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Purpose Data on differences in overall survival and molecular characteristics between incidental (iLGG) and symptomatic lower grade Glioma (sLGG) are limited. The aim of this study was to investigate differences between patients with iLGG and sLGG. Methods All adult patients with a histologically proven diffuse (WHO°II) or anaplastic (WHO°III) glioma who underwent their first surgery at the authors’ institution between 2010 and 2019 were retrospectively included. Tumor volume on pre- and postoperative MRI scans was determined. Clinical and routine neuropathological data were gained from patients’ charts. If IDH1, ATRX and EGFR were not routinely assessed, they were re-determined. Results Out of 161 patients included, 23 (14%) were diagnosed as incidental findings. Main reasons for obtaining MRI were: headache(n = 12), trauma(n = 2), MRI indicated by other departments(n = 7), staging examination for cancer(n = 1), volunteering for MRI sequence testing(n = 1). The asymptomatic patients were significantly younger with a median age of 38 years (IqR28-48) vs. 50 years (IqR38-61), p = 0.011. Incidental LGG showed significantly lower preoperative tumor volumes in T1 CE (p = 0.008), FLAIR (p = 0.038) and DWI (p = 0.028). Incidental LGG demonstrated significantly lower incidence of anaplasia (p = 0.004) and lower expression of MIB-1 (p = 0.008) compared to sLGG. IDH1-mutation was significantly more common in iLGG (p = 0.024). Incidental LGG showed a significantly longer OS (mean 212 vs. 70 months, p = 0.005) and PFS (mean 201 vs. 61 months, p = 0.001) compared to sLGG. Conclusion Our study is the first to depict a significant difference in molecular characteristics between iLGG and sLGG. The findings of this study confirmed and extended the results of previous studies showing a better outcome and more favorable radiological, volumetric and neuropathological features of iLGG.

Background Advanced intercellular communication is a known oncogenic factor. In the central nervous system, Connexin-43 (Cx43) forms this junctional networking. Moreover, it correlates with the proliferation rate, and thus behavior, of gliomas. We assessed the expression of Cx43 and its relationship to Ki67 in other common central nervous system tumors. Methods The expression of Cx43 and Ki67 were assessed in formalin-fixed paraffin embedded samples of human brain metastases, meningiomas, and neurinomas using immunohistochemistry. Neurinomas and meningiomas were jointly evaluated due to similar non-malignant behavior. Results A total of 14 metastases of different extracerebral carcinomas, 6 meningiomas, and 10 neurinomas were evaluated. Five (36%) metastases and 5 (31%) meningiomas/neurinomas showed minor expression, whereas 6 (43%) metastases and 2 (13%) meningiomas/neurinomas showed no Cx43 expression at all. In 3 (21%) metastases and 9 (56%) meningiomas/neurinomas, moderate or strong expression of Cx43 was identified. The higher expression of Cx43 in meningiomas and neurinomas directly correlated with Ki67, r = 0.53 ( P = 0.034). For metastases no significant correlation was found. Mitotic index in meningiomas/neurinomas correlated with Ki67 expression, r = 0.74 ( P Conclusions The expression of Cx43 as a marker of cell-to-cell networking exposed a significant correlation with the Ki67-defined proliferation index in case of primary central nervous system neuroectodermal neoplasms. However, it does not seem to play a comparable role in metastases with extracerebral origin.

Purpose The Clinical Frailty Scale (CFS) evaluates patients’ level of frailty on a scale from 1 to 9 and is commonly used in geriatric medicine, intensive care and orthopedics. The aim of our study was to reveal whether the CFS allows a reliable prediction of overall survival (OS) in patients after surgical treatment of brain metastases (BM) compared to the Karnofsky Performance Score (KPS). Methods Patients operated for BM were included. CFS and KPS were retrospectively assessed pre- and postoperatively and at follow-up 3–6 months after resection. Results 205 patients with a follow-up of 22.8 months (95% CI 18.4–27.1) were evaluated. CFS showed a median of 3 (“managing well”; IqR 2–4) at all 3 assessment-points. Median KPS was 80 preoperatively (IqR 80–90) and 90 postoperatively (IqR 80–100) as well as at follow-up after 3–6 months. CFS correlated with KPS both preoperatively (r = − 0.92; p The CFS predicted the expected reduction of OS more reliably than the KPS at all 3 assessments. A one-point increase (worsening) of the preoperative CFS translated into a 30% additional hazard to decease (HR 1.30, 95% CI 1.15–1.46; p Conclusion The CFS is a feasible, simple and reliable scoring system in patients undergoing resection of brain metastasis. The CFS 3–6 months after surgery specifies the expected OS more accurately than the KPS.

Introduction The conventional microscope has the disadvantage of a potentially unergonomic posture for the surgeon, which can affect performance. Monitor-based exoscopes could provide a more ergonomic posture, as already shown in pre-clinical studies. The aim of this study was to test the usability and comfort of a novel head-mounted display (HMD) based exoscope on spinal surgical approaches in a simulated OR setting. Methods A total of 21 neurosurgeons naïve to the device were participated in this prospective trial. After a standardized training session with the device, participants were asked to perform a single-level thoracolumbar decompression surgery on human cadavers using the exoscope. Subsequently, all participants completed a comfort and safety questionnaire. For the objective evaluation of the performance, all interventions were videotaped and analyzed. Results 12 men and 9 women with a mean age of 34 (range: 24–57) were participating in the study. Average time for decompression was 15 min (IqR 9.6;24.2); 3 participants (14%) terminated the procedure prematurely. In these dropouts, a significantly higher incidence of back/neck pain (p=0.002 for back, p=0.046 for neck pain) as well as an increased frequency of HMD readjustments (p=0.045) and decreased depth perception (p=0.03) were documented. Overall, the surgeons’ satisfaction with the exoscope was 84% (IqR 75; 100). Conclusion Using a standardized, pre-interventional training, it is possible for exoscope-naïve surgeons to perform sufficient spinal decompression using the HMD-based exoscope with a high satisfaction. However, inaccurate HMD-setup prior to the start of the procedure may lead to discomfort and unsatisfactory results.

Background Radiation necrosis (RN) is a possible late complication of stereotactic radiosurgery (SRS), but only few risk factors are known. The aim of this study was to assess tumor location in correlation to the development of radiation necrosis for skull base (SB) and non-skull base tumors. Methods All patients treated with radiosurgery for benign neoplasms (2004-2020) were retrospectively evaluated. The clinical, imaging and medication data was gained and largest axial tumor diameter was determined using MRI scans in T1 weighted imaging with gadolinium. The diagnosis of RN was established using imaging parameters. Patients with tumors located at the skull base were compared to patients with tumors in non-skull base locations. Results 205 patients could be included. 157 tumors (76.6%) were located at the SB and compared to 48 (23.4%) non-SB tumors. Among SB-tumors, the most common were vestibular schwannomas (125 cases) and meningiomas (21 cases). 32 (15.6%) patients developed RN after median 10 (IqR 5-12) months. 62 patients (30.2%) had already undergone at least one surgical resection. In multivariate Cox regression, SB-tumors showed a significantly lower risk of radiation necrosis with a Hazard Ratio (HR) of 0.252, pConclusion The risk for development of RN for SB tumors appears to be low, but should not be underestimated. No difference was found between recurrent tumors and newly diagnosed tumors, which may support the value of radiosurgical treatment for patients with recurrent SB tumors.

Purpose To assess the impact of individual surgeon experience on overall survival (OS), extent of resection (EOR) and surgery-related morbidity in elderly patients with glioblastoma (GBM), we performed a retrospective case-by-case analysis. Methods GBM patients aged ≥ 65 years who underwent tumor resection at two academic centers were analyzed. The experience of each neurosurgeon was quantified in three ways: (1) total number of previously performed glioma surgeries (lifetime experience); (2) number of surgeries performed in the previous five years (medium-term experience) and (3) in the last two years (short-term experience). Surgeon experience data was correlated with survival (OS) and surrogate parameters for surgical quality (EOR, morbidity). Results 198 GBM patients (median age 73.0 years, median preoperative KPS 80, IDH-wildtype status 96.5%) were included. Median OS was 10.0 months (95% CI 8.0–12.0); median EOR was 89.4%. Surgery-related morbidity affected 19.7% patients. No correlations of lifetime surgeon experience with OS (P = .693), EOR (P = .693), and surgery-related morbidity (P = .435) were identified. Adjuvant therapy was associated with improved OS (P Conclusion Less experienced neurosurgeons achieve similar surgical results and outcome in elderly GBM patients within the setting of academic teaching hospitals. Adjuvant treatment and avoidance of surgery-related morbidity are crucial for generating a treatment benefit for this cohort.

Purpose: Data on differences in overall survival and molecular characteristics between incidental (iLGG) and symptomatic lower grade Glioma (sLGG) are limited. The aim of this study was to investigate differences between patients with iLGG and sLGG. Methods: All adult patients with a histologically proven diffuse (WHO°II) or anaplastic (WHO°III) glioma who underwent their first surgery at the authors’ institution between 2010 and 2019 were retrospectively included. Tumor volume on pre- and postoperative MRI scans was determined. Clinical and routine neuropathological data were gained from patients’ charts. Results: Out of 161 patients included, 23 (14%) were diagnosed as incidental findings. Main reasons for obtaining MRI were: headache(n=12), trauma(n=2), MRI indicated by other departments(n=7), staging examination for cancer(n=1), volunteering for MRI sequence testing(n=1). The asymptomatic patients were significantly younger with a median age of 38 years (IqR28-48) vs. 50 years (IqR38-61), p=0.011. Incidental LGG showed significantly lower preoperative tumor volumes in T1 CE (p=0.008), FLAIR (p=0.038) and DWI (p=0.028). Incidental LGG demonstrated significantly lower anaplasia levels (p=0.004) and lower expression of MIB-1 (p=0.008) compared to sLGG. IDH1-mutation was significantly more common in iLGG (p=0.024). Incidental LGG showed a significantly longer OS (mean 212 vs 70 months, p=0.005) and PFS (mean 201 vs 61 months, p=0.001) compared to sLGG. Conclusion: Our study is the first to depict a significant difference in molecular characteristics between iLGG and sLGG. The findings of this study confirmed and extended the results of previous studies showing a better outcome and more favorable radiological, volumetric and neuropathological features of iLGG.

Radiation necrosis represents a potentially devastating complication after radiation therapy in brain tumors. The establishment of the diagnosis and especially the differentiation from progression and pseudoprogression with its therapeutic implications requires interdisciplinary consent and monitoring. Herein, we want to provide an overview of the diagnostic modalities, therapeutic possibilities and an outlook on future developments to tackle this challenging topic. The aim of this report is to provide an overview of the current morphological, functional, metabolic and evolving imaging tools described in the literature in order to (I) identify the best criteria to distinguish radionecrosis from tumor recurrence after the radio-oncological treatment of malignant gliomas and cerebral metastases, (II) analyze the therapeutic possibilities and (III) give an outlook on future developments to tackle this challenging topic. Additionally, we provide the experience of a tertiary tumor center with this important issue in neuro-oncology and provide an institutional pathway dealing with this problem.

Introduction and purpose Brain metastases appear to be well resectable due to dissectable tumor margins, but postoperative MRI quite often depicts residual tumor with potential influence on tumor control and overall survival. Therefore, we introduced sodium fluoresceine into the routine workflow for brain metastasis resection. The aim of this study was to evaluate whether the use of fluorescence-guided surgery has an impact on postoperative tumor volume and local recurrence. Material and methods We retrospectively included patients who underwent surgical resection for intracranial metastases of systemic cancer between 11/2017 and 05/2021 at our institution. Tumor volumes were assessed pre- and postoperatively on T1-CE MRI. Clinical and epidemiological data as well as follow-up were gathered from our prospective database. Results Seventy-nine patients (33 male, 46 female) were included in this study. Median preoperative tumor volume amounted to 11.7cm3 and fluoresceine was used in 53 patients (67%). Surgeons reported an estimated gross total resection (GTR) in 95% of the cases, while early postoperative MRI could confirm GTR in 72%. Patients resected using fluoresceine demonstrated significantly lower postoperative residual tumor volumes with a difference of 0.7cm3 (p = 0.044) and lower risk of local tumor recurrence (p = 0.033). The use of fluorescence did not influence the overall survival (OS). Postoperative radiotherapy resulted in a significantly longer OS (p = 0.001). Discussion While GTR rates may be overrated, the use of intraoperative fluorescence may help neurosurgeons to achieve a more radical resection. Fluoresceine seems to facilitate surgical resection and increase the extent of resection thus reducing the risk for local recurrence.

Background The world currently faces the novel COVID-19 pandemic with cutbacks in patient care. Little is known about the effects of a pandemic on the presentation and admission to an outpatient clinic. Our aim was to gain a better understanding of the effects of reduced neurosurgical care access from the patient perspective, especially in terms of anxiety and urgency of treatment, and to improve outpatient management in case of a potential second wave and potential restrictions on health care. Methods: A questionnaire study over a period of four weeks following the COVID-19 lock down at our academical neurosurgical department was performed. A 15-items questionnaire was distributed to the patients with 3 additional questions to be answered by the treating neurosurgeon. Results: A total of 437 questionnaires was analyzed. Overall anxiety to visit a general practitioner or the outpatient facility within the hospital was very low among patients. A quarter of all appointments had to be postponed due to COVID-19, in 0.6 % of which postponement was perceived as incorrect by the treating neurosurgeon. 43% did not get an appointment due to the restrictions, 20 % did not want to bother the medical system and only 4 % were afraid to get infected in the hospital. Conclusion: Despite COVID-19, patients in need of neurosurgical service were hardly afraid to visit doctors and/or hospitals. Nonetheless, due to legal requirements, access has been restricted causing potential collateral damages in a small subset of neurosurgical patients.

Background Skull base (SB) surgery and radiosurgery (SRS) are an interdisciplinary concept and represent an individualized treatment option for various skull base tumors. Radiation necrosis (RN) is a possible sequela of SRS, but despite few accepted risk factors, there is very limited data on the influence of tumor location. The aim of this study was to assess tumor location in correlation to the development of radiation necrosis for skull-base tumors. METHODS All patients treated with radiosurgery for meningioma, vestibular schwannoma and other benign neoplasms between January 2004 and November 2020 were retrospectively evaluated. The clinical, imaging and medication data were gained from the patients’ charts. The diagnosis of RN was established retrospectively using imaging parameters. Patients with tumors located at the skull base were compared to patients with tumors of other location. RESULTS A total of 205 patients could be included in this study. 157 neoplasms (76.6%) were localized at the SB, while the remaining 48 (23.4%) were non-SB. 32 (15.6%) of all patients developed RN after median 10 (IqR 5-12) months during a median follow-up of 24 (IqR 6-62) months. SB-tumors showed a significantly lower risk of radiation necrosis with a Hazard Ratio (HR) of 0.252, p < 0.001, independently of the applied radiation dose. Furthermore, higher radiation doses had a significant impact on the occurrence of RN (HR 1.372, p = 0.002). No significant difference could be shown for age, previous resection or previous radiosurgery. Administered dose of dexamethasone did not correlate with the risk of radiation necrosis. CONCLUSION The risk for development of RN for SB-tumors appears to be low. No difference between recurrent and newly diagnosed tumors was found, which may underpin the value of radiosurgical treatment for patients with recurrent SB-tumors. For extensive tumors of the SB, combinations of surgery and radiosurgery represents a valuable approach.

Purpose: single-staged stereotactic radiosurgery (SRS) is an established part of the multimodal treatment in neuro-oncology. Radiation necrosis after high-dose irradiation is a known complication, but there is a lack of evidence about the risk factors. The aim of this study was to evaluate possible risk factors for radiation necrosis in patients undergoing radiosurgery. Methods: patients treated with radiosurgery between January 2004 and November 2020 were retrospectively analyzed. The clinical data, imaging and medication were gathered from electronic patient records. The largest diameter of the tumors was measured using MRI scans in T1 weighted imaging with gadolinium and the edema in T2 weighted sequences. The diagnosis of a radiation necrosis was established analyzing imaging criteria combined with clinical course or pathologically confirmed by subsequent surgical intervention. Patients developing radiation necrosis detected after SRS were compared to patients without evidence of an overshooting irradiation reaction. Results: 388 patients were included retrospectively, 61 (15.7%) of whom developed a radiation necrosis. Median follow-up was 24 (6–62) months with a radiation necrosis after 8 (6–12) months. The most frequent tumors were metastases in 47.2% of the cases, followed by acoustic neuromas in 32.2% and meningiomas in 13.4%. Seventy-three (18.9%) patients already underwent one or more previous radiosurgical procedures for different lesions. The mean largest diameter of the tumors amounted to 16.3 mm (± 6.1 mm). The median—80%—isodose administered was 16 (14–25) Gy. Of the radiation necroses, 25 (43.1%) required treatment, in 23 (39.7%) thereof, medical treatment was applied and in 2 (3.4%) cases, debulking surgery was performed. In this study, significantly more radiation necroses arose in patients with higher doses (HR 1.3 [CI 1.2, 1.5], p &lt, 0.001) leading to a risk increment of over 180% between a radiation isodose of 14 and 20 Gy. The maximum diameter was a second significant risk factor (p = 0.028) with an HR of 1065 for every 1 mm increase in multivariate analysis. Conclusion: large diameter and high doses were reliable independent risk factors leading to more frequent radiation necroses, regardless of tumor type in patients undergoing radiosurgery. Alternative therapeutic procedures may be considered in lesions with large volume and an expected high radiation doses due to the increased risk of developing radiation necrosis.

BACKGROUND With an aging population, acquisition of a better understanding of prognostic factors in elderly patients with Glioblastoma multiforme (GBM) is of utmost importance. Epileptic seizures have been found to correlate with improved overall survival (OS) in low-grade gliomas; however, the impact of epilepsy in GBM patients on outcome parameters is poorly defined. This study aims at specifically evaluating the impact of epilepsy in elderly GBM patients. Material & METHODS Two Austrian academic neurosurgical centers retrospectively analyzed all elderly (≥ 65 years) GBM patients with de-novo tumors, who underwent surgery between 09/2006 and 07/2021. Epidemiological, histopathological and survival data were gained from patients’ electronic charts and screened for presence of epilepsy preoperatively or during follow-up. Tumor volume was assessed using standardized software. RESULTS 391 patients (55% males, 45% females) with a median age at surgery of 73 years (IqR 68.5-77.5) were analyzed. The mean predicted OS was 12.4 months (CI95% 10.9-14.0). Mean follow-up was 10.4 months (CI95% 9.1-11.6) in our cohort. Median tumor volume amounted to 26.47 cm3 (IqR 12.65-43.49). 95 patients (24%) suffered from preoperative epilepsy. 17 (18%) patients showed epilepsy after tumor resection. Four patients (1.0%) showed a worsening of already preoperatively diagnosed seizures. Patients with lower tumor volumes experienced significantly more often seizures compared to patients with larger tumors, p< 0.001. Survival did not correlate with preoperative epilepsy (p > 0.05). However, Cox-regression revealed that multifocal tumor location (HR=1.777, p=0.025) and thalamic involvement (HR=11.121, p=0.030) influenced OS. Surgery-associated complications shortened OS significantly (HR=1.945 [CI95% 1,296-2,916], p=0.025). CONCLUSION Even though epilepsy was not found to directly impact survival in elderly GBM patients, we found that surgery led to epilepsy freedom in a significant proportion of our patient cohort, thereby potentially leading to improved QoL. Greatest focus should be set on avoiding any surgery-associated deficits, since these severely influence the OS.

Background. Distant intercellular communication in gliomas is based on the expansion of tumor microtubuli (TMs), where actin forms cytoskeleton and GAP-43 mediates the axonal conus growth. We aimed to investigate the impact of GAP-43 and actin expression on overall survival (OS) as well as crucial epidemiologic, radiological and neuropathological prognostic factors. Methods. FFPE tissue of adult patients with diffuse and anaplastic gliomas, who underwent first surgery in our center between 2010 and 2019, were selected. GAP-43 and actin expression was analyzed using immunohistochemistry and semi-quantitatively ranked. Clinical, neuropathological as well as follow-up-data were gained from the institutional neuro-oncological database. Results. 118 patients with a median age of 46 years (IqR: 35 – 57) were evaluated. 48 (41%) presented with a diffuse glioma and 70 (59%) revealed anaplasia. 96 (82%) cases presented with intermediate or strong GAP-43 expression and 78 (67%) with no or light actin expression. Tumors with higher expression of GAP-43 (p=0.024, HR=1.71/rank) and actin (p< 0.001, HR=2.28/rank) showed significantly reduced OS. IDH1 wildtype glioma demonstrated significantly more expression of both proteins: GAP-43 (p=0.009) and actin (p< 0.001). The same was confirmed for anaplasia (GAP-43 p=0.028, actin p=0.029), higher proliferation rate (GAP-43 p=0.016, actin p=0.038), contrast-enhancement in MRI (GAP-43 p=0.023, actin p=0.037) and age (GAP-43 p=0.004, actin p

The biologic behavior and the therapeutic resistance of diffuse and anaplastic gliomas varies greatly. This may be explained by differences in cell-to-cell communication, determined by the Cx43-associated junctional activity and the microtubules-defined network, in which GAP-43 is the dominant structural component. We assessed the expression of these crucial communication proteins in samples of patients harboring WHO°II and III gliomas, graded according to the current 4th revised WHO classification. Tissue of adult patients with WHO°II and III gliomas, who underwent surgery between 2014 and 2018, were selected from our institutional biobank. GAP-43 and Cx43 expression was analyzed using IHC. Routine clinical and neuropathological findings were additionally retrieved from our institutional prospective database. 43 (57%) males and 33 (43%) females with a median age of 47 (IqR: 35–61) years were selected. IDH1 wildtype tumors showed a significantly higher expression of Cx43 (p = 0.014) and a tendency for increased GAP-43 production. Advanced Cx43 expression significantly correlated with lower mitosis rate (p = 0.014): more in IDH1 wildtype (r = − 0.57, p = 0.003) than in mutated gliomas (r = − 0.37, p = 0.019). There was no difference in Cx43 or GAP-43 expression in relation to anaplastic phenotype, Gadolinum-contrasted enhancement (CE) on MRI and advanced EGFR or p53 expression. Intercellular communication tends to be more relevant in slower proliferating, e.g. lower malignant tumors. They could have more time to establish this network, providing longitudinally acquired resistance against specific oncological therapy. This feature matches the unfavorable IDH1 wildtype status of glioma and supports the noted malignant behavior of these tumors in the upcoming 5th WHO classification of gliomas.

With the rising life expectancy and availability of neuroimaging, increased number of older patients will present with diffuse and anaplastic gliomas. The aim of our study was therefore to investigate age-related prognostic clinical, neuropathological and radiological features of lower-grade gliomas. All consecutive patients with diffuse or anaplastic glioma WHO grade 2 and 3 who underwent first tumor resection between 2010 and 2018, were selected from the institutional neuro-oncological database and evaluated. The mean age of 55 males and 44 females was 46 years (SD ± 16). Wild-type IDH1 (p = 0.012), persistent nuclear ATRX expression (p = 0.012) and anaplasia (p