Through the orbit and beyond: Current state and future perspectives in endoscopic orbital surgery on behalf of the EANS frontiers committee in orbital tumors and the EANS skull base section.

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

Spinal metastases of bronchopulmonary cancer: Role of spinal surgery and value of prognostic scores (Modified Tokuhashi and Tomita).

INTRODUCTION: Bone metastasis is frequent in bronchopulmonary cancer. We report a series of 52 patients, and analyze indications and the efficacy of surgery. MATERIALS AND METHODS: We retrospectively studied the records of 52 patients operated on for spinal metastases of bronchopulmonary cancer over a 6-year period from January 2009 to December 2014 in the neurosurgery department of the North Hospital of Marseille, France. RESULTS: Mean age was 63.6years; with a sex ratio of 3:1 (M:F). Spinal pain associated with vertebral fracture and spinal cord compression was the most frequent clinical presentation (59.6%). SINS score was≥7 in 78.9% of cases. Karnofski Performance Status was average in 67.4% of cases. Predicted survival beyond 12months was zero according to the modified Tokuhashi score. The surgical indication was essentially palliative. Evolution showed regression of pain in 84.6% of cases, and stabilization and improvement in motor deficit in 80.6%. Median postoperative survival was 16months. CONCLUSION: Our results highlight the interest of surgery for pain relief, spinal stabilization and improvement in neurological function in patients with spinal metastases of bronchopulmonary cancer, and the unreliability of predictive survival scores.

Sustainable neurosurgical training around the globe. A review and outline.

Sharing an equal and quality neurosurgical training across the globe without exclusion may seem utopian. However, such training is possible through educational opportunities and the ongoing digital revolution. The aim is to present the current state of neurosurgery training and education methods indicating strengths, weaknesses and opportunities. The thoughts, comments and suggestions of the authors are based on their academic experiences, training missions around the world and particularly in low- and middle-income countries by pointing out the French experience. The learning must be interactive and programmed over time, integrating varied courses and activities. Virtual reality and neurosurgical simulation need to be developed. The content of the teaching including e-learning must be evidence-based and peer-reviewed. Pedagogical training of trainers is fundamental. It is critical to evaluate the training under real working conditions. The optimization of human resources should create economies of scale that would attenuate the financial burden. The commitment of the teams, tutoring are success factors.

Myasthenia gravis and pregnancy.

Myasthenia gravis is an autoimmune disease characterised by fluctuating muscle weakness, which worsens during activity. It affects particularly scapular and pelvic girdles, axial and bulbar muscles. Myasthenia gravis is twice more frequent in women and symptoms often appear in the second and third decade of life. Thus, a growing number of women affected by this condition become pregnant. To minimise the effects of myasthenia gravis on pregnancy and the newborn, and to avoid myasthenia crisis in the post-partum, the pregnancy must be planned as far as possible. During pregnancy, treatment must be reviewed due to the threat of teratogenic effects (mycophenolate mofetil, rituximab), and the follow-up must be multidisciplinary.

The presigmoid retrolabyrinthine approach: Technical note.

BACKGROUND: The retrolabyrinthine approach is classified among the posterior petrosectomies. Its goal is to achieve an enlarged mastoidectomy while sparing the intrapetrous neurotologic structures in order to offer maximal exposure of the posterior cerebellopontine angle compound. METHODS: The stages of the procedure are subsequently the skeletonization of the sigmoid sinus, wide opening of the mastoid antrum and exposure of the semicircular canals. We present herein the technique, indications and limitations of the retrolabyrinthine approach. CONCLUSION: The retrolabyrinthine approach is a demanding technique. Nowadays the retrolabyrinthine approach is routinely combined to additional resections of the petrous bone, so-called "combined petrosectomies", to target the jugular foramen or the petroclival area.

Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo.

Exosomes support cell-to-cell communication in physiology and disease, including cancer. We currently lack tools, such as small chemicals, capable of modifying exosome composition and activity in a specific manner. Building on our previous understanding of how syntenin, and its PDZ partner syndecan (SDC), impact on exosome composition we optimized a small chemical compound targeting the PDZ2 domain of syntenin. In vitro , in tests on MCF-7 breast carcinoma cells, this compound is non-toxic and impairs cell proliferation, migration and primary sphere formation. It does not affect the size or the number of secreted particles, yet it decreases the amounts of exosomal syntenin, ALIX and SDC4 while leaving other exosomal markers unaffected. Interestingly, it also blocks the sorting of EpCAM, a bona fide target used for carcinoma exosome immunocapture. Our study highlights the first characterization of a small pharmacological inhibitor of the syntenin-exosomal pathway, of potential interest for exosome research and oncology.

A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

Reform of the 3rd cycle in surgery training.

The main objectives of the reform of the 3rd cycle of medical studies in France that was instituted in 2017 after eight years of preparation, are to train future specialists in a consistent and equitable fashion and to replace the previous time-based qualification by training based on the progressive acquisition of skills. This reform was an opportunity for the 13 different French surgical specialty Colleges involved to share reflections on what a surgeon actually was and to define training in surgical sub-specialties. The current reform is well adapted to these specifications and has fostered training models that are consistent with each other. This article discusses the historical construction of this reform, what will change in the training of future surgeons, as well as some points that warrant caution. The third cycle reform has also triggered a reform of the second cycle, which is expected to come into force for the 2020 academic year. Its objective will be to eliminate the guillotine effect created by the National Classifying Examinations and to allow students to better understand and test their desire and skills for a given specialty. It will be up to these same surgical Colleges to determine how to do this for the sub-specialties of the "surgery" discipline.

Toward the development of 3-dimensional virtual reality video tutorials in the French neurosurgical residency program. Example of the combined petrosal approach in the French College of Neurosurgery.

BACKGROUND: The present study developed 3D video tutorials with commentaries, using virtual reality headsets (VRH). VRHs allow 3D visualization of complex anatomy from the surgeon's point of view. Students can view the surgery repeatedly without missing the essential steps, simultaneously receiving advice from a group of experts in the field. METHODS: A single-center prospective study assessed surgical teaching using 3D video tutorials designed for French neurosurgery and ENT residents participating in the neuro-otology lateral skull-base workshop of the French College of Neurosurgery. At the end of the session, students filled out an evaluation form with 5-point Likert scale to assess the teaching and the positive and negative points of this teaching tool. RESULTS: Twenty-two residents in neurosurgery (n=17, 81.0%) and ENT (n=5) were included. Eighteen felt that the 3D video enhanced their understanding of the surgical approach (81.8%). Fifteen (68.2%) thought the video provided good 3D visualization of anatomical structures and 20 that it enabled better understanding of anatomical relationships (90.9%). Most students had positive feelings about ease of use and their experience of the 3D video tutorial (n=14, 63.6%). Twenty (90.9%) enjoyed using the video. Twelve (54.5%) considered that the cadaver dissection workshop was more instructive. CONCLUSIONS: 3D video via a virtual reality headset is an innovative teaching tool, approved by the students themselves. A future study should evaluate its long-term contribution, so as to determine its role in specialized neurosurgery and ENT diploma courses.

Long term surgical results of 154 petroclival meningiomas: A retrospective multicenter study.

BACKGROUND: Outcomes of petroclival meningiomas (PCM) (morbidity, permanent cranial nerves deficit, tumor removal and recurrence) are inconsistent in the literature, making it a challenge to predict surgical morbidity. METHODS: A multicenter study of patients with PCMs larger than 2.5cm between 1984 and 2017 was conducted. The authors retrospectively reviewed the patients' medical records, imaging studies and pathology reports to analyze presentation, surgical approach, neurological outcomes, complications, recurrence rates and predictive factors. RESULTS: There were 154 patients. The follow-up was 76.8 months on average (range 8-380 months). Gross total resection (GTR) was achieved in 40 (26.0%) patients, subtotal resection (STR) in 101 (65.6%), and partial resection in 13 (8.3%). Six (2.6%) perioperative deaths occurred. The 5-year, 10-year and 15-year progression-free survival (PFS) of GTR and STR with radiation therapy (RT) was similar (100%, 90% and 75%). PFS of STR without adjuvant radiation was associated with progression in 71%, 51% and 31%, respectively. Anterior petrosectomy and combined petrosectomy were associated with higher postoperative CN V and CN VI deficits compared to the retrosigmoid approach. The latter had a significantly higher risk of CN VII, CN VIII and LCN deficit. Temporal lobe dysfunction (seizure and aphasia) were significantly associated with the anterior petrosectomy approach. CONCLUSIONS: Our study shows that optimal subtotal resection of PCMs associated with postoperative RT or stereotactic radiosurgery results in long-term tumor control to equivalent radical surgery. Case selection and appropriate intraoperative judgement are required to reduce the morbidity.

Delayed hemorrhagic complication after complete embolization of a brain arteriovenous malformation.

Endovascular embolization is an essential therapeutic approach in the multidisciplinary management of cerebral arteriovenous malformations (AVM). However, it rarely occludes the AVM in its entirety. It is often combined with surgery or stereotactic radiosurgery. The aim of embolization is to reduce the size of the nidus and the intra-nidal flow in order to facilitate the microsurgical or the radiosurgical procedure. We report the case of a 61-year-old patient with a right frontal hemorrhagic AVM treated with complete embolization in a single session. Initially, a surgical procedure for excision of the AVM was scheduled 24hours post-embolization. This surgery was canceled due to a good angiographic result of the embolization. Eight days post-embolization, there was a massive re-bleed of the AVM which justified emergency surgical management. This case illustrates a delayed post-embolization hemorrhagic complication of an occluded AVM and prompts a review of the therapeutic strategy of the cerebral AVM to select the most effective and least morbid procedure or combination of procedures.

Long-term results of Gamma-knife stereotactic radiosurgery for vestibular schwannomas in patients with type 2 neurofibromatosis.

INTRODUCTION: The aim of this study was to analyze the long-term results of Gamma-knife radiosurgery treatment of vestibular schwannomas in type 2 neurofibromatosis patients. MATERIALS AND METHODS: A cohort of 129 treatments for vestibular schwannomas in 103 patients was selected from a prospectively-maintained clinical database. Tumor control was assessed by volumetric analysis of the tumor at the last follow-up. Any need of a further procedure such as microsurgical removal or second treatment was regarded as a failure of tumor control. Hearing function was assessed based on Gardner-Robertson classification. Progression-free survival and functional hearing preservation rates were estimated using the Kaplan-Meier method. RESULTS: The median age at treatment was 34 years with no gender predominance. The median tumor volume was 1.5cm3. At a median clinical follow-up of 5.9 years, five patients had died, four underwent a second radiosurgical procedure and eight underwent microsurgical resection. Progression-free survival was 88 and 75% respectively at 5 and 10 years. Hearing was considered serviceable in 70 ears and remained functional in 28 ears. Kaplan-Meier estimates for 5 and 10 years functional hearing was 47 and 34%, respectively. Three patients developed new facial nerve palsy after radiosurgery at 15 days, 6 and 19 months respectively and only one partially recovered. Five patients complained of a subjective instability worsening. Four cases developed trigeminal neuropathy. No predictive factors were found to be statistically correlated with a better hearing outcome or an improved tumor growth control. CONCLUSION: Results prove less satisfying than in sporadic unilateral schwannomas. However, the lower rate of mortality and morbidity compared with microsurgical resection may support a proactive role of Gamma-knife in this pathology.

Extradural resection of the anterior clinoid process: How I do it.

BACKGROUND: The anterior clinoid process shares a close relationship with the optic canal, the internal carotid artery, the superior orbital fissure and the cavernous sinus. These structures may be involved in diseases whose surgical exposure requires prior clinoid process resection. METHOD: Based on operative cases we describe the different steps of this surgical technique and illustrate our surgical procedure with a video. Dividing the orbito-temporal periosteal fold is a key-step in order to optimize the elevation of the periosteal dural layer at the level of the superior orbital fissure to expose the contours of the anterior clinoid process. The clinoid tip is removed after "debulking" the bony content inside the anterior clinoid process in order to leave only a thin shell of bony contour. The bony shell is then detached from the dura, twisted and pulled out. The indications and limitations of the technique are presented. CONCLUSION: The extradural approach of the anterior clinoid process totally provides a full resection of the anterior clinoid process and safety for the paraclinoid space structures. Meticulous stepwise bony resection and optimized dura opening contribute to reduce the risk inherent to this technique.

Emission of Nonclassical Radiation by Inelastic Cooper Pair Tunneling.

We show that a properly dc-biased Josephson junction in series with two microwave resonators of different frequencies emits photon pairs in the resonators. By measuring auto- and intercorrelations of the power leaking out of the resonators, we demonstrate two-mode amplitude squeezing below the classical limit. This nonclassical microwave light emission is found to be in quantitative agreement with our theoretical predictions, up to an emission rate of 2 billion photon pairs per second.

"Giant cell reparative tumor: An exceptional differential diagnosis for a lytic lesion of the temporal bone".

BACKGROUND AND IMPORTANCE: Giant cell reparative granuloma is a very rare benign osteolytic lesion. It typically arises in the mandible and rarely involves the skull. CLINICAL PRESENTATION: A 25-year-old male was admitted in August 2002 for a painless left preauricular mass of several months duration. CT scan revealed an osteolytic extradural lesion located in the temporal bone, with extension to infratemporal fossa. We performed a surgical partial resection of the tumour via a frontotemporal approach. At 36 months after surgery, the lesion continued growth and subsequently we decided to perform a preauricular infratemporal approach. After a ten year-follow-up, the patient remained asymptomatic and a small tumour remnant was visible and stable. CONCLUSION: Giant cell reparative granulomas that originate from the temporal bone are exceptional. There are no typical radiological features of this disease. Diagnosis is confirmed by analysis of the surgical specimen. Tumor growth requires surgical resection.

Cerebellopontine angle gangliogliomas: Report of two cases.

BACKGROUND: Gangliogliomas are rare tumors of the central nervous system. We report two unusual cases of gangliogliomas located in the cerebellopontine angle (CPA). POPULATION AND METHODS: The first patient was a 57-year-old woman, who presented with dizziness and harbored a non-enhanced heterogeneous mass located in the cisternal space of the CPA. A partial microsurgical removal was performed, and the pathological examination concluded a grade I ganglioglioma according to the WHO Classification. The postoperative course was uneventful without any adjuvant treatment and the 5-year imaging follow-up indicated a stable remnant tumor. The second patient was a 35-year-old male who presented with acute vertigo and imbalance associated with recent prominent headaches; MR imaging showed a large heterogeneous and post-contrast enhanced tumor mass located in the CPA cistern with a mass effect on the brain. An optimal subtotal surgical resection was performed. The pathologists concluded a WHO grade III ganglioglioma. In spite of adjuvant radiotherapy and chemotherapy, the evolution proved unfavorable and patient died from cancer complications within a 2-year period. In both cases, the precise origin of the tumor could not be clearly identified even if the major component was present in the cisternal space. CONCLUSION: Gangliogliomas growing into the cisternal spaces are exceedingly rare particularly in the CPA. Due to its infiltrating behavior and major difficulties to identify the tumor margins, total resection is not routinely feasible. The histological grading is the most important predictor for oncological prognosis.