Gender gap in deep brain stimulation for Parkinson's disease: preliminary results of a retrospective study.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment of PD for both women and men. However, discussions have been reported about the impact of STN-DBS surgery in PD. The aim of our study is to identify differences between men and women in terms of pre- and post-DBS symptoms and try to explain the possible causes. In the current study, we evaluated the gender impact on STN-DBS in PD at the Department of Neurosurgery of University of Naples "Federico II" from 2013 to 2021. Motor and non-motor symptoms were evaluated. To compare the data before and after surgery and between the genders, Wilcoxon-Mann-Whitney tests were performed. A total of 43 patients with PD were included; of them, 17 (39%) were female. Baseline evaluation revealed no gender differences in the age of onset (p = 0.87). Not significant differences were noted in the Unified Parkinson's Disease Rating Scale (UPDRS) pre-surgery score, but if we consider UPDRS subscores of motor examination, significant clinical improvement was reported in both male and female in terms of UPDRS pre- and post-surgery (p < 0.001). STN-DBS is a highly effective treatment for motor and non-motor symptoms of PD for both women and men but our study hints towards gender-specific outcomes in motor domains. Improving our knowledge in this field can allow us to implement strategies to identify new directions in the development of an adequate treatment of PD in terms of surgical intervention and in consideration of the gender.

Management and treatment of brain tumors during pregnancy: an Italian survey.

PURPOSE: The management of brain tumors during pregnancy is challenging. The clinical rarity and prognostic heterogeneity of such condition makes it difficult to develop standardized guidelines of treatment. The aim of this study was to assess the treatment options used in pregnant women with brain tumors that are currently used in Italy, considering the management of these patients reported in current literature in this field. METHODS: A survey addressing the treatments options and management of brain tumors during pregnancy was designed on behalf of an ad-hoc task-force Neuro-Oncology committee of the Società Italiana di Neurochirurgia (SINch) to analyze the management of pregnant patients with brain tumors. We conducted a search of the literature published between January 2011 and September 2021, using MEDLINE (PubMed) in accordance to PRISMA guidelines. Data were discussed to obtain recommendations after evaluation of the selected articles and discussion among the experts. RESULTS: A total of 18 Neurosurgical centers participated in the survey. A total of 31 pregnant women were included in this retrospective study. Meningiomas and gliomas were the two most common types of brain tumors diagnosed during pregnancy. An emergency surgical procedure was required in 12.9% of cases. CONCLUSION: A multidisciplinary and tailored approach is fundamental. In women showing clinical stability, neurosurgical options should preferably be delayed if possible, and considered during the second trimester or after delivery. In patients with acute neurological symptoms or tumor progression, medical abortion in the first trimester or a C-section in the second and third trimester need to be considered.

Impact of deep brain stimulation therapy on the vertebral sagittal balance in Parkinson's disease patients.

Parkinson's disease (PD) is characterized by cardinal motor signs: 4-6 Hz resting tremor, rigidity, and bradykinesia. In addition, 3-18% of PD patients have camptocormia, an abnormal forward flexion of the thoracolumbar spine, which may have a negative impact on patients' quality of life. Different possible treatments have been suggested for such a condition, but no one is resolutive. This study aims to define the possible impact of DBS, with selective targeting on the dorsal-lateral region of the STN, on the sagittal balance of patients affected by PD. Among all patients that have undergone DBS procedures in our institution, we selected eight subjects, four females and four males, with selective targeting on the dorsal-lateral region of the subthalamic nucleus (STN) because of camptocormia and other severe postural changes. Radiological assessments of spinal balance parameters before surgery and at 6 and 12 months postoperatively were carried out. Comparison of preoperative and postoperative spine X-ray data showed a statistically significant improvement in dorsal kyphosis angle (D-Cobb) 12 months after the operation. Deep brain stimulation with selective targeting of the dorsal lateral part of the STN may induce changes of the posture in patients with Parkinson's disease 12 months after the operation, which appears to improve in this small sample size, but larger observational and controlled trials would be required to confirm this observation.

Persisting embryonal infundibular recess (PEIR) and transsphenoidal-transsellar encephaloceles: distinct entities or constituents of one continuum?

Persisting embryonal infundibular recess (PEIR) is a very rare anomaly of the floor of the third ventricle in which the embryonic morphology of the infundibular recess (IR) persists. The exact underlying mechanism of development of PEIR is unknown, and the anomaly has been reported as an isolated finding or in association with other conditions. On the other hand, trans-sphenoidal encephaloceles are the rarest form of basal encephaloceles. The trans-sphenoidal trans-sellar encephalocele (TSE) is the least common variant in which the pituitary gland, pituitary stalk, optic pathways, parts of the third ventricle and IR may be present within the encephalocele. We recently treated one patient with TSE. Based on the observed morphological similarity of the IR in our patient and in the published cases of PEIR, we reviewed the literature in order to validate the hypothesis that PEIR and TSE may possibly belong to one spectrum of malformations. Across the published reports, the morphology of the IR in TSE is very closely similar to PEIR. Moreover, radiological, patho-anatomical, and embryological evidence is in support to our hypothesis that PEIR and TSE are most likely the two extremes of the same continuum of malformations.

The sellar barrier on preoperative imaging predicts intraoperative cerebrospinal fluid leak: a prospective multicenter cohort study.

BACKGROUND: The type of sellar barrier observed between a pituitary tumor and cerebrospinal fluid (CSF) on preoperative magnetic resonance imaging (MRI) may predict intraoperative CSF leak during endonasal pituitary surgery. This is the first multicentric prospective cohort trial to study the sellar barrier concept and CSF leak rate during endoscopic pituitary surgery. METHODS: This multi-center, international study enrolled patients operated for pituitary adenomas via fully endoscopic endonasal surgery over a period of 4 months. The independent variable was the subtype of sellar barrier observed on preoperative MRI (strong, mixed or weak); the dependent variable was the presence of an intraoperative CSF leak. The primary goal was to determine the association between a particular type of sellar barrier and the risk of intraoperative CSF leak. Appropriate statistical methods were then applied for data analysis. RESULTS: Over the study period, 310 patients underwent endoscopic endonasal surgery for pituitary tumor. Preoperative imaging revealed a weak sellar barrier in 73 (23.55%), a mixed sellar barrier in 75 (24.19%), and a strong sellar barrier in 162 (52.26%) patients. The overall rate of intraoperative CSF leak among all patients was 69 (22.26%). A strong sellar-type barrier was associated with significantly reduced rate of intraoperative CSF leak (RR = 0.08; 95% CI 0.03-0.19; p < 0.0001), while a weak sellar barrier associated with higher rates of CSF leak (RR = 8.54; 95% CI 5.4-13.5; p < 0.0001). CONCLUSIONS: The preoperative MRI of pituitary patients can suggest intraoperative CSF leak rates, utilizing the concept of the sellar barrier. Patients with a weak sellar barrier carry a higher risk for an intraoperative CSF leak, whereas a strong sellar barrier on MRI seems to mitigate intraoperative CSF leak. We propose that preoperatively assessment of the sellar barrier can prepare surgeons for intraoperative CSF leak repair.

Prediction of pituitary adenoma surgical consistency: radiomic data mining and machine learning on T2-weighted MRI.

PURPOSE: Pituitary macroadenoma consistency can influence the ease of lesion removal during surgery, especially when using a transsphenoidal approach. Unfortunately, it is not assessable on standard qualitative MRI. Radiomic texture analysis could help in extracting mineable quantitative tissue characteristics. We aimed to assess the accuracy of texture analysis combined with machine learning in the preoperative evaluation of pituitary macroadenoma consistency in patients undergoing endoscopic endonasal surgery. METHODS: Data of 89 patients (68 soft and 21 fibrous macroadenomas) who underwent MRI and transsphenoidal surgery at our institution were retrospectively reviewed. After manual segmentation, radiomic texture features were extracted from original and filtered MR images. Feature stability analysis and a multistep feature selection were performed. After oversampling to balance the classes, 80% of the data was used for hyperparameter tuning via stratified 5-fold cross-validation, while a 20% hold-out set was employed for its final testing, using an Extra Trees ensemble meta-algorithm. The reference standard was based on surgical findings. RESULTS: A total of 1118 texture features were extracted, of which 741 were stable. After removal of low variance (n = 4) and highly intercorrelated (n = 625) parameters, recursive feature elimination identified a subset of 14 features. After hyperparameter tuning, the Extra Trees classifier obtained an accuracy of 93%, sensitivity of 100%, and specificity of 87%. The area under the receiver operating characteristic and precision-recall curves was 0.99. CONCLUSION: Preoperative T2-weighted MRI texture analysis and machine learning could predict pituitary macroadenoma consistency.

Is age an additional factor in the treatment of elderly patients with glioblastoma? A new stratification model: an Italian Multicenter Study.

OBJECTIVE: Approximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients. METHODS: Clinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score. RESULTS: Survival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell's c-index of 0.75 (95% CI 0.76-0.81). CONCLUSIONS: The CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

The nose lid for the endoscopic endonasal procedures during COVID-19 era: technical note.

BACKGROUND: COVID-19 pandemic has disrupted the global health systems worldwide. According to the tremendous rate of interhuman transmission via aerosols and respiratory droplets, severe measures have been required to contain contagion spread. Accordingly, medical and surgical maneuvers involving the respiratory mucosa and, among them, transnasal transsphenoidal surgery have been charged of maximum risk of spread and contagion, above all for healthcare professionals. METHOD: Our department, according to the actual COVID-19 protocol national guidelines, has suspended elective procedures and, in the last month, only three patients underwent to endoscopic endonasal procedures, due to urgent conditions (a pituitary apoplexy, a chondrosarcoma causing cavernous sinus syndrome, and a pituitary macroadenoma determining chiasm compression). We describe peculiar surgical technique modifications and the use of an endonasal face mask, i.e., the nose lid, to be applied to the patient during transnasal procedures for skull base pathologies as a further possible COVID-19 mitigation strategy. RESULTS: The nose lid is cheap, promptly available, and can be easily assembled with the use of few tools available in the OR; this mask allows to both operating surgeon and his assistant to perform wider surgical maneuvers throughout the slits, without ripping it, while limiting the nostril airflow. CONCLUSIONS: Transnasal surgery, transgressing respiratory mucosa, can definitely increase the risk of virus transmission: we find that adopting further precautions, above all limiting high-speed drill can help preventing or at least reducing aerosol/droplets. The creation of a non-rigid face mask, i.e., the nose lid, allows the comfortable introduction of instruments through one or both nostrils and, at the same time, minimizes the release of droplets from the patient's nasal cavity.

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

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

Surgical management of Tuberculum sellae Meningiomas: Myths, facts, and controversies.

BACKGROUND: The optimal management of tuberculum sellae (TS) meningiomas, especially the surgical strategy, continues to be debated along with several controversies that persist. METHODS: A task force was created by the EANS skull base section committee along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumors on a European perspective. To achieve this, the task force also reviewed in detail the literature in this field and had formal discussions within the group. RESULTS: The constituted task force dealt with the practice patterns that exist with respect to pre-operative radiological investigations, ophthalmological and endocrinological assessments, optimal surgical strategies, and follow-up management. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the surgical treatment of tuberculum sellae meningiomas. Areas of uncertainty where further clinical research is required were identified.

Surgical management of craniopharyngiomas in adult patients: a systematic review and consensus statement on behalf of the EANS skull base section.

BACKGROUND AND OBJECTIVE: Craniopharyngiomas are locally aggressive neuroepithelial tumors infiltrating nearby critical neurovascular structures. The majority of published surgical series deal with childhood-onset craniopharyngiomas, while the optimal surgical management for adult-onset tumors remains unclear. The aim of this paper is to summarize the main principles defining the surgical strategy for the management of craniopharyngiomas in adult patients through an extensive systematic literature review in order to formulate a series of recommendations. MATERIAL AND METHODS: The MEDLINE database was systematically reviewed (January 1970-February 2019) to identify pertinent articles dealing with the surgical management of adult-onset craniopharyngiomas. A summary of literature evidence was proposed after discussion within the EANS skull base section. RESULTS: The EANS task force formulated 13 recommendations and 4 suggestions. Treatment of these patients should be performed in tertiary referral centers. The endonasal approach is presently recommended for midline craniopharyngiomas because of the improved GTR and superior endocrinological and visual outcomes. The rate of CSF leak has strongly diminished with the use of the multilayer reconstruction technique. Transcranial approaches are recommended for tumors presenting lateral extensions or purely intraventricular. Independent of the technique, a maximal but hypothalamic-sparing resection should be performed to limit the occurrence of postoperative hypothalamic syndromes and metabolic complications. Similar principles should also be applied for tumor recurrences. Radiotherapy or intracystic agents are alternative treatments when no further surgery is possible. A multidisciplinary long-term follow-up is necessary.

Endoscopic anatomy of the sellar barrier: From the anatomical model to the operating room.

BACKGROUND: The sellar barrier concept reflects the association between the components of the roof of the pituitary fossa and the risk of intraoperative cerebrospinal fluid (CSF) leak in the surgery of pituitary adenomas. We based our concept in previous reports on the microsurgical anatomy of the pituitary fossa's superior wall. However, proof of the usefulness of this concept in endoscopic approaches is yet missing. The aim of this study was to describe the endoscopic anatomy of the sellar barrier and its subtypes in a laboratory setting and to provide evidence of its clinical usefulness. METHODS: We provided anatomical models in six fresh-frozen head and neck specimens. We performed an endoscopic endonasal approach and recreated a pathological model of each possible subtype of sellar barrier. To demonstrate the usefulness of this model in clinical practice, we conducted a prospective study including all patients with pituitary adenoma operated by an endoscopic approach between June and July 2019. RESULTS: We successfully recreated the models for each subtype of sellar barrier. When analyzing the clinical cases, we found that intraoperatively, 73.69% (14) had a strong sellar barrier; 21.05% (4) had mixed sellar barrier, and 5.26% (1) had weak sellar barrier. We recorded one case of intraoperative CSF leak in a patient with a weak sellar barrier by magnetic resonance imaging. CONCLUSION: We described the endoscopic anatomy of the sellar barrier and we recreated the three subtypes in anatomical models. We also identified these subtypes in a series of clinical cases, proving its clinical usefulness.

Prediction of high proliferative index in pituitary macroadenomas using MRI-based radiomics and machine learning.

PURPOSE: Pituitary adenomas are among the most frequent intracranial tumors. They may exhibit clinically aggressive behavior, with recurrent disease and resistance to multimodal therapy. The ki-67 labeling index represents a proliferative marker which correlates with pituitary adenoma aggressiveness. Aim of our study was to assess the accuracy of machine learning analysis of texture-derived parameters from pituitary adenomas preoperative MRI for the prediction of ki-67 proliferation index class. METHODS: A total of 89 patients who underwent an endoscopic endonasal procedure for pituitary adenoma removal with available ki-67 labeling index were included. From T2w MR images, 1128 quantitative imaging features were extracted. To select the most informative features, different supervised feature selection methods were employed. Subsequently, a k-nearest neighbors (k-NN) classifier was employed to predict macroadenoma high or low proliferation index. Algorithm validation was performed with a train-test approach. RESULTS: Of the 12 subsets derived from feature selection, the best performing one was constituted by the 4 highest correlating parameters at Pearson's test. These all showed very good (ICC ≥ 0.85) inter-observer reproducibility. The overall accuracy of the k-NN in the test group was of 91.67% (33/36) of correctly classified patients. CONCLUSIONS: Machine learning analysis of texture-derived parameters from preoperative T2 MRI has proven to be effective for the prediction of pituitary macroadenomas ki-67 proliferation index class. This might aid the surgical strategy making a more accurate preoperative lesion classification and allow for a more focused and cost-effective follow-up and long-term management.

The endoscopic endonasal approach for pediatric craniopharyngiomas: the key lessons learned.

PURPOSE: The aim of this study is to highlight the role of the endoscopic endonasal approach (EEA) in pediatric craniopharyngiomas by reviewing our experience and the key lessons learned from the application of this approach in children. METHODS: Between 1998 and 2017, 12 pediatric craniopharyngiomas were treated via EEA at our institution. Demographic data, preoperative assessment, tumor features, surgical results, complications, and recurrences were analyzed. RESULTS: Visual defects were the most frequent presenting sign. Seven craniopharyngiomas were infradiaphragmatic, and five were supradiaphragmatic. The EEA was successfully performed in all cases with no complication related to children's sinonasal anatomy. Gross total resection (GTR) rate was of 75%. Endocrinological disturbances improved in one case (20%) and worsened in three (60%). New onset of diabetes insipidus was observed in four (36%) children. Visual defect improved in 91% of cases, with no new postoperative deficit. Postoperative cerebrospinal fluid (CSF) leak occurred in one patient (8%). Three patients (27%) experienced tumor regrowth, and one craniopharyngioma recurred (mean follow-up, 78 months). CONCLUSIONS: The EEA offers a straight route to the sellar-suprasellar, making it the ideal approach for pediatric infradiaphragmatic craniopharyngiomas. In supradiaphragmatic craniopharyngiomas, the extended EEA provides a clearer and close-up visualization of the tumor-hypothalamus interface, which can grant better results in terms of quality of life. The pediatric skull base anatomy should not represent a contraindication for the endoscopic technique. Larger series encompassing a wider spectrum of pediatric craniopharyngiomas are needed to further support the benefits of this surgical approach.

Ventral Brainstem Anatomy: An Endoscopic Transoral Perspective.

In recent years the use of the endoscope through the transclival route has gained new attention as a minimally invasive operative method to successfully treat numerous clival pathologies such as chordomas, meningiomas, haemangiopericytomas, enterogenous and epidermoid cysts, and metastasis(Cappabianca et al. Neurosurgery 55:933-940, 2004; Cappabianca et al. Childs Nerv Syst 20:796-801, 2004; Cappabianca et al. Adv Tech Stand Neurosurg 33:151-199, 2008; Cappabianca et al. Neurosurgery 49:473-475, 2001; Cappabianca et al. Surg Neurol 62:227-233, 2004; Dehdashti et al. Neurosurgery 63:299-307, 2008; Kerschbaumer et al. Spine (Phila Pa 1976) 25:2708-2715, 2000; Saito et al. Acta Neurochir (Wien) 154:879-886, 2012; Stippler et al. Neurosurgery 64:268-277, 2009). Here we describe the endoscopic anatomy of the region reached through an endoscopic transoral approach. Fresh and formalin-fixed cadaver specimens were used to demonstrate both the feasibility of an endoscopic transoral-transclival intradural approach and its potential exposure. The transoral approach was performed using a clival opening of 20 × 15 mm. This smaller access point through the clivus, which allowed insertion of the endoscope and its instruments, did not limit the complete exposure of the cisternal spaces and permitted reconstruction of all anatomical layers.This endoscopic approach thus provides excellent exposure of some of the most dangerous and inaccessible territories of the brain, respecting the anatomy and remaining a minimally invasive approach. Further extensive clinical experience is necessary to prove its safety. The endoscopic transoral-transclival approach will presumably be selected to gain access to lesions of the lower ventral brainstem and the surrounding cisternal spaces, with development of new and more efficient surgical strategies for dural and bone defect repair.

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

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

Anti-Apoptotic and Anti-Oxidant Proteins in Glioblastomas: Immunohistochemical Expression of Beclin and DJ-1 and Its Correlation with Prognosis.

DJ-1 deglycase is a protein with anti-oxidative and anti-apoptotic properties and its role in oncogenesis is controversial. Indeed in primary breast cancer and non-small-cell lung carcinoma, its higher expression was shown in more aggressive tumors while in other neoplasms (e.g., pancreatic adenocarcinoma), higher expression was related to better prognosis. Beclin has a relevant role in autophagy and cellular death regulation, processes that are well known to be impaired in neoplastic cells. DJ-1 shows the ability to modulate signal transduction. It can modulate autophagy through many signaling pathways, a process that can mediate either cell survival or cell death depending on the circumstances. Previously, it has been suggested that the involvement of DJ-1 in autophagy regulation may play a role in tumorigenesis. The aim of our study was to investigate the link between DJ-1 and Beclin-1 in glioblastoma through the immunohistochemical expression of such proteins and to correlate the data obtained with prognosis. Protein expression was assessed by immunohistochemistry and the immunoscores were correlated with clinicopathologic parameters. Kaplan-Meier survival curves were generated. A statistically significant association between DJ-1 score and recurrence (p = 0.0189) and between the former and Isocitrate Dehydrogenase 1 (IDH1) mutation (p = 0.0072) was observed. Kaplan-Meier survival curve analysis revealed that a higher DJ-1 score was associated with longer overall survival (p = 0.0253, ĸ2 = 5.005). Furthermore, an unexpected direct correlation (p = 0.0424, r = 0.4009) between DJ-1 and Beclin score was evident. The most significant result of the present study was the evidence of high DJ-1 expression in IDH-mutant tumors and in cases with longer overall survival. This finding could aid, together with IDH1, in the identification of glioblastomas with better prognosis.

ATM and p53 combined analysis predicts survival in glioblastoma multiforme patients: A clinicopathologic study.

Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo- and radiotherapy represents the current standard of care, and chemo- and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair. To study the effects of the immunohistochemical expression of p-ATM and p53 in glioblastoma patients, 21 cases were retrospectively examined. In normal brain tissue, p-ATM was expressed only in neurons; conversely, in tumors cells, the protein showed a variable cytoplasmic expression (score: +,++,+++), with being completely undetectable in three cases. Statistical analysis revealed that high p-ATM score (++/+++) strongly correlated to shorter survival (P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients (P = 0.669). Survival analysis performed on the results from combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox-regression analysis confirmed this finding (HR = 0.025; CI 95% = 0.002-0.284; P = 0.003). Our study outlined the immunohistochemical expression of p-ATM/p53 in glioblastomas and provided data on their possible prognostic/predictive of response role. A "non-oncogene addiction" to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs.

Tuberculum sellae meningiomas: grading scale to assess surgical outcomes using the transcranial versus transsphenoidal approach.

OBJECTIVE Tuberculum sellae meningiomas (TSMs) are surgically challenging tumors that can severely impair vision. Debate exists regarding whether the transcranial (TC) or endoscopic transsphenoidal (TS) approach is best for resecting these tumors, and there are few large series comparing these approaches. METHODS A retrospective chart review was performed at 2 academic centers comparing TC and TS approaches with respect to vision, extent of resection, recurrence, and complications. The authors report surgical outcomes and propose a simple preoperative tumor grading scale that scores tumor size (1-2), optic canal invasion (0-2), and arterial encasement (0-2). The authors performed univariate, multivariate, and recursive partitioning analysis (RPA) to evaluate outcomes. RESULTS The TSMs were resected in 139 patients. The median follow-up was 29 months. Ninety-five (68%) cases were resected via a TC and 44 (32%) via a TS approach. Tumors treated via a TC approach had a higher tumor (p = 0.0007), artery (p < 0.0001), and total score (p = 0.0012) on the grading scale. Preoperative visual deficits were present in 87% of patients. Vision improved in 47%, stayed the same in 35%, declined in 10%, and was not recorded in 8%. The extent of resection was 65% gross-total resection, 23% near-total resection (95%-99% resection), and 12% subtotal resection (< 95%). A lower tumor score was significantly associated with better or stable vision postoperatively (p = 0.0052). The RPA confirmed low tumor score as the key predictor of postoperative visual improvement or stability. Multivariate analysis and RPA demonstrate that lower canal score (p < 0.0001) and TC approach (p = 0.0019) are associated with gross-total resection. Complications occurred in 20 (14%) patients, including CSF leak (5%) and infection (4%). There was no difference in overall complication rates between TC and TS approaches; however, the TS approach had more CSF leaks (OR 5.96, 95% CI 1.10-32.04). The observed recurrence rate was 10%, and there was no difference between the TC and TS approaches. CONCLUSIONS Tuberculum sellae meningiomas can be resected using either a TC or TS approach, with low morbidity and good visual outcomes in appropriately selected patients. The simple proposed grading scale provides a standard preoperative method to evaluate TSMs and can serve as a starting point for selection of the surgical approach. Higher scores were associated with worsened visual outcomes and subtotal resection, regardless of approach. The authors plan a multicenter review of this grading scale to further evaluate its utility.

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

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