Neurophysiologic Monitoring of Oculomotor Nerves During Transorbital Surgery: Proof of Concept and Anatomic Demonstration.

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.

Endonasal versus supraorbital approach for anterior skull base meningiomas: Results and quality of life assessment from a single-surgeon cohort.

OBJECTIVE: In this prospective non-randomized study we reported our experience related to planum sphenoidale (PS) and tuberculum sellae (TS) meningiomas in a similar cohort of patients operated via the endonasal or the supraorbital route. A comprehensive quality of life analysis has been performed. METHODS: Being comparable in general features, between November 2017 to January 2020, a total of 20 patients with anterior skull base meningioma were included. Hence, 10 patients were treated using the supraorbital keyhole procedure (SO) while 10 patients received an endoscopic endonasal approach (EEA). Both surgical techniques were analyzed and compared. Quality of life has been analyzed with the SF-36 questionnaire. RESULTS: Twenty patients were identified who underwent either EEA (n=10) or SO (n=10). The average extent of resection achieved was not significantly different between the 2 groups. Post-operatively, the EEA group demonstrated a longer hospital stay and bed days compared with SO patients as well as a longer surgical time. There was a significant rate of more CSF leakage after EEA then after SO (20% vs 0%, p=0,0491). The follow-up period resulted shorter in the SO group, with a slight increased recurrence rate. Overall, no differences in visual outcome were detected. There were no differences in terms of quality of life between the two groups in all the explored items. CONCLUSIONS: In this single-center single-surgeon study of similarly sized and located PS and TS meningiomas, EEA showed longer hospital stays with higher degree of CSF leak compared with the SO group. Supraorbital craniotomy via eyebrow incision reported a comparable quality of life results, even if with a slightly higher percentage of recurrence and less follow-up.

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.

The ghost tumour revisited. Corticosteroids in primary central nervous system lymphoma: diagnostic, prognostic and therapeutic implications.

OBJECTIVE: The cytolytic effect of corticosteroids on primary central nervous system lymphoma (PCNSL) has established the clinical dogma of avoiding steroid therapy prior to surgery for diagnostic purposes. However, since steroids are very useful during the initial management of intracranial lesions with vasogenic oedema, it was our aim to determine whether they cause a drawback in the diagnosis and prognosis of PCNSL. METHODS: A retrospective cohort study of patients diagnosed with PCNSL between 2000 and 2020 in our tertiary neurosurgical centre. Data on steroid administration, surgery type and complications, haematopathological findings and prognostic factors were compiled. A second cohort was used as a control group to compare the ratio of non-diagnostic biopsies; this series comprised patients who underwent stereotactic brain biopsy for any reason between 2019 and 2020. RESULTS: Forty patients with PCNSL were included in the study, of which 28 (70%) had received steroids before surgery. The use of steroids was more prevalent in patients with poorer performance status at diagnosis. No relevant differences were found in the diagnostic accuracy regardless of steroid exposure (93% under steroids vs 100% without steroids) or type of surgery performed. Furthermore, steroid withdrawal did not seem to augment the diagnostic ratio. The notable diagnostic delay was not influenced by the use of steroids. CONCLUSIONS: Novel imaging and surgical techniques might obviate the need to withhold corticosteroids from patients suffering from PCNSL prior to biopsy. Moreover, when steroids have been given, tapering them and delaying the surgery might not be justified. This could hold relevant therapeutic implications in the early clinical stages.

Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy.

BACKGROUND: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)-mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. METHODS: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. RESULTS: 5-ALA (50 and 100 µg/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. CONCLUSIONS: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies.

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.

Photodynamic therapy in glioblastoma: Detection of intraoperative inadvertent 5-ALA mediated photodynamic therapeutical effect after gross total resection.

Introduction: Glioblastoma (GBM) remains the most frequent and lethal primary brain tumor in adults, despite advancements in surgical resection techniques and adjuvant chemo- and radiotherapy. The most frequent recurrence pattern (75-90%) occurs in the form of continuous growth from the border of the surgical cavity, thus emphasizing the need for locoregional tumor control. Fluorescence-guided surgical resection using 5-ALA has been widely implemented in surgical protocols for such tumors. Recent literature also highlights the applicability of 5-ALA-mediated photodynamic therapy to obtain locoregional tumor control further. This study aims to identify if 5-ALA mediated photodynamic therapeutic effect after gross total glioblastoma resection has inadvertently occurred due to the exposition of protoporphyrin IX charged peripheral tumoral cells to operative room light sources. Methods: Of 146 patients who were intervened from glioblastoma between 2015 and 2020, 33 were included in the present study. Strict gross total resection (without supralocal resection) had been accomplished, and adjuvant chemoradiotherapy protocol was administered. Two comparison groups were created regarding the location of the recurrence (group A: up to 1 centimeter from the surgical cavity, and group B: beyond 1 centimeter from the surgical cavity). The cutoff point was determined to be 1 centimeter because of the visible light penetrance to the normal brain tissue. Results: In univariate analysis, both groups only differed regarding 5-ALA administration, which was significantly related to a minor relative risk of presenting the recurrence within the first centimeter from the surgical cavity (Relative Risk = 0,655 (95% CI 0,442-0,970), p-value=0,046). Results obtained in univariate analysis were corroborated posteriorly in multivariate analysis (RR=0,730 (95% CI 0,340-0,980), p=0,017). Discussion: In the present study, a probable inadvertent 5-ALA photodynamic therapeutical effect has been detected in vivo. This finding widely opens the door for further research on this promising theragnostic tool.

Superior eyelid endoscopic transorbital approach to the tentorial area: A qualitative and quantitative anatomic study.

Objective: Superior eyelid endoscopic transorbital approach (SETOA) is nowadays gaining progressive application in neurosurgical scenarios. Both anatomic and clinical reports have demonstrated the possibility of taking advantage of the orbital corridor as a minimally invasive route to reach anterior and middle cranial fossae and manage selected surgical lesions developing in these areas. The aim of this paper is to further shed light on other anatomic regions of the skull base as seen from a transorbital perspective, namely, the posterior cranial fossa and tentorial area, describing technical feasibility and steps in reaching this area through an extradural-transtentorial approach and providing quantitative evaluations of the "working area" obtained through this route. Material and methods: Four cadaveric heads (eight sides) were dissected at the Laboratory of Surgical Neuroanatomy (LSNA) of the University of Barcelona, Spain. A stepwise dissection of the transorbital approach to the tentorial area was described. Qualitative anatomical descriptions and quantitative analyses of working were evaluated by using pre- and postdissections CT and MRI scans, and three-dimensional reconstructions were made using Amira software. Results: With the endoscopic transorbital approach, posterior cranial fossa dura was reached by an extradural middle cranial fossa approach and drilling of the petrous apex. After clipping the superior petrosal sinus, the tentorium was divided and cut. An endoscope was then introduced in the posterior cranial fossa at the level of the tentorial incisura. Qualitative analysis provided a description of the tentorial and petrosal surfaces of the cerebellum, middle tentorial incisura, cerebellopontine fissures, and, after arachnoid dissection, by a 30° endoscopic visualization, the posterior aspect of the cerebellomesencephalic fissure. Quantitative analysis of the "working area" obtained after bone removal was also provided. Conclusions: This anatomic qualitative and quantitative study sheds light on the anatomy of the posterior cranial fossa contents, such as the tentorial area and incisura, as seen through a transorbital perspective. The first aim of the article is to enrich the anatomical knowledge as seen through this relatively new corridor and to provide quantitative details and insights into the technical feasibility of reaching these regions in a surgical scenario.

Is intraoperative ultrasound more efficient than magnetic resonance in neurosurgical oncology? An exploratory cost-effectiveness analysis.

Objective: Intraoperative imaging is a chief asset in neurosurgical oncology, it improves the extent of resection and postoperative outcomes. Imaging devices have evolved considerably, in particular ultrasound (iUS) and magnetic resonance (iMR). Although iUS is regarded as a more economically convenient and yet effective asset, no formal comparison between the efficiency of iUS and iMR in neurosurgical oncology has been performed. Methods: A cost-effectiveness analysis comparing two single-center prospectively collected surgical cohorts, classified according to the intraoperative imaging used. iMR (2013-2016) and iUS (2021-2022) groups comprised low- and high-grade gliomas, with a maximal safe resection intention. Units of health gain were gross total resection and equal or increased Karnofsky performance status. Surgical and health costs were considered for analysis. The incremental cost-effectiveness ratio (ICER) was calculated for the two intervention alternatives. The cost-utility graphic and the evolution of surgical duration with the gained experience were also analyzed. Results: 50 patients followed an iMR-assisted operation, while 17 underwent an iUS-guided surgery. Gross total resection was achieved in 70% with iMR and in 60% with iUS. Median postoperative Karnofsky was similar in both group (KPS 90). Health costs were € 3,220 higher with iMR, and so were surgical-related costs (€ 1,976 higher). The ICER was € 322 per complete resection obtained with iMR, and € 644 per KPS gained or maintained with iMR. When only surgical-related costs were analyzed, ICER was € 198 per complete resection with iMR and € 395 per KPS gained or maintained. Conclusion: This is an unprecedented but preliminary cost-effectiveness analysis of the two most common intraoperative imaging devices in neurosurgical oncology. iMR, although being costlier and time-consuming, seems cost-effective in terms of complete resection rates and postoperative performance status. However, the differences between both techniques are small. Possibly, iMR and iUS are complementary aids during the resection: iUS real-time images assist while advancing towards the tumor limits, informing about the distance to relevant landmarks and correcting neuronavigation inaccuracy due to brain shift. Yet, at the end of resection, it is the iMR that reliably corroborates whether residual tumor remains.

Endoscopic transorbital avenue to the skull base: Four-step conceptual analysis of the anatomic journey.

Background: In the last decades, skull base surgery had passed through an impressive evolution. The role of neuroanatomic research has been uppermost, and it has played a central role in the development of novel techniques directed to the skull base. Indeed, the deep and comprehensive study of skull base anatomy has been one of the keys of success of the endoscopic endonasal approach to the skull base. In the same way, dedicated efforts expended in the anatomic lab has been a powerful force for the growth of the endoscopic transorbital approach to the lateral skull base.Therefore, in this conceptual paper, the main steps for the anatomic description of the endoscopic transorbital approach to the skull base have been detailed. Methods: The anatomic journey for the development of the endoscopic transorbital approach to the skull base has been analyzed, and four "conceptual" steps have been highlighted. Results: As neurosurgeons, the eyeball has always represented a respectful area: to become familiar with this complex and delicate anatomy, we started by examining the orbital anatomy on a dry skull (step 1). Hence, step 1 is represented by a detailed bone study; step 2 is centered on cadaveric dissection; step 3 consists in 3D quantitative assessment of the novel endoscopic transorbital corridor; and finally, step 4 is the translation of the preclinical data in the real surgical scenario by means of dedicated surgical planning. Conclusions: The conceptual analysis of the anatomic journey for the description of the endoscopic transorbital approach to the skull base resulted in four main methodological steps that should not be thought strictly consequential but rather interconnected. Indeed, such steps should evolve following the drives that can arise in each specific situation. In conclusion, the four-step anatomic rehearsal can be relevant for the description, diffusion, and development of a novel technique in order to facilitate the application of the endoscopic transorbital approach to the skull base in a real surgical scenario.

Endoscopic Transorbital Approach to the Middle Fossa: Qualitative and Quantitative Anatomic Study.

BACKGROUND: The endoscopic superior eyelid transorbital route to the skull base is gaining progressive popularity in the neurosurgical community. OBJECTIVE: To evaluate the anatomy of the middle cranial fossa from this novel ventral perspective to reach the skull base through the transorbital route and to show limits for possible safe middle fossa drilling from the transorbital route. METHODS: Anatomic study was performed; 5 cadaveric specimens (ie, 10 sides) and 2 dry skulls (ie, 4 sides) were dissected. RESULTS: To obtain a functional result, there are boundaries that correspond to neurovascular structures that traverse, enter, or leave the middle fossa that must be respected: inferiorly, the lateral pterygoid muscle; medially, the Gasserian ganglion and the lateral border of the foramen rotundum; laterally, the foramen spinosum with the middle meningeal artery; superiorly, the lesser sphenoid wing; posteriorly, the anterior border of the foramen ovale. Average bone resected was 6.49 ± 0.80 cm3 which is the 63% of total middle fossa floor. The mean axial surgical length calculated was 3.85 cm (3.18-5.19 cm) while the mean sagittal surgical length was 5.23 cm (4.87-6.55 cm). The mean horizontal angle of approach was 38.14° (32.87°-45.63°), while the mean vertical angle of approach was 18.56° (10.81°-26.76°). CONCLUSION: Detailed anatomy of the middle cranial fossa is presented, and herewith we demonstrated that from the endoscopic superior eyelid transorbital approach removal of middle cranial fossa floor is possible when anatomic landmarks are respected.

Validation of Presurgical Simulation of White Matter Damage Using Diffusion Tensor Imaging.

BACKGROUND: The understanding of white matter (WM) was revolutionized by the emergence of tractography based on diffusion tensor imaging (DTI). Currently, DTI simulations are implemented in preoperative planning to optimize surgical approaches. The reliability of these simulations has been questioned and investigated seeking for correlation between neurological performance and anomalies in DTI parameters. However, the ability of preoperative WM simulations to predict a surgical injury has not been thoroughly evaluated. Our objective was to assess the reliability of preoperatively simulated WM injuries for conventional neurosurgical procedures. METHODS: WM surgical damage was preoperatively simulated by creating a 3-dimensional volume representing the endoscope or the surgical trajectory. This volume was used as an additional region of interest in the fascicle reconstruction to be subtracted from the original fascicle. Simulated, injured fascicles were compared in terms of the number of fibers and volume to those created from postoperative DTI studies. Reliability was assimilated into the correlation between the simulation and the postoperative reconstruction; evaluated using the intraclass correlation coefficient or Lin's Concordance correlation coefficient (CCC), and represented on Bland-Altman plots. RESULTS: The preoperative and postoperative DTI studies of 30 patients undergoing various neurosurgical approaches were processed. The correlation between simulated injuries and postoperative studies was high in terms of fibers (Concordance correlation coefficient = Rho.C = 0.989 [95% confidence interval = 0.979-0.995]) and volume (intraclass correlation coefficient = 0.95 [95% CI = 0.89-0.97]). Bland-Altman plots demonstrated that the great majority of cases fell within the mean ± 2 Standard deviations. CONCLUSIONS: Presurgical simulation of WM fascicles based on DTI is consistent with postoperative DTI studies. These findings require further validation by neurophysiological and clinical correlation.

Current and Future Frontiers of Molecularly Defined Oligodendrogliomas.

Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The World Health Organization (WHO) 2021 brain tumor classification highlighted defining molecular markers, including 1p19q codeletion and IDH mutations which have become key in diagnosing and treating oligodendrogliomas. The management for patients with oligodendrogliomas includes observation or surgical resection potentially followed by radiation and chemotherapy with PCV (Procarbazine, Lomustine, and Vincristine) or Temozolomide. However, most of the available research about oligodendrogliomas includes a mix of histologically and molecularly diagnosed tumors. Even data driving our current management guidelines are based on post-hoc subgroup analyses of the 1p19q codeleted population in landmark prospective trials. Therefore, the optimal treatment paradigm for molecularly defined oligodendrogliomas is incompletely understood. Many questions remain open, such as the optimal timing of radiation and chemotherapy, the response to different chemotherapeutic agents, or what genetic factors influence responsiveness to these agents. Ultimately, oligodendrogliomas are still incurable and new therapies, such as targeting IDH mutations, are necessary. In this opinion piece, we present relevant literature in the field, discuss current challenges, and propose some studies that we think are necessary to answer these critical questions.

The Vascular Microenvironment in Glioblastoma: A Comprehensive Review.

Glioblastoma multiforme, the deadliest primary brain tumor, is characterized by an excessive and aberrant neovascularization. The initial expectations raised by anti-angiogenic drugs were soon tempered due to their limited efficacy in improving the overall survival. Intrinsic resistance and escape mechanisms against anti-VEGF therapies evidenced that tumor angiogenesis is an intricate multifaceted phenomenon and that vessels not only support the tumor but exert indispensable interactions for resistance and spreading. This holistic review covers the essentials of the vascular microenvironment of glioblastoma, including the perivascular niche components, the vascular generation patterns and the implicated signaling pathways, the endothelial-tumor interrelation, and the interconnection between vessel aberrancies and immune disarrangement. The revised concepts provide novel insights into the preclinical models and the potential explanations for the failure of conventional anti-angiogenic therapies, leading to an era of new and combined anti-angiogenic-based approaches.

Minimally Invasive Surgery for Spontaneous Intracerebral Hematoma. Real-Life Implementation Model and Economic Estimation.

Objective: Spontaneous intracerebral hemorrhage is characterized by high fatality outcomes, even under best medical treatment. Recently, minimally invasive surgical (MIS) evacuation of the hematoma has shown promising results and may soon be implemented in the clinical practice. Hereby, we intended to foresee the logistic requirements for an early hematoma evacuation protocol, as well as to evaluate in a real-life implementation model the cost-utility of the two main MIS techniques for hemorrhagic stroke (catheter evacuation plus thrombolysis and neuroendoscopic aspiration). Methods: Data were obtained from the pool of hemorrhagic-stroke patients admitted to our institution during an annual period (2020-2021) and contrasted to the reported results in published trials of MIS techniques. Potential candidates for surgical treatment were identified according to the inclusion/exclusion criteria established in these trials. Then, a cost-utility analysis was performed, which explored the incremental cost per unit of health gained with a given treatment. The treatment effect was measured by differences in modified Rankin Score, and subsequently converted to quality-adjusted life years (QALY). Results: Of the 137 patients admitted to our center with supratentorial spontaneous intracerebral hemorrhage in a 1-year period, 17 (12.4%) were potential candidates for the catheter evacuation plus thrombolysis technique (Minimally Invasive Surgery with Thrombolysis in Intracerebral Hemorrhage Evacuation trial, MISTIE III criteria) and 59 (43.0%) for the neuroendoscopic aspiration technique (Dutch Intracerebral Hemorrhage Surgery Trial Pilot Study, DIST criteria). The incremental cost-utility ratio was € 76,533.13 per QALY for the catheter-based evacuation and € 60,703.89 per QALY for the endoscopic-based technique. Conclusion: Around 12-43% of patients admitted to hospital with spontaneous hemorrhagic stroke could be potential candidates to MIS early evacuation of the cerebral hematoma. In our real-life implementation model, the cost-utility analysis favored the neuroendoscopic evacuation over the catheter aspiration technique. Further studies are advisable as new data from the ongoing randomized trials becomes available.

The Prognostic-Based Approach in Growth Hormone-Secreting Pituitary Neuroendocrine Tumors (PitNET): Tertiary Reference Center, Single Senior Surgeon, and Long-Term Follow-Up.

Postoperative deserved outcomes in acromegalic patients are to normalize serum insulin-like growth factor (IGF-1), reduce the tumoral mass effect, improve systemic comorbidities, and reverse metabolic alterations. Pituitary neuroendocrine tumors (PitNET) are characterized to present a heterogeneous behavior, and growth hormone (GH)-secreting PitNET is not an exception. Promptly determining which patients are affected by more aggressive tumors is essential to guide the optimal postoperative decision-making process [prognostic-based approach]. From 2006 to 2019, 394 patients affected by PitNET were intervened via endoscopic endonasal transsphenoidal approach by the same senior surgeon. A total of 44 patients that met the criteria to be diagnosed as acromegalic and were followed up at least for 24 months (median of 66 months (26-156) were included in the present study. Multiple predictive variables [age, gender, preoperative GH and IGF-1 levels, maximal tumor diameter, Hardy's and Knosp's grade, MRI. T2-weighted tumor intensity, cytokeratin expression pattern, and clinicopathological classification] were evaluated through uni- and multivariate statistical analysis. Sparse probability of long-term remission was related to younger age, higher preoperative GH and- or IGF-1, group 2b of the clinicopathological classification, and sparsely granulated cytokeratin expression pattern. Augmented recurrence risk was related to elevated preoperative GH levels, tumor MRI T2-weighted hyperintensity, and sparsely granulated cytokeratin expression pattern. Finally, elevated risk for reintervention was related to group 2b of the clinicopathological classification, Knosp's grade IV, and tumor MRI T2-weighted hyperintensity. In this study, the authors determined younger age, higher preoperative GH and- or IGF-1 levels, group 2b of the clinicopathological classification, Knosp's grade IV, MRI T2-weighted tumor hyperintensity and sparsely granulated cytokeratin expression pattern are related to worse postoperative outcomes in long-term follow-up patients affected with GH-secreting PitNET.

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.

Intraoperative magnetic resonance imaging for cerebral cavernous malformations: When is it maybe worth it?

OBJECTIVE: Intraoperative magnetic resonance imaging (iMRI) can be useful for cerebral cavernous malformations (CCM) surgery. However, literature on this topic is scarce. We aim to investigate its clinical utility and propose criteria for the selection of patients who may benefit the most from iMRI. METHODS: From 2017 to 2019, all patients with CCMs who required surgery assisted with iMRI were included in the study. Clinical and radiological features were analyzed. Outcome measures included the need for an immediate second-look resection and clinical course in early post-surgery -Timepoint 1- (Tp1) and at the 6-to-12-month follow-up -Timepoint2- (Tp2). RESULTS: Out of 19 patients with 20 CCMs, 89% had bleeding in the past, and in 75% the CCM affected an eloquent area. According to the iMRI results, an immediate second-look resection was needed in 16% of them. In one patient, a remnant was not seen on iMRI. The mRS worsened in the immediate post-surgical exam (median, 1; IQR, 1) with improvements on the 6-month visit (median, 1; IQR, 2), (p = 0.018). When comparing the outcome of patients with and without symptoms at baseline, the latter fared better at Tp2 (p = 0.005). CONCLUSIONS: iMRI is an intraoperative imaging tool that seems safe for CCM surgery and might reduce the risk of lesion remnants. In our series, it allowed additional revision for further resection in 16% of the patients. In our experience, iMRI may be especially useful for lesions in eloquent areas, those with a significant risk of brain shift and for large CCMs.