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Introduction: Orbital surgery has always been disputed among specialists, mainly neurosurgeons, otorhinolaryngologists, maxillofacial surgeons and ophthalmologists. The orbit is a borderland between intra- and extracranial compartments; Krönlein's lateral orbitotomy and the orbitozygomatic infratemporal approach are the historical milestones of modern orbital-cranial surgery. Research question: Since its first implementation, endoscopy has significantly impacted neurosurgery, changing perspectives and approaches to the skull base. Since its first application in 2009, transorbital endoscopic surgery opened the way for new surgical scenario, previously feasible only with extensive tissue dissection. Material and methods: A PRISMA based literature search was performed to select the most relevant papers on the topic. Results: Here, we provide a narrative review on the current state and future trends in endoscopic orbital surgery. Discussion and conclusion: This manuscript is a joint effort of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Background: Endoscopic transorbital approach (eTOA) has been recently proposed as an alternative skull base approach. However, its feasibility for deeper lesions can be hampered by a reduced surgical maneuverability. Aim of this study is to consider how its extension through orbital rim resection can overcome this limitation, and to compare two different techniques for its removal., Methods: Both sides of seven cadaveric fresh frozen head were dissected. Three different surgical approaches were performed consequentially (standard eTOA, its expansion with lateral orbital rim hinge removal, and with its complete resection). Distance to target and angle of attack have been measured for superior orbital fissure (SOF), lateral wall of cavernous sinus (LWCS), anterior clinoid process (ACP), foramen rotudum (FR) and foramen ovale (FO)., Results: The angle of attack to the SOF (p = 0.01), to the LWCS (p = 0.001), to the ACP (p = 0.01), to the FR (p = 0.01) and to FO (p = 0.01) resulted larger in extended approaches with orbital rim resection, as well as the distance to target of LWCS (p = 0.04). Particularly, we observed that hinge lateral orbital rim removal improved the angle of attack to SOF (p = 0.02), APC (p = 0.01), FR (p = 0.01 and FO (p = 0.01) in comparison to the standard eTOA., Conclusion: Our study confirms that the lateral orbital rim resection could significantly expand the surgical room and the instruments maneuverability for the considered target skull base targets. Its hinge removal could balance the clinical outcome with the increase of the angles of attack for the more medial and deeper structures., Competing Interests: Declarations. Ethics approval: Ethics committee approval was waived because this study was performed in de-identified cadaveric specimens in adherence with institutional regulations governing the use of human cadaveric tissues. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The diagnosis of pituitary microprolactinomas is often obscured by relatively low levels of elevated prolactin compared to macroprolactinomas. This may lead to varying patterns of medical therapy versus observation. We sought to correlate prolactin levels in suspected microprolactinomas with tumor volumes and clinical outcomes. This was a multicenter retrospective study of patients with pituitary microadenomas with baseline prolactin levels > 18ng/ml for males and > 30ng/ml for females. A linear-mixed model was used to depict changes in tumor volume over time. There were 65 patients with a mean tumor volume of 95.9mm 3 and mean prolactin level of 59.4ng/ml. There were significantly higher prolactin levels in patients with tumors above the mean volume versus below (74.0 versus 53.4ng/ml, p = 0.027). 26 patients were observed, 31 were treated with anti-dopaminergic therapy, and 8 had surgery. There were significantly greater baseline prolactin levels for patients who were treated surgically (mean 86.4ng/ml) than those treated medically (mean 61.7 g/ml) or observed (mean 48.5ng/ml) (p = 0.02). Among the 26 patients who were surveilled, 13 patients demonstrated spontaneous tumor shrinkage, 12 remained stable, and 1 patient's tumor grew but was lost to follow-up. Linear mixed modeling demonstrated a statistically significant rate of tumor shrinkage over time of 3.67mm 3 /year (p = 0.03). When analyzing patients who were observed versus those requiring surgery after initially being surveilled, there were significantly greater baseline PRL/volume ratios in surgical patients versus those observed (8.1 ng/ml/mm 3 versus 2.4 ng/ml/mm 3 , p = 0.025). Suspected microprolactinomas may demonstrate more convincingly elevated prolactin levels when measuring over 95.9mm 3 . Tumors with baseline prolactin levels over 50ng/ml may be more inclined to undergo medical treatment. In tumors with levels below 50ng/ml, it may be reasonable to undergo surveillance as these tumors tend to spontaneously shrink over time. In tumors that are surveilled, an elevated baseline PRL/volume ratio of > 8 ng/ml/mm 3 may be indicate serial tumor growth that may necessitate medical and/or surgical intervention., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pituitary tumors present heterogeneous biochemical, clinico-radiological, and histological features. Although histologically benign, a non-negligible number of cases present an unpredictable aggressive behavior with local invasiveness, partial/complete resistance to treatment and/or recurrence after surgery, and, rarely, metastasize, overall leading to a significant increase of morbidity, and, thus, requiring skilled multidisciplinary management in referral Centers. Histopathological diagnosis is essential to stratify cancer patient risk and uniform follow-up among Centers. Classification of pituitary neoplasia is continuously evolving in relation to the increased knowledge of mechanisms underlying adenohypophyseal cell tumorigenesis, and the attempts of combining clinico-radiological, biochemical, intraoperative, histological, and molecular elements, with the aim of identifying aggressive forms through. An integrated standardized histopathological report has been proposed in 2019 by the European Pituitary Pathology Group, based on the indications of the 2017 WHO classification of pituitary tumors. The last edition of the WHO Classification of Central Nervous System Tumors and of Endocrine and Neuroendocrine Tumors brought substantial novelties: 1) the replacement of the term "adenoma" with "Pituitary Neuroendocrine Tumor" (PitNET), and of "carcinoma" with "metastatic PitNET," and the consequent ICD-11 recoding from benign to malignant disease; and 2) the pivotal role of lineage restricted pituitary transcription factors for histological typing and subtyping. However, this approach does not reflect the spectrum of tumor phenotypes based on hormone secretion, nor include molecular features. Efforts of interdisciplinary groups of pituitary experts should be strongly encouraged to better understand factors involved in PitNETs evolution and, consequently, standardize diagnosis and reporting based on the most recent knowledges, essential to stratify cancer patient risk and uniform follow-up among centers.

Introduction: Intraoperative fluorescence guidance is a well-established surgical adjunct in high-grade glioma surgery. In contrast, the clinical use of such dyes and technology has been scarcely reported in skull base surgery., Research Question: We aimed to systematically review the clinical applications of different fluorophores in both open and endonasal skull base surgery., Material and Methods: We performed a systematic review and discussed the current literature on fluorescence guidance in skull base surgery., Results: After a comprehensive literature search, 77 articles on skull base fluorescence guidance were evaluated. A qualitative analysis of the articles is presented, discussing clinical indications and current controversies. The use of intrathecal fluorescein was the most frequently reported in the literature. Beyond that, 5-ALA and ICG were two other fluorescent dyes most extensively discussed, with some experimental fluorophore applications in skull base surgery., Discussion and Conclusion: Intraoperative fluorescence imaging can serve as an adjunct technology in skull base surgery. The scope of initial indications of these fluorophores has expanded beyond malignant glioma resection alone. We discuss current use and controversies and present an extensive overview of additional indications for fluorescence imaging in skull base pathologies. Further quantitative studies will be needed in the future, focusing on tissue selectivity and time-dependency of the different fluorophores currently commercially available, as well as the development of new compounds to expand applications and facilitate skull base surgeries., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eric Suero Molina reports a relationship with Carl Zeiss Meditec AG that includes: funding grants. Walter Stummer has received speaker and consultant fees from Medac, Carl Zeiss Meditec AG, Leica Microsystems, Photonamic, and NXDC and funding grants from Carl Zeiss Meditec AG. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Intraorbital foreign bodies (IOFBs) represent a clinical challenge: surgical management can be controversial and different strategies have been proposed. When removal is recommended, depending on the location and nature of the IOFB both external and endoscopic approaches have been proposed, with significantly different surgical corridors to the orbit and different morbidities., Methods: We performed a literature review of cases of IOFBs that received exclusive endoscopic transnasal surgical treatment to evaluate the role of this surgery in these occurrences. We also present a case of an intraorbital intraconal bullet that was successfully removed using an endoscopic transnasal approach with good outcomes in terms of ocular motility and visual acuity., Results: A limited number of cases of IOFBs have been treated with an exclusive endoscopic transnasal approach. When in the medial compartment, this approach appears to be safe and effective. In our case, two months after surgery the patient showed complete recovery with no significant long-term sequelae., Conclusions: When feasible, an endoscopic transnasal approach for intraorbital foreign bodies represents a valid surgical technique with optimal outcomes and satisfactory recovery., (Copyright © 2024 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

The authors present the life and art of Giuseppe Dagnini, a renowned Italian physician who was born in Bologna in 1866. He was the chief of the Maggiore Hospital in Bologna and authored valuable scientific works on the trigemino-cardiac reflex which is still applied in modern clinical practice. Dr. Dagnini firstly described the reflex in 1908 postulating that stimulation of one of the 3 branches of the trigeminal nerve triggers the afferent pathway in lowering heart rate. The authors also provide a modern outlook on the clinical implications of the TCR in neurosurgery, neuroanesthesia, and other medical specialties., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/Objectives : Clivus metastases from distant neoplasms are uncommon occurrences both in clinical practice and the neurosurgical literature. Surgical management is debated, particularly about the role of surgery and the preferable approach. The aim of this study was to report our surgical experience and review the concerning literature. Methods : Our institutional registry was retrospectively reviewed, and patients who underwent surgical treatment for clival metastasis from 1998 to 2023 were included. A PRISMA systematic review of the literature was performed. Results : Four patients were enrolled, and all of them underwent an endoscopic endonasal approach (EEA). Three presented with cranial nerve (CN) VI palsy. The aim of surgery was biopsy in all cases. No complications were reported. Mean overall survival (OS) was 6 ± 1 months. The systematic review retrieved 27 papers reporting 39 patients who underwent the surgical treatment of clivus metastases. Most of them (79.5%) presented with CN palsies, and EEA was the preferred approach in 92.3% of the cases, to perform a biopsy in most patients (59%). Two hemorrhagic complications (5.1%) were reported, and the mean OS was 9.4 ± 5.6 months. Conclusions : Clival metastases are uncommonly observed, in most cases, during advanced stages of oncological disease. The aim of surgery should be the confirmation of diagnosis and symptomatic relief, balancing the risk-benefit ratio in a multidisciplinary context. EEA is the approach of choice, and it should be carried out in experienced tertiary skull base centers.

X-linked acrogigantism (X-LAG) is a rare form of pituitary gigantism that is associated with growth hormone (GH) and prolactin-secreting pituitary adenomas/pituitary neuroendocrine tumors (PitNETs) that develop in infancy. It is caused by a duplication on chromosome Xq26.3 that leads to the misexpression of the gene GPR101 , a constitutively active stimulator of pituitary GH and prolactin secretion. GPR101 normally exists within its own topologically associating domain (TAD) and is insulated from surrounding regulatory elements. X-LAG is a TADopathy in which the duplication disrupts a conserved TAD border, leading to a neo-TAD in which ectopic enhancers drive GPR101 over-expression, thus causing gigantism. Here we trace the full diagnostic and therapeutic pathway of a female patient with X-LAG from 4C-seq studies demonstrating the neo-TAD through medical and surgical interventions and detailed tumor histopathology. The complex nature of treating young children with X-LAG is illustrated, including the achievement of hormonal control using a combination of neurosurgery and adult doses of first-generation somatostatin analogs., Competing Interests: AD, GT, and AB hold a patent on GPR101 and its function US Patent No. 10,350,273, Treatment of Hormonal Disorders of Growth. The remaining 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., (Copyright © 2024 Caruso, Mazzatenta, Asioli, Costanza, Trivellin, Franke, Abboud, Hanson, Raverot, Pétrossians, Beckers, Cappa and Daly.)

Purpose: Intraoperative ultrasonography (ioUS) is an established tool for the real-time intraoperative orientation and resection control in intra-axial oncological neurosurgery. Conversely, reports about its implementation in the resection of vestibular schwannomas (VS) are scarce. The aim of this study is to describe the role of ioUS in microsurgical resection of VS., Methods: ioUS (Craniotomy Transducer N13C5, BK5000, B Freq 8 MHz, BK Medical, Burlington, MA, USA) is integrated into the surgical workflow according to a 4-step protocol (transdural preresection, intradural debulking control, intradural resection control, transdural postclosure). Illustrative cases of patients undergoing VS resection through a retrosigmoid approach with the use of ioUS are showed to illustrate advantages and pitfalls of the technique., Results: ioUS allows clear transdural identification of the VS and its relationships with surgically relevant structures of the posterior fossa and of the cerebellopontine cistern prior to dural opening. Intradural ioUS reliably estimates the extent of tumor debulking, thereby helping in the choice of the right moment to start peripheral preparation and in the optimization of the extent of resection in those cases where subtotal resection is the ultimate goal of surgery. Transdural postclosure ioUS accurately depicts surgical situs., Conclusion: ioUS is a cost-effective, safe, and easy-to-use intraoperative adjunctive tool that can provide a significant assistance during VS surgery. It can potentially improve patient safety and reduce complication rates. Its efficacy on clinical outcomes, operative time, and complication rate should be validated in further studies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma., Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies., Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost., Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that., Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources., (© 2024 The Authors.)

Introduction: Endoscopic endonasal approach (EEA) plays a central role in the treatment of GH-secreting pituitary adenomas (PAs)/pituitary neuroendocrine tumors (PitNETs), allowing to treat not only micro- or regular macro- PAs/PitNEts, but also more complex cases, otherwise requiring a transcranial or other open approaches., Materials and Methods: All consecutive cases of GH-secreting PAs/PitNETs treated by EEA from May 1998 to June 2023 at our Institution were included. Patients clinical, bio-chemical, and neuroradiological features were considered, as well the surgical approach adopted for each case and its related complications. Surgical and endocrinological was determined at 3 months follow-up., Results: Our series is composed of 356 patients (57.6% females, mean age: 47 ± 12.7 years old): 118 (33.1%) micro-, 180 (50.6%) regular macro- and 58 (16.3%) irregular/invasive PAs/PitNEts. Radical removal was achieved in 296 (83.1%) patients and biochemical control in 270 (75.8%) at 3 months follow-up. Better surgical results and higher hypersecretion remission rate were demonstrated for micro- and regular endo-/endosuprasellar PAs/PitNETs than for irregular ones (respectively p < 0.001 and p < 0.001). Higher complication and endocrinological function permanent worsening rates were observed in the group of tumors with a supradiaphragmatic extension., Conclusions: Our study confirmed the efficacy and safety of EEA in the short-term follow-up in patients with GH-secreting PAs/PitNETs. This approach has demonstrated to be highly versatile, allowing to tailor the surgery to each specific case, with the aim of obtaining the radical removal and consequently the biochemical remission with minimal complications, patients discomfort, or endocrinological sequelae in a large number of cases., (© 2024 S. Karger AG, Basel.)

Acromegaly is a rare disorder characterized by chronic hypersecretion of growth hormone (GH) and, consequently, of its mediator, insulin-like growth factor 1 (IGF-1), due in >95% of the cases to a GH-secreting pituitary adenoma (PA)/Pituitary Neuroendocrine Tumor (PitNET). PAs/PitNETs are extremely heterogeneous for clinical, biochemical, radiological, intra-operative, and histological features and, differently from other histologically benign lesions, can cause significant morbidity because of locally aggressive behavior, resistance/recurrence after treatment, and, although very rarely, metastasization. PAs/PitNETs' classification and nomenclature have consistently changed in the course of time, reflecting knowledges about their complex biology, with the aim of stratifying patient risk and, therefore, uniform therapeutic strategies. According to the last WHO Classification, based on pituitary transcription factors (i.e., Pit-1, TPIT, and SF-1), GH-secreting PAs/PitNETs pertain to the Pit-1-lineage. Several subtypes can be distinguished, i.e., somatotroph (sparsely and densely granulated), mixed (mammosomatotroph, mixed somatotroph-lactotroph, and acidophilic stem cell), and plurihormonal (mature and immature Pit-1 lineage), based on hormone staining at immunohistochemistry and granulation, with distinct clinical and radiological features. Unfortunately, this classification does not fully reflect the spectrum of tumor phenotypes, does not consider the presence of drug-target receptors (i.e., somatostatin), nor molecular features that, on the contrary, have been increasingly demonstrated to influence biological behavior. Therefore, efforts of pituitary expert of the various disciplines are still necessary to reach a more comprehensive and detailed PitNET stratification to improve patient care through precision medicine., (© 2024 S. Karger AG, Basel.)

Background: Brain stroke is a rare, life-threatening condition associated with pituitary apoplexy (PA), resulting from direct arterial occlusion due to mechanical compression secondary to the sudden enlargement of the pituitary adenoma, or to vessel vasospasm, induced by tumor hemorrhage., Case Report: We report the case of a 64-year-old woman with PA complicated by bilateral anterior circulation stroke due to critical stenosis of both anterior cerebral arteries (ACA). Despite the quick surgical decompression and consequent blood flow restoration, the neurological conditions of the patient did not improve and she died 18 days later. Ten other cases of anterior circulation stroke due to PA were retrieved in a systematic review of literature. Clinical and neuroradiological features of these patients and treatment outcome were assessed to suggest the most proper management., Conclusion: The onset of neurological symptoms suggestive for brain stroke in patients with PA requires performing an emergency Magnetic Resonance Imaging (MRI), including Diffusion-weighted and angiographic MR-sequences. The role of surgery in these cases is debated, however, transsphenoidal adenomectomy would permit us to decompress the ACA and restore blood flow in their territories. Although the prognosis of PA-induced anterior circulation stroke is generally poor, a timely diagnosis and treatment would be paramount for improving patient outcome., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Primary diffuse large B-cell lymphoma of the primary central nervous system (CNS-DLBCL) is an aggressive disease, with dismal prognosis despite the use of high-dose methotrexate-based polychemotherapy. Our study aimed to expand the biologic profiles of CNS-DLBCL and to correlate them with clinical/imaging findings to gain diagnostic insight and possibly identify new therapeutic targets. We selected 61 CNS-DLBCL whose formalin-fixed paraffin-embedded samples were available at first diagnosis. These were investigated by immunohistochemistry, cMYC rearrangements were explored by fluorescence in situ hybridization, and CNS-DLBCL mutated genes were evaluated by next-generation sequencing. CD10, BCL6, and IRF4 were observed in 16%, 83.6%, and 93% of cases, respectively. As typical of CNS lymphoma, 10 (16.4%) of 61 cases were classified as germinal center (GCB) type and 51 (83.6%) of 61 as non-germinal center (non-GCB) type according to the Hans algorithm. Double-expression status for BCL2 and cMYC was detected in 36 (59%) of 61 cases whereas 25 (41%) of 61 were non-DE. Rearrangement of the cMYC gene was detected in 2 cases, associated with BCL6 translocation only in 1 case MYD88, PIM1, CD79B, and TP53 were mutated in 54.5%, 53.5%, 30.2%, and 18.4% cases, respectively. Novel mutations not previously reported in CNS-DLBCL were found: AIP in 23.1%, PI3KCA in 15%, NOTCH1 in 11.4%, GNAS in 8.1%, CASP8 in 7.9%, EGFR in 6.4%, PTEN in 5.1, and KRAS in 2.6% of cases. Survival was significantly longer for patients with mutated MYD88 (8.7 months vs 1.7 months; log-rank test = 5.43; P = .020) and for patients with mutated CD79B (10.8 months vs 2.5 months; log-rank test = 4.64; P = .031). MYD88 and CD79B predicted a longer survival in patients affected by CNS-DLBCL. Notably, we identified novel mutations that enrich the mutational landscape of CNS-DLBCL, suggest a role of PTEN-PI3K-AKT and receptor tyrosine kinase-RAS-mitogen-activated protein kinase signaling in a subset of CNS-DLBCL, and provide new potential therapeutic targets., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Introduction  The endoscopic endonasal route has demonstrated to be the approach of choice for a large majority of clival chordomas (CCs). However, its results in elderly patients are under-evaluated in the literature. The aim of this study is to assess the surgical outcome for these patients, determining the factors associated with a larger tumor resection in this population. Materials and Methods  Our institutional database of CC has been retrospectively reviewed, to identify all cases over 65 years old, operated through an endoscopic endonasal approach (EEA). Preoperative clinical and radiological features were considered, as well as surgical results, morbidity, and patients' outcome at follow-up. Results  Out of our series of 143 endoscopic surgical procedures for CC, 34 (23.8%) were in patients older than 65 and 10 in older than 75 (7.0%). Gross tumor removal was achieved in 22 cases (64.7%). Complications consisted of 2 (5.9%) postoperative cerebrospinal leaks, 1 (2.9%) meningitis, 1 (2.9%) permanent cranial nerve VI palsy, 1 (2.9%) pneumonia, and 2 (5.9%) urinary infections. In 39.1% of cases, the preoperative ophthalmoplegia improved or resolved. Twenty-seven patients (79.4%) underwent radiation therapy. At follow-up (37.7 ± 44.9 months), 13 patients (38.2%) showed a recurrence/progression and 13 (38.3%) deceased. Conclusion  EEA can be a useful approach in elderlies, balancing the large tumor removal with an acceptable morbidity rate, even if higher than that for general CC population. However, patient selection remains crucial. A multidisciplinary evaluation is important to assess not only their medical conditions, but also their social and familiar conditions., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Introduction and Research Question: The use of an endoscope in skull base surgery provides a panoramic close-up view over the intracranial structures from multiple angles with excellent illumination, thus permitting greater extent of resection of tumors arising at sellar area, mostly represented by PitNet - Pituitary neuroendocrine tumors, with higher likelihood of preserving vital/intact gland tissue. For this refined specialty of neurosurgery, unique skills need to be acquired along a steep learning curve., Material and Methods: EANS (European Association of Neurosurgical Societies) skull base section panelists were enrolled and 11 completed the survey: the goal was to provide a consensus statement of the endoscopic endonasal approach for pituitary adenoma surgery., Results: The survey consisted of 44 questions covering demographics data (i.e., academic/non-academic center, case load, years of experience), surgical techniques (i.e., use of neuronavigation, preoperative imaging), and follow-up management., Discussion and Conclusions: In this paper we identified a series of tips and tricks at different phases of an endoscopic endonasal pituitary surgery procedure to underline the crucial steps to perform successful surgery and reduce complications: we took in consideration the principles of the surgical technique, the knowledge of the anatomy and its variations, and finally the importance of adjoining specialties experts., Competing Interests: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2023 The Authors.)

Background: Cavernous hemangioma represents a rare vascular malformation usually located in the cavernous sinus that could be exceptionally found purely in the intrasellar region. The clinical presentation of intrasellar cavernous hemangioma (ICH), frequently variable and unspecific, poses the patient at risk for misdiagnosis and the clinical consequences of suboptimal treatment. We present a case of ICH and describe the advanced magnetic resonance imaging (MRI) features that should direct toward the clinical suspicion of ICH., Case Presentation: An illustrative case of a 61-year-old man complaining of recurrent headaches and diagnosed with a sellar and parasellar lesion was reported and used as a cue to discuss MRI imaging sequences that may aid in the distinction of ICH from pituitary adenoma and other skull base lesions. Heterogeneous enhancement followed by intense homogeneous enhancement at the dynamic contrast-enhanced sequences ("fill-in" phenomenon), absence of blooming signs at the gradient recalled echo (GRE) T2*-weighted and/or susceptibility-weighted imaging (SWI) MRI sequences, and elevated apparent diffusion coefficient (ADC) values usually characterize ICH instead of pituitary adenoma., Conclusion: Advanced MRI imaging plays an invaluable role in the pre-operative characterization of skull base lesions. Although rare, skull base surgeons should be aware of the ICH in the differential diagnosis process in case of the intrasellar lesion, and a tailored MRI examination should be performed to direct the patient toward the safest and optimal treatment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A minimally invasive option of colloid cyst surgical treatment is endoscopic resection, well validated in various reports and clinical practice. A rare complication of the surgical treatment, previously reported only once in literature, is the entrapment of the lateral ventricle. In this study we aim to outline our experience in the management of this occurrence, hypothesizing possible etiopathogenetic causes., Methods: Among patients who underwent neuroendoscopic resection for a colloid cysts at our Institution between 2013 and 2022, cases who developed a postoperative lateral ventricle entrapment were retrospectively reviewed and included. Clinical history, imaging and treatment were reported., Results: Among 34 patients treated for a colloid cysts, two (5.9 %) patients developed an ipsilateral ventricular entrapment with dilation from two to five months after the resection. Both patients were substantially asymptomatic and neurologically intact, and therefore treated conservatively. One case underwent complete spontaneous radiological resolution one month later, and the other one has remained neurological asymptomatic at follow-up., Conclusions: Isolated asymptomatic ventricular entrapment with significant dilation after endoscopic colloid cyst resection is a rare occurrence which can be plausibly caused by scar tissue at the level of the foramen of Monro. Because they can have an indolent course with spontaneous resolution, conservative treatment is a viable option, with strict radiological and clinical follow - up. Given the rarity of the occurrence, further studies with larger cohorts are warranted to confirm the etiopathogenetic hypothesis and validate the clinical management., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Gross total resection (GTR), Biochemical Remission (BR) and restitution of a priorly disrupted hypothalamus pituitary axis (new improvement, IMP) are important factors in pituitary adenoma (PA) resection surgery. Prediction of these metrics using simple and preoperatively available data might help improve patient care and contribute to a more personalized medicine., Research Question: This study aims to develop machine learning models predicting GTR, BR, and IMP in PA resection surgery, using preoperatively available data., Material and Methods: With data from patients undergoing endoscopic transsphenoidal surgery for PAs machine learning models for prediction of GTR, BR and IMP were developed and externally validated. Development was carried out on a registry from Bologna, Italy while external validation was conducted using patient data from Zurich, Switzerland., Results: The model development cohort consisted of 1203 patients. GTR was achieved in 207 (17.2%, 945 (78.6%) missing), BR in 173 (14.4%, 992 (82.5%) missing) and IMP in 208 (17.3%, 167 (13.9%) missing) cases. In the external validation cohort 206 patients were included and GTR was achieved in 121 (58.7%, 32 (15.5%) missing), BR in 46 (22.3%, 145 (70.4%) missing) and IMP in 42 (20.4%, 7 (3.4%) missing) cases. The AUC at external validation amounted to 0.72 (95% CI: 0.63-0.80) for GTR, 0.69 (0.52-0.83) for BR, as well as 0.82 (0.76-0.89) for IMP., Discussion and Conclusion: All models showed adequate generalizability, performing similarly in training and external validation, confirming the possible potentials of machine learning in helping to adapt surgical therapy to the individual patient., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: the aim of this multicenter study is to preliminarily assess the role of the Endoscopic Endonasal Approach (EEA) in ultra-early (i.e., within 12 h) management of selected neurosurgical emergencies in terms of clinical and radiological outcomes., Methods: 26 patients affected by sellar/parasellar pathologies with rapid progression of symptoms were managed with EEA within 12 h from diagnosis in three Italian tertiary referral Centers from January 2016 to December 2019. Both clinical and radiological data have been collected preoperatively as well as post-operatively in order to perform retrospective analysis., Results: The average time from admission to the operating room was 5.5 h (±2.3). The extent of resection was gross-total in 20 (76.9%), subtotal in 6 (23.1%) patients. One patient experienced re-bleeding after a subtotal removal of a hemorrhagic lesion. Patients with a longer time from admission (>4 h) to the operatory room (OR) experienced stable impairment of the visual acuity ( p = 0.033) and visual field ( p = 0.029) in the post-operative setting., Conclusions: The Endoscopic Endonasal Approach represents a safe, effective technique that can be efficiently used with good results in the management of selected neurosurgical emergencies in centers with adequate experience.

Background: Hemorrhage is the most devastating complication of brain arteriovenous malformations (bAVMs), and to date, there is still concern about the needing for treatment in case of unruptured and asymptomatic bAVM. In fact, the morbidity and mortality of treatments may exceed that of the AVM's natural history. None of the classifications and scores for bAVM allows to predict the risk of bleeding. In this study, we aimed to identify the angio-architectural characteristics of brain AVMs associated with bleeding., Methods: We retrospectively evaluated all consecutive patients diagnosed with cerebral AVMs, between January 2010 and December 2019 from our prospective bAVM database. Univariate and multivariate logistic regression analysis were used to evaluate relationships between angio-architectural features of ruptured and unruptured bAVMs., Results: Of the 143 retrieved bAVMs, 65 were unruptured and 78 were ruptured. The univariate logistic regression analysis demonstrated statistically significant differences into angio-architectural features of unruptured and ruptured bAVMs. The multivariate logistic regression analysis fitted well ( p =.113) with a good discrimination capacity (ROC = 0.83) of three independent angio-architectural features mainly related to bleeding in bAVMs: a smaller diameter of the nidus ( p < .001), the absence of venous drainage alterations ( p = .047), of the presence of prenidal aneurysms ( p = .005)., Conclusions: In our study, several features resulted related to an increased probability of rupture for bAVMs, among which the more relevant were a small diameter of the nidus, the absence of venous drainage alterations, and the presence of prenidal aneurysms.

The role of the endoscopic transplanum-transtuberculum approach (ETTA) in the treatment of pituitary adenomas/PitNETs (PAs) is sparsely analyzed in the literature, and its use is still debated in the current practice. The aim of this study was to report our experience with this approach. Our institutional registry was retrospectively reviewed, and patients who underwent ETTA for a PA from 1998 to 2022 were included. Fifty-seven cases were enrolled over a time span of 25 years, corresponding to 2.4% of our entire PA caseload. Radical resection was achieved in 57.9% of cases, with re-do surgery ( p = 0.033) and vessel encasement/engulfment ( p < 0.001) as predictors of partial resection. CSF leak incidence stood at 8.8%, with higher BMI ( p = 0.038) as its only significant predictor. Partial or full improvement of the visual field deficits was achieved in 73.5% of cases. No surgical mortality was observed. According to our results, ETTA for the treatment of PAs is characterized by a satisfactory surgical outcome but with greater morbidity than the conventional endoscopic approach. Therefore, it should be reserved for the few selected cases otherwise unsuitable for the endoscopic trans-sphenoidal route, representing a valid alternative and an effective complementary route for the transcranial approach for these challenging PAs.

Introduction: The loss of SMARCB1/INI1 protein has been recently described in poorly differentiated chordoma, an aggressive and rare disease variant typically arising from the skull base., Methods: Retrospective study aimed at 1) examining the differential immunohistochemical expression of SMARCB1/INI1 in conventional skull base chordomas, including the chondroid subtype; 2) evaluating SMARCB1 gene deletions/copy number gain; and 3) analyzing the association of SMARCB1/INI1 expression with clinicopathological parameters and patient survival., Results: 65 patients (35 men and 30 women) affected by conventional skull base chordoma, 15 with chondroid subtype, followed for >48 months after surgery were collected. Median age at surgery was 50 years old (range 9-79). Mean tumor size was 3.6 cm (range 2-9.5). At immunohistochemical evaluation, a partial loss of SMARCB1/INI1 (>10% of neoplastic examined cells) was observed in 21 (32.3%) cases; the remaining 43 showed a strong nuclear expression. Fluorescence in situ hybridization (FISH) analysis was performed in 15/21 (71.4%) cases of the chordomas with partial SMARCB1/INI1 loss of expression. Heterozygous deletion of SMARCB1 was identified in 9/15 (60%) cases and was associated to copy number gain in one case; no deletion was found in the other 6 (40%) cases, 3 of which presenting with a copy number gain. No correlations were found between partial loss of SMARCB1/INI1 and the clinicopathological parameters evaluated (i.e., age, tumor size, gender, tumor size and histotype). Overall 5-year survival and 5-year disease-free rates were 82% and 59%, respectively. According to log-rank test analysis the various clinico-pathological parameters and SMARCB1/INI1 expression did not impact on overall and disease free-survival., Discussion: Partial loss of SMARCB1/INI1, secondary to heterozygous deletion and/or copy number gain of SMARCB1, is not peculiar of aggressive forms, but can be identified by immunohistochemistry in a significant portion of conventional skull base chordomas, including the chondroid subtype. The variable protein expression does not appear to correlate with clinicopathological parameters, nor survival outcomes, but still, it could have therapeutic implications., 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., (Copyright © 2023 Righi, Cocchi, Maioli, Zoli, Guaraldi, Carretta, Magagnoli, Pasquini, Melotti, Vornetti, Tonon, Mazzatenta and Asioli.)

Background: Transorbital neuroendoscopic surgery (TONES) comprises a group of approaches with indications expanding from orbital tumors to more complex skull base lesions. We analyzed the role of the endoscopic transorbital approach (eTOA) for spheno-orbital tumors, reporting the results of our clinical series and of a systematic review of the literature., Materials and Methods: All patients operated on from 2016 to 2022 at our institution for a spheno-orbital tumor through an eTOA were included in a clinical series, and a systematic review of the literature was performed., Results: Our series consisted of 22 patients (16 females, mean age 57 ± 13 years). Gross tumor removal was achieved in 8 patients (36.4%) after the eTOA and in 11 (50.0%) after a multistaged strategy combining the eTOA with the endoscopic endonasal approach. Complications included 1 chronic subdural hematoma and 1 permanent extrinsic ocular muscle deficit. Patients were discharged after 2.4 ± 1.3 days. The most common histotype was meningioma (86.4%). Proptosis improved in all cases, visual deficit in 66.6%, and diplopia in 76.9%. These results were confirmed by the review of the 127 cases reported in the literature., Conclusions: Despite its recent introduction, a significant number of spheno-orbital lesions treated with an eTOA are being reported. Its main advantages are favorable patient outcome and optimal cosmetic results, with minimal morbidity and quick recovery. This approach can be combined with other surgical routes or adjuvant therapies for complex tumors. However, it is a technically demanding procedure, requiring specific skills in endoscopic surgery, that should be reserved to dedicated centers., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Phospholipases are essential intermediaries that work as hydrolyzing enzymes of phospholipids (PLs), which represent the most abundant species contributing to the biological membranes of nervous cells of the healthy human brain. They generate different lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid, representing key elements of intra- and inter-cellular signaling and being involved in the regulation of several cellular mechanisms that can promote tumor progression and aggressiveness. In this review, it is summarized the current knowledge about the role of phospholipases in brain tumor progression, focusing on low- and high-grade gliomas, representing promising prognostic or therapeutic targets in cancer therapies due to their influential roles in cell proliferation, migration, growth, and survival. A deeper understanding of the phospholipases-related signaling pathways could be necessary to pave the way for new targeted therapeutic strategies.

Introduction: and Research Question: Invasive growth of meningiomas into CNS tissue is rare but of prognostic significance. While it has entered the WHO classification as a stand-alone criterion for atypia, its true prognostic impact remains controversial. Retrospective analyses, on which the current evidence is based, show conflicting results. Discordant findings might be explained by different intraoperative sampling methodologies., Material and Methods: To assess the applied sampling methods in the light of the novel prognostic impact of CNS invasion, an anonymous survey was designed and distributed via the EANS website and newsletter. The survey was open from June 5th until July 15th, 2022., Results: After exclusion of 13 incomplete responses, 142 (91.6%) datasets were used for statistical analysis. Only 47.2% of participants' institutions utilize a standardized sampling method, and 54.9% pursue a complete sampling of the area of contact between the meningioma surface and CNS tissue. Most respondents (77.5%) did not change their sampling practice after introduction of the new grading criteria to the WHO classification of 2016. Intraoperative suspicion of CNS invasion changes the sampling for half of the participants (49.3%). Additional sampling of suspicious areas of interest is reported in 53.5%. Dural attachment and adjacent bone are more readily sampled separately if tumor invasion is suspected (72.5% and 74.6%, respectively), compared to meningioma tissue with signs of CNS invasion (59.9%)., Discussion and Conclusions: Intraoperative sampling methods during meningioma resection vary among neurosurgical departments. There is need for a structured sampling to optimize the diagnostic yield of CNS invasion., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: The measurement of optic nerve sheath diameter (ONSD) as a non-invasive method of estimating intracranial pressure has been widely reported in the literature. However, few studies have evaluated the accuracy of magnetic resonance imaging (MRI) in assessing ONSD measurements, although it is considered a very reliable method, it is not easily repeatable, expensive and is not readily available bedside. Herein, an assessment of the intra- and inter-rater reliability of ONSD assessment using MRI was conducted., Methods: A consecutive, prospective cohort of patients with suspected idiopathic normal-pressure hydrocephalus was analyzed. ONSD MRI measurements of the transverse and sagittal diameters at a distance of 3 mm behind the papilla were evaluated twice each by two expert neuroradiologists. The correlations between MRI examiners were calculated using the concordance correlation coefficient (CCC)., Results: Fifty patients were included in the study. ONSD MRI average measurements were substantially higher than clinically expected (>5 mm). Considering intra-rater concordance, only one of the two neuroradiologists achieved an excellent score at CCC. Only a moderate inter-observer CCC for MRI assessment was found at all diameters., Conclusions: The use of a widespread MRI sequence (3D T1) to measure ONSD is not an accurate method since it may overestimate measurements and is dependent upon an operator.

The anterior optic pathway (AOP) is a system of three structures (optic nerves, optic chiasma, and optic tracts) that convey visual stimuli from the retina to the lateral geniculate nuclei. A successful reconstruction of the AOP using tractography could be helpful in several clinical scenarios, from presurgical planning and neuronavigation of sellar and parasellar surgery to monitoring the stage of fiber degeneration both in acute (e.g., traumatic optic neuropathy) or chronic conditions that affect AOP structures (e.g., amblyopia, glaucoma, demyelinating disorders or genetic optic nerve atrophies). However, its peculiar anatomy and course, as well as its surroundings, pose a serious challenge to obtaining successful tractographic reconstructions. Several AOP tractography strategies have been adopted but no standard procedure has been agreed upon. We performed a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines in order to find the combinations of acquisition and reconstruction parameters that have been performed previously and have provided the highest rate of successful reconstruction of the AOP, in order to promote their routine implementation in clinical practice. For this purpose, we reviewed data regarding how the process of anatomical validation of the tractographies was performed. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias and thus the study quality We identified thirty-nine studies that met our inclusion criteria, and only five were considered at low risk of bias and achieved over 80% of successful reconstructions. We found a high degree of heterogeneity in the acquisition and analysis parameters used to perform AOP tractography and different combinations of them can achieve satisfactory levels of anterior optic tractographic reconstruction both in real-life research and clinical scenarios. One thousand s/mm 2 was the most frequently used b value, while both deterministic and probabilistic tractography algorithms performed morphological reconstruction of the tract satisfactorily, although probabilistic algorithms estimated a more realistic percentage of crossing fibers (45.6%) in healthy subjects. A wide heterogeneity was also found regarding the method used to assess the anatomical fidelity of the AOP reconstructions. Three main strategies can be found: direct visual direct visual assessment of the tractography superimposed to a conventional MR image, surgical evaluation, and computational methods. Because the latter is less dependent on a priori knowledge of the anatomy by the operator, computational methods of validation of the anatomy should be considered whenever possible., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Differential diagnosis of primary and secondary hyperthyroidism can be challenging. Moreover, although extremely rare, the two conditions can coexist., Case Presentation: A 58-year-old woman presented with symptoms of thyrotoxicosis, gradual changes in face shape, headache and progressive enlargement of hands and feet in the last year. When she was 46 years old, she was diagnosed with Graves' disease, and treated with 4-year methimazole therapy. Since 2016, a progressive increase of free-T4 and free-T3 with normal-TSH and positive TrAb was noticed., Results: At biochemical examination, fT3 was 5.3pg/ml (n. v. 2.5 - 3.9 pg/ml), fT4 was 20.6 pg/ml (n.v 6-12 pg/ml), IGF1 was 698 ng/ml (57 - 240 ng/ml*), GH (basally and after OGTT), and prolactin were significantly increased; while TSH was 1.8 (n.v. 0.35-4.0 mcUI/ml). A pituitary MRI demonstrated a large sellar tumor with suprasellar extension. The patient underwent endoscopic transsphenoidal surgery. Histological examination revealed a plurihormonal (GH-PRLTSH- secreting) PIT-1-positive pituitary adenoma/pituitary neuroendocrine tumor (PitNET). At 3- month follow-up, the pituitary function was normal, and no residual tumor was detected at the MRI., Conclusion: We report a rare case of Graves' disease coexisting with a plurihormonal PIT-1-positive pituitary adenoma/PitNET., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Recently, endoscopic approaches for orbital lesions have been proposed. Their results seem promising; however, orbital surgery remains challenging with possible significant morbidity, mostly because of orbital structures manipulation. Ultrasonography is an innovative intraoperative imaging technique that can assist the surgeon in these approaches., Objective: To assess the role of intraoperative ultrasound (IOUS) in endoscopic orbital surgery., Methods: All consecutive patients with orbital tumors operated in our institution through an endoscopic approach with IOUS have been prospectively collected from 2019 to May 2021., Results: Fifteen patients were included. Based on tumor location, evaluated on preoperative MRI, the endoscopic endonasal approach was preferred in 7 tumors in medial quadrants while the endoscopic transpalpebral in 8 lateral ones. During surgery, IOUS allowed us to identify the tumors and the most relevant anatomic structures in all cases. Time spent for IOUS preparation before the first scan was 8 ± 6 minutes on average, and each intraoperative scan took approximately 30 to 120 seconds. Gross tumor removal was achieved in 8 patients, subtotal in 3, while in 4 patients, surgery was limited to a biopsy. No surgical complications were observed., Conclusion: IOUS has allowed us to localize the lesion and to identify the straighter surgical corridor and assess the tumor resection, effectively helping the surgeon and potentially reducing operative complications. This tool provides a real-time image, not affected by the orbital structures shift, which can be dynamically assessed multiple times during surgery. However, it is hampered by the need of specific training and possible artifacts., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Introduction: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered., Methods: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations., Results: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide., Conclusion: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To profile clinically non-aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)-post-transcriptional regulators and therapy targets., Design: Retrospective observational study., Patients and Measurements: A total of 64 non-aggressive and 41 aggressive PAs/PitNETs and 6 pituitary carcinomas treated by endoscopic surgery with ≥1-year follow-up were included. Somatic mutations of 17 genes and DNA methylation of 22 genes were assessed. Ten normal pituitaries were used as control., Results: We found at least one mutation in 17 tumours, including 6/64 non-aggressive, 10/41 aggressive PAs/PitNETs, and 1/6 pituitary carcinoma. AIP (N = 6) was the most frequently mutated gene, followed by NOTCH (4), and TP53 (3). Hypermethylation of PARP15, LINC00599, ZAP70 was more common in aggressive than non-aggressive PAs/PITNETs (p &lt; .05). Lower levels of methylation of AIP, GNAS and PDCD1 were detected in aggressive PAs/PITNETs than non-aggressive ones (p &lt; .05). For X-linked genes, males presented higher level of methylation of FLNA, UXT and MAGE family (MAGEA11, MAGEA1, MAGEC2) genes in aggressive vs. non-aggressive PAs/PITNETs (p &lt; .05). In pituitary carcinomas, methylation of autosomal genes PARP15, LINC00599, MIR193 and ZAP70 was higher than in PAs/PITNETs, while X-linked genes methylation level was lower., Conclusions: Somatic mutations and methylation levels of genes involved in cell proliferation/differentiation, miRNA/LncRNA-post-transcriptional regulators and targets of antineoplastic therapies are different in non-aggressive and in aggressive PAs/PitNETs. Methylation profile also varies according to gender. Combined genetic-epigenetic analysis, in association with clinico-radiological-pathological data, may be of help in predicting PA/PitNET behaviour., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Introduction: Hyperprolactinemia has been proven to induce hypogonadism and metabolic derangements in both genders, while the consequences of prolactin (PRL) deficiency have been poorly investigated., Areas Covered: To systematically review and analyze data from clinical studies focusing on the metabolic consequences of abnormally high prolactin levels (HPRL) and low prolactin levels (LPRL). In addition, data from preclinical studies about underlying pathophysiological mechanisms were summarized and discussed., Expert Opinion: PRL contributes to providing the correct amount of energy to support the mother and the fetus/offspring during pregnancy and lactation, but it also has a homeostatic role. Pathological PRL elevation beyond these physiological conditions, but also its reduction, impairs metabolism and body composition in both genders, increasing the risk of diabetes and cardiovascular events. Hence, hypoprolactinemia should be avoided as much as possible during treatment with dopamine agonists for prolactinomas. Patients with hypoprolactinemia, because of endogenous or iatrogenic conditions, deserve, as those with hyperprolactinemia, careful metabolic assessment.

Objective: The endoscope and exoscope are gaining momentum as alternative visualization tools in the neurosurgical field, trying to overcome the limitations of an operative microscope and support minimally invasive approaches. However, few case series are available in the literature regarding their use in skull base surgery, especially in combined assisted resection, and their usefulness still needs to be proved., Methods: An illustrative case to present the feasibility and minimally invasive advantages of a combined exoscopic- and endoscopic-assisted resection is reported., Results: A 22-year-old man presented with a history of seizures and dizziness. Brain imaging showed a lesion involving the anteromedial middle fossa invading the interpeduncular cistern and impinging the brainstem, suggestive of an epidermoid cyst. A combined exoscopic- and endoscopic-assisted resection through a pterional transcavernous approach was planned and performed. No neurologic deficit occurred after the surgery, providing further evidence about the usefulness and safety of this hybrid technique., Conclusions: Combined exoscopic and endoscopic resection is also feasible and safe in complex skull base surgery. Moreover, this technique seems to be effective for minimizing the surgical invasiveness in skull base lesions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

•OGM surgery is much more complex than a simple debate of "from above or from below" (transcranial vs endoscopic).•Lateral Sub-frontal and Superior Interhemispheric seem the most effective, superior and versatile approaches for OGM.•Minimally Invasive Transcranial approaches showed no inferiority in OGM sized <4 ​cm.•Endoscopic Endonasal Approaches showed inferior results in surgical and in functional outcomes for OGM., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.Image 2, (© 2022 The Author(s).)

Background: Sonographic assessment of the optic nerve sheath diameter represents a promising non-invasive technique for estimation of the intracranial pressure. A wide inter-observer variability, along with a lack of a standardized protocol for the optic nerve sheath diameter measurements, could lead to over- or under-estimation. The present study was aimed at evaluating feasibility of color-Doppler for better delineating optic nerve sheath borders, comparing it to B-mode imaging, using the magnetic resonance measurements as a comparison., Methods: Optic nerve sheath diameters were evaluated using magnetic resonance by an expert radiologist in a cohort of patients with suspected idiopathic normal pressure hydrocephalus. Magnetic resonance findings were evaluated twice. In the first half of this cohort, optic nerve sheath diameters were measured using B-mode only, in the second half applying color-Doppler. Measurements obtained using these two techniques were compared to magnetic resonance imaging measurements. The Bland-Altman analysis and concordance correlation coefficient were computed to quantify the strength of agreement between the two magnetic resonance assessments. Box plots and average (± SD) were used to compare assessments by sonographic and magnetic resonance methods., Results: Fifty patients were included. MRI assessment showed a moderate concordance correlation coefficient. Optic nerve sheath diameters measured applying color-Doppler were lower (p < 0.001) and less scattered compared to B-mode assessment, which approached more to magnetic resonance measurements., Conclusions: In this cohort of patients, magnetic resonance showed high intra-rater variability in optic nerve sheath diameter assessments. Optic nerve sheath diameter assessments using color-Doppler yielded lower and less scattered diameters compared to B-mode only., (© 2022. The Author(s).)

Purpose: Artificial Intelligence (AI) involves several and different techniques able to elaborate a large amount of data responding to a specific planned outcome. There are several possible applications of this technology in neuro-oncology., Methods: We reviewed, according to PRISMA guidelines, available studies adopting AI in different fields of neuro-oncology including neuro-radiology, pathology, surgery, radiation therapy, and systemic treatments., Results: Neuro-radiology presented the major number of studies assessing AI. However, this technology is being successfully tested also in other operative settings including surgery and radiation therapy. In this context, AI shows to significantly reduce resources and costs maintaining an elevated qualitative standard. Pathological diagnosis and development of novel systemic treatments are other two fields in which AI showed promising preliminary data., Conclusion: It is likely that AI will be quickly included in some aspects of daily clinical practice. Possible applications of these techniques are impressive and cover all aspects of neuro-oncology., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Cushing's disease is a state of chronic and excessive cortisol levels caused by a pituitary adenoma., Research Question: CD is a complex entity and often entails difficulties in its diagnosis and management. For that reason, there are still controversial points to that respect. The aim of this consensus paper of the skull base section of the EANS is to review the main aspects of the disease a neurosurgeon has to know and also to offer updated recommendations on the controversial aspects of its management., Material and Methods: PUBMED database was used to search the most pertinent articles published on the last 5 years related with the management of CD. A summary of literature evidence was proposed for discussion within the EANS skull base section and other international experts., Results: This article represents the consensual opinion of the task force regarding optimal management and surgical strategy in CD., Discussion and Conclusion: After discussion in the group several recommendations and suggestions were elaborated. Patients should be treated by an experienced multidisciplinary team. Accurate clinical, biochemical and radiological diagnosis is mandatory. The goal of treatment is the complete adenoma resection to achieve permanent remission. If this is not possible, the treatment aims to achieving eucortisolism. Radiation therapy is recommended to patients with CD when surgical options have been exhausted. All patients in remission should be tested all life-long., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of EUROSPINE, the Spine Society of Europe, EANS, the European Association of Neurosurgical Societies.)

•EEA represents an ideal approach for loco-regional recurrent CCs.•EEA is well tolerated, with preservation of patients QoL.•EEA can be considered for patients with perspectives of adjuvant therapies.•Otherwise, EEA can be considered only in selected cases with a palliative aim., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Objective: Infradiaphragmatic craniopharyngiomas (ICs) represent a distinct subtype, harboring a sellar-suprasellar origin and generally growing in the extra-arachnoidal space contained by the diaphragma sellae. They have been considered ideal for surgical removal through the transsphenoidal approach since the 1960s. The authors present a multicentric national study, intending to selectively analyze IC behavior and the impact of the transsphenoidal endoscopic endonasal approach (EEA) on surgical outcomes., Methods: Craniopharyngiomas that were intraoperatively recognized as infradiaphragmatic and removed with standard EEA between 2000 and 2021 at 6 Italian neurosurgical departments were included in the study. Clinical, radiological, and surgical findings and outcomes were evaluated and reviewed., Results: In total, 84 patients were included, with 45.23% identified as pediatric cases and 39.28% as having recurrent tumors. The most common presenting symptoms were endocrine (75%), visual (59.52%), and hypothalamic (26.19%) disorders. ICs were classified as extending below (6 intrasellar and 41 occupying the suprasellar cistern) or above (26 obliterating the anterior recesses of the third ventricle and 11 extending up to the foramina of Monro) the chiasmatic cistern. Gross-total resection (GTR) was achieved in 54 cases (64.28%). Tumor extension above the chiasmatic cistern and calcifications were associated with lower likelihood of GTR. The cumulative rate of postoperative complications was 34.53%, with CSF leak being the most common (14.28%). Endocrine, visual, and hypothalamic functions deteriorated postoperatively in 41/78 patients (52.56%), 5/84 (5.95%), and 14/84 (16.67%), respectively. Twenty-eight patients (33.33%) had recurrence during follow-up (mean 63.51 months), with a mean 5-year progression-free survival (PFS) rate of 58%. PFS was greater in patients who achieved GTR than patients with other extent of resection., Conclusions: This is the largest series in the literature to describe ICs removed with standard EEA, without the need for additional bone and dural opening over the planum sphenoidale. EEA provides a direct route to ICs, the opportunity to manage lesions extending up to the third ventricle without breaching the diaphragma, and high rates of GTR and satisfactory clinical outcomes. Increased surgical complexity and morbidity should be expected in patients with extensive suprasellar extension and involvement of the surrounding vital neurovascular structures.