Open access peer-reviewed chapter - ONLINE FIRST

Spheno-Orbital Meningiomas

Written By

Guillaume Baucher, Lucas Troude and Pierre-Hugues Roche

Submitted: September 16th, 2021 Reviewed: December 13th, 2021 Published: March 9th, 2022

DOI: 10.5772/intechopen.101983

Skull Base Surgery Edited by Hamid Borghei-Razavi

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Skull Base Surgery [Working Title]

Dr. Hamid Borghei-Razavi, Dr. Mauricio Mandel and Dr. Eric Suero-Molina

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Spheno-orbital meningiomas are mainly defined as primary en plaque tumors of the lesser and greater sphenoid wings, invading the underlying bone and adjacent anatomical structures. The patients, mostly women in their fifties, generally present with a progressive, unilateral, and nonpulsatile proptosis, often associated with cosmetic deformity and optic nerve damage. Surgical resection is currently the gold standard of treatment in case of optic neuropathy, significant symptoms, or radiological progression. The surgical strategy should take into account the morphology of the tumor, its epicenter at the level of the sphenoid wing, and the invasion of adjacent anatomical structures. Surgery stabilizes or improves visual function and oculomotricity in most cases but it is rare that the proptosis recovers completely. Gross total resection is hard to achieve considering the complex anatomy of the spheno-orbital region and the risk of inducing cranial nerve deficits. Rare cases of WHO grade II or III meningiomas warrant adjuvant radiotherapy. Tumor residues after subtotal resections of WHO grade I meningiomas are first radiologically monitored and then treated by stereotactic radiosurgery in case of progression.


  • meningioma
  • spheno-orbital meningioma
  • optic nerve
  • optic canal
  • anterior clinoid process
  • superior orbital fissure
  • sphenoid wing
  • cavernous sinus
  • proptosis

1. Introduction

As early as 1922, Harvey Cushing distinguished two types of meningiomas: spherical en massetumors with lobulated and sometimes irregular growth, and en plaquetumors, which are slightly elevated from and extend along the inner dural layer [1, 2]. En plaquemeningiomas are classically associated with significant underlying hyperostosis caused by tumor invasion of the bone and overexpression of osteogenic molecules influencing the osteoblast/osteoclast activity (e.g., osteoprotegerin and insulin-like growth factor 1), [3, 4]. Their preferred location in the pterional region and the sphenoid ridge could be due to the important intraosseous branching of meningeal vessels and venous sinuses at this level [1, 5]. Due to the anatomical complexity of this region, many different names have been used to describe this pathological entity (e.g., en plaquesphenoid wing meningioma, en plaquepterional meningioma, invading meningioma of the sphenoid ridge, hyperostoting meningioma of the sphenoid ridge, pterional-orbital meningioma…); however, spheno-orbital meningioma (SOM) seems to be both the most appropriate and the most frequently used term [6]. Consequently, SOMs are mainly defined as primary en plaquetumors of the lesser and greater sphenoid wings that invade the underlying bone and potentially adjacent anatomical structures [7]. They can progressively extend to the temporal and infratemporal fossae, orbit, anterior clinoid process (ACP) and cavernous sinus (CS), compromising the integrity of the optic canal, the superior orbital fissure (SOF), and the cranial nerves passing through [8].


2. Epidemiological data and clinical presentation

While meningiomas account for approximately 20% of all intracranial tumors in males and 38% in females (with a 2:1 female-to-male ratio) [9, 10], SOMs comprise between 4% and 9% of all meningiomas [11]. In a meta-analysis of 38 retrospective studies about SOM that included a total of 1486 patients, Fisher et al.reported a mean age of 51 ± 6 years old, with a high proportion of women (82%) [12].

In a review of the literature, Apra et al.demonstrated a greater female predominance in SOM (86% across 14 different series with a total of 867 patients) than in meningiomas from all locations (74% female in a total of 110,359 patients in the largest meningioma study) [13, 14]. In their own retrospective study of 175 histologically confirmed cases of SOM, women were found to be significantly younger than men at the time of diagnosis (51 ± 5 vs. 63 ± 8 years) [13]. Notably, progesterone receptors were identified much more frequently in women than in men (96% vs. 50%), and exogenous hormone intake (predominantly progesterone) was identified in 83% of women in this same series, indicating that this is a risk factor for developing SOM [13].

Patients typically present with progressive, unilateral, and nonpulsatile proptosis (84%), often associated with cosmetic deformity [12, 15]. The frequent optic nerve (ON) disturbances result in unilateral decreased visual acuity (46%), constricted visual field (31%), and sometimes loss of color vision (5%) [12]. Ophthalmoplegia is seen in 25% of patients with SOM, often due to cranial oculomotor nerves deficit (oculomotor nerve 11%; trochlear nerve 6%; abducens nerve 4%). Diplopia can also be caused by intraorbital compression of the oculomotor muscles. Deficits in other cranial nerves (trigeminal, vestibulocochlear, and facial nerves) are less common. Finally, other general neurological signs, such as headaches (25%) and epileptic seizures (4%), are observed in patients with SOM.


3. Preoperative assessment

Skull radiographs were historically used to diagnose SOM by demonstrating unilateral sphenoid hyperostosis. With the emergence of computed tomography (CT) and magnetic resonance imaging (MRI), these techniques became the standard before any surgical procedure involving the removal of a SOM.

CT precisely demonstrates the bone features of the SOM, as well as its extension (Figures 1 and 2). Using CT, the involvement of the orbit walls, floor of the middle cranial fossa (including the foramens rotundum and ovale), SOF, ACP, and optic canal can be easily identified.

Figure 1.

(a) Axial contrast-enhanced T1-weighted magnetic resonance imaging demonstrates thickening of the temporopolar dura mater on the right side, with a deviated optic nerve compared to the left side. A temporopolar arachnoid cyst is seen on the left side. (b) Axial computed tomographic scan shows hyperostosis of both the lesser and greater sphenoid wings, sparing the anterior clinoid process. Proptosis can be easily measured on axial brain slices passing through the lens on both sides, by firstly taking as reference the line joining the two lateral orbital margins. This line is then projected to the level of each cornea and the distance between these two new lines is measured, giving an accurate and relevant estimate of proptosis for follow-up.

Figure 2.

(a) Axial contrast-enhanced T1-weighted magnetic resonance imaging demonstrates a large right spheno-orbital meningioma with middle sphenoid wing center, invading the temporal fossa (TF), the superior orbital fissure (SOF), and the orbit (O). There was no true invasion of the optic canal (OC) by the meningioma on thin-section MRI analysis. (b) Axial computed tomographic scan shows hyperostosis of the lesser and greater sphenoid wings (L&GSW) and anterior clinoid process (ACP) on the right side.

MRI completes the radiological assessment, showing the globoid or plaque-like shape of the intradural portion of the meningioma and its impact on the brain parenchyma (mass effect and edema). The epicenter of the tumor on the sphenoid wing is identified, and the specific involvement of the temporal and infratemporal fossae, orbit, SOF, optic canal, and CS is determined. At this stage, it is important to differentiate between simple involvement of the lateral wall of the CS and true intracompartment invasion. Similarly, the presence of meningioma within the optic canal or SOF should be similarly distinguished from tumor bony involvement of these structures (Figures 1 and 2). All of these details are critical, as they contribute to the planning of the upcoming surgical procedure for optimal tumor resection.

A comprehensive preoperative ophthalmological exam is mandatory and should include at least an objective assessment of visual acuity and field, a dilated-pupil fundus examination and ideally an optical coherence tomography (OCT). The Lancaster red-green test for assessment of oculomotor muscle function is performed according to the presence of diplopia. Accurate measurement of the proptosis can be achieved with an exophthalmometer or with correctly oriented cerebral imaging (Figure 1).


4. Differential diagnosis

At this time, differential diagnosis for hyperostosis due to SOM should also be considered. These include fibrous dysplasia, osteoma, osteoblastoma, Paget’s disease, hyperostosis frontalis interna, osteoblastic metastases, and erythroid hyperplasia [15].


5. Therapeutic strategy and decision-making algorithm

As with all other meningiomas, the decision-making process for SOM must be tailored to each patient. Mass effect of the tumor, age, general condition, comorbidities, symptomatology, its impact on daily life, and the patient’s wishes must be taken into account. In cases with absent or mild symptoms without mass effect on imaging, simple clinical and radiological monitoring can be chosen initially, with patient follow-up on a regular basis (every 3–6 months). In contrast, the presence of optic neuropathy, severe neurological symptoms, significant proptosis, or serious mass effect warrants surgical operation. Although a subject of debate, optimal surgical resection remains the current reference treatment for SOM, in accordance with the general EANO (European Association of Neuro-Oncology) guidelines for the management of meningiomas published in 2016 [16]. If the patient is in a fragile state of health or categorically refuses the operation, radiation treatment may be offered as an alternative. The choice of technique is then mainly based on the tumor volume, stereotactic radiosurgery being preferred for smaller tumors and radiotherapy being preferred for larger tumors. To summarize this reasoning, we propose a simple algorithm highlighting the main points to be taken into account during decision-making in cases of SOM (Figure 3).

Figure 3.

Decision-making algorithm of first-line treatment for spheno-orbitary meningiomas, in accordance with the 2016 EANO guidelines [16]. The choice of radiation treatment is mainly based on the tumor volume, stereotactic radiosurgery being preferred for smaller tumors and radiotherapy being preferred for larger tumors.


6. Classification

Despite their common features, SOMs are a heterogeneous group of tumors due to the complex anatomy of the sphenoid bone, which is a part of both the skull base and the orbit. Few attempts have been made to classify SOMs. Roser et al.approached the classification of SOMs by first identifying the morphology of the meningioma (globoid, en plaque,and purely intraosseous), then detailing the involvement of the sphenoid wing and the CS [17]. Kong et turn proposed a slightly simplified version, focusing on the location of the tumor epicenter at the level of the greater wing of the sphenoid bone, which they divided into three thirds (medial, middle, and lateral) [18]. We suggest our own classification system derived from the previous schemes. Our proposed classification system successively takes into account the general morphology of the meningioma, its epicenter in the sphenoid wing, and the tumor invasion of specific anatomical regions and structures (Figure 4). These three main parameters are intended to assist in the surgical strategy planning by helping surgical teams determine the anatomical targets, how to reach them, and how to decompress them.

Figure 4.

Classification of spheno-orbital meningiomas according to their morphology (a), sphenoid wing epicenter (b), and specific extensions (c).


7. Surgical technique

7.1 Positioning of the patient and general settings

The patient is placed in a supine position with the head rotated 30° to the contralateral side and fixed in a three-pin Mayfield head-holder. The neck is slightly extended to 15°, as is done for a classical pterional approach. Neuronavigation is used to delineate the craniotomy and skin incision. We recommend using millimeter slices of the bone window of the CT scan for registration, to both highlight bone tumor extension and increase the accuracy of this technique [19, 20]. The CT scan is then merged with the MRI, including the gadolinium-enhanced 3D T1-weighted sequence, for intra- and extracranial tumor extensions (Figure 4). A paraumbilical field is prepared and draped to harvest abdominal fat for closure if needed.

7.2 Extracranial steps

The frontotemporal arciform incision starts 1 cm in front of the tragus, with the medial extent adjusted to the size of the surgical target. The scalp is progressively elevated in one layer and reclined forward, preserving the pericranial tissue for dural repair at the time of closure. A standard interfascial dissection is performed over the anterior quarter of the temporal muscle in order to spare the frontotemporal branches of the facial nerve [21, 22]. The orbital rim and zygomatic arch are progressively exposed in a subperiosteal manner. The temporal muscle is incised along the lateral orbital rim, along the superior temporal line, and at its posterior part along the skin incision. Retrograde dissection of the temporal muscle is performed using a cutting spatula from anterior to posterior and from inferior to superior in order to preserve the deep vascularization and innervation of the muscle and thus prevent postoperative atrophy [23]. Tumor-infiltrating of the muscle (1.) temporal fossa extension) must be resected at this stage. If the infratemporal fossa is invaded by the meningioma (2.) infratemporal fossa extension), the zygomatic arch must be cut anteriorly and posteriorly, maintaining its attachment to the masseter muscle, in order to recline the temporal muscle downwards as much as possible. This optional step facilitates resection of the tumor portion located in the infratemporal fossa, with particular attention to the mandibular nerve exiting the foramen ovale. In cases of major invasion of this location, the collaboration of an ear, nose, and throat surgeon is required.

7.3 Cranial steps

Depending on the extension of the intraosseous portion of the SOM, either a classical pterional craniotomy or a more complex orbitozygomatic approach is performed [24]. Guided by neuronavigation, the tumor-infiltrated bone must be resected as completely as possible using a high-speed drill and rongeurs, without overlooking the craniotomy part. The lateral wall and the roof of the orbit are drilled, initially respecting the periorbita (Figure 5). The intraorbital tumor extension (3.) mostly remains extraconal and can therefore be easily removed once the orbit is correctly opened. Nevertheless, the periorbit must be longitudinally opened and resected in cases of intraconal invasion [25]. If the tumor adheres too much to the cranial nerves, it is recommended to leave a residue in place to avoid postoperative deficits. The drilling continues medially at the level of the greater and lesser wings of the sphenoid bone, opening the SOF (4.), and inferiorly at the level of the floor of the middle cranial fossa, opening the foramens rotundum and ovale if necessary. With the involvement of the ACP (5.) and the invasion of the optic canal (6.), an extradural anterior clinoidectomy, which is carried out under magnification and constant irrigation, must be performed to optimize the decompression of the ON and prevent thermic lesions [26]. This step also allows the surgeon to extradurally split the lateral wall of the CS (7.) when there is a tumor at this level, in order to improve the devascularization of the meningioma.

Figure 5.

Intraoperative views of the resection of a left sphenoid-orbital meningioma with invasion of the anterior clinoid process (ACP), optic canal, and orbit. (a) Left pterional approach with drilling of the lesser sphenoid wing (LSW) and lateral wall of the orbit, in order to open the superior orbital fissure (SOF). The orbito-temporal periosteal fold is then identified at the external part of the SOF and divided to optimize the retraction of the frontal and temporal lobes and expose the contours of the ACP. (b) The final step of the extradural resection of the ACP. The LSW, optic strut, and roof of the optic canal were drilled before resecting the bony content inside the ACP. A thin shell of bony contour is preserved in order to remove the clinoid tip en bloc. (c) Once the drilling is completed, the orbit is properly exposed in continuity with the SOF and optic canal which have been opened. (d) The dura mater is opened in an arciform fashion, revealing the intradural portion of the meningioma (asterisk). (e) The dura mater of the optic canal is gently opened with a fine scalpel to remove the tumor fragments compressing the optic nerve at this level. (f) At the end of the procedure, the chiasma and the two optic nerves are correctly exposed. The coagulated portion of the dura mater at the level of the tuberculum sellae can be seen (asterisk; Simpson grade 2 resection).

7.4 Intradural steps

The dura mater is opened in a curvilinear fashion and the intradural portion of the tumor is progressively resected using conventional microsurgical methods, alternating debulking and peripheral dissection from the brain parenchyma and vessels. An additional dural incision directed medially toward the optic canal may cautiously be performed to complete the extradural anterior clinoidectomy. Once the optic canal has been widely opened intradurally (Figure 5), the tumor fragments at this level can be easily removed using a small blunt hook.

Complete resection is not always possible due to true intracavernous invasion (as opposed to a simple extension to the lateral wall) or excessive tumor adherence in the SOF or optic canal. In such situations, the key is to optimally decompress the ON so that the residual tumor can later be effectively treated with radiation therapy. The radiosensitivity of the ON justifies the creation of a safety zone around it, in order to avoid deleterious iatrogenic irradiation during radiation treatment. It is essential to preserve the function of the cranial nerves as much as possible, as their postoperative recovery is often uncertain.

7.5 Closure and reconstruction

If the ethmoidal or sphenoidal sinuses are open during the extradural steps, either autologous fat or a temporal muscle graft should be harvested to plug the defect, depending on the size of the opening (for example, the muscle should be used for a small aperture of a pneumatized ACP and fat should be used for a large sinus opening secondary to intranasal tumor invasion). A synthetic fibrin sealant may be used in addition to these measures to prevent postoperative cerebrospinal fluid leakage. The dural and periorbital defects are ideally managed using a vascularized and pedicled pericranial graft that is rotated over the orbit. Alternative solutions include using the temporal fascia or synthetic dura patches. Finally, the remaining dead space left by the tumor removal can be filled with a fat graft.

Bone reconstruction for SOM is often more complex than for other meningiomas due to the extensive bony resection, which sometimes involves the superior and lateral orbital rims. Various options are available to perform cranioplasty and obtain a satisfactory cosmetic result. If the orbital margins are intact, the healthy part of the craniotomy can be replaced using grids that are cut to a suitable shape and serve as anchor points for the reinsertion of the temporal muscle. For larger defects, hydroxyapatite cement can be shaped easily. A custom-made polymethylmethacrylate or polyetheretherketone (PEEK) prosthesis can be ordered before the procedure, especially when the orbital rims are planned to be resected. The design of the prosthesis can also compensate for temporal muscle atrophy by incorporating an increased thickening at the level of the temporal fossa. Trimming of the edges of the prosthesis is often required to perfectly match the craniotomy. The zygomatic osteotomy must be reattached with standard plates before reinserting the temporal muscle and suturing the scalp in layers according to the usual technique.


8. Complications and postoperative care

The first postoperative night is ideally spent in an intensive care unit, so that the patient can be closely monitored, and any respiratory, hemodynamic, or neurological failures can be detected at an early stage, particularly in the event of a surgical site hematoma. Most postoperative complications of SOM are related to the cranial nerves affected by the tumor. In their meta-analysis of retrospective series of operated SOM, Fisher et al.summarized the incidence of occurrence of these complications [12]. Ophthalmoplegia was frequent (16%) and mainly related to oculomotor nerves damage (oculomotor III 11%; trochlear IV 2%; abducens VI 6%; not specified 13%). In addition, ptosis or diplopia (neuropathic or restrictive) was observed in 17% of cases each. Regarding the optic nerve, visual field loss was described in 4% of cases, while visual acuity was decreased in 9%, and blindness was reported in 3% of cases. Trigeminal hypoesthesia was the most frequent complication (19%); in contrast, facial paralysis was rare (4%). Regarding complications related to the brain, the incidence of epilepsy was estimated to be 8%, while motor and phasic deficits, or diabetes insipidus were uncommon. Enophthalmos and cerebrospinal fluid leaks were encountered in 5% of cases each. Meningitis occurred in 7% and wound infections occurred in 3% of cases, which is consistent with the general rate of infection in cranial surgery, which was reported to be 9% [27]. Finally, pulmonary embolism was diagnosed in 4% of the patients who underwent an operation for SOM.


9. Postoperative course

9.1 Visual function

In most cases, SOM surgery stabilizes or improves visual function. In a large retrospective study of 130 patients, Terrier et al.demonstrated improvement in 45% of cases, stabilization in 39%, and worsening in 16% [28]. Fisher et al.highlighted in their meta-analysis that visual acuity and visual field were stabilized or improved in 91% and 87% of cases, respectively [12]. However, these encouraging results must be put into perspective, since improvement does not mean a complete restoration of visual function. Anatomically, invasion of the optic canal is associated with severe visual impairment both preoperatively and postoperatively [29], and tumor extension to the periorbit appears to be a negative predictive factor for visual acuity [8]. Therefore, it is essential to propose surgery to patients with SOM as soon as the optic pathways are threatened by the tumor, so that they can be optimally decompressed.

Regarding oculomotion, the reporting of results is generally less detailed, but seems to indicate a long-term improvement of the preoperative symptomatology that could reach 96% (although the degree of this improvement was not specified) [12]. Postoperative oculomotor deficits are frequent, varying from 8 to 68% depending on the series, but they recover in the majority of cases and persist in only 0–17% of cases [6, 11, 30, 31].

9.2 Proptosis

Proptosis, the most common sign encountered in patients with SOM, may be explained by different, yet interrelated, factors. From a mechanical point of view, the bony involvement of the orbital walls and the intraorbital tumor extension exert a direct mass effect on the eyeball. From a vascular point of view, the meningioma invasion of the SOF is responsible for a decrease in venous drainage and subsequently exacerbates the proptosis by increasing the intraorbital venous engorgement [32, 33]. This multifactorial physiopathology may explain the varied results from retrospective clinical series, which report improvements ranging from 50 to 100% [34, 35, 36, 37, 38, 39]. Thus, if mechanical compression is relieved by surgical opening of the orbit and resection of the intraorbital portion of the tumor, exophthalmos will certainly improve. Nevertheless, it is rare that the proptosis recovers completely, likely due to persistent disturbances of venous drainage and potential trophic disorders of the oculomotor muscles. Removal of the periorbit appears to have a beneficial effect and seems to be a key factor in reducing proptosis [29].

9.3 Oncological outcome

The quality of surgical resection of meningiomas, assessed by Simpson’s grading system, remains an important prognostic factor in the evolution of these tumors, regardless of the histological subtypes considered [40, 41]. Gross total resection, defined as Simpson grade I to III, is achieved in 25–70% of SOM cases depending on the series [34, 42, 43, 44]. Given the complex anatomy of the spheno-orbital region, Simpson grade I or II resections are rarely feasible without risking the induction of cranial nerve deficits, especially at the level of the orbital apex, SOF, and CS [43]. In this context, the current trend is strongly in favor of symptom-oriented surgery rather than radical surgery, targeting optic nerve decompression to improve visual function, and intraorbital tumor resection to reduce proptosis [30, 32].

Histologically, SOMs are commonly World Health Organization (WHO) grade I tumors (77–100%, depending on the series), with the meningothelial subtype being the most frequent [11, 13, 28, 43]. Although much less frequent, WHO grade II (atypical) or III (anaplastic) meningiomas may be encountered, together representing 11% of the cases in the retrospective series presented by Belinsky et al.Moreover, the authors highlighted the strong correlation between WHO grading, Ki67 proliferation index, and clinical progression [45]. Thus, WHO grade II and III meningiomas, which are associated with an aggressive clinical course and high recurrence rate compared to WHO grade I tumors, have Ki67 proliferation indices that proportionally predict their behavior (14.9 and 58.3, respectively). When considering only WHO grade I SOM, a Ki67 index ≥3.3 is associated with a higher risk of recurrence. Comparing these different histological subgroups, Agi et al.reported a recurrence rate of 22% in the WHO grade I tumors and 50% in the WHO grade II tumors, with a mean follow-up of 57 months [46].

The highly variable recurrence rate of SOM in the scientific literature, ranging from 10 to 56%, is likely due to differences in the follow-up duration [34, 47, 48, 49]. Indeed, the risk of recurrence logically increases with the duration of follow-up (6% at 3 years and 46% at 6 years after the intervention) [28].

The role and timing of radiation therapy remain a matter of debate for meningiomas in general and SOM in particular. However, experts (Response Assessment in Neuro-Oncology Committee) agree on the importance of using adjuvant radiotherapy for WHO grade III meningiomas, regardless of the quality of surgical resection [40]. For WHO grade II meningiomas, the European Association of Neuro-Oncology guidelines recommends observation or fractioned radiotherapy in cases of gross total resection and fractioned radiotherapy in cases of subtotal resection [16]. For WHO grade I meningiomas, simple observation is indicated after gross total resection, and stereotactic radiosurgery or fractioned radiotherapy may be proposed after subtotal resection. We suggest radiological monitoring of the tumor residue for subtotal resections of WHO grade I meningiomas initially. Stereotactic radiosurgery is then justified in cases of objective progression. Cases of meningiomas of WHO grade II or III must be discussed in a collegial manner in a multidisciplinary consultation meeting.


10. Conclusion

Spheno-orbital meningiomas are usually slow-growing skull base tumors revealed by proptosis or visual impairment. They typically present with significant tumoral spheno-orbital hyperostosis and a globoid or en plaqueintradural portion. As their epicenter is located at the level of the lesser and greater sphenoid wings, they progressively extend to the temporal and infratemporal fossae, orbit, anterior clinoid process, and cavernous sinus, compromising the integrity of the optic canal, the superior orbital fissure, and the cranial nerves passing through. The reference treatment is currently optimal surgical resection after complete ophthalmological examination and radiological evaluation by MRI and CT scan. Although the risk of recurrence appears to be clearly correlated with the quality of the surgical resection, in cases with excessive meningioma adherence to critical anatomical structures, the removal of the tumor must be restricted in order to limit the comorbidities related to induced cranial nerves deficits. Radiation therapy is a safe option after surgery for recurrent or aggressive meningiomas.


ACPAnterior clinoid process
CSCavernous sinus
CTComputed tomography
MRIMagnetic resonance imaging
OCTOptical coherence tomography
ONOptic nerve
SOFSuperior orbital fissure
SOMSpheno-orbital meningioma
WHOWorld Health Organization


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Written By

Guillaume Baucher, Lucas Troude and Pierre-Hugues Roche

Submitted: September 16th, 2021 Reviewed: December 13th, 2021 Published: March 9th, 2022