Complications of the Superior Eyelid Endoscopic Transorbital Approach to the Skull Base: Preliminary Experience With Specific Focus on Orbital Outcome.

BACKGROUND: The endoscopic superior eyelid approach is a relatively novel mini-invasive technique that is currently investigating for skull base cancers. However, questions remain regarding specific approach-related complications when treating different skull base tumors. This study aims to analyze any surgical complications that occurred in our preliminary consecutive experience, with specific focus on orbital outcome. METHODS: A retrospective and consecutive cohort of patients treated via a superior eyelid endoscopic transorbital approach at the Division of Neurosurgery of the Hospital Clinic in Barcelona was analyzed. Patients features were described in detail. Complications were divided into 2 groups to analyze separately the approach-related complications, and those resulting from tumor removal. The ocular complications were subdivided into early ocular status (<3 weeks), late ocular status (3-8 weeks), and persistent ocular complications. The "Park questionnaire" was used to determine patient's satisfaction related to the transorbital approach. RESULTS: A total of 20 patients (5 spheno-orbital meningiomas, 1 intradiploic Meningioma, 2 intraconal lesions, 1 temporal pole lesion, 2 trigeminal schwannoma, 3 cavernous sinus lesions, and 6 petroclival lesions) were included in the period 2017-2022. Regarding early ocular status, upper eyelid edema was detected in all cases (100%) associated with diplopia in the lateral gaze in 30% of cases, and periorbital edema in 15% of cases. These aspects tend to resolve at late ocular follow-up (3-8 weeks) in most cases. Regarding persistent ocular complications, in one case of intraconal lesion, a limitation of eye abduction was detected (5%). In another patient with intraconal lesion, an ocular neuropathic pain was reported (5%). In 2 cases of petroclival menigioma, who were also treated with a ventriculo-peritoneal shunt, slight enophthalmus was observed as a persistent complication (10%). According to the Park questionnaire, no cosmetic complaints, no head pain, no palpable cranial irregularities, and no limited mouth opening were reported, and an average of 89% of general satisfaction was encountered. CONCLUSIONS: The superior eyelid endoscopic transorbital approach is a safe and satisfactory technique for a diversity of skull base tumors. At late follow-up, upper eyelid edema, diplopia, and periorbital edema tend to resolve. Persistent ocular complications are more frequent after treating intraconal lesions. Enophthalmus may occur in patients with associated ventriculo-peritoneal shunt. According to patient's satisfaction, fairly acceptable results are attained.

Endoscopic Transorbital Approach for the Management of Spheno-Orbital Meningiomas: Literature Review and Preliminary Experience.

OBJECTIVE: The endoscopic transorbital approach (ETOA) is a minimally invasive approach that could be particularly appropriate for management of spheno-orbital meningiomas. The aim of this study was to perform a systematic review of the literature on the management of spheno-orbital meningiomas via the minimally invasive ETOA, searching for clinical scenarios in which this approach could be best indicated. A secondary aim was to describe 4 illustrative cases. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data including patient demographics, tumor features, and surgical and postoperative outcomes were collected. Cases from our initial experience with ETOA were included in the data. RESULTS: Data of 58 patients from 9 selected records and from our surgical series were collected. Subtotal, near-total, and gross total resection rates were 44.8%, 10.3%, and 32.7%, respectively. Symptom improvement after surgery was 100% for proptosis, 93% for visual impairment, and 87% for ophthalmoplegia. The most common postoperative complications were transient ophthalmoplegia and maxillary nerve hypoesthesia. Cerebrospinal fluid leak was reported in 2 patients. CONCLUSIONS: Our findings support the use of the ETOA for management of spheno-orbital meningiomas, particularly in at least 3 clinical scenarios: 1) when predominant hyperostotic bone is present; 2) when a globular tumor not showing excessive medial or inferior infiltration is being treated; 3) as part of a multistage treatment for diffuse lesions.

Ultrasound-Oriented Surgical Planning ("UOSP") for Intracranial Lesions: A Systematic Integration to the Standard Preoperative Planning.

OBJECTIVE: Intraoperative ultrasound (iUS) is a well-established technique whose aim is to provide real-time visualization of deep lesions during brain surgery. The lack of definition of anatomic semeiotics and the unusual direction of the insonation plane make interpretation and orientation challenging for the surgeon who newly approaches to such a tool. We propose a novel protocol to be applied during the surgical planning for intracranial lesions surgery, a so-called ultrasound-oriented surgical planning ("UOSP") protocol, and we provide a retrospective analysis of 21 patients who underwent surgery for an intracranial lesion in which UOSP was applied. To further enlighten different surgical orientation strategies and possible limitations given by the technique, we discuss 3 illustrative cases assigned to 3 categories ("basic," "intermediate," and "challenging" lesions) with progressively growing difficulty in anatomic orientation during a surgical procedure. METHODS: A total of 21 patients operated between March 2021 and July 2021 and where the UOSP protocol was applied during surgical planning were evaluated retrospectively. The UOSP protocol was performed the days before the surgical intervention by the same surgical team. RESULTS: The UOSP protocol was successfully applied in all 21 patients. In all cases, the preoperative imaging obtained during surgical planning corresponded to the images observed during the application of iUS. CONCLUSIONS: The introduction of the UOSP protocol during the planification of the surgical intervention for an intracerebral lesion may serve as a key factor to overcome the actual limitations inherent to the iUS technique. Utilization of this protocol may facilitate wider use of iUS in neurosurgery.

Activity and Resistance of a Brain-Permeable Paradox Breaker BRAF Inhibitor in Melanoma Brain Metastasis.

The therapeutic benefit of approved BRAF and MEK inhibitors (BRAFi/MEKi) in patients with brain metastatic BRAF V600E/K-mutated melanoma is limited and transient. Resistance largely occurs through the restoration of MAPK signaling via paradoxical BRAF activation, highlighting the need for more effective therapeutic options. Aiming to address this clinical challenge, we characterized the activity of a potent, brain-penetrant paradox breaker BRAFi (compound 1a, C1a) as first-line therapy and following progression upon treatment with approved BRAFi and BRAFi/MEKi therapies. C1a activity was evaluated in vitro and in vivo in melanoma cell lines and patient-derived models of BRAF V600E-mutant melanoma brain metastases following relapse after treatment with BRAFi/MEKi. C1a showed superior efficacy compared with approved BRAFi in both subcutaneous and brain metastatic models. Importantly, C1a manifested potent and prolonged antitumor activity even in models that progressed on BRAFi/MEKi treatment. Analysis of mechanisms of resistance to C1a revealed MAPK reactivation under drug treatment as the predominant resistance-driving event in both subcutaneous and intracranial tumors. Specifically, BRAF kinase domain duplication was identified as a frequently occurring driver of resistance to C1a. Combination therapies of C1a and anti-PD-1 antibody proved to significantly reduce disease recurrence. Collectively, these preclinical studies validate the outstanding antitumor activity of C1a in brain metastasis, support clinical investigation of this agent in patients pretreated with BRAFi/MEKi, unveil genetic drivers of tumor escape from C1a, and identify a combinatorial treatment that achieves long-lasting responses. SIGNIFICANCE: A brain-penetrant BRAF inhibitor demonstrates potent activity in brain metastatic melanoma, even upon relapse following standard BRAF inhibitor therapy, supporting further investigation into its clinical utility.

Endoscopic Anatomy of Transcallosal Hemispherotomy: Laboratory Study with Advanced Three-Dimensional Modeling.

BACKGROUND: Epilepsy surgery has an important role in the treatment of patients with medically intractable seizures. Various authors have proposed an endoscopic technique to perform disconnective procedures. A detailed description of intracerebral anatomy seen through an endoscopic transcallosal corridor has not been reported. The aim of this study was to present a cadaveric step-by-step anatomical demonstration of endoscopic transcallosal hemispherotomy using a dedicated three-dimensional model. METHODS: Anatomical dissections were performed on 6 cadaveric heads (12 hemispheres), and the disconnective procedure was performed using an endoscopic transcallosal approach. A dedicated three-dimensional model was used to better illustrate each step. A simulation of the disconnective procedure was performed by recreating the surgical steps on a subject from the Human Connectome Project dataset, and a calculation of the fiber tracts intersected was performed. RESULTS: Analyzing data extracted from the three-dimensional model and tractography simulation, 100% of the fibers (streamlines) of corpus callosum, corticopontine tracts, corticospinal tract, and inferior fronto-occipital fascicle were transected. Moreover, a satisfactory number of fibers (>95%) of the thalamocortical tracts, corticostriatal tracts, corona radiata, fornix, and uncinate fascicle were disconnected. CONCLUSIONS: This anatomical study described the relevant neurovascular structures to enable prediction of feasibility and control of the surgical procedure using the endoscopic transcallosal approach. The quantitative analysis permitted estimation of the theoretical efficacy of the procedure, confirming its relevant role in disconnective surgery.

Combined endoscopic endonasal and transorbital approach to skull base tumors: a systematic literature review.

INTRODUCTION: In the last decades, there has been a marked evolution in skull base surgery techniques and more recently a combination of different corridors has been proposed and used in order to improve angles of attack, shorten working distances, and ameliorate visualization of skull base lesions. Recently, the endoscopic endonasal and transorbital routes have been combined as multiportal approach to reach and treat complex skull base neoplasms. The aim of this paper is to examine data extracted from the recent literature about the feasibility and effectiveness of combined endonasal and transorbital endoscopic multiportal surgery. EVIDENCE ACQUISITION: A PubMed comprehensive search of literature published until October 2020 was conducted. Nine studies, regarding 24 patients, were included. EVIDENCE SYNTHESIS: The majority of tumors were meningiomas (62.5%), mostly located at the spheno-orbital region (93.3%). GTR was accomplished in 10 patients (41.7%), NTR in two patients (8.3%). Endonasal transpterygoid approach (N.=8) and superior eyelid access (N.=17) were the most used routes used. No case of CSF fistula was observed, and the most common complication was a transient periorbital edema. The average hospitalization time (days) was five days. CONCLUSIONS: A combined endoscopic endonasal and transorbital multiportal approach grants an adequate corridor to access several skull base tumors, such as those extending towards the paramedian aspects, providing good outcomes in terms of extent of tumor resection with acceptable rates of complications. These preliminary results might encourage the use of multiportal approaches in selected complex skull base neoplasms.

Extradural anterior clinoidectomy through endoscopic transorbital approach: laboratory investigation for surgical perspective.

BACKGROUND: The endoscopic transorbital approach (eTOA) is a new mini-invasive procedure used to explore different areas of the skull base. Authors propose an extradural anterior clinoidectomy (AC) through this corridor, defining the anatomical landmarks of the anterior clinoid process (ACP) projection onto the posterior orbit wall and the technical feasibility of this approach. We describe the exposure of the opticocarotid region and the surgical freedom and the angles of attack obtained with this novel approach. METHODS: Five cadaver heads underwent an eTOA at the Laboratory of Surgical Neuroanatomy of the University of Barcelona. A step-by-step description of the extradural endoscopic transorbital clinoidectomy was provided. A volumetric analysis of the morphometrics characteristics of the sphenoid wings was evaluated before and after dissection using CT scans. Pterional approach was performed to ascertain ACP removal. RESULTS: In all the specimens, it was possible to resect the ACP endo-orbitally aiming an optimal optic canal (OC) unroofing. The surface of the triangle corresponding to the ACP projection onto the posterior orbit wall was 0.42 ± 0.20 cm2. The drilled area to perform the extradural clinoidectomy via eTOA was 3.11 ± 2.27 cm2, and the volume of bone removal corresponding to the greater sphenoid wing (GSW) and lesser sphenoid wing (LSW) was 2.55 ± 1.41 and 0.26 ± 0.18 cm3 respectively. The area of surgical freedom provided by the eTOA was (3.11 ± 2.27cm2), and the angles of attack were 21.39 ± 9.13° in the horizontal axel and 30.63 ± 18.51° in the vertical. CONCLUSIONS: The described extradural anterior clinoidectomy by eTOA uses specific landmarks to localize the ACP on the posterior orbit wall. Resection of the ACP is a technically feasible approach, achieving the main goals of any clinoidectomy.

Endoscopic endonasal and transorbital routes to the petrous apex: anatomic comparative study of two pathways.

BACKGROUND AND OBJECTIVE: Surgical approaches to the petrous apex region are extremely challenging; while subtemporal approaches and variations represent the milestone of the surgical modules to reach such deep anatomical target, in a constant effort to develop minimally invasive neurosurgical routes, the endoscopic endonasal approach (EEA) has been tested to get a viable corridor to the petroclival junction. Lately, another ventral endoscopic minimally invasive route, i.e., the superior eyelid endoscopic transorbital approach, has been proposed to access the most lateral aspect of the skull base, including the petrous apex region. Our anatomic study aims to compare and combine such two endoscopic minimally invasive pathways to get full access to the petrous apex. Three-dimensional reconstructions and quantitative and morphometric data have been provided. MATERIAL AND METHODS: Five human cadaveric heads (10 sides) were dissected. The lab rehearsals were run as follows: (i) preliminary pre-operative CT scans of each specimen, (ii) pre-dissection planning of the petrous apex removal and its quantification, (iii) petrous apex removal via endoscopic endonasal route, (iv) post-operative CT scans, (v) petrous apex removal via endoscopic transorbital route, and (v) final post-operative CT scan with quantitative analysis. Neuronavigation was used to guide all dissections. RESULTS: The two endoscopic minimally invasive pathways allowed a different visualization and perspective of the petrous apex, and its surrounding neurovascular structures. After both corridors were completed, a communication between the surgical pathways was highlighted, in a so-called connection area, surrounded by the following important neurovascular structures: anteriorly, the internal carotid artery and the Gasserian ganglion; laterally, the internal acoustic canal; superiorly, the abducens nerve, the trigeminal root, and the tentorium cerebelli; inferomedially, the remaining clivus and the inferior petrosal sinus; and posteriorly, the exposed area of the brainstem. Used in a combined fashion, such multiportal approach provided a total of 97% of petrous apex removal. In particular, the transorbital route achieved a mean of 48.3% removal in the most superolateral portion of the petrous apex, whereas the endonasal approach provided a mean of 48.7% bone removal in the most inferomedial part. The difference between the two approaches was found to be not statistically significant (p = 0.67). CONCLUSION: The multiportal combined endoscopic endonasal and transorbital approach to the petrous apex provides an overall bone removal volume of 97% off the petrous apex. In this paper, we highlighted that it was possible to uncover a common path between these two surgical pathways (endonasal and transorbital) in a so-called connection area. Potential indications of this multiportal approach may be lesions placed in or invading the petrous apex and petroclival regions that can be inadequately reached via transcranial paths or via an endonasal endoscopic route alone.

Endoscopic endo- and extra-orbital corridors for spheno-orbital region: anatomic study with illustrative case.

BACKGROUND AND OBJECTIVE: Management of selected spheno-orbital meningiomas via the endoscopic transorbital route has been reported. Surgical maneuverability in a narrow corridor as that offered by the orbit may be challenging. We investigate the additional use of an extra-orbital (EXO) path to be used in combination with the endo-orbital (EO) corridor. MATERIAL AND METHODS: Three human cadaveric heads (six orbits) were dissected at the Laboratory of Surgical Neuroanatomy at the University of Barcelona. The superior eyelid endoscopic transorbital approach was adopted, introducing surgical instruments via both corridors. Surgical freedom analysis was run to determine directionality of each corridor and to calculate the surgical maneuverability related to three anatomic targets: superior orbital fissure (SOF), foramen rotundum (FR), and foramen ovale (FO). We also reported of a 37-year-old woman with a spheno-orbital meningioma with hyperostosis of the lateral wall of the right orbit, treated with such combined endo-orbital and extra-orbital endoscopic approach. RESULTS: Combining both endo-orbital and extra-orbital corridors permitted a greater surgical freedom for all the targets compared with the surgical freedom of each corridor alone (EO + EXO to SOF: 3603.8 mm2 ± 2452.5 mm2; EO + EXO to FR: 1533.0 mm2 ± 892.2 mm2; EO + EXO to FO: 1193.9 mm2 ± 782.6 mm2). Analyzing the extra-orbital pathway, our results showed that the greatest surgical freedom was gained in the most medial portion of the considered area, namely the SOF (1180.5 mm2 ± 648.3 mm2). Regarding the surgical case, using both pathways, we gained enough maneuverability to nearly achieve total resection with no postoperative complications. CONCLUSION: An extra-orbital corridor may be useful to increase the instruments' maneuverability, during a pure endoscopic superior eyelid approach, and to reach the most medial portion of the surgical field from a lateral-to-medial trajectory. Further studies are needed to better define the proper indications for such strategy.

Endoscopic transorbital route to the petrous apex: a feasibility anatomic study.

BACKGROUND: While the subtemporal approach represents the surgical module milestone designed to reach the petrous apex, a novel ventral route, which is the superior eyelid endoscopic transorbital approach, has been proposed to access the skull base. Accordingly, we aimed to evaluate the feasibility of this route to the petrous apex, providing a qualitative and quantitative analysis of this relatively novel pathway. METHODS: Five human cadaveric heads were dissected at the Laboratory of Surgical NeuroAnatomy of the University of Barcelona. After proper dissection planning, anterior petrosectomy via the endoscopic transorbital route was performed. Specific quantitative analysis, as well as dedicated three-dimensional reconstruction, was done. RESULTS: Using the endoscopic transorbital approach, it was possible to reach the petrous apex with an average volume bone removal of 1.33 ± 0.21 cm3. Three main intradural spaces were exposed: cerebellopontine angle, middle tentorial incisura, and ventral brainstem. The first one was bounded by the origin of the trigeminal nerve medially and the facial and vestibulocochlear nerves laterally, the second extended from the origin of the oculomotor nerve to the entrance of the trochlear nerve into the tentorium free edge while the ventral brainstem area was hardly accessible through the straight, ventral endoscopic transorbital trajectory. CONCLUSION: This is the first qualitative and quantitative anatomic study concerning details of the lateral aspect of the incisura and ventrolateral posterior fossa reached via the transorbital window. This manuscript is intended as a feasibility anatomic study, and further clinical contributions are mandatory to confirm the effectiveness of this approach, defining its possible role in the neurosurgical armamentarium.

Endoscopic endonasal medial-to-lateral and transorbital lateral-to-medial optic nerve decompression: an anatomical study with surgical implications.

OBJECTIVE Different surgical routes have been used over the years to achieve adequate decompression of the optic nerve in its canal including, more recently, endoscopic approaches performed either through the endonasal corridor or the transorbital one. The present study aimed to detail and quantify the amount of bone removal around the optic canal, achievable via medial-to-lateral endonasal and lateral-to-medial transorbital endoscopic trajectories. METHODS Five human cadaveric heads (10 sides) were dissected at the Laboratory of Surgical Neuroanatomy of the University of Barcelona (Spain). The laboratory rehearsals were run as follows: 1) preliminary preoperative CT scans of each specimen, 2) anatomical endoscopic endonasal and transorbital dissections and Dextroscope-based morphometric analysis, and 3) quantitative analysis of optic canal bone removal for both endonasal and transorbital endoscopic approaches. RESULTS The endoscopic endonasal route permitted exposure and removal of the most inferomedial portion of the optic canal (an average of 168°), whereas the transorbital pathway allowed good control of its superolateral part (an average of 192°). Considering the total circumference of the optic canal (360°), the transorbital route enabled removal of a mean of 53.3% of bone, mainly the superolateral portion. The endonasal approach provided bone removal of a mean of 46.7% of the inferomedial aspect. This result was found to be statistically significant (p < 0.05). The morphometric analysis performed with the aid of the Dextroscope (a virtual reality environment) showed that the simulation of the transorbital trajectory may provide a shorter surgical corridor with a wider angle of approach (39.6 mm; 46.8°) compared with the simulation of the endonasal pathway (52.9 mm; 23.8°). CONCLUSIONS Used together, these 2 endoscopic surgical paths (endonasal and transorbital) may allow a 360° decompression of the optic nerve. To the best of the authors' knowledge, this is the first anatomical study on transorbital optic nerve decompression to show its feasibility. Further studies and, eventually, surgical case series are mandatory to confirm the effectiveness of these approaches, thereby refining the proper indications for each of them.