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.

Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification.

The sellar region represents a complex anatomical area, composed of multiple structures of different embryological derivation, including the skull base and the pituitary gland, along with vascular, nervous, and meningeal structures. Masses arising in this region include benign and malignant lesions arising from the pituitary gland itself, but also from vestigial embryological residues or surrounding tissues, that may require different therapeutic approaches. While assessing sellar region masses, the combination of clinical presentation and imaging features is fundamental to define hypotheses about their nature. MR represents the imaging modality of choice, providing information about the site of the lesion, its imaging features, and relation with adjacent structures, while CT is useful to confirm the presence of lesion calcifications or to reveal tumor invasion of bony structures. The aim of this pictorial review is to provide an overview of the common neoplasms and tumor-like conditions of the sellar region, according to the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition), with an emphasis on the radiologic-pathologic correlation. After a brief introduction on the anatomy of this region and the imaging and pathological techniques currently used, the most relevant MRI characteristics, clinical findings, and pathological data, including histologic and molecular features, will be shown and discussed, with the aim of facilitating an appropriate differential diagnosis among these entities.

Surgical Approaches to the Third Ventricle: An Update.

The third ventricle is located in the deepest part of the brain and is delimited by both telencephalic and diencephalic structures. Its location makes every surgical procedure inside or around it quite challenging, due to the distance from the surface to the fragility of the neurovascular structures that is necessary to dissect before entering its cavity and to the narrow surgical corridors through which it is necessary to work. Its geometric localization inside the cranial cavity and the anatomical relationship with the interhemispheric fissure offers nevertheless to the surgeon an impressive variety of surgical approaches, which allow to reach every millimeter of the third ventricle lumen. Mastering properly all these approaches requires an impressive anatomical knowledge, the best available technology, and most refined technical skills, making the surgery of the third ventricle a point of excellence in the evolution of each neurosurgeon. The development of neuronavigation and neuroendoscopy has been a revolution in neurosurgery in the last 20 years and offered special advantages for the surgery of the third ventricle. In fact, the narrow corridors of approach make the precision of the neuronavigation and the enlightenment and magnification of the neuroendoscopy especially useful to reach the third ventricle cavity and working inside or around it. This chapter reviews the history of the surgery of the third ventricle and offers an update of the variety of surgical corridors identified and of the technology now available to properly work through them and inside the third ventricle cavity.

Surgeon's Eyes on the Relevant Surgical Target.

The resolution of the naked eye has been a challenge for the neurosurgical endeavor since the very first attempts of cranial surgery, and advances have been achieved over the centuries, driven by a synergism between the application of emerging technology into the surgical environment and the expansion of the capabilities of neurosurgery. The understanding of the principles of the optical properties of lenses by Abbè (1840-1905) led to the introduction of loupes in the surgical practice, increasing the visual performance during macroscopic procedures. Modern neurosurgery began with the possibility of illumination and magnification of the surgical field as provided by the microscope. Pioneering contributions from Donaghy and Yasargil opened the way to the era of minimalism with reduction of operative corridors and surgical trauma through the adoption of the microsurgical technique. Almost at the same time, engineering mirabilia of Hopkins in terms of optics and lenses allowed for introduction of rigid and flexible endoscopes as a viable tool in neurosurgery. Nowadays, neurosurgeons are aware of and confident using effective and modern tools of visualization in their armamentarium. Herein we present a cogent review of the evolution of visualization tools in neurosurgery, with a special glimpse into the current development and future achievements.

The feasibility of three port endonasal, transorbital, and sublabial approach to the petroclival region: neurosurgical audit and multiportal anatomic quantitative investigation.

PURPOSE: The petroclival region represents the "Achille's heel" for the neurosurgeons. Many ventral endoscopic routes to this region, mainly performed as isolated, have been described. The aim of the present study is to verify the feasibility of a modular, combined, multiportal approach to the petroclival region to overcome the limits of a single approach, in terms of exposure and working areas, brain retraction and manipulation of neurovascular structures. METHODS: Four cadaver heads (8 sides) underwent endoscopic endonasal transclival, transorbital superior eyelid and contralateral sublabial transmaxillary-Caldwell-Luc approaches, to the petroclival region. CT scans were obtained before and after each approach to rigorously separate the contribution of each osteotomy and subsequentially to build a comprehensive 3D model of the progressively enlarged working area after each step. RESULTS: The addition of the contralateral transmaxillary and transorbital corridors to the extended endoscopic endonasal transclival in a combined multiportal approach provides complementary paramedian trajectories to overcome the natural barrier represented by the parasellar and paraclival segments of the internal carotid artery, resulting in significantly greater area of exposure than a pure endonasal midline route (8,77 cm2 and 11,14 cm2 vs 4,68 cm2 and 5,83cm2, extradural and intradural, respectively). CONCLUSION: The use of different endoscopic "head-on" trajectories can be combined in a wider multiportal extended approach to improve the ventral route to the most inaccessible petroclival regions. Finally, by combining these approaches and reiterating the importance of multiportal strategy, we quantitatively demonstrate the possibility to reach "far away" paramedian petroclival targets while preserving the neurovascular structures.

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.

Primary ectopic orbital craniopharyngioma.

Craniopharyngiomas (CP) ectopic localizations off the midline outside the sellar-suprasellar region are very rare and most often associated to secondary tumor dissemination, being primary ectopic CPs extremely unusual. We herein report the first case of a primary ectopic craniopharyngioma within the orbit. A 15-year-old patient presented with progressive right ptosis, proptosis, and retro ocular pain. Magnetic resonance imaging (MRI) showed a predominantly cystic lesion, occupying the superolateral right corner of the orbit, outside the intraconal space with no evidence of intracranial involvement. An endoscopic transorbital eyelid approach was adopted. Pathology report disclosed a primary ectopic craniopharyngioma.

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.

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.

Multicenter external validation of the Zurich Pituitary Score.

PURPOSE: Recently, the Zurich Pituitary Score (ZPS) has been proposed as a new quantitative preoperative classification scheme for predicting gross total resection (GTR), extent of resection (EOR), and residual tumor volume (RV) in endoscopic pituitary surgery. We evaluated the external validity of the ZPS. METHODS: In three reference centers for pituitary surgery, the ZPS was applied and correlated to GTR, EOR, and RV. Furthermore, its inter-rater agreement was assessed. RESULTS: A total of 485 patients (53% male; age, 53.8 ± 15.7) were included. ZPS grades I, II, III, and IV were observed in 110 (23%), 270 (56%), 64 (13%), and 41 (8%) patients, respectively. GTR was achieved in 358 (74%) cases, with mean EOR of 87.6% ± 20.3% and RV of 1.42 ± 2.80 cm3. With increasing ZPS grade, strongly significant decreasing trends for GTR (I, 92%; II, 77%; III, 67%; IV, 15%; p < 0.001) and EOR (I, 93.8%; II, 89.9%; III, 88.1%; IV, 75.4%; p < 0.001) were found. Similarly, RV increased steadily ([cm3] I, 0.16; II, 0.61; III, 2.01; IV, 3.84; p < 0.001). We observed intraclass correlation coefficients of 0.837 (95% CI, 0.804-0.865) for intercarotid distance and 0.964 (95% CI, 0.956-0.970) for adenoma diameter, and Cohen's kappa of 0.972 (95% CI, 0.952-0.992) for the ZPS grades. CONCLUSIONS: Application of the ZPS in three external cohorts was successful. The ZPS generalized well in terms of GTR, EOR, and RV; demonstrated excellent inter-rater agreement; and can safely and effectively be applied as a quantitative classification of adenomas with relevance to surgical outcome.

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

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

Endoscopic 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.

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.