Search

Abstract Numerous materials of implants used for cranioplasty after decompressive craniectomy (DC) have been investigated to meet certain demanded key features, such as stability, applicability, and biocompatibility. We aimed to evaluate the feasibility and safety of biocompatible calcium-phosphate (CaP) implants for cranioplasty compared to polymethylmethacrylate (PMMA) implants. In this retrospective observational cohort study, the medical records of all patients who underwent cranioplasty between January 1st, 2015, and January 1st, 2022, were reviewed. Demographic, clinical, and diagnostic data were collected. Eighty-two consecutive patients with a mean age of 52 years (range 22–72 years) who received either a PMMA (43/82; 52.4%) or CaP (39/82; 47.6%) cranial implant after DC were included in the study. Indications for DC were equally distributed in both groups. Time from DC to cranioplasty was 143.8 ± 17.5 days (PMMA) versus 98.5 ± 10.4 days (CaP). The mean follow-up period was 34.9 ± 27.1 months. Postoperative complications occurred in 13 patients with PMMA and 6 in those with CaP implants (13/43 [30.2%] vs. 6/39 [15.4%]; p = 0.115). Revision surgery with implant removal was necessary for 9 PMMA patients and in 1 with a CaP implant (9/43 [20.9%] vs. 1/39 [2.6%]; p = 0.0336); 6 PMMA implants were removed due to surgical site infection (SSI) (PMMA 6/43 [14%] vs. CaP 0/39 [0%]; p = 0.012). In this study, a biocompatible CaP implant seems to be superior to a PMMA implant in terms of SSI and postoperative complications. The absence of SSI supports the idea of the biocompatible implant material with its ability for osseointegration.

H3K27M mutant (mut) diffuse midline glioma (DMG) is a lethal cancer with no effective cure. The glycosphingolipids (GSL) metabolism is altered in these tumors and could be exploited to develop new therapies. We tested the effect of the glucosylceramide synthase inhibitors (GSI) miglustat and eliglustat on cell proliferation, alone or in combination with temozolomide or ionizing radiation. Miglustat was included in the therapy protocol of two pediatric patients. The effect of H3.3K27 trimethylation on GSL composition was analyzed in ependymoma. GSI reduced the expression of the ganglioside GD2 in a concentration and time-dependent manner and increased the expression of ceramide, ceramide 1-phosphate, sphingosine, and sphingomyelin but not of sphingosine 1-phosphate. Miglustat significantly increased the efficacy of irradiation. Treatment with miglustat according to dose recommendations for patients with Niemann–Pick disease was well tolerated with manageable toxicities. One patient showed a mixed response. In ependymoma, a high concentration of GD2 was found only in the presence of the loss of H3.3K27 trimethylation. In conclusion, treatment with miglustat and, in general, targeting GSL metabolism may offer a new therapeutic opportunity and can be administered in close proximity to radiation therapy. Alterations in H3K27 could be useful to identify patients with a deregulated GSL metabolism.

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.

Background Spine surgeons are usually exposed to high workload and demanding work conditions. Although the relationship between pharmacological neuroenhancement (PNE) and resilience (i.e., the ability to recover from stress), as well as perceived stress and resilience-enhancing factors, has been investigated in the general population, less is known about the impact of those factors in spine surgeons. This study aimed to close that gap by investigating the relationship between PNE use and resilience, perceived stress, or resilience-enhancing factors in spine surgeons. Methods We conducted a cross-sectional survey in a sample of 582 spine surgeons in German-speaking countries (Austria, Germany, and Switzerland). Potentially predictive variables as well as the use of PNE were assessed by self-report questionnaires. We conducted stepwise logistic regression with backward elimination to assess the relationship among PNE use, perceived stress, resilience, and resilience-enhancing factors. Results Lifetime prevalence for PNE use was 5.7%, with highest prevalence rates for antidepressants (2.6%). Each additional unit on the Perceived Stress Scale increased the risk for PNE use (odds ratio, 2.271; 95% confidence interval, 0.1.363–3.785; P = 0.002). No statistically significant results were found for the individual ability to recover from stress or resilience-enhancing factors. Conclusions Spine surgeons with higher levels of stress seem to be more prone to nonmedical use of PNE. Tailored interventions may improve the ability to cope with high perceived stress and prevent the use of PNE. Further research should examine the efficacy of those interventions on the prevention of PNE in spine surgeons.

Background Surgery is, next to medical and radiation therapy, the mainstay therapy for pituitary adenomas. While scientific consensus regarding the key aspects of pituitary surgery exists among neurosurgeons, procedures are not standardized and might vary significantly between hospitals and surgeons. Objective To provide an overview of how neurosurgical departments in Germany manage pituitary surgery. Methods Responses from the European Pituitary Adenoma Surgery Survey were analyzed. The survey contained 60 questions regarding demographics, training, surgical and endocrinological aspects, and patient management. Results Sixty neurosurgical centers from Germany responded to the survey. Among the centers, 35.3% (n=18) exclusively use the microscopic and 31.1% (n=14) the endoscopic technique; all other centers (n=28) use both approaches. Of responding centers, 20% (n=12) perform less than 10 transsphenoidal pituitary surgeries per year, and 1.7% (n=1), more than 100 operations. The number of transcranial pituitary operations is significantly smaller, with 53.3% of centers performing only 0–2 per year, 35% performing 3–5, and only one center (1.7%) performing more than 15 transcranial operations per year. In 8 centers (13.3%), surgeries are always performed together with an ENT surgeon; in 29 centers (48.4%) ENT surgeons are never involved. In most centers (n=54, 90%) intraoperative MRI is not available. Image guidance (with preoperative CT and/or MRI data) is used by 91.7% of respondents (n=55). Forty-two centers (72.4%) routinely prescribe hydrocortisone after pituitary surgery, and 75% (n=45) have pituitary board meetings with endocrinologists, radiologists, and radiosurgeons. Fifty-two (86.7%) respondents perform the first follow-up scan by MRI 3–4 months after surgery. Conclusions The data showed differences as well as similarities between centers and could help to discuss the standardization of methods and the formation of networks and certification to improve patient care.

Purpose Neuro-oncology tumor boards (NTBs) hold an established function in cancer care as multidisciplinary tumor boards. However, NTBs predominantly exist at academic and/or specialized centers. In addition to increasing centralization throughout the healthcare system, changes due to the COVID-19 pandemic have arguably resulted in advantages by conducting clinical meetings virtually. We therefore asked about the experience and acceptance of (virtualized) NTBs and their potential benefits. Methods A survey questionnaire was developed and distributed via a web-based platform. Specialized neuro-oncological centers in Germany were identified based on the number of brain tumor cases treated in the respective institution per year. Only one representative per center was invited to participate in the survey. Questions targeted the structure/organization of NTBs as well as changes due to the COVID-19 pandemic. Results A total of 65/97 institutions participated in the survey (response rate 67%). In the context of the COVID-19 pandemic, regular conventions of NTBs were maintained by the respective centers and multi-specialty participation remained high. NTBs were considered valuable by respondents in achieving the most optimal therapy for the affected patient and in maintaining/encouraging interdisciplinary debate/exchange. The settings of NTBs have been adapted during the pandemic with the increased use of virtual technology. Virtual NTBs were found to be beneficial, yet administrative support is lacking in some places. Conclusions Virtual implementation of NTBs was feasible and accepted in the centers surveyed. Therefore, successful implementation offers new avenues and may be pursued for networking between centers, thereby increasing coverage of neuro-oncology care.

Objective Numerous materials used for cranioplasty (CP) after decompressive craniectomy (DC) have been investigated to meet certain demanded key features, such as stability, surgical applicability, and biocompatibility. We aimed to evaluate the feasibility and safety of biocompatible calcium-phosphate (CaP) titanium-enhanced implants for CP compared to polymethylmethacrylate (PMMA) implants. Methods The medical records of all patients who underwent CP between January 1st, 2015, and January 1st, 2022, were reviewed. Demographic, clinical, and diagnostic data were collected before and after the CP. Results 82 consecutive patients with a mean age of 52 years (range 22–72 years) who received either a PMMA (43) or CaP (39) cranial implant after DC were included in our study. Indications for DC were equally distributed in both groups, including middle cerebral artery infarction (35 cases), traumatic brain injury (24 cases), subarachnoid hemorrhage (15 cases), intracerebral hemorrhage (3 cases). Time from DC to CP was similar in both groups 143.8 ± 17.46 days (PMMA) versus 98.46 ± 10.37 days (CaP). The mean follow-up period was 34.9 ± 27.1 months. 13 procedure-related complications occurred in patients with PMMA, 6 in those with CaP implants (p = 0.126). Revision surgery with implant removal was necessary for 9 patients with PMMA implants, one in those with CaP implants. The probability of implant removal was significantly higher in the PMMA implant group (p = 0.039). Conclusions In the present study, a titanium-enhanced biocompatible CaP implant proved superior to a PMMA implant in terms of surgical site infection. This supports the idea of the biocompatible implant material with its ability for tissue integration.

Simple Summary Medulloblastoma is the most common malignant childhood brain tumor and it is considered poor immunogenic because of its low mutational burden. Nevertheless, several clinical trials are currently evaluating immunotherapy for medulloblastoma patients, since new treatment strategies for this entity are a matter of utmost urgency. Tumor specific antigens resulting from gene fusions are potentially highly immunogenic. In our study, we identified a new medulloblastoma-specific fusion transcript EPC2-GULP1.The resulting protein sequence produced a neoantigen, which was able to activate CD8+ T cells. Thus, our data indicate an immunotherapeutic approach for pediatric medulloblastoma patients carrying the EPC2-GULP1 fusion or other fusions generating immunogenic neoantigens. Abstract Medulloblastoma is the most common malignant brain tumor in children. Immunotherapy is yet to demonstrate dramatic results in medulloblastoma, one reason being the low rate of mutations creating new antigens in this entity. In tumors with low mutational burden, gene fusions may represent a source of tumor-specific neoantigens. Here, we reviewed the landscape of fusions in medulloblastoma and analyzed their predicted immunogenicity. Furthermore, we described a new in-frame fusion protein identified by RNA-Seq. The fusion involved two genes on chromosome 2 coding for the enhancer of polycomb homolog 2 (EPC2) and GULP PTB domain containing engulfment adaptor 1 (GULP1) respectively. By qRT-PCR analysis, the fusion was detected in 3 out of 11 medulloblastoma samples, whereby 2 samples were from the same patients obtained at 2 different time points (initial diagnosis and relapse), but not in other pediatric brain tumor entities. Cloning of the full-length sequence indicated that the fusion protein contains the N-terminal enhancer of polycomb-like domain A (EPcA) of EPC2 and the coiled-coil domain of GULP1. In silico analyses predicted binding of the neoantigen-derived peptide to HLA-A*0201. A total of 50% of the fusions described in the literature were also predicted to produce an immunogenic peptide. The EPC2-GULP1 fusion peptide was able to induce a de novo T cell response characterized by interferon gamma release of CD8+ cytotoxic T cells in vitro. While the functional relevance of this fusion in medulloblastoma biology remains to be clarified, our data support an immunotherapeutic approach for pediatric medulloblastoma patients carrying the EPC2-GULP1 fusion and other immunogenic fusions.

Background After cranioplasty, in many cases a not negligible soft tissue defect remains in the temporozygomatical area, also referred to as a hollowing defect of the temple. Objective To assess the precise localization and volume of the hollowing defect, to optimize future cranioplasties. Methods CT data of patients who received craniectomy and conventional CAD cranioplasty in our institution between 2012 and 2018 were analyzed. CT datasets prior to craniectomy and after cranioplasty were subtracted to quantify the volume and localization of the defect. Results Out of 91 patients, 21 had suitable datasets. Five cases had good cosmetic results with no defect visible, 16 patients had an apparent hollowing defect. Their average defect volume was 5.0 cm3 ± 4.5 cm3. The defect localizations were in the area behind the zygomatic process and just below the superior temporal line, covering an area of app. 3x3 cm2. Surgical attempts of temporal muscle restoration were more often found in reports of good results (p Conclusion This work supplies evidence for the indication of a surgical corrective during cranioplasty in the small but cosmetically relevant area of the “frontozygomatic shadow”. Based on our 3D data analysis, future focused surgical strategies may obtain better aesthetical results here.

Neuroblastoma (NBL) and medulloblastoma (MB) are aggressive pediatric cancers which can benefit from therapies targeting gangliosides. Therefore, we compared the ganglioside profile of 9 MB and 14 NBL samples by thin layer chromatography and mass spectrometry. NBL had the highest expression of GD2 (median 0.54 nmol GD2/mg protein), and also expressed complex gangliosides. GD2-low samples expressed GD1a and were more differentiated. MB mainly expressed GD2 (median 0.032 nmol GD2/mg protein) or GM3. Four sonic hedgehog-activated (SHH) as well as one group 4 and one group 3 MBs were GD2-positive. Two group 3 MB samples were GD2-negative but GM3-positive. N-glycolyl neuraminic acid-containing GM3 was neither detected in NBL nor MB by mass spectrometry. Furthermore, a GD2-phenotype predicting two-gene signature (ST8SIA1 and B4GALNT1) was applied to RNA-Seq datasets, including 86 MBs and validated by qRT-PCR. The signature values were decreased in group 3 and wingless-activated (WNT) compared to SHH and group 4 MBs. These results suggest that while NBL is GD2-positive, only some MB patients can benefit from a GD2-directed therapy. The expression of genes involved in the ganglioside synthesis may allow the identification of GD2-positive MBs. Finally, the ganglioside profile may reflect the differentiation status in NBL and could help to define MB subtypes.

While many centers nowadays offer minimally invasive techniques for the treatment of single suture synostosis, surgical techniques and patient management vary significantly. We provide an overview of how scaphocephaly treated with endoscopic techniques is managed in the reported series and analyze the crucial steps that need to be dealt with during the management process. We performed a review of the published literature including all articles that examined sagittal-suture synostosis treated with endoscopic techniques as part of single- or multicenter studies. Fourteen studies reporting results of 885 patients were included. We identified 5 key steps in the management of patients. A total of 188 patients were female and 537 male (sex was only specified in 10 articles, for 725 included patients, respectively). Median age at surgery was between 2.6 and 3.9 months with a total range from 1.5 to 7.0 months. Preoperative diagnostics included clinical and ophthalmologic examinations as well as neuropsychological and genetic consultations if needed. In 5 publications, a CT scan was routinely performed. Several groups used anthropometric measurements, mostly the cephalic index. All groups analyzed equally recommended to perform endoscopically assisted craniosynostosis surgery with postoperative helmet therapy in children < 3 months of age, at least for non-syndromic cases. There exist significant variations in surgical techniques and patient management for children treated endoscopically for single suture sagittal synostosis. This heterogeneity constitutes a major problem in terms of comparability between different strategies.

Background and Purpose— The treatment of patients with acute ischemic stroke has been revolutionized by endovascular mechanical thrombectomy (MT), leading to dramatically improved outcomes. Here, we analyzed the impact of recent changes in stroke management on nationwide trends in patient characteristics, treatment modalities, and outcomes. Methods— The National Inpatient Sample was analyzed using International Classification of Diseases, Ninth and Tenth Editions , Clinical Modification codes to identify adult stroke patients with anterior-circulation, large-vessel occlusion in the pre- (2012–2014) and the post-MT trial period (2015–2016). Univariate and multivariable predictors of decompressive hemicraniectomy (DHC) were ascertained in patients developing malignant cerebral edema. Results— The nationwide query identified 519 320 adult stroke patients with annually increasing volume (92 320 to 129 340), stroke severity, and treatment at urban teaching centers. DHC was performed in 9.5% of patients developing malignant cerebral edema (n=33 530) and was associated with a high rate of discharge to long-term nursing care (65%) and mortality (23%). Over time, the rate of MT (3.4% to 9.8%) increased whereas the rate of DHC for malignant cerebral edema declined from 11.4% to 4.8% ( P Conclusions— Nationwide trends indicated that successful reperfusion of penumbra with MT in stroke patients leads to a declining indication for DHC whereas stroke volume increases over time.

Among spinal tumors that occur intradurally, meningiomas, nerve sheath tumors, ependymomas, and astrocytomas are the most common. While a spinal MRI is the state of the art to diagnose intradural spinal tumors, in some cases CT scans, angiography, CSF analyses, and neurophysiological examination can be valuable. The management of these lesions depends not only on the histopathological diagnosis but also on the clinical presentation and the anatomical location, allowing either radical resection as with most extramedullary lesions or less invasive strategies as with intramedullary lesions. Although intramedullary lesions are rare and sometimes difficult to manage, well-planned treatment can achieve excellent outcome without treatment-related deficits. Technical advances in imaging, neuromonitoring, minimally invasive approaches, and radiotherapy have improved the outcome of intradural spinal tumors. However, the outcome in malignant intramedullary tumors remains poor. While surgery is the mainstay treatment for many of these lesions, radiation and chemotherapy are of growing importance in recurrent and multilocular disease. We reviewed the literature on this topic to provide an overview of spinal cord tumors, treatment strategies, and outcomes. Typical cases of extra- and intramedullary tumors are presented to illustrate management options and outcomes.

Osteonecrosis of bone flaps after cranioplasty with autologeous cryo-conserved bone flaps is a common phenomenon. The exact reason for it remains unknown. We present a case of a 67-year old patient who had a bone flap necrosis after elective craniotomy and underwent secondary cranioplasty. A low-grade infection with Propionibacterium acnes was detected in microbiological samples from the bone flap as cause of the lysis. We discuss similarities with aseptic implant loosening and present recent evidence that low-grade infections might be the underlying reason in several cases. We conclude that low-grade infections play an underestimated role in bone flap necrosis after cranioplasty as well and encourage routine microbiological sampling (extended culture and PCR) to rule out infection in all similar cases and suggest a routine antibiotic therapy until final microbiological results.

Medulloblastoma is the most common malignant brain tumor in children. Immunotherapy is yet to demonstrate dramatic results in medulloblastoma, one reason being the low rate of mutations creating new antigens in this entity. In tumors with low mutational burden, gene fusions may represent a source of tumor-specific neoantigens. Here, we reviewed the landscape of fusions in medulloblastoma and analyzed their predicted immunogenicity. Furthermore, we described a new in-frame fusion protein identified by RNA-Seq. The fusion involved two genes on chromosome 2 coding for the enhancer of polycomb homolog 2 (EPC2) and GULP PTB domain containing engulfment adaptor 1 (GULP1) respectively. By qRT-PCR analysis, the fusion was detected in 3 out of 11 medulloblastoma samples, whereby 2 samples were from the same patients obtained at 2 different time points (initial diagnosis and relapse), but not in other pediatric brain tumor entities. Cloning of the full-length sequence indicated that the fusion protein contains the N-terminal enhancer of polycomb-like domain A (EPcA) of EPC2 and the coiled-coil domain of GULP1. In silico analyses predicted binding of the neoantigen-derived peptide to HLA-A*0201. A total of 50% of the fusions described in the literature were also predicted to produce an immunogenic peptide. The EPC2-GULP1 fusion peptide was able to induce a de novo T cell response characterized by interferon gamma release of CD8+ cytotoxic T cells in vitro. While the functional relevance of this fusion in medulloblastoma biology remains to be clarified, our data support an immunotherapeutic approach for pediatric medulloblastoma patients carrying the EPC2-GULP1 fusion and other immunogenic fusions.

In 1955, Vincent du Vigneaud (1901–1978), the chairman of the Department of Biochemistry at Cornell University Medical College, was awarded the Nobel Prize for Chemistry for his research on insulin and for the first synthesis of the posterior pituitary hormones—oxytocin and vasopressin. His tremendous contribution to organic chemistry, which began as an interest in sulfur-containing compounds, paved the way for a better understanding of the pituitary gland and for the development of diagnostic and therapeutic tools for diseases of the pituitary. His seminal research continues to impact neurologists, endocrinologists, and neurosurgeons, and enables them to treat patients who had no alternatives prior to du Vigneaud’s breakthroughs in peptide structure and synthesis. The ability of neurosurgeons to aggressively operate on parasellar pathology was directly impacted and related to the ability to replace these hormones after surgery. The authors review the life and career of Vincent du Vigneaud, his groundbreaking discoveries, and his legacy of the understanding and treatment of the pituitary gland in health and disease.

OBJECT Although the endonasal endoscopic approach has been applied to remove olfactory groove meningiomas, controversy exists regarding the efficacy and safety of this approach compared with more traditional transcranial approaches. The endonasal endoscopic approach was compared with the supraorbital (eyebrow) keyhole technique, as well as a combined “above-and-below” approach, to evaluate the relative merits of each approach in different situations. METHODS Nineteen cases were reviewed and divided according to operative technique into 3 different groups: purely endonasal (6 cases); supraorbital eyebrow (microscopic with endoscopic assistance; 7 cases); and combined endonasal endoscopic with either the bicoronal or eyebrow microscopic approach (6 cases). Resection was judged on postoperative MRI using volumetric analysis. Tumors were assessed based on the Mohr radiological classification and the presence of the lion’s mane sign. RESULTS The mean age at surgery was 61.4 years. The mean tumor volume was 19.6 cm3 in the endonasal group, 33.5 cm3 in the supraorbital group, and 37.8 cm3 in the combined group. Significant frontal lobe edema was identified in 10 cases (52.6%). The majority of tumors were either Mohr Grade II (moderate) (42.1%) or Grade III (large) (47.4%). Gross-total resection was achieved in 50% of the endonasal cases, 100% of the supraorbital eyebrow cases with endoscopic assistance, and 66.7% of the combined cases. The extent of resection was 87.8% for the endonasal cases, 100% for the supraorbital eyebrow cases, and 98.9% for the combined cases. Postoperative anosmia occurred in 100% of the endonasal and combined cases and only 57.1% of the supraorbital eyebrow cases. Excluding anosmia, permanent complications occurred in 83.3% of the cases in the endoscopic group, 0% of the cases in the supraorbital eyebrow group, and 16.7% of cases in the combined group (p = 0.017). There were 3 tumor recurrences: 2 in the endonasal group and 1 in the combined group. CONCLUSIONS The supraorbital eyebrow approach, with endoscopic assistance, leads to a higher extent of resection and lower rate of complications than the purely endonasal endoscopic approach. The endonasal endoscopic approach by itself may be suitable for a small percentage of cases. The combined above-and-below approaches are useful for large tumors with invasion of the ethmoid sinuses.

To describe the clinical, radiographic and surgical outcomes in a cohort of patients with BRAF V600E mutant papillary craniopharyngiomas. A retrospective review was performed to identify all patients with a histological diagnosis of CP operated upon at a single institution between 2005 and 2017. All cases with adequate material were sequenced to confirm the presence of BRAF V600E mutation. Sixteen patients were included in the present study. Approach was endoscopic endonasal (EEA) in 14 and transcranial (TCA) in 2. All patients were adult with an average age of 50 years (24–88). Radiographic review demonstrated that the majority (93.7%) were suprasellar and twelve (75%) had third ventricular involvement. No tumor showed evidence of calcifications and 68.7% were mixed solid-cystic. All patients had some evidence of hypopituitarism and 62.5% had hypothalamic disturbances. GTR was achieved in 11/14 (78.6%) EEA and 0/2 (0%) TCA (p

Background: Ventral brainstem compression secondary to complex craniovertebral junction abnormality is an infrequent cause of neurologic deterioration in pediatric patients. However, in cases of symptomatic, irreducible ventral compression, 360° decompression of the brainstem supported by posterior stabilization may provide the best opportunity for improvement in symptoms. More recently, the endoscopic endonasal corridor has been proposed as an alternative method of odontoidectomy associated with less morbidity. We report the largest single case series of pediatric patients using this dual-intervention surgical technique. The purpose of this study was to evaluate the surgical outcomes of pediatric patients who underwent posterior occipitocervical decompression and instrumentation followed by endoscopic endonasal odontoidectomy performed to relieve neurologic impingement involving the ventral brainstem and craniocervical junction. Methods: Between January 2011 and February 2017, 7 patients underwent posterior instrumented fusion followed by endonasal endoscopic odontoidectomy at our unit. Standardized clinical and radiological parameters were assessed before and after surgery. A univariate analysis was performed to assess clinical and radiologic improvement after surgery. Results: A total of 14 operations were performed on 7 pediatric patients. One patient had Ehlers-Danlos syndrome, 1 patient had a Chiari 1 malformation, and the remaining 5 patients had Chiari 1.5 malformations. Average extubation day was postoperative day 0.9. Average day of initiation of postoperative feeds was postoperative day 1.0. Conclusions: The combined endoscopic endonasal odontoidectomy and posterior decompression and fusion for complex craniovertebral compression is a safe and effective procedure that appears to be well tolerated in the pediatric population. Key words: Axis, Basilar invagination, Chiari, Endonasal, Endoscopic, Odontoidectomy, Pediatric

Background Resident education has to adapt to a changing health care environment. Although aspects such as working hours and attrition rates have been studied in detail, data about the residents' perspective, especially in European countries, are underrepresented in the scientific literature. The aim of this study was to assess and report aspects of neurosurgical education in German-speaking countries and to identify risk factors for quitting or changing the neurosurgical residency program. Methods We conducted a nonanonymous online survey among neurosurgical residents in Germany, Austria, and Switzerland. Log-binomial regression models were calculated to further assess risk factors. Results Of 201 residents who responded to the survey, 37.3% (n = 75) dropped out of neurosurgical training programs, including 20 residents (10%) who ultimately quit neurosurgery and changed to another specialty. Only female gender (relative risk, 2.97; 95% confidence interval, 1.3–6.78) and starting residency in a city one studied or grew up in (2.38; 1.01–5.62) were significant risk factors. Residents who had close supervision at work (0.39; 0.17–0.89), who observed the residency program for >3 days before applying (0.54; 0.31–0.95), who had well-defined guidelines within the program (0.57; 0.35–0.92), and who were working in a university hospital (0.41; 0.26–0.64) were significantly less likely to quit or change their program. Conclusions The high attrition rate, especially among female residents, in Germany, Austria, and Switzerland should encourage program directors to specifically address the issues reported by this survey during interviews and to further improve their residency program accordingly.

OBJECTIVEAnterior skull base meningiomas are benign lesions that cause neurological symptoms through mass effect on adjacent neurovascular structures. While traditional transcranial approaches have proven to be effective at removing these tumors, minimally invasive approaches that involve using an endoscope offer the possibility of reducing brain and nerve retraction, minimizing incision size, and speeding patient recovery; however, appropriate case selection and results in large series are lacking.METHODSThe authors developed an algorithm for selecting a supraorbital keyhole minicraniotomy (SKM) for olfactory groove meningiomas or an expanded endoscopic endonasal approach (EEA) for tuberculum sella (TS) or planum sphenoidale (PS) meningiomas based on the presence or absence of olfaction and the anatomical extent of the tumor. Where neither approach is appropriate, a standard transcranial approach is utilized. The authors describe rates of gross-total resection (GTR), olfactory outcomes, and visual outcomes, as well as complications, for 7 subgroups of patients. Exceptions to the algorithm are also discussed.RESULTSThe series of 57 patients harbored 57 anterior skull base meningiomas; the mean tumor volume was 14.7 ± 15.4 cm3 (range 2.2–66.1 cm3), and the mean follow-up duration was 42.2 ± 37.1 months (range 2–144 months). Of 19 patients with olfactory groove meningiomas, 10 had preserved olfaction and underwent SKM, and preservation of olfaction in was seen in 60%. Of 9 patients who presented without olfaction, 8 had cribriform plate invasion and underwent combined SKM and EEA (n = 3), bifrontal craniotomy (n = 3), or EEA (n = 2), and one patient without both olfaction and cribriform plate invasion underwent SKM. GTR was achieved in 94.7%. Of 38 TS/PS meningiomas, 36 of the lesions were treated according to the algorithm. Of these 36 meningiomas, 30 were treated by EEA and 6 by craniotomy. GTR was achieved in 97.2%, with no visual deterioration and one CSF leak that resolved by placement of a lumbar drain. Two patients with tumors that, based on the algorithm, were not amenable to an EEA underwent EEA nonetheless: one had GTR and the other had a residual tumor that was followed and removed via craniotomy 9 years later.CONCLUSIONSUtilizing a simple algorithm aimed at preserving olfaction and vision and based on maximizing use of minimally invasive approaches and selective use of transcranial approaches, the authors found that excellent outcomes can be achieved for anterior skull base meningiomas.

Background Basilar invagination can result from systemic diseases that can weaken structural integrity of the craniocervical junction. Definitive treatment often requires ventral decompression and posterior decompression and fusion. Endonasal odontoidectomy is a relatively new minimal access procedure; quality of life (QOL) after this procedure has not been reported. Methods We reviewed a consecutive database of endonasal odontoidectomy cases and identified patients having posterior decompression and fusion. Two QOL questionnaires were administered postoperatively: Sino-Nasal Outcome Test and 36-Item Short Form Survey. Comparisons with other endonasal or Chiari procedures were performed. Results The study comprised 14 patients; 79% had Chiari malformation in addition to basilar invagination. Mean follow-up was 17.2 months. Symptomatic improvement occurred in 78.6% after surgery. Average postoperative Sino-Nasal Outcome Test scores were 39.2 ± 17.93, with worst scores in areas related to fatigue and sleep patterns but not nasal function. 36-Item Short Form Survey scores were lower in areas of physical function and general health but better for emotional health and pain. Compared with patients undergoing Chiari malformation surgery without endonasal odontoid resection or fusion, patients undergoing odontoidectomy had higher QOL in areas of role emotional, emotional well-being, and pain but worse QOL in general health and role physical. Conclusions Patients undergoing posterior decompression and fusion with endonasal odontoidectomy do well after surgery with respect to nasal function and emotional health. Patients who also have severe basilar invagination associated with systemic diseases demonstrate reduced QOL after surgery in areas of physical function and sleep leading to fatigue, irritability, and concentration difficulty, likely related to their systemic disease.

Hamartomas are well described but yet incompletely understood sporadic benign lesions that can arise in various locations. Hypothalamic hamartomas of infancy are often associated with severe developmental disturbances. We present a case of an infant boy with a hamartoma that arises from the optic nerve and lead to progressive unspecific seizure activity, behavioral problems and precautious puberty. A 1-year-old male patient was presented with horizontal nystagmus and developmental retardation. Magnetic resonance imaging (MRI) with contrast revealed an isointense mass ventral of the chiasm consistent with a hamartoma. Soon after the MRI, the mother of the patient reported gelastic-like seizures. The patient was evaluated by an interdisciplinary team, and surgery was recommended. Intraoperatively, a firm attachment to the optic nerve was recognized and a thin remnant layer of tissue was left behind. After an uncomplicated near total resection, the patient improved significantly. After 6 months, the frequency of seizures reoccurred, which were again unresponsive to antiepileptic medication. In a second operation, a complete resection of the remnants was performed, and the patient showed lasting clinical improvement. We conclude that hamartomas mimicking hypothalamic symptoms can also arise from the optic pathway and that a reoperation, if feasible, of even small remnants is essential in order to achieve lasting symptom relieve.

Objective To analyze the current clinical use of navigation at the lateral skull base among skull base surgeons in Germany. Methods A web-based questionnaire was provided to surgeons being head of the department and member of one of the following scientific societies: German Society of Head and Neck Surgery, Maxillo-Facial Surgery, Neurosurgery, and German Skull Base Society. Replies were recorded anonymously. The questionnaire included the estimated case load per year and percent of surgery performed with navigation (middle and posterior fossa), type of navigation, estimates of intraoperative inaccuracy, and reasons for not using navigation. Results Eighty nine out of 99 replies met requirements for final analysis. Overall, 37% of skull base surgeons use navigation on a regular basis (15% use no navigation). Optical tracking is more frequently used than magnetic tracking (71 vs 19). At the middle fossa, ENT surgeons split into routine users (n = 10/36) and rare users (n = 16/36), the latter stating navigation inaccuracy as a major reason for neglecting navigation. Neurosurgeons use navigation at the middle fossa significantly more often and criticize navigation inaccuracy less. At the posterior fossa, navigation is used less frequently by both ENT and neurosurgeons with similar rates of estimated inaccuracy. Conclusions A moderate use of navigation at the lateral skull base was demonstrated. Insufficient accuracy causes ENT surgeons to frequently omit navigation at the middle fossa (not neurosurgeons) and posterior fossa (also neurosurgeons). Higher intraoperative navigation accuracy is needed to enhance the use of navigation at the lateral skull base.

OBJECTIVEResection of supratentorial meningiomas is generally considered a low-risk procedure, but tumors involving the rolandic cortex present a unique challenge. The rate of motor function deterioration associated with resecting such tumors is not well described in the literature. Thus, the authors sought to report the rates and predictors of postoperative motor deficit following the resection of rolandic meningiomas to assist with patient counseling and surgical decision-making.METHODSAn institution’s pathology database was screened for meningiomas removed between 2000 and 2017, and patients with neuroradiological evidence of rolandic involvement were identified. Parameters screened as potential predictors included patient age, sex, preoperative motor severity, tumor location, tumor origin (falx vs convexity), histological grade, FLAIR signal (T2-weighted MRI), venous involvement (T1-weighted MRI with contrast), intratumoral hemorrhage, embolization, and degree of resection (Simpson grade). Variables of interest included preoperative weakness and postoperative motor decline (novel or worsened permanent deficit). The SPSS univariate and bivariate analysis functions were used, and statistical significance was determined with alpha < 0.05.RESULTSIn 89 patients who had undergone resection of convexity (80.9%) or parasagittal (19.1%) rolandic meningiomas, a postoperative motor decline occurred in 24.7%. Of 53 patients (59.6%) with preoperative motor deficits, 60.3% improved, 13.2% were unchanged, and 26.4% worsened following surgery. Among the 36 patients without preoperative deficits, 22.2% developed new weakness. Predictors of preoperative motor deficit included tumor size (41.6 vs 33.2 cm3, p = 0.040) and presence of FLAIR signal (69.8% vs 50.0%, p = 0.046). Predictors of postoperative motor decline were preoperative motor deficit (47.2% vs 22.2%, p = 0.017), minor (compared with severe) preoperative weakness (25.6% vs 21.4%, p < 0.001), and preoperative embolization (54.5% vs 20.5%, p = 0.014). Factors that trended toward significance included parafalcine tumor origin (41.2% vs 20.8% convexity, p = 0.08), significant venous involvement (44.4% vs 23.5% none, p = 0.09), and Simpson grade II+ (34.2% vs 17.6% grade I, p = 0.07).CONCLUSIONSResection of rolandic area meningiomas carries a high rate of postoperative morbidity and deserves special preoperative planning. Large tumor size, peritumoral edema, preoperative embolization, parafalcine origin, and venous involvement may further increase the risk. Alternative surgical strategies, such as aggressive internal debulking, may prevent motor decline in a subset of high-risk patients.

Craniopharyniomas arise from the sellar region and are particularly challenging because of their close proximity to critical neurovascular structures, including cranial nerves, brainstem, internal carotid arteries, posterior cerebral arteries, hypothalamus, and the pituitary gland. The tumors are benign on histology but can cause serious symptoms by compression of surrounding vital structures. While radical surgery and gross total resection (GTR) remains the first line treatment, choosing the optimal surgical approach is critical for the minimization of complications and postoperative morbidity. The extended endoscopic endonasal approach (EEEA) offers a direct route towards the sellar and suprasellar regions and has proven to be a safe and effective for GTR, with lower rates of complications and postoperative morbidity than open transcranial approaches. However, traditional transcranial approaches remain relevant in tumors with significant lateral extension. Radiotherapy can be considered in cases of subtotal resection (STR) or if surgery is not possible, although progressive growth of cysts with neurological deterioration has been demonstrated no infrequently. Newly developed chemotherapy for papillary craniopharygniomas might expand treatment options in the future.

Objective Suprasellar meningiomas have been resected via various open cranial approaches. During the past 2 decades, the endoscopic endonasal approach has been shown to be an option in selected patients. We wished to examine the learning curve for parameters such as extent of resection, visual outcome, and complications. Methods We retrospectively reviewed a consecutive series of patients in whom suprasellar meningiomas were resected via an endonasal endoscopic approach between 2005 and 2013 at our institution. After June 2008, our surgical technique matured. Using this time point, we divided our case series into 2 chronological groups, group 1 (n = 8) and group 2 (n = 12). This cut-off also was used to examine rates of gross total resection (GTR) and visual improvement. Case selection criteria in successful and unsuccessful cases were examined to determine important principals for case selection. Results Mean patient age at surgery was 57.05 years (range, 31–81 years). Mean tumor volume was 11.98 cm3 (range, 0.43−28.93 cm3). Overall, GTR was achieved in 80%, and vision improved or normalized in 14 patients (82.4%) with no occurrence of postoperative visual deterioration. Rates of GTR increased from 62.5% (group 1) to 91.7% (group 2). Visual improvement increased from 75% (group 1) to 88.9% (group 2). Rates of cerebrospinal fluid leak were 25% in group 1 and 0% in group 2. Average follow-up was 51.5 month (range, 3−96 months). Conclusion Once the learning curve is overcome, surgeons performing endonasal endoscopic resection of suprasellar meningiomas can achieve high rates of GTR with low complication rates in well-selected cases.

Cavernous sinus cavernous hemangiomas in pregnancy are extremely rare lesions. The precise management of these lesions remains unknown. The authors present a case of a cavernous hemangioma in pregnancy, centered within the cavernous sinus that underwent postpartum involution without surgical intervention. A 34-year-old pregnant patient (gravida 1, para 0) presented to an otolaryngologist with persistent headache and left-sided facial pain and numbness in the V1 distribution. While being treated for sinusitis, her symptoms progressed to include a left-sided oculomotor palsy and abducens palsy. Magnetic resonance imaging without contrast revealed an expansile mass within the left cavernous sinus consistent with a cavernous hemangioma. The patient was evaluated by a neurosurgeon who recommended close follow-up and postpartum imaging without surgical intervention. Although the lesion enlarged during pregnancy, the patient was able to undergo an uncomplicated cesarean section at 37 weeks. All facial and ocular symptoms resolved by 9 months postpartum, and MRI showed a decrease in lesion size and reduced mass effect. The authors conclude that nonsurgical management may be a viable approach in patients who have an onset or exacerbation of symptoms associated with cavernous sinus cavernous hemangiomas during pregnancy because postpartum involution may negate the need for surgical intervention.

For the second time, The Brain Tumor Center of the Weill Cornell Brain and Spine Center, in collaboration with Voices Against Brain Cancer, hosted The Brain Tumor Biotech Summit in New York City in June 2013. After a very successful first summit in 2012, this innovative event has established a platform for intensive networking between neuro-oncologists, neurosurgeons, neuroscientists, members of the biotechnology and pharmaceutical communities, members of the financial community and leaders of non-profit organizations. This year's summit highlighted dendritic cell vaccines, novel antibody, heat shock protein and targeted therapies as well as exosome technologies, MRI-guided therapies and other novel drug delivery tools. This report presents a short overview of the current progress in brain tumor research and therapy as presented at the 2013 Brain Tumor Biotech Summit.

Greater extent of resection (EOR) of low-grade gliomas is associated with improved survival. Proximity to eloquent cortical regions often limits resectability and elevates the risk of surgery-related deficits. Therefore, functional localization of eloquent cortex or subcortical fiber tracts can enhance the EOR and functional outcome. Imaging techniques such as functional MRI and diffusion tensor imaging fiber tracking, and neurophysiological methods like navigated transcranial magnetic stimulation and magnetoencephalography, make it possible to identify eloquent areas prior to resective surgery and to tailor indication and surgical approach but also to assess the surgical risk. Intraoperative monitoring with direct cortical stimulation and subcortical stimulation enables surgeons to preserve essential functional tissue during surgery. Through tailored pre- and intraoperative mapping and monitoring the EOR can be maximized, with reduced rates of surgery-related deficits.

Cavernous sinus cavernous hemangiomas in pregnancy are extremely rare lesions. The precise management of these lesions remains unknown. The authors present a case of a cavernous hemangioma in pregnancy, centered within the cavernous sinus that underwent postpartum involution without surgical intervention. A 34-year-old pregnant patient (gravida 1, para 0) presented to an otolaryngologist with persistent headache and left-sided facial pain and numbness in the V1 distribution. While being treated for sinusitis, her symptoms progressed to include a left-sided oculomotor palsy and abducens palsy. Magnetic resonance imaging without contrast revealed an expansile mass within the left cavernous sinus consistent with a cavernous hemangioma. The patient was evaluated by a neurosurgeon who recommended close follow-up and postpartum imaging without surgical intervention. Although the lesion enlarged during pregnancy, the patient was able to undergo an uncomplicated cesarean section at 37 weeks. All facial and ocular symptoms resolved by 9 months postpartum, and MRI showed a decrease in lesion size and reduced mass effect. The authors conclude that nonsurgical management may be a viable approach in patients who have an onset or exacerbation of symptoms associated with cavernous sinus cavernous hemangiomas during pregnancy because postpartum involution may negate the need for surgical intervention.

Background Endoscopic endonasal (EE) transsphenoidal surgery is an important surgical approach to the treatment of sellar pathology, particularly for pituitary adenomas. Risk factors for the radiographic recurrence of pituitary adenomas resected using a purely endoscopic approach have not been established. This study investigates outcomes and identifies risk factors for recurrence following EE transsphenoidal surgery for pituitary adenoma. Methods We performed a retrospective review of 64 patients with pituitary adenomas undergoing EE surgery by a single, right-handed surgeon preferentially operating through the right nares. Post-operative MRI studies were utilized to monitor for residual disease or disease recurrence. Results Residual tumor was found in 31.2% of patients. Over a median follow-up period of 23.1 months (range 4–62.5), 4 (20%) of these patients showed recurrence. Two patients with inconclusive post-operative imaging had subsequent imaging consistent with recurrence, making the total recurrence in our series 9.4%. While no statistically significant effects of gender, age or history of previous treatment were seen, amenorrhea on presentation and maximum tumor diameter >10 mm were significant risk factors for radiographic recurrence (p = 0.044 and 0.005, respectively). No predominant side of residual tissue was identified in these tumors operated through the right nares. Conclusions Only 20% of patients with residual tumor developed recurrent disease over a median follow up of 23.1 months. This recurrence rate may be an important consideration in cases where gross total resection is not feasible. Preferentially operating from the right does not seem to influence the location of residual tumor.

Background and Importance Even though dilated Virchow-Robin spaces (VRS) are a very rare entity, they can compel the clinician to start immediate intervention in the case of acute onset of symptoms. To allow a well-balanced management decision, we compiled a summary of all cases published in the literature and discuss the different methods and indications for neurosurgical intervention in relation to dilated VRS. Clinical Presentation We report a case of a 43-year-old female patient who came to admission after syncope with a history of unspecific neck pain, fatigue, diplopia, and dizziness. Dilated VRS type III causing a noncommunicating hydrocephalus were found to be responsible. Although the patient was initially awake, within 72 hours after admission, a deterioration of consciousness and repeated vomiting were observed. The patient underwent an urgent endoscopic third ventriculostomy (ETV) and was discharged in a good condition. Conclusion To the best of our knowledge, the case presented here is the first case of acute decompensation of a noncommunicating hydrocephalus caused by dilated VRS. Neurosurgical intervention is required in cases of noncommunicating hydrocephalus caused by giant tumefactive VRS. The treatment options are mono- or biventricular shunt surgery or ETV. Because ETV provides the possibility of cyst fenestration and membrane sampling, it appears to be the most advantageous treatment option.

Background Costimulatory signaling has been implicated as a potential regulator of antitumor immunity in various human cancers. In contrast to the negative prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the role of B7-H3 is still unknown. Therefore, we investigated the expression pattern and clinical significance of B7-H3 expression in human pancreatic cancer. Methods B7-H3 expression was evaluated by immunohistochemistry in 68 patients with pancreatic cancer who underwent surgical tumor resection. Expression data was correlated with clinicopathologic features and with the number of tumor-infiltrating T cells. Results B7-H3 expression was significantly upregulated in pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with high tumor B7-H3 levels had a significantly better postoperative prognosis than patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3 expression significantly correlated with the number of tumor-infiltrating CD8+ T cells (p = 0.018). Conclusion We demonstrate for the first time that B7-H3 is abundantly expressed in pancreatic cancer and that tumor-associated B7-H3 expression significantly correlates with prolonged postoperative survival. Our findings suggest that B7-H3 might play an important role as a potential stimulator of antitumor immune response in pancreatic cancer.

In this article the authors discuss the development of neurosurgical approaches and the advances in science and technology that influenced this development throughout history. They provide a broad overview of this interesting topic from the first attempts of trephination by ancient cultures to the work of the pioneers of neurosurgery and the introduction of microsurgery.