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Introduction: Artificial Intelligence (AI) applications in healthcare are growing exponentially. The field of neurosurgery is particularly suited to implement AI solutions given its technology-driven nature. It is of paramount importance to understand the basics of AI to make informed decision on how to shape current and future applications. Research question: What is the level of confidence, knowledge and the attitude of the global neurosurgical community towards AI basic concepts and applications? Material and methods: A 24-item survey was designed and distributed. The survey results reported on level of knowledge, confidence and interest in AI, perspectives and attitude towards the application of AI technologies in neurosurgery. The potential influence of demographics and work-related environment features on AI knowledge was investigated. Results: We received a total of 250 responses from 61 countries. The correct definition of ‘Machine Learning’, ‘Deep Learning’ and main Big Data features were identified by respectively 42%, 23% and 23% of the respondents. The survey unveiled a strong interest and a positive attitude towards the introduction of AI in the neurosurgical practice. The main concerns included trustworthiness and liability, the main barriers to implementation were considered lack of funding, infrastructure, knowledge and multidisciplinary collaboration. Discussion and conclusion: There is a low familiarity with basic AI concepts in the neurosurgical community. Nevertheless, there is a strong interest and a positive attitude towards AI implementation. The systematization of training and the production of educational resources will be key in guaranteeing a successful implementation of AI in the evolving history of neurosurgery.

Abstract Hormone-secreting adenomas are treated in many neurosurgical centers within Europe. The goal of the survey is to understand variance in practice management of pituitary tumors amongst neurosurgical centers. A list of departments performing pituitary surgery was created. The survey consisted of 58 questions. This study focuses on neurosurgical care of hormone-secreting adenomas. For analysis, the departments were divided into four subgroups: academic/non-academic, high-volume/low-volume, “mainly endoscopic/mainly microscopic practice” and geographical regions. Data from 254 departments from 34 countries were obtained. Most centers surgically treat 1–5 hormone-secreting adenomas per year. In prolactinomas this is the case in 194 centers, (76.4%), in GH-secreting adenomas: 133 centers, (52.4%), ACTH-secreting adenomas: 172 centers, (69.8%). Surgery as a primary treatment of prolactinomas is considered in 64 centers (25.2%). In 47 centers (18.8%), GH-secreting microadenomas are often treated pharmacologically first. Debulking surgery for an invasive GH-secreting adenoma in which hormonal remission is not a realistic goal of the surgery and the patient has no visual deficit surgery is always or mostly indicated in 156 centers (62.9%). Routine postoperative hydrocortisone replacement therapy is administered in 147 centers (58.6%). Our survey shows that in most centers, few hormone-secreting adenomas are treated per year. In about 25% of the centers, prolactinoma surgery may be regarded as first-line treatment; in about 20% of the centers, medical treatment is the first-line treatment for GH-secreting adenomas. Pretreatment for ACTH-secreting adenomas is routinely used in 21% of centers. This survey may serve as plea for neurosurgical care centralization of hormone-secreting adenomas.

Objective. Pituitary adenoma surgery has evolved rapidly in recent decades. This study aims to determine current practice across a wide range of European neurosurgical centers. Methods. A list of eligible departments performing pituitary adenoma surgery was created. The survey consisted of 58 questions. For analysis, the departments were divided into four subgroups: academic/nonacademic, high-volume/low-volume, “mainly endoscopic/mainly microscopic practice,” and geographical regions. Results. Data from 254 departments from 34 countries were obtained. In 108 centers (42.5%), 100 adenoma surgeries per year. Number of neurosurgeons performing endonasal surgeries are as follows: 1 in 24.9% of centers and 2 in 49.8% of centers. All residents assisted endonasal surgeries in 126 centers (49.8%). In 28 centers (21.1%), all residents performed endonasal surgery under supervision during residency. In 141 centers (56.8%), the endoscopic approach was used in >90% of the surgeries. Regular pituitary board (either weekly or once a month) meetings were held in 147 centers (56.3%). Nonfunctioning adenomas represent >70% of pituitary caseload in 149 centers (58.7%). Conclusions. In our survey, most centers perform less than 100 surgeries for pituitary adenomas. In most centers, pituitary surgeries are performed by one or two neurosurgeons. Residents have a limited exposure to this type of surgery, and the formal pituitary board is not a standard. Nonfunctioning adenomas make up most of surgically treated adenomas. This study can serve as a benchmark for further analyses of pituitary adenoma centers in Europe.

Introduction: Professionalism entails expert knowledge, self-regulation, accountability, and professional ethics. These factors are influenced by culture, political observance, professional maturity, education, and occupation; ethical practices may thus vary between countries and affect how neurosurgery is practiced. Research question: This paper aims to conduct a survey that addresses whether ethico-legal practices differ in European countries and whether existing ethical guidelines have been implemented. Material and methods: A questionnaire survey was used to examine the ethico-legal situation in 29 European countries or regions. The reports were validated by representatives of each nation. Results: Existing guidelines had been implemented to a minimal extent. Major regional and national differences were found in attitudes toward life and death, prioritization, and issues related to professional conduct. Discussion and conclusion: The results of this survey reveal inadequacies and weaknesses of policies and resources, which should spark national discussions to improve the conditions that influence professional ethics. Unfortunately, only a minority of neurosurgeons know the neurosurgical ethics guidelines and apply them in their decision making. Our findings highlight the importance of values and professional ethics in decision making.

Objectives: To describe the treatment and clinical results in patients diagnosed with atypical meningioma treated at the Donostia University Hospital. We evaluated recurrence, overall survival, and disease-free survival. Methods: From 284 meningiomas treated in our center over 16 years, 32 cases of grade II atypical meningioma were selected. Clinical and surgical notes were retrospectively evaluated. Pre and postoperative clinical and radiological parameters, the modality of radiotherapeutic treatment and its clinical results were evaluated. The histological classification was consistent with the 2007 WHO (World Health Organization) classification. The Simpson classification system was used to assess the degree of surgical resection. Results: we found 18 men and 14 women with a mean age of 60 years. Parasagittal location and convexity were the most frequent locations respectively (14 and 12 cases). The mean follow-up was 50 months. Simpson I-III resection was performed in 28 cases (87%). 22 patients (20 Simpson I-III and 2 Simpson IV) received postoperative radiotherapy (20 cases fractionated radiotherapy and radiosurgery in 2), while 10 patients (8 Simpson I-II and 2 Simpson IV) did not receive postoperative radiotherapy. The recurrence rate in patients who received radiotherapy was 45% and 60% in those who did not receive radiotherapy. Recurrence-free survival and overall survival in patients under radiotherapy was 36 and 48 months, respectively. On the contrary, in those who did not receive radiotherapy it was 44 and 56 months. Conclusions: In this study, the most important prognostic factor related to survival was the degree of surgical resection. Therefore, adjuvant radiotherapy should be used in those cases without complete surgical resection. In addition, we recommend evaluating reoperation in recurrent symptomatic cases.

Background: High frequency stimulation (HFS) may provide pain relief without the paresthesias typical of traditional low-frequency Spinal cord stimulation (SCS). Methods: A consecutive single-center series of patients was retrospectively reviewed to evaluate safety and efficacy of HF10 therapy. In this 24-month study, 62 patients with variables pathologies (44 patients with back failure surgery syndrome (FBSS), 18 patients with chronic peripheral neuropathic pain in the lower limbs (NeppL) were included to be treated with HF10. Pain outcomes were compared from preoperative baseline and at the conclusion of each study period. Clinical features, outcomes and complications were reviewed. Results: 62 patients completed this study. All patients had a successful trial before the definitive implantation of a spinal cord stimulator at the low dorsal level. The mean follow-up period was 11 months, ranging from 6 to 24 months. 6 patients showed no change from baseline visual analogue scale (VAS) after permanent implant and 2 had improved during the trial but was aggravated after the permanent implant placement. At 1 month, 63% of implanted HF10 therapy subjects were responders and 77% at 6 months. The average baseline, trial and postoperative Visual Analogue Scale (VAS) was 8.1, 3.6 and 4.2 respectively. When compared to the baseline, the average reduction achieved during the VAS trial was 4.5 points, accounting for a 56% pain reduction. The long-term failure rate was 22%. Conclusions: This study generated preliminary evidence showing improved VAS current pain scores in absence of paresthesias and increase patient satisfaction with HF10 spinal cord stimulation.

Background: Strengthening health systems requires attention to workforce, training needs, and barriers to service delivery. The World Federation of Neurosurgical Societies Young Neurosurgeons Committee survey sought to identify challenges for residents, fellows, and consultants within 10 years of training. Methods: An online survey was distributed to various neurosurgical societies, personal contacts, and social media platforms (April–November 2018). Responses were grouped by World Bank income classification into high-income countries (HICs), upper middle-income countries (UMICs), low-middle-income countries (LMICs), and low-income countries (LICs). Descriptive statistical analysis was performed. Results: In total, 953 individuals completed the survey. For service delivery, the limited number of trained neurosurgeons was seen as a barrier for 12.5%, 29.8%, 69.2%, and 23.9% of respondents from HICs, UMICs, LMICs, and LICs, respectively (P < 0.0001). The most reported personal challenge was the lack of opportunities for research (HICs, 34.6%; UMICs, 57.5%; LMICs, 61.6%; and LICs, 61.5%; P = 0.03). Other differences by income class included limited access to advice from experienced/senior colleagues (P < 0.001), neurosurgical journals (P < 0.0001), and textbooks (P = 0.02). Assessing how the World Federation of Neurosurgical Societies could best help young neurosurgeons, the most frequent requests (n = 953; 1673 requests) were research (n = 384), education (n = 296), and subspecialty/fellowship training (n = 232). Skills courses and access to cadaver dissection laboratories were also heavily requested. Conclusions: Young neurosurgeons perceived that additional neurosurgeons are needed globally, especially in LICs and LMICs, and primarily requested additional resources for research and subspecialty training.

Background: Providing a comprehensive and effective neurosurgical service requires adequate numbers of well-trained, resourced, and motivated neurosurgeons. The survey aims to better understand 1) the demographics of young neurosurgeons worldwide; 2) the challenges in training and resources that they face; 3) perceived barriers; and 4) needs for development. Methods: This was a cross-sectional study in which a widely disseminated online survey (April 2018–November 2019) was used to procure a nonprobabilistic sample from current neurosurgical trainees and those within 10 years of training. Data were grouped by World Bank income classifications and analyzed using χ2 tests because of its categorical nature. Results: There were 1294 respondents, with 953 completed responses included in the analysis. Of respondents, 45.2% were from high-income countries (HICs), 23.2% from upper-middle-income countries, 26.8% lower-middle-income countries, and 4.1% from low-income countries. Most respondents (79.8%) were male, a figure more pronounced in lower-income groups. Neuro-oncology was the most popular in HICs and spinal surgery in all other groups. Although access to computed tomography scanning was near universal (98.64%), magnetic resonance imaging access decreased to 66.67% in low-income countries, compared with 98.61% in HICs. Similar patterns were noted with access to operating microscopes, image guidance systems, and high-speed drills. Of respondents, 71.4% had dedicated time for neurosurgical education. Conclusions: These data confirm and quantify disparities in the equipment and training opportunities among young neurosurgeons practicing in different income groups. We hope that this study will act as a guide to further understand these differences and target resources to remedy them.

Abstract Long non-coding RNAs (LncRNAs) have emerged as a relevant class of genome regulators involved in a broad range of biological processes and with important roles in tumor initiation and malignant progression. We have previously identified a p53-regulated tumor suppressor signature of LncRNAs (PR-LncRNAs) in colorectal cancer. Our aim was to identify the expression and function of this signature in gliomas. We found that the expression of the four PR-LncRNAs tested was high in human low-grade glioma samples and diminished with increasing grade of disease, being the lowest in glioblastoma samples. Functional assays demonstrated that PR-LncRNA silencing increased glioma cell proliferation and oncosphere formation. Mechanistically, we found an inverse correlation between PR-LncRNA expression and SOX1, SOX2 and SOX9 stem cell factors in human glioma biopsies and in glioma cells in vitro. Moreover, knock-down of SOX activity abolished the effect of PR-LncRNA silencing in glioma cell activity. In conclusion, our results demonstrate that the expression and function of PR-LncRNAs are significantly altered in gliomagenesis and that their activity is mediated by SOX factors. These results may provide important insights into the mechanisms responsible for glioblastoma pathogenesis.

We undertook this study to understand how the transcription factor Sox2 contributes to the malignant phenotype of glioblastoma multiforme (GBM), the most aggressive primary brain tumor. We initially looked for unbalanced genomic rearrangements in the Sox2 locus in 42 GBM samples and found that Sox2 was amplified in 11.5% and overexpressed in all the samples. These results prompted us to further investigate the mechanisms involved in Sox2 overexpression in GBM. We analyzed the methylation status of the Sox2 promoter because high CpG density promoters are associated with key developmental genes. The Sox2 promoter presented a CpG island that was hypomethylated in all the patient samples when compared to normal cell lines. Treatment of Sox2-negative glioma cell lines with 5-azacitidine resulted in the re-expression of Sox2 and in a change in the methylation status of the Sox2 promoter. We further confirmed these results by analyzing data from GBM cases generated by The Cancer Genome Atlas project. We observed Sox2 overexpression (86%; N = 414), Sox2 gene amplification (8.5%; N = 492), and Sox 2 promoter hypomethylation (100%; N = 258), suggesting the relevance of this factor in the malignant phenotype of GBMs. To further explore the role of Sox2, we performed in vitro analysis with brain tumor stem cells (BTSCs) and established glioma cell lines. Downmodulation of Sox2 in BTSCs resulted in the loss of their self-renewal properties. Surprisingly, ectopic expression of Sox2 in established glioma cells was not sufficient to support self-renewal, suggesting that additional factors are required. Furthermore, we observed that ectopic Sox2 expression was sufficient to induce invasion and migration of glioma cells, and knockdown experiments demonstrated that Sox2 was essential for maintaining these properties. Altogether, our data underscore the importance of a pleiotropic role of Sox2 and suggest that it could be used as a therapeutic target in GBM.