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s Background Malignant isocitrate dehydrogenase wild-type (IDHwt) gliomas impose a high symptomatic and psychological burden. Wide distances from patients’ homes to cancer centers may affect the delivery of psycho-oncological care. Here, we investigated, in a large brain tumor center with a rural outreach, the initiation of psycho-oncological care depending on spatial distance and impact of psycho-oncological care on emergency visits. Methods Electronic patient charts, the regional tumor registry, and interviews with the primary care physicians were used to investigate clinical data, psycho-oncological care, and emergency unit visits. Interrelations with socio-demographic, clinical, and treatment aspects were investigated using univariable and multivariable binary logistic regression analysis and the Pearson’s Chi-square test. Results Of 491, 229 adult patients of this retrospective cohort fulfilled the inclusion criteria for analysis. During the last three months of their lives, 48.9% received at least one psycho-oncological consultation, and 37.1% visited the emergency unit at least once. The distance from the cancer center did neither affect the initiation of psycho-oncological care nor the rate of emergency unit visits. Receiving psycho-oncological care did not correlate with the frequency of emergency unit visits in the last three months of life. Conclusion We conclude that the distance of IDHwt glioma patients’ homes from their cancer center, even in a rural area, does not significantly influence the rate of psycho-oncological care.

Background: Tractography based on diffusion-weighted magnetic resonance imaging (DWI) models the structural connectivity of the human brain. Deep brain stimulation (DBS) targeting the subthalamic n...

Suppl. Fig. 3. Flow cytometry analysis of T-cell surface marker expression

Supplementary Legends and Methods

Purpose:Mesenchymal stem cells (MSCs) show an inherent brain tumor tropism that can be exploited for targeted delivery of therapeutic genes to invasive glioma. We assessed whether a motile MSC-based local immunomodulation is able to overcome the immunosuppressive glioblastoma microenvironment and to induce an antitumor immune response.Experimental Design:We genetically modified MSCs to coexpress high levels of IL12 and IL7 (MSCIL7/12, Apceth-301). Therapeutic efficacy was assessed in two immunocompetent orthotopic C57BL/6 glioma models using GL261 and CT2A. Immunomodulatory effects were assessed by multicolor flow cytometry to profile immune activation and exhaustion of tumor-infiltrating immune cells. Diversity of the tumor-specific immune response as analyzed using T-cell receptor sequencing.Results:Intratumoral administration of MSCIL7/12 induced significant tumor growth inhibition and remission of established intracranial tumors, as demonstrated by MR imaging. Notably, up to 50% of treated mice survived long-term. Rechallenging of survivors confirmed long-lasting tumor immunity. Local treatment with MSCIL7/12 was well tolerated and led to a significant inversion of the CD4+/CD8+ T-cell ratio with an intricate, predominantly CD8+ effector T-cell–mediated antitumor response. T-cell receptor sequencing demonstrated an increased diversity of TILs in MSCIL7/12-treated mice, indicating a broader tumor-specific immune response with subsequent oligoclonal specification during generation of long-term immunity.Conclusions:Local MSC-based immunomodulation is able to efficiently alter the immunosuppressive microenvironment in glioblastoma. The long-lasting therapeutic effects warrant a rapid clinical translation of this concept and have led to planning of a phase I/II study of apceth-301 in recurrent glioblastoma.

A multitude of pathological and inflammatory processes determine the clinical course after aneurysmal subarachnoid hemorrhage (aSAH). However, our understanding of predictive factors and therapeutic consequences is limited. We evaluated the predictive value of clinically relevant factors readily available in the ICU setting, such as white blood cell (WBC) count and CRP, for two of the leading comorbidities, delayed cerebral ischemia (DCI) and ventriculoperitoneal (VP) shunt dependency in aSAH patients with and without corticosteroid treatment. We conducted a retrospective analysis of 484 aSAH patients admitted to our institution over an eight-year period. Relevant clinical factors affecting the risk of DCI and VP shunt dependency were identified and included in a multivariate logistic regression model. Overall, 233/484 (48.1%) patients were treated with corticosteroids. Intriguingly, predictive factors associated with the occurrence of DCI differed significantly depending on the corticosteroid treatment status (dexamethasone group: Hunt and Hess grade (p = 0.002), endovascular treatment (p = 0.016); no-dexamethasone group: acute hydrocephalus (p = 0.018), peripheral leukocyte count 7 days post SAH (WBC at day 7) (p = 0.009)). Similar disparities were found for VP shunt dependency (dexamethasone group: acute hydrocephalus (p = 0.002); no-dexamethasone group: WBC d7 (p = 0.036), CRP peak within 72 h (p = 0.015)). Our study shows that corticosteroid-induced leukocytosis negates the predictive prognostic potential of systemic inflammatory markers for DCI and VP shunt dependency, which has previously been neglected and should be accounted for in future studies.

Background The coronavirus pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is posing unprecedented challenges to health care systems around the globe. Consequently, various lockdown scenarios have been politically imposed to get control over the spread of this disease. We examined the impact of the lockdown situation on the number of neurosurgical emergency patients admitted to our tertiary care center with a catchment area of ∼2.2 million inhabitants in the south of Germany to ensure adequate neurosurgical emergency care during a pandemic lockdown. Methods All emergency admissions (with consecutive inpatient treatment) to the Department of Neurosurgery at the University Medical Center Regensburg, Germany, between March 1 and May 8 (69 days) of the years 2018, 2019, and 2020 were retrospectively identified and reviewed for this study. Demographic data, diagnoses, urgency of surgery, and duration of the journey to the emergency room were examined. Results Between March 1 and May 8, 2020, 59 emergency patients were neurosurgically treated at our department. Compared with 2018 and 2019, emergency admissions in 2020 had thus declined by 37.2 and 27.1%, respectively. Regarding the year 2020, we found a significant drop from 1.71 and 1.52 emergency patients per day in January and February 2020, respectively, to 0.86 during lockdown (p Conclusion Our findings are in line with other observational studies of neurosurgical, neurologic, and cardiologic centers in Europe that have described a drop in emergency cases. The reasons for this drop that seems to affect various medical fields and countries across Europe are still unidentified. Morbidity and mortality rates are still unknown, and efforts should be made to facilitate neurosurgical emergency care during a pandemic lockdown.

Background: Brain-tumor-initiating cells (BTICs) of proneural and mesenchymal origin contribute to the highly malignant phenotype of glioblastoma (GB) and resistance to current therapies. Methods: BTICs of different subtypes representing tumor heterogeneity were challenged with OXPHOS (oxidative phosphorylation) inhibition to assess the differential effects of metabolic intervention on key resistance features. Results: Whereas mesenchymal BTICs were more invasive, more glycolytic and less responsive to OXPHOS-inhibition, proneural BTICs were less invasive, catabolized glucose more via the pentose phosphate pathways, and responded better to OXPHOS inhibition. Conclusion: Targeting glycolysis may be a promising approach to inhibit highly invasive tumor cells of mesenchymal origin, whereas proneural cells are more responsive to OXPHOS inhibition. Future clinical trials exploring metabolic interventions should account for metabolic heterogeneity of brain tumors to overcome resistance to current treatments.

INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (nGBM). A crucial parameter for TTFields efficacy is compliance to treatment. In this prospective study, we assessed 5 psychological domains known to influence treatment compliance using a standardized interview in nGBM patients. The results of this psychological assessment were correlated to TTF compliance. METHODS A cohort of 49 nGBM patients (female 22; male 27, median age 62 years) were recruited. Most patients received a gross total resection (51%), the postsurgical treatment consisted of concomitant radiochemotherapy plus TTF in most cases (81%), only 2 patients received chemotherapy only, and 7 patients were additionally enrolled in clinical drug trials. The psychological assessment system consisted of 5 domains: Social support, confidence in treatment efficacy, communication status about treatment, anxiety, and depression. The interview was repeated every 8 weeks over a period of 8 months or if patients stopped treatment or developed second tumor progression. Additional phone interviews were conducted every 4 weeks. RESULTS Median and mean compliance was 98% and 81.6%, respectively (range 5%-100%), drops of compliance below 75%, which were classified as a threshold value, occurred 2259 times. Over-dispersed Poisson and multivariate negative binomial regression analysis revealed depression to be significantly correlated with the number of drops below 75% and with the mean compliance in the first 4 months of treatment. In addition, at later time points, confidence in treatment efficacy significantly correlated with the number of drops below 75%. All other domains did not appear to be associated with TTF treatment compliance. CONCLUSION Overall, compliance to TTF was high, however, drops below 75% of compliance occurred frequently during the measurement periods. In the initial treatment phase, depression was associated with these events, whereas confidence in treatment efficacy was correlated at later time points.

Background and Study Aims Aneurysm clips must have adequate closing forces because residual blood flow in clipped aneurysms may result in aneurysm recurrence. Such flow can be intraoperatively detected by visual inspection, microvascular Doppler sonography, indocyanine green videoangiography (ICG-V), angiography, and puncture. Patients We present two patients with ruptured very small middle cerebral artery aneurysms (3 and 2.9 mm). The necks of both aneurysms were microsurgically clipped with Yasargil aneurysm clips without any complications. Results In both aneurysms, visual inspection suggested complete occlusion, but ICG-V showed persistent residual blood flow between the middle parts of the clip blades.The first patient was treated with a 5.4-mm FT744T clip (closing force of 1.47 N). After the ICG-V finding, a second 3.9-mm FT714T clip (closing force of 1.08 N) was placed on the tips of the already implanted clip to increase the closing forces. Subsequent ICG-V did not show any further residual blood flow. In the second patient, the aneurysm was clipped with an 8.0-mm FE764K clip (closing force of 1.77 N). Intraoperative ICG-V showed persistent residual blood flow within the aneurysmal dome despite complete closure of the clip. The clip was repositioned closer to the parent vessel. Consecutive ICG-V did not show any residual blood flow. Conclusion Visually undetected incomplete aneurysm occlusion can be revealed with ICG-V. In very small aneurysms, standard closing forces of clips may not be sufficient and complete closure of the clip branches should be intraoperatively validated with ICG-V.

Background Brain metastases (BM) frequently cause focal neurological deficits leading to a reduced Karnofsky performance score (KPS). Since KPS is routinely used to guide the choice of adjuvant therapy, we hypothesized that improving KPS by surgical resection may improve the chance for adjuvant treatment and ultimately result in better survival. We therefore analyzed the course of a large cohort undergoing resection of symptomatic brain metastases in the context of further treatment and clinical outcome. Patients and methods In a bi‐centric retrospective analysis we retrieved baseline, clinical, and treatment‐related parameters of patients operated on BM between 2010 and 2019. Survival was calculated using Kaplan‐Meier estimates; prognostic factors for survival were analyzed by Log‐rank test and Cox proportional hazards. Results We included 750 patients with a median age of 61 (19‐87) years. The functional status was significantly improved by surgical resection, with a median preoperative (KPS) of 80 (10‐100) increasing to 90 (0‐100) after surgery (P, In patients with symptomatic brain metastases systemic oncological treatment is the strongest factor for further survival. Resection of a symptomatic brain metastasis results in an improved clinical status which facilitates further treatment.

Recent updates in the classification of central nervous system (CNS) tumors have increased the need for molecular testing. Assessment of multiple alterations in parallel, complex combinations of gene sequence and chromosomal changes, as well as therapy prediction by identification of actionable mutations are the major challenges. We here report on a customized next generation sequencing (NGS)-based DNA panel assay that combines diagnostic and predictive testing and -as a comprehensive approach- allows for simultaneous single nucleotide variant (SNP) / small insertion/deletion (InDel), copy number variation (CNV) and loss of heterozygosity (LOH) detection. We analyzed formalin-fixed and paraffin-embedded (FFPE) DNA from a total of 104 patients with CNS tumors. After amplicon capture-based library preparation, sequencing was performed on the relatively cost-efficient Illiumina MiniSeq platform and evaluated with freely available bioinformatical tools. 57 genes for exonic SNP/InDel calling (19 of those in intronic regions for CNV analysis), 3 chromosomal arms and 4 entire chromosomes for CNV and LOH analysis were covered. Results were extensively validated. Our approach yielded high accuracy, sensitivity and specificity. It led to refined diagnoses in a relevant number of analyzed cases, reliably enabled complex subclassifications (e.g. for medulloblastomas) and identified actionable targets for clinical use. Thus, our single-platform approach is an efficient and powerful tool to comprehensively support molecular testing in neurooncology. Future functionality is guaranteed as novel upcoming biomarkers can be easily incorporated in a modular panel design.

Infectious spondylodiscitis of the lumbar spine is a common serious disease for which evidence-based therapeutic concepts are still lacking.This retrospective study compared the impact of the health status of patients on the length of hospital stay with regard to the treatment concept, i.e., antibiotic therapy or antibiotic therapy in combination with fixation surgery.The study included 54 consecutive patients with infectious spondylodiscitis of the lumbar spine who had been treated at our clinic between 2004 and 2013. Records included patient demographics, concomitant diseases, the neurological status and treatment modality, and the length of hospital stay.40 men and 14 women with a mean age of 64.2 (30-89) years were included. 13 patients were only treated with antibiotics (group A), 7 patients with abscess decompression (group B), 18 patients with early dorsal fusion (10 days after admission) (group C), and 16 patients with late dorsal fusion (≥10 days after admission; group D). Patients undergoing early dorsal fusion had a significantly shorter hospital stay (33.2 days) than patients undergoing late dorsal fusion (57.0 days), P = 0.016. Mean hospital stay of patients treated with antibiotics was 30.3 days, that of patients receiving abscess decompression 57.8 days. Patients receiving only antibiotics had a significantly lower CRP level at admission than patients undergoing early fusion, P0.05.Patients with one or more relevant chronic concomitant diseases showed faster recovery, shorter hospital stays, and earlier return to daily routine after early dorsal fusion than after late dorsal fusion or abscess evacuation alone.

The dentato-rubro-thalamic tract (DRTT) has been found to play a major role in the mechanisms of tremor alleviation by deep brain stimulation (DBS) in essential tremor (ET). Still, the influence of the two different parts of the DRTT, consisting of crossing and nondecussating fibers, is not yet clear with respect to tremor reduction. The aim of this study was to assess the influence of the crossing and the nondecussating part of the DRTT on tremor control in ET.We investigated 80 electrode contacts in ten patients with ET who received bilateral DBS of the Nucleus ventralis intermedius of the thalamus (VIM). Preoperatively and with patients under general anesthesia, 3T magnetic resonance imaging scans were performed, including Diffusion Tensor Imaging scans with 64 gradient directions. We calculated the course of the two parts of the DRTT based on a workflow for probabilistic fiber tracking including protocols for correction of susceptibility- and eddy current-induced distortions. Distances of electrode contacts were correlated with clinical data from neurologic single pole testing.Voltage- and current-steered systems were analyzed separately. Regarding postural tremor, effective contacts showed significantly lower distances to both parts of the DRTT (crossing p 0.001, nondecussating p 0.05) in voltage-steered systems. Regarding intentional tremor, significant results were only found for the crossing part (p 0.01). Regarding both tremor types, effective contacts were closer to the crossing part, unlike less effective contacts. Nonlinear regression analyses using a logistic model showed higher coefficients for the crossing part of the DRTT. Multivariate regression models including distances to both parts of the DRTT showed a significant influence of only the crossing part. Analysis of current-steered systems showed unstable data, probably because of the small number of analyzed patients.Our data suggest an involvement of both parts of the DRTT in tremor reduction, indicating mediation of DBS effects by both fiber bundles, although the crossing part showed stronger correlations with good clinical responses. Nevertheless, special attention should be paid to methodologic aspects when using probabilistic tractography for patient-specific targeting to avoid uncertain and inaccurate results.

Background The BRAF V600E mutation is present in approximately 50% of patients with melanoma brain metastases and an important prerequisite for response to targeted therapies, particularly BRAF inhibitors. As heterogeneity in terms of BRAF mutation status may occur in melanoma patients, a wild-type extracranial primary tumor does not necessarily rule out a targetable mutation in brain metastases using BRAF inhibitors. We evaluated the potential of MRI radiomics for a noninvasive prediction of the intracranial BRAF mutation status. Methods Fifty-nine patients with melanoma brain metastases from two university brain tumor centers (group 1, 45 patients; group 2, 14 patients) underwent tumor resection with subsequent genetic analysis of the intracranial BRAF mutation status. Preoperative contrast-enhanced MRI was manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses. Results Twenty-two of 45 patients (49%) in group 1, and 8 of 14 patients (57%) in group 2 had an intracranial BRAF V600E mutation. A linear support vector machine classifier using a six-parameter radiomics signature yielded an area under the ROC curve of 0.92 (sensitivity, 83%; specificity, 88%) in the test data. Conclusions The developed radiomics classifier allows a noninvasive prediction of the intracranial BRAF V600E mutation status in patients with melanoma brain metastases with high diagnostic performance.

BACKGROUND Validation of the 2016 LANO MRI scorecard for leptomeningeal metastasis failed for multiple reasons. The objective of this joint EORTC Brain Tumor Group and RANO effort was to validate the feasibility of the revised MRI scorecard for assessing response in leptomeningeal metastasis. METHODS Coded paired cerebrospinal MRI of 20 patients with leptomeningeal metastases from solid cancers at baseline and follow-up after treatment and instructions for assessment were provided via the EORTC imaging platform. The kappa coefficient (K) was used to evaluate inter-observer pairwise agreement. Statistical analyses were performed using SAS V9.4 software (Cary, NC). The sponsor of the study was the University Hospital Zurich (2018-00192). RESULTS Thirty-five raters participated, including 9 neuroradiologists, 17 neurologists, 4 radiation oncologists, 3 neurosurgeons and 2 medical oncologists. Among leptomeningeal metastases-related items at baseline, the best median concordance was noted for hydrocephalus (K=0.63), and the worst median for spinal linear enhancing disease (K=0.46). The median concordance for overall response was moderate (K=0.44). Notably, the interobserver agreement for the presence of parenchymal brain metastases at baseline was minimal (K=0.29). Significant differences were observed when considering the specialty of the raters. Only 394 of 700 ratings (56%) were fully completed. Among 394 fully completed ratings, perfect concordance was noted in 293 ratings (74%) when comparing the overall response according to the guidelines provided in the scorecard and the overall response provided by the raters. The main discordances were noted for partial response according to the rater versus stable disease according to the guidelines (n=44), followed by progression according to the raters versus stable disease according to the guidelines (n=23). CONCLUSION Electronic case report forms with "blocking solutions" are probably required to enforce completeness and quality of scoring. These results confirm the necessity of central review and the need for training of MRI assessment in clinical trials.

Glioblastoma are highly invasive and associated with limited therapeutic options and a grim prognosis. Using stem cells to extend current therapeutic strategies by targeted drug delivery to infiltrated tumors cells is highly attractive. This study analyzes the tumor homing and therapeutic abilities of clinical grade human mesenchymal stem cells (MSCs) in an orthotopic glioblastoma mouse model. Our time course analysis demonstrated that MSCs display a rapid targeted migration to intracerebral U87 glioma xenografts growing in the contralateral hemisphere within the first 48h hours after application as assessed by histology and 7T magnetic resonance imaging. MSCs accumulated predominantly peritumorally but also infiltrated the main tumor mass and targeted distant tumor satellites while no MSCs were found in other regions of the brain. Intratumoral application of MSCs expressing herpes simplex virus thymidine kinase followed by systemic prodrug application of ganciclovir led to a significant tumor growth inhibition of 86% versus the control groups (p

OBJECTIVEGiant posterior circulation aneurysms (GPCirAs) usually cause substantial mass effect on the brainstem, which may lead to neurological deficits. So far, there has been no systematic investigation of factors associated with such deficits in GPCirA. The authors aim to examine the risk factors for cranial nerve deficit (CND), motor deficit, and disability in patients with GPCirA.METHODSUsing MR images obtained in 30 patients with unruptured GPCirA, the authors examined GPCirA volume, presence of hydrocephalus or partial thrombosis (PT) of the aneurysm, and the degree of brainstem displacement measured by the distance between the McRae line and the tip of the GPCirA (∆MT). They evaluated associations between these factors and neurological deficits.RESULTSThirty GPCirAs in 30 patients were included. The prevalence of CNDs was 50%. Patients with CNDs significantly differed from those without CNDs in terms of age (mean 51.0 years [SD 15.0 years] vs 69.0 years [SD 21.0 years], p = 0.01) and in ∆MT (median 50.7 mm [IQR 39.2–53.9 mm] vs 39.0 mm [IQR 32.3–45.9 mm], p = 0.02). The prevalence of motor deficits was 33.3%. Patients with motor deficits showed a larger ∆MT (median 50.5 mm [IQR 40.8–54.6 mm]) compared with those without (∆MT: median 39.1 mm [IQR 32.8–50.5 mm], p = 0.04). GPCirA volume was larger in patients with poor modified Rankin Scale (mRS) scores (median 14.9 cm3 [IQR 8.6–18.7 cm3]) than in those with mRS scores of 0–2 (median 6.8 cm3 [IQR 4.4–11.7 cm3], p = 0.03). After adjusting for patient age and the occurrence of hydrocephalus or PT, the authors found that higher degrees of disability were significantly associated with aneurysm volume (OR 1.13, 95% CI 1.0–1.3; p = 0.04), but not with ∆MT. The occurrence of CND or motor deficit was not associated with any of the examined variables. There was no correlation between GPCirA volume and ∆MT (rs = 0.01, p = 0.96). The prevalence of neurological deficits did not differ between GPCirA at the basilar apex, the basilar trunk, the vertebrobasilar junction, or the vertebral artery.CONCLUSIONSIn this study, the neurological condition of the patients was associated only with GPCirA volume and not with the degree of brainstem displacement, the occurrence of PT or hydrocephalus, or the exact location of the GPCirA. These findings highlight the clinical relevance of GPCirA volume and suggest that factors such as brainstem displacement or PT should play less of a role when finding arguments for or against treatment of GPCirA.Clinical trial registration no.: NCT02066493 (clinicaltrials.gov)

Introduction Postoperative nausea and vomiting (PONV) is common in patients after craniotomy and may lead to severe postoperative complications. The aim of this study was to identify risk factors and postoperative complications associated with PONV in the context of perioperative high-dose dexamethasone administration. Patients and Methods In this prospective single-center study, all patients planned for elective craniotomy for supra- and infratentorial lesions were eligible to be included. Any PONV in a 24-hour period after craniotomy was recorded and analyzed with regard to time to postoperative complications and the administration of perioperatively administered high-dose dexamethasone. Results The overall PONV rate of 421 patients during a 9-month period was 18.1% (76 patients). Multivariate analysis revealed a significant association of PONV with female sex, infratentorial localization, age, and history of PONV. There was no association between PONV and postoperative complications such as intracranial hemorrhage, cerebrospinal fluid (CSF) leaks, or pneumonia. Perioperative administration of high-dose dexamethasone for prophylactic prevention of edema was the only significant risk factor for postoperative complications (odds ratio [OR]: 3.34; confidence interval [CI], 1.39–8.05; p Conclusion The low PONV rate of 18.1% in this study may be the result of the frequent perioperative administration of high-dose dexamethasone for the prevention of edema. Our data indicate that perioperative high-dose dexamethasone is significantly associated with CSF leaks and can therefore not be recommended on a regular basis.

The demographic change results in an ever increasing number of older patients with pre-existing medical conditions who require spinal surgery, and recovery is often severely impaired by procedure-related complications. The purpose of this retrospective study was to determine patients at risk of medical and surgical complications.Using our database, we reviewed 1244 patients with lumbar degenerative disk disease, spinal stenosis, and instability, who had undergone surgery at our department between 2009 and 2014. We screened for medical complications (thromboembolic and cardiac events, pneumonia, and sepsis) and surgical complications (hemorrhage, wound infection, and CSF fistula). Furthermore, a matched 1:1 control group consisted of 103 patients without any surgical and medical complications in the randomly selected period of May 2009 to October 2014.93 patients (46 women, 47 men), mean age 70 years (range 33-86 years, median 67.4 years), with complications were identified (overall morbidity 7.6 %): 22.6 % (n = 26) had medical complications and 77.4 % (n = 89) surgical complications. In 93 patients (46 females, 47 males), mean age 70 years (range 33-86 years, median 67.4 years), a total of 115 complications were noted (overall morbidity of the 93 patients 7.6 %): 22.6 % (n = 26) medical complications and 77.4 % (n = 89) surgical complications. Age and pre-existing conditions were independently associated with medical complications (p lt; 0.001). Infections (pneumonia and sepsis) were correlated with multi-segmental interventions (p = 0.009), duration of surgery (p = 0.009), and pre-existing conditions (p = 0.014). Surgical complications were significantly correlated with age (p = 0.016) and duration of surgery (p = 0.014) and occurred significantly more often in patients with instability (p lt; 0.001). Wound healing disorders were associated with coagulopathy (p = 0.013) and transfusion (p lt; 0.001).We identified predictors that help identify patients at risk of medical and surgical complications. These correlations should be taken into account when advising older patients with pre-existing conditions on lumbar spine surgery.

Tinnitus, the phantom perception of sound, is a frequent disorder that can lead to severe distress and stress-related comorbidity. The pathophysiological mechanisms involved in the etiology of tinnitus are still under exploration. Electrophysiological and functional neuroimaging studies provide increasing evidence for abnormal functioning in auditory but also in non-auditory, e.g., emotional, brain areas. In order to elucidate alterations of affective processing in patients with chronic tinnitus, we used functional magnetic resonance imaging (fMRI) to measure neural responses to emotionally expressive and neutral faces. Twelve patients with chronic tinnitus and a group of 11 healthy controls, matched for age, sex, hearing loss and depressive symptoms were investigated. While viewing emotionally expressive faces compared to neutral faces brain activations in the tinnitus patients differed from those of the controls in a cluster that encompasses the amygdala, the hippocampus and the parahippocampal gyrus bilaterally. Whereas in controls affective faces induced higher brain activation in these regions than neutral faces, these regions in tinnitus patients were deactivated. Our results (1) provide evidence for alterations of affective processing of facial expressions in tinnitus patients indicating general domain-unspecific dysfunctions in emotion processing and (2) indicate the involvement of medial temporal areas in the pathophysiology of tinnitus.

Objective The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. Methods We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. Result In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families. Conclusions and Relevance The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.

OBJECTIVE Space-occupying brain lesions as brain tumors in the occipital lobe have only been sparsely investigated so far, as this localization is extremely rare with only 1% of cases. It is still unclear how this affects the overall organization of the visual system. We investigated functional connectivity of functional networks associated with higher visual processing between patients with occipital space-occupying lesion in the occipital cortex and healthy controls. METHODS 12 patients with brain tumors, 7 patients with vascular lesions in the occipital cortex and 19 healthy subjects matched for age and sex were included. During functional MRI patients and subjects performed a visual excentricity mapping task. Data analysis was done using CONN toolbox based on Matlab. See-to-ROI connectivities of 23 Regions of Interest (ROIs) implemented in the CONN toolbox which were assigned to the Default Mode, Visual, Salience, Dorsal Attention, and Frontoparietal network were assessed. For each subject, connectivity was calculated using Fischer transformed pairwise correlations. These correlations were first considered separately for each group in one-sample analyses and then compared between the groups. RESULTS Main results show, that compared to control subjects and vascular patients, tumor patients showed weaker intra-network connectivity of components of all networks except the default-network. Tumor patients showed even stronger between-network connectivity in the default-mode network compared to the other groups. Weaker connectivity was observed within the salience network in both patient groups compared to controls. CONCLUSION The results indicate that in the course of the disease, compensatory countermeasures take place in the brain against a brain tumor or a space-occupying brain lesion with the aim of maintaining the performance level and cognitive processes for as long as possible. However, more research is needed in this area to understand the mechanisms and effects of brain tumors and space-consuming brain lesions on surrounding tissue.

The multidisciplinary management of patients with brain metastases (BM) consists of surgical resection, different radiation treatment modalities, cytotoxic chemotherapy, and targeted molecular treatment. This review presents the current state of neurosurgical technology applied to achieve maximal resection with minimal morbidity as a treatment paradigm in patients with BM. In addition, we discuss the contribution of neurosurgical resection on functional outcome, advanced systemic treatment strategies, and enhanced understanding of the tumor biology.

(1) Background—Mapping language using direct cortical stimulation (DCS) during an awake craniotomy is difficult without using more than one language paradigm that particularly follows the demand of DCS by not exceeding the assessment time of 4 s to prevent intraoperative complications. We designed an intraoperative language paradigm by combining classical picture naming and verb generation, which safely engaged highly relevant language functions. (2) Methods—An evaluation study investigated whether a single trial of the language task could be performed in less than 4 s in 30 healthy subjects and whether the suggested language paradigm sufficiently pictured the cortical language network using functional magnetic resonance imaging (fMRI) in 12 healthy subjects. In a feasibility study, 24 brain tumor patients conducted the language task during an awake craniotomy. The patients’ neuropsychological outcomes were monitored before and after surgery. (3) Results—The fMRI results in healthy subjects showed activations in a language-associated network around the (left) sylvian fissure. Single language trials could be performed within 4 s. Intraoperatively, all tumor patients showed DCS-induced language errors while conducting the novel language task. Postoperatively, mild neuropsychological impairments appeared compared to the presurgical assessment. (4) Conclusions—These data support the use of a novel language paradigm that safely monitors highly relevant language functions intraoperatively, which can consequently minimize negative postoperative neuropsychological outcomes.

Tinnitus, the phantom perception of sound, is a frequent disorder that can lead to severe distress and stress-related comorbidity. The pathophysiological mechanisms involved in the etiology of tinnitus are still under exploration. Electrophysiological and functional neuroimaging studies provide increasing evidence for abnormal functioning in auditory but also in non-auditory, e.g., emotional, brain areas. In order to elucidate alterations of affective processing in patients with chronic tinnitus, we used functional magnetic resonance imaging (fMRI) to measure neural responses to emotionally expressive and neutral faces. Twelve patients with chronic tinnitus and a group of 11 healthy controls, matched for age, sex, hearing loss and depressive symptoms were investigated. While viewing emotionally expressive faces compared to neutral faces brain activations in the tinnitus patients differed from those of the controls in a cluster that encompasses the amygdala, the hippocampus and the parahippocampal gyrus bilaterally. Whereas in controls affective faces induced higher brain activation in these regions than neutral faces, these regions in tinnitus patients were deactivated. Our results (1) provide evidence for alterations of affective processing of facial expressions in tinnitus patients indicating general domain-unspecific dysfunctions in emotion processing and (2) indicate the involvement of medial temporal areas in the pathophysiology of tinnitus.

In patients with brain metastases (BM), advanced age is considered a negative prognostic factor. To address the potential reasons for that, we assessed 807 patients who had undergone BM resection; 315 patients aged at least 65 years (group A) were compared with 492 younger patients (group B). We analyzed the impact of the pre- and postoperative Karnofsky performance status (KPS), postoperative treatment structure and post-treatment survival. BM resection significantly improved KPS scores in both groups (p = 0.0001). Median survival after BM resection differed significantly between the groups (A: 5.81 vs. B: 8.12 months; p = 0.0015). In both groups, patients who received postoperative systemic treatment showed significantly longer overall survival (p = 0.00001). However, elderly patients less frequently received systemic treatment (p = 0.0001) and the subgroup of elderly patients receiving such therapies had a significantly higher postsurgical KPS score (p = 0.0007). In all patients receiving systemic treatment, age was no longer a negative prognostic factor. Resection of BM improves the functional status of elderly patients, thus enhancing the likeliness to receive systemic treatment, which, in turn, leads to longer overall survival. In the context of such a treatment structure, age alone is no longer a prognostic factor for survival.

INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (GBM). One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity, which depends on the dielectric properties of the tumor tissue. In this study we determined the dielectric properties of GBM by analyzing resected tissue following a fast acquisition protocol. To account for the intratumoral heterogeneity, different regions of the tumor were analyzed separately. METHODS A cohort of 38 patients with newly diagnosed GBM were analyzed. Tissue probes were acquired from the vital tumor area and perinecrotic compartment. The tissue was measured immediately to avoid artifacts. A fragment was dissected from each tissue sample and was placed into a cylindrical cell with a known diameter. The impedance was recorded at frequencies 20Hz-1MHz using a software specifically developed for this study, which controls the LCR meter. The measured impedance was translated into dielectric properties of the sample (conductivity and relative permittivity) based on the parallel plate model, the recorded complex impedance and the geometry of the samples. Each tissue probe was fixed, and stained with H&E to visualize cellularity, luxol fast blue to analyze the myelinated fiber content and against factor VIII related antigen to assess tumor vascularity. RESULTS We found significant differences between the conductivity and permittivity of tissue samples from each individual tumor (mean conductivity [S/m]: 0.302; range: 0.607 – 0.100; mean permittivity [Farad/m]: 3519.8; range: 11182.5 – 135.7). Consistently, the perinecrotic areas displayed lower conductivity values compared to the solid tumor compartments. Histological analysis revealed significantly higher cellularity and lower myelinated fiber content in tissue samples with high conductivity and permittivity. CONCLUSION The dielectric properties of GBM show a high intratumoral heterogeneity which correlate to the extent of cellularity and myelin fiber content within the tissue.

Severe refractory cerebral vasospasm (CV) is a major cause of disability and death in patients with aneurysmal subarachnoid hemorrhage (SAH). One rescue therapy in selected patients is intra-arterial nimodipine, either given as a single shot or as continuous infusion. To evaluate treatment efficacy, we analyzed outcome factors such as the incidence of craniectomy, ventriculo-peritonial (VP) shunting, and tracheotomy after intra-arterial nimodipine infusion. We retrospectively analyzed the rates of cerebral infarction, decompressive craniectomy, VP shunting, and tracheotomy in patients with severe CV after SAH. Three different patient groups were compared: group 1 had only been treated with oral nimodipine and hypervolemic hypertensive therapy (HHT) (2006–2010), group 2 with a single shot of intra-arterial nimodipine (SSN) in addition to oral conservative treatment (2006–2010), and group 3 with continuous intra-arterial nimodipine (CIAN) (2011–2017). The incidence of cerebral infarction was significantly lower in CIAN group (p = 0.005) than in conservative and SSN group. The indication for consecutive decompressive craniectomy was significantly lower in CIAN group in comparison with the conservative group (p = 0.018). The rates of VP shunting and tracheotomy were significantly higher in the CIAN group than in the conservative group (p = 0.028 for VP, and p = 0.003 for tracheotomy). The significantly lower rate of craniectomy in the CIAN group was most probably attributable to the significantly lower rate of CV-induced infarction. The higher rate of tracheotomy reflects more extensive sedation and the need of longer stays on the intensive care unit. Thus, the effect on long-term neurological outcome and quality of life has to be evaluated separately.

Background Texture-related factors such as consistency, vascularity, and adherence vary considerably in meningioma and are thought to be linked with surgical resectability and morbidity. However, data analyzing the true impact of meningioma texture on the surgical management is sparse. Methods Patients with intracranial meningioma treated between 08/2014 and 04/2018 at our institution were prospectively collected for demographics, clinical presentation, histology, and surgical treatment with related morbidity and extend of resection. Tumor characteristics were reported by the surgeon using a standardized questionnaire including items such as tumor consistency, homogeneity, vascularization, and adherence to surrounding neurovascular structure and analyzed for their impact surgical outcome parameters using univariate and logistic regression analyses. Results Tumor texture-related parameters of 300 patients (72.3% female) with meningioma were analyzed. Meningioma localizations were grouped into 3 different cohorts namely convexity, skull base, and posterior. Postoperative occurrence of a neurological deficit (transient 23.0%; permanent 6.1%) was associated with the duration of surgery (P = .001), size of tumor (P = .046), tumor vascularization (P = .015), and adherence to neurovascular structures (P = .002). Coherently, the duration of surgery (mean 230.99 ± 101.33 min) was associated with size of tumor (P < .0001), vascularization (P < .0001), and adherence (P < .0001). Similar associations were recapitulated in subgroup analyses of different tumor localizations. Noteworthy, tumor rigidity had no significant impact on time of surgery and neurological outcome. Conclusions Our analysis demonstrates that tumor texture has an impact on the surgical management of meningioma and provides data that tumor vascularization and adherence are significant factors influencing surgical outcome whereas the influence of tumor consistency has less impact than previously thought.