgical multidisciplinary treatment




of neurosurgery, like a hybrid anterolateral transcondylar                      cal approaches. Childs Nerv Syst 2018;34:1451-1458. https://doi.
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                                                                                McMaster ML, Goldstein AM, Bromley CM, et al. Chordoma: incidence
num with early control of the extradural vertebral artery                       and survival patterns in the United States, 1973-1995. Cancer Causes
and the major venous structures. The greatest advantage                         Control 2001;12:1-11. https://doi.org/10.1023/a:1008947301735
showed by this study is the extension of the surgical cor-                 7
                                                                                Walcott BP, Nahed BV, Mohyeldin A, et al. Chordoma: current con-
ridor to the middle and upper clivus up to the sphenoid si-                     cepts, management, and future directions. Lancet Oncol 2012;13:e69-
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                                                                                Neelakantan A, Rana AK. Benign and malignant diseases of the
keyhole endoscope-assisted concept a complete resection is                      clivus. Clin Radiol 2014;69:1295-1303. https://doi.org/10.1016/j.
achieved, using a single operative corridor rather than com-                    crad.2014.07.010
bining endoscopic endonasal and anterolateral approaches.                  9
                                                                                Ditzel Filho LFS, Prevedello DM, Dolci RL, et al. The endoscopic
Reviewing literature and published experiences, the conclu-                     endonasal approach for removal of petroclival chondrosarcomas.
sion is that many variables must be considered when sur-                        Neurosurg Clin N Am 2015;26:453-462. https://doi.org/10.1016/j.
                                                                                nec.2015.03.008
gery is planned 39: which is the part of the clivus involved               10
                                                                                Hofmann E, Prescher A. The clivus anatomy, normal variants and
(superior, middle or inferior part), which is the pathology                     imaging pathology. Clin Neuroradiol 2012;22:123-139. https://doi.
with regard to the histology, the lateral extension and the                     org/10.1007/s00062-011-0083
structures involved; the anatomy of the patient; previous                  11
                                                                                Mohyeldin A, Prevedello DM, Jamshidi AO, et al. Nuances in the
treatments and need for further therapies; comorbidities.                       treatment of malignant tumors of the clival and petroclival region.
The surgical approach, therefore, shouldn’t be chosen apri-                     Int Arch Otorhinolaryngol 2014;18(Suppl 2):S157-172. https://doi.
                                                                                org/10.1055/s-0034-1395267
oristically but based on a patient-centred analysis. Moreover,             12
                                                                                Dekker SE, Wasman J, Yoo KK, et al. Clival metastasis of a duodenal
the combination of multiple surgical corridors, one comple-                     adenocarcinoma: a case report and literature review. World Neurosurg
mentary to another, allows the surgeon to work around the                       2017;100:62-68. https://doi.org/10.1016/j.wneu.2016.12.078
relevant anatomy and to avoid dissection passing the plane of              13
                                                                                Cathel A, Khan YR, Blais D, et al. Metastatic disease to clivus: biopsy
cranial nerves. With this principle, the optimization of the re-                or not? Cureus 2019;11:e5658. https://doi.org/10.7759/cureus.5658
section and the decrease of morbidity is achieved, also when               14
                                                                                Pallini R, Sabatino G, Doglietto F, et al. Clivus metastases: re-
facing big tumors involving the CVJ 40,41.                                      port of seven patients and literature review. Acta Neurochir
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                                                                                s00701-009-0229-1
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                                                                                Amita R, Sandhyamani S, Nair S, et al. Plasmacytoma of
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From diagnosis to surgery and medical treatment, clival                         org/10.4103/1793-5482.148788
pathologies require the multidisciplinary management                       16
                                                                                Lee J, Kulubya E, Pressman BD, et al. Sellar and clival plasmacy-
of ENT surgeon and neurosurgeon, whose partnership is                           tomas: case series of 5 patients with systematic review of 65 pub-
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anatomopathologist, radioterapist, oncologist and infec-                   17
                                                                                Emanuelli E, Ciorba A, Bianchini C, et al. Transnasal endoscopic
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survival rate to aggressive and recurrent diseases with po-                     s00405-012-2229-7
tential lethal course and complications.                                   18
                                                                                Hoa M, House JW, Linthicum FH, et al. Petrous apex cholesterol
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