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Background and Objectives: Transorbital neuroendoscopic surgery (TONES) is continuously evolving and gaining terrain in approaching different skull base pathologies. The objective of this study was to present our methodology for introducing recording electrodes, which includes a new transconjunctival pathway, to monitor the extraocular muscle function during TONES., Methods: A translational observational study was performed from an anatomic demonstration focused on the transconjunctival electrode placement technique to a descriptive analysis in our series of 6 patients operated using TONES in association with intraoperative neurophysiologic monitoring of the oculomotor nerves from 2017 to 2023. The stepwise anatomic demonstration for the electrode placement and correct positioning in the target muscle was realized through cadaveric dissection. The descriptive analysis evaluated viability (obtention of the electromyography in each cranial nerve [CN] monitored), security (complications), and compatibility (interference with TONES)., Results: In our series of 6 patients, 16 CNs were correctly monitored: 6 (100%) CNs III, 5 (83.3%) CNs VI, and 5 (83.3%) CNs IV. Spontaneous electromyography was registered correctly, and compound muscle action potential using triggered electromyography was obtained for anatomic confirmation of structures (1 CN III and VI). No complications nor interference with the surgical procedure were detected., Conclusion: The methodology for introducing the recording electrodes was viable, secure, and compatible with TONES., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Objective: The endoscopic transorbital approach (ETOA) has been demonstrated to be a feasible ventral route to the petrous apex. Yet, it has been pointed to as a deep and narrow corridor for anterior petrosectomy; particularly, medialization of the instruments can become an issue when targeting the petroclival area. To overcome this limitation, an ETOA with orbital rim removal (ETOA-OR) has been suggested, but not de facto compared, with a transorbital approach without removal of the rim. This addition could augment the surgical exposure and freedom of movement when accessing the petrous apex area., Methods: Five human cadaveric heads (10 sides) were dissected. First, anterior petrosectomy was performed via a conventional ETOA (without orbital rim removal). Second, en bloc removal of the orbital rim was performed, with enlargement of the orbital craniectomy and, subsequently, further drilling of the medial petrous apex. Qualitative and quantitative comparisons are provided. An illustrative surgical case is also shown., Results: The transorbital route allowed the authors to perform an anterior petrosectomy in all specimens. The landmarks of bone removal are superposed onto those in the transcranial route. The ETOA-OR increased the volume of craniectomy (from 4.0 mL to 5.5 mL), the lateromedial angulation, and superoinferior angulation of the instruments within the petrous area. Thus, this approach improved the exposure of the medial petroclival area, allowing for an augmented petrosectomy (from 1.4 mL to 2.0 mL, 39.5% increase) and for increased maneuverability, both in the petrous area (from 44.1 cm2 to 76.5 cm2, 73.3% increase) and in the posterior fossa (from 20.2 cm2 to 52.0 cm2, 158% increase). The ETOA-OR was also pragmatically applied to treat a recurrent petroclival meningioma. Complete removal was achieved, the abducens nerve palsy improved, and the trigeminal neuralgia decreased in severity, yet still required medication., Conclusions: The authors provide the first formal anatomical comparison between the transorbital approach with preservation of the orbital rim and a transorbital approach with removal of the rim to access the petrous apex. In addition, an illustrative case is used as a proof of concept and feasibility. According to the authors' data, the ETOA-OR significantly improves surgical exposure and the surgeon's comfort in this deep region. The bony defect can be reconstructed to avoid cosmetic deformities, maintaining the minimally disruptive concept of transorbital surgery.

Background: Virtual reality-based learning of neuroanatomy is a new feasible method to explore, visualize, and dissect interactively complex anatomic regions. We provide a new interactive photorealistic three-dimensional (3D) model of sellar region microsurgical anatomy that allows side-by-side views of exocranial and endocranial surfaces to be explored, with the aim of assisting young neurosurgery residents in learning microsurgical anatomy of this complex region., Methods: Four head specimens underwent an endoscopic endonasal approach extended to the anterior and posterior skull base to expose the main bony anatomic landmarks of the sellar region. The same bony structures were exposed from a transcranial perspective. By using a photogrammetry method, multiple photographs from both endocranial and exocranial perspectives, different for angulations and depth, were captured, fused, and processed through dedicated software., Results: All relevant bony structures were clearly distinguishable in the 3D model reconstruction, which provides several benefits in neuroanatomy learning: first, it replicates bony structures with high degrees of realism, accuracy, and fidelity; in addition, it provides realistic spatial perception of the depth of the visualized structures and their anatomic relationships; again, the 3D model is interactive and allows a 360° self-guided tour of the reconstructed object, so that the learner can read the bones and their anatomic relationship from all desired points of view., Conclusions: Detailed knowledge of key surgical landmarks representing keyholes and/or anatomic structures to not violate is mandatory for safer surgery, especially for a complex region such as the skull base. Highly accurate virtual and functional neurosurgical models, such as photogrammetry, can generate a realistic appearance to further improve surgical simulators and learn neuroanatomy., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The cavernous sinus (CS) is a demanding surgical territory, given its deep location and the involvement of multiple neurovascular structures. Subjected to recurrent discussion on the optimal surgical access, the endoscopic transorbital approach has been recently proposed as a feasible route for selected lesions in the lateral CS. Still, for this technique to safely evolve and consolidate, a comprehensive anatomical description of involved cranial nerves, dural ligaments, and arterial relations is needed., Objective: Detailed anatomical description of the CS, the course of III, IV, VI, and V cranial nerves, and C3-C7 segments of the carotid artery, all described from the ventrolateral endoscopic transorbital perspective., Methods: Five embalmed human cadaveric heads (10 sides) were dissected. An endoscopic transorbital approach with lateral orbital rim removal, anterior clinoidectomy, and petrosectomy was performed. The course of the upper cranial nerves was followed from their apparent origin in the brainstem, through the middle fossa or cavernous sinus, and up to their entrance to the orbit. Neuronavigation was used to follow the course of the nerves and to measure their length of surgical exposure., Results: The transorbital approach allowed us to visualize the lateral wall of the CS, with cranial nerves III, IV, V1-3, and VI. Anterior clinoidectomy and opening of the frontal dura and the oculomotor triangle revealed the complete course of the III nerve, an average of 37 (±2) mm in length. Opening the trigeminal pore and cutting the tentorium permitted to follow the IV nerve from its course around the cerebral peduncle up to the orbit, an average of 54 (±4) mm. Opening the infratrochlear triangle revealed the VI nerve intracavernously and under Gruber's ligament, and the extended petrosectomy allowed us to see its cisternal portion (27 ± 6 mm). The trigeminal root was completely visible and so were its three branches (46 ± 2, 34 ± 3, and 31 ± 1 mm, respectively)., Conclusion: Comprehensive anatomic knowledge and extensive surgical expertise are required when addressing the CS. The transorbital corridor exposes most of the cisternal and the complete cavernous course of involved cranial nerves. This anatomical article helps understanding relations of neural, vascular, and dural structures involved in the CS approach, essential to culminating the learning process of transorbital surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer [FC] declared a past co-authorship with the authors [AS and AP-G] to the handling editor., (Copyright © 2024 Mosteiro, Codes, Tafuto, Manfrellotti, Torales, Enseñat, Di Somma and Prats-Galino.)

Objective: The endoscopic superior eyelid transorbital approach has garnered significant consideration and gained popularity in recent years. Detailed anatomical knowledge along with clinical experience has allowed refinement of the technique as well as expansion of its indications. Using bone as a consistent reference, the authors identified five main bone pillars that offer access to the different intracranial targeted areas for different pathologies of the skull base, with the aim of enhancing the understanding of the intracranial areas accessible through this corridor., Methods: The authors present a bone-oriented review of the anatomy of the transorbital approach in which they conducted a 3D analysis using Brainlab software and performed dry skull and subsequent cadaveric dissections., Results: Five bone pillars of the transorbital approach were identified: the lesser sphenoid wing, the sagittal crest (medial aspect of the greater sphenoid wing), the anterior clinoid, the middle cranial fossa, and the petrous apex. The associations of these bone targets with their respective intracranial areas are reported in detail., Conclusions: Identification of consistent bone references after the skin incision has been made and the working space is determined allows a comprehensive understanding of the anatomy of the approach in order to safely and effectively perform transorbital endoscopic surgery in the skull base.

Pheochromocytomas (PCCs) and Paragangliomas (PGLs), commonly known as PPGLs to include both entities, are rare neuroendocrine tumors that may arise in the context of hereditary syndromes or be sporadic. However, even among sporadic PPGLs, identifiable somatic alterations in at least one of the known susceptibility genes can be detected. Therefore, about 3/4 of all PPGL patients can be assigned to one of the three molecular clusters that have been identified in the last years with difference in the underlying pathogenetic mechanisms, biochemical phenotype, metastatic potential, and prognosis. While surgery represents the mainstay of treatment for localized PPGLs, several therapeutic options are available in advanced and/or metastatic setting. However, only few of them hinge upon prospective data and a cluster-oriented approach has not yet been established. In order to render management even more personalized and improve the prognosis of this molecularly complex disease, it is undoubtable that genetic testing for germline mutations as well as genome profiling for somatic mutations, where available, must be improved and become standard practice. This review summarizes the current evidence regarding diagnosis and treatment of PPGLs, supporting the need of a more cluster-specific approach in clinical practice.

The endoscopic superior eyelid transorbital approach has emerged as a notable and increasingly utilized surgical technique in recent years. This chapter presents an overview of the approach, tracing its historical development and highlighting its growing acceptance within the skull base community.Beginning with an introduction and historical perspective, the chapter outlines the evolution of the transorbital approach, shedding light on its origins and the factors driving its adoption. Subsequently, a comprehensive exploration of the anatomic bone pillars and intracranial spaces accessible via this approach is provided. Hence, five bone pillars of the transorbital approach were identified, namely the lesser sphenoid wing, the anterior clinoid, the sagittal crest, the middle cranial fossa, and the petrous apex. A detailed correlation of those bone targets with respective intracranial areas has been reported.Furthermore, the chapter delves into the practical application of the technique through a case example, offering insights into its clinical utility, indications, and limitations., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

A series of 5 patients treated with the fourth ventricle to spinal subarachnoid space stent (FVSSS) is presented. Indication for surgery, surgical technique, pre-operative and post-operative images, and outcome are analyzed. A systematic review of the pertinent literature has also been performed. This is a retrospective cohort review of a series of 5 consecutive patients with refractory syringomyelia who underwent a fourth ventricle to spinal subarachnoid space shunt surgery. The surgical indication was based on the presence of refractory syringomyelia in patients already treated for Chiari malformation or in patients who developed scarring at the level of the outlets of the fourth ventricle following posterior fossa tumor surgery. The mean age at FVSSS was 11.30 ± 5.88 years. Cerebral MRI revealed crowded posterior fossa, with a membrane at the level of the foramen of Magendie. Spinal MRI showed syringomyelia in all patients. Before surgery, the averages of the craniocaudal and the anteroposterior diameter were 22.66 and 1.01 cm, respectively, whereas the volume was 28.16 cm 3 . The post-operative period was uneventful in 4 out of 5 patients; one child died on the 1st post-operative day due to complications unrelated to surgery. In remaining cases, syrinx marked improvement. The post-operative volume was 1.47 cm 3 with an overall reduction of 97.61%. With regard to literature, 7 articles with a total of 43 patients were analyzed. After FVSSS, syringomyelia reduction was observed in 86.04% of cases. Three patients underwent reoperation due to syrinx recurrence. Four patients presented a catheter displacement, one a wound infection and meningitis and one CSF leak requiring placement of a lumbar drain. FVSSS is highly effective in restoring CSF dynamics, with dramatic improvement of syringomyelia. In all our cases, the volume of the syrinx was reduced by at least 90%, with improvement/resolution of accompanying symptomatology. This procedure should be reserved to patients in which other causes of gradient pressure between the fourth ventricle and subarachnoid space are excluded, for example, tetraventricular hydrocephalus. Surgical procedure is not simple, because it requires meticulous microdissection of cerebello-medullary fissure and upper cervical spine, in already operated patients. To avoid migration of the stent, it should be carefully sutured to the dura mater or thick arachnoid membrane., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established., Background: A search of peer-reviewed and English articles reporting on 177Lu-DOTATATE and 90Y-DOTATOC efficacy was performed through Medline and Scopus. A subsequent meta-analysis was performed to evaluate the pooled effect size on disease control rate (DCR) with PRRT. Secondary endpoints were description of patients' genetic characteristics, hematologic toxicity, and time-to-outcome. The pooled effect was estimated with both a mixed-effects model and a random-effects model., Results: Twelve studies met the criteria for this meta-analysis: ten with 177Lu- and two with 90Y-PRRTs (213 patients). The largest one included 46 patients. Median ages ranged from 32.5 to 60.4 years. When reported, mutations of SDHB were the most frequent genetic alterations. The pooled DCRs were 0.83 (95% CI: 0.75-0.88) and 0.76 (95% CI: 0.56-0.89) for 177Lu- and 90Y-PRRT, respectively. The pooled DCR for PRRT was 0.81 (95% CI: 0.74-0.87)., Conclusions: We report an updated and solid estimate of DCR achieved with 177Lu- and 90Y-PRRT in PCCs and PGLs, showing that these therapies can be considered in the multidisciplinary treatment of PCCs and PGLs as alternatives to I-131 MIBG and chemotherapy., Competing Interests: The authors declare no conflict of interest.

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O 6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.

Nucleocytoplasmic transport has been found dysregulated in many types of cancer and is often described as a poor prognostic factor. Specifically, Exportin-1 (XPO1) has been found overexpressed in many tumors and has become an attractive target in molecular oncology and therapeutics development. The selective inhibitor of nuclear export, Selinexor, is one of the most scientifically interesting drugs that targets XPO1 in clinical development. In this review, we summarized the most relevant preclinical and clinical results achieved for non-solid tumors, sarcomas, and other kind of solid tumors.

Tumors of nasal cavity and paranasal sinuses (TuNSs) are rare and heterogeneous malignancies, presenting different histological features and clinical behavior. We reviewed the literature about etiology, biology, and clinical features of TuNSs to define pathologic features and possible treatment strategies. From a diagnostic point of view, it is mandatory to have high expertise and perform an immunohistochemical assessment to distinguish between different histotypes. Due to the extreme rarity of these neoplasms, there are no standard and evidence-based therapeutic strategies, lacking prospective and large clinical trials. In fact, most studies are retrospective analyses. Surgery represents the mainstay of treatment of TuNSs for small and localized tumors allowing complete tumor removal. Locally advanced lesions require more demolitive surgery that should be always followed by adjuvant radio- or chemo-radiotherapy. Recurrent/metastatic disease requires palliative chemo- and/or radiotherapy. Many studies emphasize the role of specific genes mutations in the development of TuNSs like mutations in the exons 4-9 of the TP53 gene, in the exon 9 of the PIK3CA gene and in the promoter of the TERT gene. In the near future, this genetic assessment will have new therapeutic implications. Future improvements in the understanding of the etiology, biology, and clinical features of TuNSs are warranted to improve their management.