Endoscopic Transpterygoid Approach to Meckel ’ s Cave: Technical Considerations and Retrospective Analysis of a Clinical Series

Objective: Tumors located within the Meckel ’ s cave (MC) pose a significant surgical challenge. Although several corridors to access this complex region have been described, the endoscopic transpterygoid approach (ETPA) and the endoscopic transorbital superior eyelid approach (ETOA) have emerged in recent years, as viable alternatives to traditional microsurgical transcranial approaches (MTA). To date, there is a limited literature on surgical series considering endoscopic-assisted approaches to the MC. Methods: We conducted a retrospective analysis of patients with primary MC tumors treated at our Institution between 2015 and 2022, specifically those managed via the ETPA assisted by intraoperative Endoscopic Diving Technique (EDT). Lesion resection extent was evaluated using pre-and post-intervention radiological images and surgical videos. Moreover, a literature review on ETPA was performed. Results: This series comprises 7 patients affected by 4 trigeminal schwannomas, 1 benign notochordal cell tumor, 1 dermoid cyst and 1 mesenchymal tumor. In 71 % of cases, trigeminal neuralgia was the presenting symptom. Post-operative clinical improvement was observed in all but one case. Notably, 85.7 % of patients achieved total or near-total resection (NTR), with the remaining case undergoing subtotal resection (STR). No significant intraoperative complications occurred, and no recurrences were observed during the mean follow-up period of 41 months. Conclusions: In selected cases, the ETPA offers a direct and safe path to lesions located into the MC. This approach circumvents complications and constraints associated with ETOA or MTA. Moreover, the use of the EDT reduces manipulation of critical neurovascular structures, enhancing the efficacy of the ETPA.


Introduction
Meckel's Cave (MC) is a dural pouch located in the medial portion of the middle cranial fossa (MCF) [1].It harbors the Gasserian ganglion (GG) of the trigeminal nerve, after which it divides into 3 segmental branches that leave the MCF through their respective foramina [2,3].The MC sits inferior, posterior and lateral to the cavernous sinus (CS), with which shares the superficial thicker dural layer in its postero-lateral part [4].The intricate anatomical placement, its adjacency to the temporal lobe, and its proximity to vital neurovascular structures represent a substantial surgical challenge.
In contrast to well-established microsurgical transcranial approaches (MTA) such us the pterional, subtemporal, and retrosigmoid approaches [5], the last two decades have seen the validation of endoscopic endonasal approaches (EEA) to the ventral skull base [6,7].Specifically, the anteromedial corridor introduced by Kassam et al. in 2009 unlocked a "front-door" approach to Meckel's cave [8].Moreover, in recent years, the transorbital approaches to the middle cranial fossa are increasingly gaining interest, emerging as valid alternatives to endonasal corridors [9][10][11].
The importance of choosing the right corridor becomes crucial, especially for reaching off-midline lesions like those in MC, which require lateral paths around the internal carotid artery (ICA) [12].
This study aims to demonstrate the feasibility and efficacy of ETPA in treating selected tumors of MC, according to the pertinent literature.This experience analyzes the advantages and limitations of this approach, in order to guide the choice of the most appropriate surgical corridor to address lesions located in such a complex anatomical area.

Material and methods
We conducted a retrospective analysis of patients treated for Skull Base pathologies via an EEA at our Skull Base Surgery Division (University of Insubria, Ospedale di Circolo e Fondazione Macchi) between 2015 and 2022.Our study specifically focused on patients with primary tumors in Meckel's Cave (MC) or tumors with their main location in this region.Only cases treated exclusively through the Endoscopic Transpterygoid Approach (ETPA) were included.Lesion extending to MC from other compartments or demonstrating pluricompartimental involvement (e.g.extending into anterior cranial fossa and/or middle cranial fossa) and managed using multiportal approaches (MTA and/or ETOA and/or EEA) were excluded.All patients underwent preoperative brain computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging (MRI), along with MR angiography of the intracranial circulation.Clinical assessments on ocular motility were conducted if the CS was involved.Post-discharge, tailored follow-up included brain MRI at 3, 6, and then 12 months.Tumor removal was assessed based on intraoperative surgical videos and neuroimaging data.Specifically, total resection (TR) was defined as the absence of residual tumor, near total resection (NTR) in case of removal greater than 90 %, while subtotal removal (STR) if constituted residual tumor <90 %.The mean follow-up duration was 41 months (range: 12-84).
The results were compared with a non-systematic review of the literature focusing on the ETPA to MC. Reviews, original research papers, multicenter studies, clinical series, and case reports were reviewed.The search was conducted using the PubMed and Scopus platforms.The following terms (alone and/or in combination) were used: surgical approaches to Meckel's cave, transpterygoid, endoscopic endonasal, endoscopic transorbital, trigeminal schwannoma, middle cranial fossa, and radiosurgery.

Surgical technique
The patient is positioned supine in an anti-Trendelenburg position, with the head slightly flexed and without any rigid fixation.The standard equipment includes a Neuronavigation system, an endoscopic Doppler ultrasound probe, and neurophysiological cranial nerves monitoring.For the EDT [13], an endoscope irrigation system (Clearvision II, Karl Storz and Co., Tuttlingen, Germany) is required.
During the procedure, we adopt the "two nostrils -four hands technique" to expand the surgical field, thus enhancing surgical efficacy [14].
The ETPA represents a lateral extension of a standard transethmoidal approach [15] (Fig. 1).The procedure begins with the use of a 0 • endoscope, involving a subtotal uncinectomy followed by a middle antrostomy extended posteriorly up to the pterygoid process.Then, a standard sphenoidotomy and complete ethmoidectomy are performed.A rescue nasoseptal flap (NSF) [16] is harvested with an incision below the sphenoidal ostium, just above the tail of the superior turbinate, to preserve the septal branches of the sphenopalatine artery (SPA).The pterygopalatine fossa (PPF) is opened at the level of the sphenopalatine foramen by removing the orbital process of the palatine bone and the medial part of the posterior wall of maxillary sinus.Mucoperiosteum on the basisphenoid is stripped down to allow better visualization of the bony landmarks and then the contents of the PPF are gently mobilized laterally inside a periosteal box, in order not to injure its neurovascular contents [8].Therefore, the NSF can be mobilized into the maxillary sinus or nasopharynx to protect it during the subsequent stages of surgery.The vidian nerve (VN) and the vidian artery, as well as the descending and palatovaginal arteries, are identified.The VN is a crucial surgical landmark as it points to the anterior genu of the petrous ICA.After drilling out the basisphenoid and the base of the pterygoids, the vidian canal is traced up to the foramen lacerum and the petrous segment of the ICA.The paraclival and petrous horizontal portions of the ICA are located, and the bone inferior to the ICA is drilled out until reaching the lesion.At this point, after identifying the ICA's course with either US Doppler or neuronavigation, the dura mater of Meckel's cave is opened.The tumor is dissected and removed with the assistance of hydrodissection provided by the EDT [13].This technique involves irrigating the surgical cavity during tumor removal with a continuous flow of pressurized saline solution [17].
Finally, for skull base reconstruction, two different techniques can be used.In cases of large defects and/or intraoperative identification of CSF leak, a multilayer reconstruction is performed using autologous fat intradurally, fascia lata extradurally, and a NSF extracranially to resurface the defect.If the craniectomy is not extensive and CSF leakage is excluded, marsupialization of the surgical cavity with a NSF can be performed to drain any residual fluid in the cavity and prevent the risk of post-operative mucocele [18].

Results
This series includes 4 males and 3 females, with a mean age of 49 years (range: 37-64), treated by ETPA to the MC at our Department between 2015 and 2022.Pre-and post-operative data are summarized in Tables 1 and 2, respectively.Five patients presented with trigeminal nerve-related deficits as an onset symptom (71.4 %), diplopia was observed in 4 cases (57.1 %).Notably, two of them exhibited involvement of the VI cranial nerve.The mean maximum diameter of the lesions was 25 mm, and adjacent structures were involved in 5 cases (sphenoidal sinus, cavernous sinus, intra and extraconal orbital compartment).No significant intraoperative or early postoperative complications occurred.Skull base reconstruction was accomplished with a multilayer technique in 3 cases, with a NSF in 2 cases and marsupialisation of the surgical cavity in the remaining 2 cases.No postoperative CSF leakage occurred.The histopathological examinations highlighted 4 schwannomas, 1 benign notochordal cell tumor, 1 dermoid cyst and 1 malignant unclassified mesenchymal tumor.A total resection was achieved in 2 cases (28.7 %), while a near-total resection (>90 %) was achieved in 5 patients (57.1 %), totaling 6 out of 7 cases with a resection exceeding 90 %.The only case with a subtotal resection (STR) involved a malignant tumor subsequently treated with adjuvant chemotherapy.Only one patient developed a late minor complication, such as turbinoseptal synechiae, which required further intervention.
Post-operative clinical improvement was observed in 6 cases with but one, which remained unchanged in regard to both trigeminal and IV nerve deficits.Although improvements, patients complained of residual trigeminal discomforts.2 patients needed adjuvant therapies (CHT and RT), while remaining patients underwent a mean follow-up period of 41 months (range: 12-84) in which no recurrence and stable residuals were observed.

Illustrative case
A case report is presented herein (Fig. 2), detailing the clinical presentation of a 37-year-old woman who sought medical attention due to numbness and hypoesthesia affecting the left hemiface (Case 1 from Tables 1 and 2).A brain MRI revealed a left parasellar extra-axial lesion suggestive for trigeminal neuroma (15x15x25 mm in size).Subsequently, an ETPA assisted by intra-operative EDT was undertaken to achieve complete lesion removal (Fig. 3, Video 1).The EDT is a singleinstrument safe procedure that allows wide exploration of the surgical cavity [13].This hydrodissection technique ensures piecemeal tumor removal and bleeding control, optimizing the effectiveness of EEAs.Skull base reconstruction was accomplished using a NSF to marsupialize the surgical cavity.This technique ensures re-epithelization while mitigating the risk of mucocele formation [18].Histological analysis confirmed the nature of the lesion as Schwannoma.The postoperative course was uneventful, the patient was discharged home three days after standing improvement in facial sensation.The 3-month follow-up MRI verifies complete removal and reduction of the surgical cavity, ensured by the reconstruction technique.At the neurological evaluation, symptoms associated with V3 involvement were resolved, whereas mild paresthesia in the V2 territories persisted.

Surgical approaches to Meckel's cave
Gaining access to MC presents a complex surgical challenge.During the planning phase of the approach, meticulous attention must be directed towards the critical neurovascular structures surrounding this region, as well as the individual anatomical variations.Recently, alongside the standard microsurgical corridors, endonasal and transpalpebral endoscopic approaches have been proposed.Nevertheless, none of those surgical approaches provides unlimited access to this very region [5,19].
1) Microsurgical transcranial approaches (MTA).Despite the increasing popularity of endoscopic techniques for accessing the skull base, the transcranial approaches represent the most used surgical routes.Specifically, when dealing with lesions extending into the posterior fossa and causing medial displacement of the cavernous sinus and the GG, a transcranial approach to Meckel's cave should be considered.MTA offers clear visualization of nearby cranial nerve anatomy and access to the posterior cranial fossa [20].Nevertheless, MTA have drawbacks, including the necessity for brain retraction, extended hospitalization, heightened invasiveness with potential cosmetic implications, and an elevated risk of morbidity attributed to osteotomy [4,21].Specifically, every transcranial approach (e.g., pterional, orbitozygomatic) necessitate temporal lobe retraction to access the anterior portion of the Meckel's Cave [12].Similarly, transpetrosal lateral approaches offer wider exposure but still require temporal lobe manipulation, risking damage to intrapetrous structures like the facial nerve, inner ear, and carotid artery [8].In contrast, retrosigmoid approaches avoid temporal lobe manipulation but involve cerebellar retraction, confining surgical access to the corridors between cranial nerves [8].
2) Endoscopic transorbital approach (ETOA).Among the other endoscope-assisted approaches to Meckel's cave, the transorbital corridor deserves an honorable mention.The ETOA entails gaining access to the cranial cavity through the orbit, by means of a blepharoplasty incision.Its primary advantage includes access to the lateral aspect of the Meckel's regions from the orbit, thereby minimizing disruption to the nasal cavity 13,24 .However, it is accompanied by inherent drawbacks, including potential damage to ocular tissues such as Abbreviations: CHT: chemotherapy; NTR: near total resection (>90 %); RT: radiotherapy; STR: subtotal resection (<90 %); TR: total resection (100 %).enophthalmos, pulsatile exophthalmos, mild ptosis, or incomplete eye closure.These risks arise from the removal of the lateral orbital wall or injury to the orbicularis or levator muscles [19].One of the main concerns during transorbital surgery is the risk of orbital injury and bradycardia, due to activation of the oculocardiac reflex during the manipulation of the orbital globe [22].Moreover, accessing the posterolateral triangle, the corridor situated between the mandibular nerve (V3) and the petrous apex, remains a challenging task with the ETOA [19].Additionally, a quantitative anatomical study by our group, has documented that targeting the foramen rotundum (FR) and so V2 and the medial portion of the superior orbital fissure (SOF) via the endoscopic endonasal route is preferable over a transorbital approach [23].Conversely, an ETOA is preferred when targeting the lateral aspect of the SOF, the lesser sphenoid wing, and the lateral part of the greater sphenoid wing.To note, if brain retraction is avoided, the exposure obtained with lateral MTA and ETOA is comparable [23].In recent years, there has been a great interest in transorbital surgery to access the anterior and middle skull base.However, the ETOA must have clear clinical-pathological indications to balance the risk-benefit ratio of this approach [24].Specifically, we prefer to indicate ETOA in selected patients with spheno-orbital meningiomas (SOM) presenting with proptosis, visual impairment, and visual field deficits [25][26][27].
3) Endoscopic transpterygoid approach (ETPA).Kassam et al. [8] was the first to describe an endoscopic endonasal approach to MC, offering an antero-inferior and medial corridor suitable for addressing various benign and malignant pathological conditions.Despite having been described for nearly fifteen years, there is a scarcity of published surgical series analyzing ETPA to date [8,12,21,28].The safety and outcomes of endoscopic endonasal transpterygoid approaches to Meckel's Cave are constrained by the retrospective, single-center, and small-scale nature of the evidence available.The most pertinent data reported by other authors have been summarized in Table 3.In this direct mini-invasive approach, the VN is a crucial surgical landmark, as it points like an arrow to the anterior genu of the ICA.Under typical anatomical conditions, the available space in the endoscopic endonasal route is limited due to the fixed boundaries of the quadrangular space, defined by the ICA medially and inferiorly, V2 laterally, and the VI cranial nerve superiorly [29].Zoli et al. [12] explained that when there is a lesion expanding within Meckel's cave, the structures of the quadrangular space [8] can be displaced.In particular, trigeminal structures are displaced laterally and posteriorly, while the ICA is medialized.This displacement leads to an enlargement of the so-called quadrangular space, which permits the entrance through the "front door" to Meckel's cave.As a result, an EEA to this region becomes feasible from a ventral transnasal perspective.A significant extension of a Meckel's tumor towards the posterior cranial fossa, therefore resulting to be hidden by the ICA, represents the primary anatomical limitation of endoscopic endonasal surgery ,8 .

Clinical considerations
In our clinical practice, if the above-mentioned anatomical prerequisites are respected, we tend to prioritize the utilization of an ETPA for approaching MC lesions.Specifically, upon comparing EEA and transorbital routes, we contend that an EEA is more suitable and secure.The ETPA, in fact, provides a direct path to Meckel's cave's anteromedial region (Fig. 4), allowing for dissection between the trigeminal nerve and the periosteal layer of the dura mater.
After undergoing the ETPA, patients commonly experience facial numbness, attributed to hypoesthesia of the V2 branch of the trigeminal nerve [12].Most of these deficits result from surgical manipulation; they are transient and tend to improve in the few weeks following surgery.Concerning trigeminal schwannomas, the potential advantage would involve minimizing manipulation of the trigeminal nerve during surgery, leading to fewer occurrences of postoperative trigeminal neuropathy [21].Our findings, with only one case of new onset postoperative numbness along V2 territory, confirm minimal morbidity associated with this approach.We believe that the intraoperative hydrodissection technique (Endoscopic Diving Technique [17]), being a monomanual instrument technique, helps in decreasing manipulation of neurovascular structures in tumor dissection and removal.
Another risk associated with this approach is damage to the VI cranial nerves (CN), which run alongside V1 toward the SOF [30].While two cases of permanent diplopia have been reported in the literature (one case in Zoli et al. and one case in Raza et al.), we did not observe any postoperative diplopia in our study.According to our current experience, the enlargement of the quadrangular space provided by both the tumor and hydrodissection by the EDT increases the working space, thereby mitigating the risk of VI or V1 nerve damage.
Despite the ETPA's medial corridor being in close proximity to the ICA, no complications related to carotid artery injury were observed in our study and in the literature.Furthermore, neither study reported major complications such as CSF leakage, meningitis, or mortality.
In terms of extent of resection, we achieved a near-total resection, defined as a lesion resection greater than 90 %, in 6 out of 7 cases (85.7 %), and one case of subtotal resection (14.3 %).

Approach selection
Selecting the appropriate approach necessitates a thorough analysis of the size, extent, and relationship of the tumor to bone, nerve, and vascular structures on each occasion.Sometimes, a multiportal combined approach (EEA and/or ETOA and/or MTA) may be considered.For instance, combining EEA and ETOA allows for the exposure of most of the spheno-orbital region (SOR) without brain retraction, enabling tumor dissection from different and complementary perspectives [10,23].
However, these experiences are limited and the real need must be assessed on a case-by-case basis.We emphasize the importance of a nuanced decision-making process as the cornerstone of addressing each case.Factors such as surgical objectives, tumor characteristics, and surgeon preferences must all be carefully considered.Without transnasal Doppler, neuronavigation, specialized endo-bipolars, and a wellestablished interdisciplinary collaboration between otolaryngologists and neurosurgeons, we do not recommend using the ETPA for tumors  located in Meckel's cave.

Management of trigeminal schwannoma recurrences
Based on both the literature and our own case studies, trigeminal schwannomas appear to be the lesions most commonly treated with this approach, representing 33.9 % (20 out of 59).
In cases of small remnants in the posterior cranial fossa, a wait-andsee approach may be preferable, while significant brainstem displacement may require a multistep surgery involving a suboccipital retrosigmoid approach [12].However, stereotactic radiosurgery (SRS) is a primary treatment option for residual tumors as it is associated with high rates of tumor control, symptom relief, and low rates of treatment-related complications [31].

Limitations
The major limitation of this study is represented by the small number of patients embedded and its retrospective nature.Furthermore, the current case series primarily included tumors with benign histology.This finding is consistent with other retrospective studies in the literature and may be related to the fact that malignant pathologies, due to their invasive nature and tendency to extend into multiple anatomical compartments, are less appropriate for a pure ETPA to the Meckel's cave.Nonetheless, without larger patient cohorts, this finding remains merely speculative.However, we believe that this contribution may be important considering that now the number of surgical series involving this approach is limited.
Therefore, studies with larger cohorts and longer follow-up periods are needed to validate the efficacy and safety of ETPA compared to traditional approaches and to elucidate its long-term outcomes.

Conclusion
Surgical access to MC remains a complex effort, demanding surgeons to meticulously evaluate the merits and drawbacks of various approaches, ultimately selecting the most optimal strategy tailored to each patient's characteristics.
In selected cases, the ETPA has proven to be a minimally invasive procedure that provides an excellent path to MC allowing for the achievement and eventual confirmation of total lesion removal with the assistance of EDT.Furthermore, the ETPA EDT-assisted decreases the extent of manipulation of neurovascular structures avoiding complications and limitations associated with ETOA or MTA.
In conclusion, although limited data are available, ETPA represents a safe and effective anteromedial corridor for the treatment of these offmidline pathologies.

Declaration of Competing Interest
The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

Fig. 1 .
Fig. 1.Anatomical specimen, endoscopic endonasal image.0 • scope.a) Identification of endonasal landmarks following right antrostomy extended posteriorly to the pterygoid process, sphenoidotomy and posterior ethmoidectomy.b) After the removal of the vertical process of the palatine bone, the PPF is opened, and the SPA foramen is exposed.Preservation of the SPA guarantees the vascularization of the ipsilateral NSF.c) PPF content is mobilized in a periosteal box and the vidian canal is exposed.The VN identifies the anterior genu of the ICA.d) Final exposure of the ETPA with visualization of paraclival and horizontal portions of the ICA, VN and the maxillary nerve (V2).Abbreviations: AgICA: anterior genu of ICA; pICA: paraclival ICA; PPF: pterygopalatine fossa; SS: sphenoidal sinus; MS: maxillary sinus; SPA: sphenopalatine artery; VN: vidian nerve.

Fig. 2 .
Fig. 2. Preoperative MRI images reveal a left Meckel's Cave lesion indicative of a trigeminal neuroma, depicted in the top section.The left panel (a) displays a T1weighted contrast-enhanced axial view, while the right panel (b) shows a T2-weighted coronal view.Below, the bottom section presents the 3-months post-operative MRI.Panel (c) exhibits a T1-weighted contrast-enhanced axial view, while panel (d) displays a coronal view.These images confirm complete tumor removal and demonstrate a reduction in the surgical cavity, achieved through the marsupialization of the surgical cavity.

Fig. 3 .
Fig. 3. Intraoperative images from an ETPA for a left trigeminal schwannoma (TS).a) The procedure begins with a subtotal uncinectomy, followed by a middle antrostomy extended posteriorly up to the pterygoid process.Subsequently, a standard sphenoidotomy and complete ethmoidectomy are performed.b) Following the opening of the PPF and dissection of the mucoperiosteum of the basisphenoid, the vidian prominence (VP) is identified.The VP points like an arrow to the left internal carotid artery (agICA).In this instance, the vidian canal was left intact to preserve the Vidian nerve (VN).c) The internal carotid artery (ICA) is located with assistance from neuronavigation and US Doppler.d) Sequential incision of the trigeminal schwannoma (TS) capsule follows.Abbreviations: AgICA: anterior genu of internal carotid artery; CR: clival recess; MC: Meckel's cave; MP: maxillary prominence; OCR: optico-carotideal recess; ON: optic nerve; SPA: sphenopalatine artery; V2: maxillary nerve.

Fig. 4 .
Fig. 4. Three-dimensional reconstruction of a postoperative CT scan demonstrating the direction of the approach to the left Meckel's Cave achieved through the ETPA.

Table 1
Overview of preoperative data of patients included in the study.

Table 2
Summary of postoperative data.

Table 3
Case series reported in the literature concerning ETPA approaches for lesions of the MC.