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Purpose Non-invasive prediction of the tumour of origin giving rise to brain metastases (BMs) using MRI measurements obtained in radiological routine and elucidating the biological basis by matched histopathological analysis. Methods Preoperative MRI and histological parameters of 95 BM patients (female, 50; mean age 59.6 ± 11.5 years) suffering from different primary tumours were retrospectively analysed. MR features were assessed by region of interest (ROI) measurements of signal intensities on unenhanced T1-, T2-, diffusion-weighted imaging and apparent diffusion coefficient (ADC) normalised to an internal reference ROI. Furthermore, we assessed BM size and oedema as well as cell density, proliferation rate, microvessel density and vessel area as histopathological parameters. Results Applying recursive partitioning conditional inference trees, only histopathological parameters could stratify the primary tumour entities. We identified two distinct BM growth patterns depending on their proliferative status: Ki67high BMs were larger (p = 0.02), showed less peritumoural oedema (p = 0.02) and showed a trend towards higher cell density (p = 0.05). Furthermore, Ki67high BMs were associated with higher DWI signals (p = 0.03) and reduced ADC values (p = 0.004). Vessel density was strongly reduced in Ki67high BM (p p ≤ 0.03 for all features) with SCLCs representing predominantly the Ki67high group, while NSCLCs rather matching with Ki67low features. Conclusion Interpretable and easy to obtain MRI features may not be sufficient to predict directly the primary tumour entity of BM but seem to have the potential to aid differentiating high- and low-proliferative BMs, such as SCLC and NSCLC.

OBJECTIVE Despite the rising number of women in higher education and leadership positions, the proportional rise of female neurosurgeons still lags behind these fields. This study evaluates the gender distribution in German neurosurgical departments across all career levels, and is aimed at heightening the awareness of gender disparity and the need for improving gender equality and its related opportunities. METHODS Data on gender distribution across all professional levels in German neurosurgical departments were obtained from departmental websites as well as by email and telephone request. Results were additionally analyzed in reference to hospital ownership type of the neurosurgical departments. RESULTS A total of 140 German neurosurgical departments employing 2324 neurosurgeons were evaluated. The analysis revealed a clear preponderance of men in leadership positions. Only 9 (6.3%) of 143 department heads were women, and there were only 1 (2.4%), 17 (14.5%), and 4 (12.5%) women among 42 vice-directors, 117 chief senior physicians, and 32 managing senior physicians, respectively. Senior physicians not holding a leadership position were female in 23.1%, whereas board-certified neurosurgeons not holding a senior physician position and residents were female in 33.6% and 35.0%, respectively. Of note, the highest proportion of female department heads (15.6%) was found in private hospitals. CONCLUSIONS The number of women in leadership positions in German neurosurgical departments is dramatically low, and with increasing leadership status gender disparity increases. Mentorship, recruitment, the perception of benefits offered by diversity and programs facilitating gender equality, job sharing, parental leave policies, and onsite childcare programs are needed to turn German neurosurgical departments into modern medical departments reflecting the gender profile of the general patient population.

BACKGROUND AND PURPOSE Progressive multifocal leukoencephalopathy (PML) constitutes a severe disease with increasing incidence, mostly in the context of immunosuppressive therapies. A detailed understanding of immune response in PML appears critical for the treatment strategy. The aim was a comprehensive immunoprofiling and radiological characterization of magnetic resonance imaging (MRI) defined PML variants. METHODS All biopsy-confirmed PML patients (n = 15) treated in our department between January 2004 and July 2019 were retrospectively analysed. Data from MRI, histology as well as detailed clinical and outcome data were collected. The MRI-defined variants of classical (cPML) and inflammatory (iPML) PML were discriminated based on the intensity of gadolinium enhancement. In these PML variants, intensity and localization (perivascular vs. parenchymal) of inflammation in MRI and histology as well as the cellular composition by immunohistochemistry were assessed. The size of the demyelinating lesions was correlated with immune cell infiltration. RESULTS Patients with MRI-defined iPML showed a stronger intensity of inflammation with an increased lymphocyte infiltration on histological level. Also, iPML was characterized by a predominantly perivascular inflammation. However, cPML patients also demonstrated certain inflammatory tissue alterations. Infiltration of CD163-positive microglia and macrophage (M/M) subtypes correlated with PML lesion size. CONCLUSIONS The non-invasive MRI-based discrimination of PML variants allows for an estimation of inflammatory tissue alterations, although exhibiting limitations in MRI-defined cPML. The association of a distinct phagocytic M/M subtype with the extent of demyelination might reflect disease progression.

Purpose With increasing patient self-empowerment and participation in decision making, we hypothesized that patients with adult-type diffuse gliomas, CNS WHO grade 4 who change sites of treatment differ from patients being entirely treated in one neuro-oncological center. Methods Prospectively collected data from all diffuse glioma grade 4 patients who underwent treatment in our neuro-oncological center between 2012 and 2018 were retrospectively examined for differences between patients having initially been diagnosed and/or treated elsewhere (External Group) and patients having entirely been treated in our neuro-oncological center (Internal Group). Additionally, a matched-pair analysis was performed to adjust for possible confounders. Results A total of 616 patients was analyzed. Patients from the External Group (n = 78) were significantly younger, more frequently suffered from IDH-mutant astrocytoma grade 4, had a greater extent of tumor resection, more frequently underwent adjuvant therapy and experienced longer overall survival (all p Conclusion The present study demonstrates that mobile diffuse glioma grade 4 patients stand out from a comprehensive diffuse glioma grade 4 patient cohort due to their favorable prognostic characteristics. However, changing treatment sites did not result in survival benefit over similar patients being entirely taken care of within one neuro-oncological institution. These results underline the importance of treatment and molecular markers in glioma disease for patients’ self-empowerment, including changing treatment sites according to patients’ needs and wishes.

Purpose Classification and treatment of WHO grade II/III gliomas have dramatically changed. Implementing molecular markers into the WHO classification raised discussions about the significance of grading and clinical trials showed overall survival (OS) benefits for combined radiochemotherapy. As molecularly stratified treatment data outside clinical trials are scarce, we conducted this retrospective study. Methods We identified 343 patients (1995–2015) with newly diagnosed WHO grade II/III gliomas and analyzed molecular markers, patient characteristics, symptoms, histology, treatment, time to treatment failure (TTF) and OS. Results IDH-status was available for all patients (259 mutant, 84 IDH1-R132H-non-mutant). Molecular subclassification was possible in 173 tumors, resulting in diagnosis of 80 astrocytomas and 93 oligodendrogliomas. WHO grading remained significant for OS in astrocytomas/IDH1-R132H-non-mutant gliomas (p p = 0.27). Chemotherapy (and temozolomide in particular) showed inferior OS compared to radiotherapy in astrocytomas (median 6.1/12.1 years; p = 0.03) and oligodendrogliomas (median 13.2/not reached (n.r.) years; p = 0.03). While radiochemotherapy improved TTF in oligodendroglioma (median radiochemotherapy n.r./chemotherapy 3.8/radiotherapy 7.3 years; p p Conclusion This is one of the largest retrospective, real-life datasets reporting treatment and outcome in low-grade gliomas incorporating molecular markers. Current histologic grading features remain prognostic in astrocytomas while being insignificant in oligodendroglioma with interfering treatment effects. Chemotherapy (temozolomide) was less effective than radiotherapy in both astrocytomas and oligodendrogliomas while radiochemotherapy showed the highest TTF in oligodendrogliomas.

OBJECTIVE Prognostication of glioblastoma survival has become more refined due to the molecular reclassification of these tumors into isocitrate dehydrogenase (IDH) wild-type and IDH mutant. Since this molecular stratification, however, robust clinical prediction models relevant to the entire IDH wild-type glioblastoma patient population are lacking. This study aimed to provide an updated model that predicts individual survival prognosis in patients with IDH wild-type glioblastoma. METHODS Databases from Germany and the Netherlands provided data on 1036 newly diagnosed glioblastoma patients treated between 2012 and 2018. A clinical prediction model for all-cause mortality was developed with Cox proportional hazards regression. This model included recent glioblastoma-associated molecular markers in addition to well-known classic prognostic variables, which were updated and refined with additional categories. Model performance was evaluated according to calibration (using calibration plots and calibration slope) and discrimination (using a C-statistic) in a cross-validation procedure by country to assess external validity. RESULTS The German and Dutch patient cohorts consisted of 710 and 326 patients, respectively, of whom 511 (72%) and 308 (95%) had died. Three models were developed, each with increasing complexity. The final model considering age, sex, preoperative Karnofsky Performance Status, extent of resection, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and adjuvant therapeutic regimen showed an optimism-corrected C-statistic of 0.73 (95% confidence interval 0.71–0.75). Cross-validation between the national cohorts yielded comparable results. CONCLUSIONS This prediction model reliably predicts individual survival prognosis in patients with newly diagnosed IDH wild-type glioblastoma, although additional validation, especially for long-term survival, may be desired. The nomogram and web application of this model may support shared decision-making if used properly.

Background DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive. Methods Multicentric cohort study including 430 patients with newly diagnosed glioblastoma subjected to global DNA methylation profiling. Outcome measures included overall survival (OS), progression-free survival (PFS), prognostic relevance of EOR and MGMT promoter methylation status as well as a surgical benefit for recurrent glioblastoma. Results 345 patients (80.2%) fulfilled the inclusion criteria and 305 patients received combined adjuvant therapy. DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES) revealed no significant survival differences (RTK I: Ref.; RTK II: HR 0.9 [95% CI, 0.64–1.28]; p = 0.56; MES: 0.69 [0.47–1.02]; p = 0.06). Patients with RTK I (GTR/near GTR: Ref.; PR: HR 2.87 [95% CI, 1.36–6.08]; p < 0.01) or RTK II (GTR/near GTR: Ref.; PR: HR 5.09 [95% CI, 2.80–9.26]; p < 0.01) tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients. The MES subclass showed no survival benefit for a maximized EOR (GTR/near GTR: Ref.; PR: HR 1.45 [95% CI, 0.68–3.09]; p = 0.33). Therapy response predictive value of MGMT promoter methylation was evident for RTK I (HR 0.37 [95% CI, 0.19–0.71]; p < 0.01) and RTK II (HR 0.56 [95% CI, 0.34–0.91]; p = 0.02) but not the MES subclass (HR 0.52 [95% CI, 0.27–1.02]; p = 0.06). For local recurrence (n = 112), re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in RTK I (p = 0.03) and RTK II (p < 0.01) tumors, but not in MES tumors (p = 0.33). Conclusion We demonstrate a survival benefit from maximized EOR for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II but not the MES subclass. Hence, it needs to be debated whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.

Background With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas. Methods We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients’ professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires. Results We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21–63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11–82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2–22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p Conclusion The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.

Background Prior studies have suggested an association between patient socioeconomic status and brain tumors. In the present study we attempt to indirectly validate the findings, using health insurance status as a proxy for socioeconomic status. Methods There are 2 types of health insurance in Germany: statutory and private. Owing to regulations, low- and middle-income residents are typically statutory insured, whereas high-income residents have the option of choosing a private insurance. We compared the frequencies of privately insured patients suffering from malignant neoplasms of the brain with the corresponding frequencies among other neurosurgical patients at our hospital and among the German population. To correct for age, sex, and distance from the hospital, we included these variables as predictors in logistic and binomial regression. Results A significant association (odds ratio [OR] = 1.59, CI = 1.45-1.74, P < .001) between health insurance status and brain tumors was found. The association is independent of patients’ sex or age. Whereas privately insured patients generally tend to come from farther away, such a relationship was not observed for patients suffering from brain tumors. Comparing the out of house and in-house brain tumor patients showed no selection bias on our side. Conclusion Previous studies have found that people with a higher income, level of education, or socioeconomic status are more likely to suffer from malignant brain tumors. Our findings are in line with these studies. Although the reason behind the association remains unclear, the probability that our results are due to some random effect in the data is extremely low.

Background Over the last decade, awake craniotomy for tumor resection has become a standard to maximize tumor resection and minimize the risk of permanent neurological deficits. Different techniques and medication regimes have been tested for this procedure. Until today there is no consensus on the optimal approach. Therefore, we investigated the effect of dexmedetomidine as an adjunct in awake cerebral tumor surgery and evaluated our improved technique. Methods Data of patients who underwent awake craniotomy for tumor resection at our institution between 09/2006 and 05/2018 were retrospectively analyzed. All patients were kept awake after cortical mapping. After changing our standard anesthetic procedure from propofol/remifentanil alone to propofol/remifentanil and dexmedetomidine, we performed an evaluation of time to arousal, drug dosages, patients' cooperation and the occurrence of periprocedural adverse events. Results Eighty-four patients received propofol/remifentanil alone (SG). A further 17 patients additionally received dexmedetomidine following craniotomy in order to induce rapid arousal (DG). In the dexmedetomidine group a significantly reduced infusion time for propofol (169.2 ± 47.4 vs. 212.9 ± 63.3 minutes; P = 0.008) and non-significantly shorter time to arousal (12.0 [10.0/16.5] vs. 15.0 [10.0/20.0] minutes; P = 0.271) could be identified. In general, the overall procedure was very well tolerated by all patients. Conclusions The asleep-awake technique is a well-accepted and safe procedure. It allows continuous surveillance of the patient's neurological function during tumor resection and the postoperative phase, minimizing complications. In addition, our data show that the use of dexmedetomidine results in a shorter time to arousal.

Introduction The concurrent presence of both central nervous system (CNS) tumors and multiple sclerosis (MS) poses various diagnostic and therapeutic pitfalls and makes the clinical management of such patients challenging. Methods In this retrospective, single-center cohort study, we searched our clinical databases (2006–2019) for patients with concurrent CNS tumors and MS and described their disease courses. Age at diagnosis of the respective disease and probabilities for MS disease activity events (DAEs) with vs. without prior tumor-specific therapy were tested pairwise using t-test for dependent samples and exact binomial test. Results N = 16 patients with concurrent CNS tumors and MS were identified. MS diagnosis preceded the CNS oncological diagnosis by an average of 9 years (p = 0.004). More DAEs occurred in patients without prior chemotherapy (83.3%) than in patients with prior chemotherapy (16.7%; p = 0.008). This effect did not reach significance for patients with prior radiation therapy/radiosurgery (66.7% vs. 33.3%, p = 0.238). The average interval between DAEs and the last documented lymphopenia was 32.25 weeks. Conclusions This study describes the clinical and demographic features of patients with concurrent CNS tumors and MS and suggests several practical approaches to their clinical management. Our findings suggest that adding a disease-modifying MS therapy to the regimen of patients treated with chemotherapy is necessary only if the patient suffers from a highly active, aggressive course of MS. In view of the lack of prospective trials, individual risk assessments should remain the foundation of the decision on MS treatment in concurrent CNS tumor diseases.

DNA methylation-based tumor classification allows an enhanced distinction into subgroups of glioblastoma. However, the clinical benefit of DNA methylation-based stratification of glioblastomas remains inconclusive. We performed a multicentric cohort study including 430 patients with newly diagnosed glioblastoma whose tumors were subjected to DNA methylation profiling. The primary outcome was overall survival (OS) and progression-free survival (PFS). Secondary outcomes were the prognostic relevance of EOR and MGMTpromoter methylation status as well as surgical benefit for recurrent glioblastoma. After stratifying patients in accordance with their DNA methylation subclasses RTK I, RTK II, and mesenchymal (MES), outcome analyses revealed no significant differences between these three methylation subclasses (p = 0.06). RTK I or RTK II tumors who underwent gross-total resection (GTR) or near GTR had a longer OS and PFS than partially resected patients (p < 0.01). In the MES subclass, no survival benefit for a maximized EOR was found (p = 0.33). In multivariate analysis, the therapy response-predictive value of MGMT promoter methylation was evident for RTK I (p < 0.01) and RTK II (p = 0.02) but failed to be an independent factor in the MES subclass (p= 0.06). For local recurrence, re-resection conveyed a progression-to-overall survival (POS) benefit (p < 0.01), which was evident in the RTK I (p = 0.03) and RTK II (p < 0.01) subclasses, but not in the MES subclass (p = 0.33).This study demonstrates a survival benefit from maximized EOR at surgery for newly diagnosed and recurrent glioblastomas of the RTK I and RTK II subclass but not the MES subclass. Hence, it needs to be carefully considered whether the MES subclass should be treated with maximal surgical resection, especially when located in eloquent areas and at time of recurrence.

Background Diffuse low-grade gliomas (DLGGs) are rare and incurable tumors. Whereas maximal safe, functional-based surgical resection is the first-line treatment, the timing and choice of further treatments (chemotherapy, radiation therapy, or combined treatments) remain controversial. Methods An online survey on the management of DLGG patients was sent to 28 expert centers from the European Low-Grade Glioma Network (ELGGN) in May 2015. It contained 40 specific questions addressing the modalities of use of chemotherapy in these patients. Results The survey demonstrated a significant heterogeneity in practice regarding the initial management of DLGG patients and the use of chemotherapy. Interestingly, radiation therapy combined with the procarbazine, CCNU (lomustine), and vincristine regimen has not imposed itself as the gold-standard treatment after surgery, despite the results of the Radiation Therapy Oncology Group 9802 study. Temozolomide is largely used as first-line treatment after surgical resection for high-risk DLGG patients, or at progression. Conclusions The heterogeneity in the management of patients with DLGG demonstrates that many questions regarding the postoperative strategy and the use of chemotherapy remain unanswered. Our survey reveals a high recruitment potential within the ELGGN for retrospective or prospective studies to generate new data regarding these issues.

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 Patients with brain tumors frequently present neurocognitive deficits. Aiming at better understanding the impact of tumor localization on neurocognitive processes, we evaluated neurocognitive function prior to glioma surgery within one of four specific regions in the left speech-dominant hemisphere. Methods Between 04/2011 and 12/2019, 43 patients undergoing neurocognitive evaluation prior to awake surgery for gliomas (WHO grade I: 2; II: 6; III: 23; IV: 11) in the inferior frontal gyrus (IFG; n = 20), the anterior temporal lobe (ATL; n = 6), the posterior superior temporal region/supramarginal gyrus (pST/SMG; n = 7) or the posterior middle temporal gyrus (pMTG; n = 10) of the language dominant left hemisphere were prospectively included in the study. Cognitive performances were analyzed regarding an influence of patient characteristics and tumor localization. Results Severe impairment in at least one neurocognitive domain was found in 36 (83.7%) patients. Anxiety and depression were observed most frequently, followed by verbal memory impairments. Verbal memory was more strongly affected in patients with ATL or pST/SMG tumors compared to IFG tumors (p = 0.004 and p = 0.013, resp.). Overall, patients suffering from tumors in the ATL were most frequently and severely impaired. Conclusion Patients suffering from gliomas involving different regions within the language dominant hemisphere frequently present impairments in neurocognitive domains also other than language. Considering individual functions at risk may help in better advising patients prior to treatment and in tailoring the individual therapeutic strategy to preserve patients' quality of life.

Evidence for cerebral reorganization after resection of low-grade glioma has mainly been obtained by serial intraoperative cerebral mapping. Noninvasively collected data on cortical plasticity in tumor patients over a surgery-free period are still scarce. The present study therefore aimed at evaluating motor cortex reorganization by navigated transcranial magnetic stimulation (nTMS) in patients after perirolandic glioma surgery.nTMS was performed preoperatively and postoperatively in 20 patients, separated by 26.1 ± 24.8 months. Further nTMS mapping was conducted in 14 patients, resulting in a total follow-up period of 46.3 ± 25.4 months. Centers of gravity (CoGs) were calculated for every muscle representation area, and Euclidian distances between CoGs over time were defined. Results were compared with data from 12 healthy individuals, who underwent motor cortex mapping by nTMS in 2 sessions.Preoperatively and postoperatively pooled CoGs from the area of the dominant abductor pollicis brevis muscle and of the nondominant leg area differed significantly compared with healthy individuals (P0.05). Most remarkably, during the ensuing follow-up period, a reorganization of all representation areas was observed in 3 patients, and a significant shift of hand representation areas was identified in further 3 patients. Complete functional recovery of postoperative motor deficits was exclusively associated with cortical reorganization.Despite the low potential of remodeling within the somatosensory region, long-term reorganization of cortical motor function can be observed. nTMS is best suited for a noninvasive evaluation of this reorganization.

Diffuse low-grade glioma form a rare entity affecting young people. Despite advances in surgery, chemotherapy, and radiation therapy, diffuse low-grade glioma are still incurable. According to current guidelines, maximum safe resection, when feasible, is the first line of treatment. Apart from surgery, all other treatment modalities (temozolomide, procarbazine-CCNU-vincristine regimen, and radiation therapy) are handled very differently among different teams, and this in spite of recent results of several phase 3 studies. Based on a European survey, this paper aimed to get a picture of this heterogeneity in diffuse low-grade glioma management, to identify clinically relevant questions raised by this heterogeneity of practice, and to propose new methodological frameworks to address these questions.

OBJECTIVE The prognosis especially of older patients with glioblastoma is poor. Novel therapies are usually reserved for patients ≤65 years. As the population is growing older, the challenge remains as to how very elderly patients ≥75 years should be treated. Only limited outcome data exist for this patient subgroup. METHODS Between 2010 and 2018 we treated a total of 977 patients with glioblastoma at our institution. Of these, 144 patients were ≥75 years at diagnosis. The primary procedure was surgery or biopsy followed by adjuvant treatment, if possible. We retrospectively investigated progression-free and overall survival (OS) and looked at potential prognostic factors influencing survival, including Karnofsky performance score (KPS), surgical therapy, adjuvant therapy as well as MGMT promoter methylation status. RESULTS In our very elderly cohort, the median age was 79 years (range: 75–110). Biopsy only was performed in 108 patients, resection was performed in 36 patients. Median OS for the entire cohort was 5.9 months. Patients without adjuvant treatment fared worse than patients receiving either radiotherapy and/or chemotherapy (1.2 vs. 8.4 months, p< 0.001). Multivariate analysis showed that KPS at presentation (≥70 vs. ≤60), surgery vs. biopsy, and MGMT status (methylated vs. non-methylated) were significantly associated with OS (6.3 vs. 3.9 months, p=0.002; 12.6 vs. 4.9 months, p=0.003; and 10.5 vs. 5.0 months, p=0.009, respectively). CONCLUSION For patients with glioblastoma ≥75 years, the natural course of the disease is devastating, and there is a negative treatment bias in these patients. Very elderly patients, too, benefit from multimodal treatment including microsurgical tumor removal. Treatment options and outcomes should be thoughtfully discussed with patients before treatment decisions are made.

OBJECTIVE Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze patients′ professional, socio-economic and psychological outcomes besides their neuro-oncological and functional evaluation after awake surgery for gliomas in eloquent areas. METHODS The neuro-oncological and functional outcomes of patients with gliomas other than glioblastoma undergoing awake surgery during a period of 5 years were prospectively assessed within our routine oncological follow-up. Repercussions of the disease on their professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with structured interviews. RESULTS We analyzed data of 37 patients with gliomas (3 WHO Grade I, 6 WHO grade II, 28 WHO grade III). Gross total and subtotal tumor resections were performed in 20 (54.1%) and 11 (29.7%) patients, respectively, whereas in 7 patients (16.2%) resection had to remain partial. Median follow up was 24.1 months (range: 5–61 months). 31 patients (83.8%) had stable disease, 2 (5.4%) patients suffered from tumor progression and 4 (10.8%) patients died. Prior to surgery, all but one patient were employed. At the time of analysis, 24 (72.7%) of 33 alive patients had resumed their profession. 5 patients (15.2%) were on incapacity pension, 2 patients were on sick leave, and 2 had retired. The median time until return to work following surgery was 5.9 ±4.6 months. Young age (< 40 years) was the only factor statistically significantly associated with the ability to return to work (p< 0.001). CONCLUSION Despite brain tumor surgery in eloquent regions, the majority of patients with WHO grade II or III gliomas are able to return to work. Employing awake techniques in order to preserve neurological function is of utmost relevance for individual patients′ quality of life and may also decrease the economic burden due to work loss frequently encountered in glioma patients.

Background World Health Organization (WHO) grade II low-grade gliomas (LGGs) in adults are rare, and patients' mean overall survival (OS) is relatively long. Epidemiological data on factors influencing tumor genesis and progression are scarce, and prospective data on surgical management are still lacking. Because of the molecular heterogeneity of LGG, a comprehensive molecular characterization is required for any clinical and epidemiological research. Further, a detailed radiologic assessment is needed as the only established objective criterion for progressive disease. Both radiologic and molecular assessments have to be standardized to produce comparable data. The aim of the registry is to improve the evidence for surgical management of LGG patients by establishing a multicenter registry with a strong surgical and clinical focus including mandatory biobanking. Methods The LoG-Glio project is a prospective national observational multicenter registry that began on November 1, 2015. Inclusion criteria encompass all patients > 18 years of age with a radiologic suspicion of LGG. Patients with severe neurologic or psychiatric disorders that may interfere with their informed consent or if there is no possibility for further follow-up are excluded. Diagnosis of glioblastoma WHO grade IV isocitrate dehydrogenase (IDH) wild type leads to a secondary exclusion of patients. In addition to demographic data, results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, add-on for patients with brain tumors, and National Health Institute Stroke Scale before and after surgery and during regular follow-ups are collected. At each time point a detailed recording of surgical and adjuvant treatment is performed. Radiologic assessment involves three-dimensional (3D) acquisition of T1, fluid-attenuated inversion recovery, and T2 sequences. For the final evaluation, a central detailed neuropathologic and molecular assessment of tumor samples and a radiologic evaluation of imaging sets are part of the study protocol. Results We report the first 100 consecutively registered patients for LoG-Glio. Three patients dropped out due to loss of follow-up. Of the remaining recruited patients, 8 were classified as wait and scan; 89 had surgery. Using the inclusion criteria described previously, 70 patients had an IDH-mutated glioma, 10 had miscellaneous rare LGGs, and 8 patients had an IDH wild-type WHO grade II or III glioma. Conclusion The LoG-Glio registry has been successfully implemented. Applied selection criteria result in an appropriately balanced patient cohort. Short-term outcome data on epidemiology as well as the influence of current surgical techniques and adjuvant treatment on patient outcomes are expected. In the long run, the aim of the registry is to validate the new molecular-based WHO classification and the influence of the extent of resection on progression-free survival and OS. The registry provides an open platform for future research projects benefiting patients with LGG.

Data about the influence of pregnancy on progression-free survival and overall survival of glioma patients are sparse and controversial. We aimed at providing further evidence on this relation. The course of 18 glioma patients giving birth to 23 children after tumor surgery was reviewed and compared to the course of 18 nulliparous female patients matched for tumor diagnosis including molecular markers, extent of resection, and tumor location. Tumor pathology was astrocytoma, oligodendroglioma, and ependymoma in 9, 6, and 3 patients, respectively. Time interval between tumor resection and delivery was 5.3 ± 4.4 years. All newborns were healthy after uneventful deliveries. Tumor progression was diagnosed before pregnancy in 4 patients and during pregnancy in 1 patient, and 4 patients displayed progressive disease 31.0 ± 11 months after delivery. Three of these latter patients underwent second surgery, whereas resection of recurrent tumor had been performed in 2 women before pregnancy. Among nulliparous patients, 9 women suffered from tumor progression, resulting in re-operation in 7 patients and/or further adjuvant treatment in 6 cases. Progression-free survival did not differ between patients with and patients without children (p = 0.4). Moreover, in both groups, median overall survival was not reached after a mean follow-up period of 9.7 ± 5.7 years in glioma patients who gave birth to a child and 8.9 ± 4.2 years in nulliparous glioma patients. Pregnancy does not seem to influence the clinical course of glioma patients. Likewise, glioma seems not to have an impact on delivered children’s health.

INTRODUCTION: Classification as well as treatment of patients with lower grade gliomas (°II+°III) have changed fundamentally during the last years. Molecular markers have augmented diagnostic workup and combined radiochemotherapy was established for most of the subgroups. However, molecular markers have not been part of the inclusion criteria of most of the relevant clinical trials. Larger analyses outside of clinical trials are rare. MATERIALS AND METHODS: We screened our clinical cancer database for patients with lower grade glioma newly diagnosed from 1995 to 2015. We identified 774 patients of whom 345 had to be excluded, resulting in an evaluable cohort of 423 patients. We evaluated general characteristics, morphological diagnosis, molecular markers, treatment, time-to-treatment-failure (TTF; initiation of a new treatment or death) and overall survival (OS). RESULTS: According to the 2007 WHO classification our cohort included 145 (34.3%) Astrocytoma WHO °II, 56 (13.3%) Oligoastrocytoma/Oligodendroglioma WHO °II, 129 (52.5%) Astrocytoma WHO °III and 93 (22.0%) Oligoastrocytoma/Oligodendroglioma WHO °III. In 235 patients we were able to molecularly classify the tumors based on the 2017 WHO classification using IDH status and 1p/19q or ATRX status. Patients with a molecularly defined Oligodendroglioma showed a median TTF of 5.2, 4.2 and 7.8 years for radiotherapy, chemotherapy and radiochemotherapy, respectively. Patients with a molecularly defined Astrocytoma showed a median TTF of 1.6, 2.9 and 6.7 years for radiotherapy, chemotherapy and radiochemotherapy, respectively. In IDH wildtype tumors TTF was below 12 months without relevant differences. Treatment with combined radiochemotherapy resulted in markedly improve TTF in molecular defined oligodendroglioma and astrocytoma compared with either radiotherapy or chemotherapy alone. Due to the short follow-up of 5.3 years (mean) median OS has not been reached for any of the IDH mutant subgroups. CONCLUSIONS: Combined treatment with radiotherapy and chemotherapy resulted in markedly improved TTF in patients with molecularly defined oligodendroglioma and astrocytoma.

Magnet resonance imaging (MRI) of gliomas is assessed by Response Assessment in Neuro-Oncology Criteria (RANO), which define new contrast-enhancing lesions as a sign for tumor recurrence. Pseudoprogression after radiotherapy may mimic tumor progression in MRI but is usually limited to the first months after irradiation. We noted a late onset pattern of new contrast-enhancing spots (NCES) appearing years after radiotherapy. We prospectively collected 23 glioma patients with 26 NCES (three patients had two separate NCES events) between 2014 and 2016 in our weekly tumor board without further selection by diagnosis, molecular markers or pretreatment. Retrospective analysis revealed a homogeneous collective of young patients (median age of 49 years at NCES) with mainly IDH-mutated glioma (61%). Initial histology showed 26% glioblastoma, 52% grade III and 22% grade II glioma. NCES occurred at late follow-up with a median of 52 months after tumor diagnosis and 30 months after the last radiotherapy. The majority of NCES regressed spontaneously within a median of 10 months (n = 11) or remained stable without further therapy with a median follow-up of 26 months (n = 7). Only 4 NCES developed MRI morphologically into tumor recurrence. Two NCES were resected without any histopathological proof of tumor recurrence, and in 2 other cases NCES were defined as ischemic stroke or radionecrosis. We hypothesize that the late onset phenomenon of NCES predominantly represents a form of radiation-induced vasculopathy that is different from early pseudoprogression and should be considered especially in younger patients with IDH-mutated glioma before initiation of new therapy.

BACKGROUND: Intraoperative neurophysiological monitoring and mapping are indispensable during surgery close to the corticospinal tract (CST). Assuming a nearly 1:1 distance-to-current relationship, a combined surgical aspiration and monopolar stimulation (cSAMS) device has recently been introduced. The present study investigates the results of the use of the cSAMS device focusing on both, postoperative motor deficits and the extent of lesion resection (EoR) MATERIALS AND METHODS: Between January 2015 and September 2017, a cSAMS device (short train stimulation, interstimulus interval 4 msec, pulse duration 500 µsec) was used in 89 patients during resection of supratentorial lesions in the vicinity of the CST. Motor function was assessed preoperatively, on the first day after surgery, at discharge and at 3 months. RESULTS: The lowest motor thresholds evoking motor evoked potentials were as follows (mA, number of patients): 10-20mA n = 25; 5–9 mA n = 23; 2 to 4 mA, n = 16; and

Contains fulltext : 195164.pdf (Publisher’s version ) (Open Access) Objective: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. Methods: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. Results: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. Conclusion: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of

For safe resection of lesions situated in or near eloquent brain regions, determination of their spatial and functional relationship is crucial. Since functional magnetic resonance imaging and intraoperative neurophysiological mapping are not available in all neurosurgical departments, we aimed to evaluate brain surface reformatted imaging (BSRI) as an additional display mode for neuronavigation. Eight patients suffering from perirolandic tumors were preoperatively studied with MRI and navigated transcranial magnetic stimulation (nTMS). Afterwards, the MRI was automatically transformed into BSR images in neuronavigation software (Brainlab, Brainlab AG, Feldkirchen, Germany). One experienced neuroradiologist, one experienced neurosurgeon, and two residents determined hand representation areas ipsilateral to each tumor on two-dimensional (2D) MR images and on BSR images. All results were compared to results from intraoperative direct cortical mapping of the hand motor cortex and to preoperative nTMS results. Findings from nTMS and intraoperative direct cortical mapping of the hand motor cortex were congruent in all cases. Hand representation areas were correctly determined on BSR images in 81.3 % and on 2D-MR images in 93.75 % (p = 0.26). In a subgroup analysis, experienced observers showed more familiarity with BSRI than residents (96.9 vs. 84.4 % correct results, p = 0.19), with an equal error rate for 2D-MRI. The time required to define hand representation areas was significantly shorter using BSRI than using standard MRI (mean 27.4 vs. 40.4 s, p = 0.04). With BSRI, a new method for neuronavigation is now available, allowing fast and easy intraoperative localization of distinct brain regions.

Despite its well-characterized side effects, dexamethasone is widely used in the pre-, peri- and postoperative neurosurgical setting due to its effective relief of tumor-induced symptoms through the reduction of tumor-associated edema. However, some patients show laboratory-defined dexamethasone induced elevation of white blood cell count, and its impact on glioblastoma progression is unknown. We retrospectively analyzed 113 patients with newly diagnosed glioblastoma to describe the incidence, risk factors and clinical features of dexamethasone-induced leukocytosis in primary glioblastoma patients. We further conducted an immunohistochemical analysis of the granulocyte and lymphocyte tumor-infiltration in the available corresponding histological sections. Patient age was identified to be a risk factor for the development of dexamethasone-induced leukocytosis (p

To date there is no established tumor marker for the clinical follow-up of glioblastoma, WHO grade IV, (GBM) which constitutes the most frequent and malignant primary brain tumor. However, since there is promising data that the serum glial fibrillary acidic protein (sGFAP) may serve as a biomarker for glial brain tumors, this prospective study aimed at evaluating the diagnostic relevance of perioperative changes in sGFAP levels for the assessment of residual glial tumor tissue in patients undergoing surgery of intracerebral tumors. Serum GFAP was measured using an electrochemiluminometric immunoassay (ElecsysR GFAP prototype test, Roche Diagnostics, Penzberg/Germany) in 32 prospectively recruited patients between September 2009 and August 2010. Twenty-five were diagnosed with glioma and seven with brain metastases (BM). We assessed sGFAP levels prior to and at different time points during the early postoperative phase until patient discharge. There were only significant differences in the pre-operative sGFAP levels of patients with gliomas compared to BM (0.18 vs. 0.08 µg/l; p = 0.0198, Welch’s t-Test). Even though there was an increase of sGFAP after surgery, there were no significant differences between glioma and BM patients at any other time point. Peak sGFAP levels where reached on postoperative day 1 followed by a slight decrease, but not reaching pre-operative levels until postop day 7. There was no significant correlation between postoperative glioma tumor volume and sGFAP levels in univariate analyses. According to our data sGFAP does not appear to be suitable to detect residual glioma tissue in the acute postoperative phase.

Sowohl die intraoperative Neurophysiologie als auch die intraoperative Bildgebung sind dazu bestimmt, die Behandlungsqualitat in der Gliomchirurgie durch Funktionserhalt oder Erhohung des Resektionsausmases zu verbessern. In diesem Sinne ist es im Interesse betroffener Patienten, diese Techniken, wann immer es moglich ist, einzusetzen. In vielen Fallen sind sie sogar als Standard zu fordern. Ihr Einsatz entbindet den Neurochirurgen nicht, intraoperativ eine Entscheidung fur oder gegen eine weitere Tumorresektion zu treffen. Dennoch dienen sie dazu, das Risiko fur den Patienten zuverlassig zu minimieren und optimale Operationsergebnisse zu erzielen. „Eher mehr als weniger“ lautet der Trend beim Neuromonitoring, was abseits des somatosensiblen und somatomotorischen Systems eine Zunahme der Frequenz an Wachoperationen bedeutet.

Background Tractography is a popular tool for visualizing the corticospinal tract (CST). However, results may be influenced by numerous variables, eg, the selection of seeding regions of interests (ROIs) or the chosen tracking algorithm. Objective To compare different variable sets by correlating tractography results with intraoperative subcortical stimulation of the CST, correcting intraoperative brain shift by the use of intraoperative MRI. Methods Seeding ROIs were created by means of motor cortex segmentation, functional MRI (fMRI), and navigated transcranial magnetic stimulation (nTMS). Based on these ROIs, tractography was run for each patient using a deterministic and a probabilistic algorithm. Tractographies were processed on pre- and postoperatively acquired data. Results Using a linear mixed effects statistical model, best correlation between subcortical stimulation intensity and the distance between tractography and stimulation sites was achieved by using the segmented motor cortex as seeding ROI and applying the probabilistic algorithm on preoperatively acquired imaging sequences. Tractographies based on fMRI or nTMS results differed very little, but with enlargement of positive nTMS sites the stimulation-distance correlation of nTMS-based tractography improved. Conclusion Our results underline that the use of tractography demands for careful interpretation of its virtual results by considering all influencing variables.

Surgical management of sphenoorbital meningiomas ranges among the most complex of intracranial tumors. We report on our experience of surgical technique, outcome, and tumor recurrence in sphenoorbital meningiomas.Between 2003 and 2013, surgical resections for sphenoorbital meningioma were performed in 18 patients (aged 49·6±9·8 years, only women), with two patients operated anew due to tumor recurrence.Main symptom was proptosis (83·3%), followed by diminished visual acuity (38·9%), and dizziness (11·1%). In all patients the lateral orbital wall was resected, whereas the orbital roof and the zygoma were removed according to the extent of their tumorous infiltration. Unroofing of the optic canal was performed in 10 cases (55·6%) and unroofing of the optic foramen in two (11·1%). For reconstruction split calvarian bone and titanium mesh were used in six (33·3%) and seven patients (38·9%), respectively; in one patient both techniques were applied. In five patients (27·8%), no reconstruction was necessary. Complete tumor resection (Simpson grade 1 and 2) was achieved in 14 cases (77·7%). Postoperatively, proptosis improved in all patients. Median follow-up was 39·5±33·3 months (range 1-105) in 16 patients; 2 patients were lost to follow-up. No tumor recurrence was noted in five (27·8%) patients, whereas in nine (50%) patients tumor remnants proved stable over time. Two (11·1%) patients experienced progression of residual tumor, resulting in reoperation after 27 and 109 months, respectively.Despite their delicate anatomical relations, surgery of sphenoorbital meningiomas is safe when combining modern techniques.

Background and Objective There is limited information on prognostic factors and outcomes in patients with secondary glioblastoma (sGBM). Herein we report on the outcomes of patients with sGBM and identify clinically relevant prognostic factors. Methods We retrospectively analyzed our institutional database for patients with histologic evidence of World Health Organization (WHO) grade II-III gliomas that went on to develop WHO grade IV sGBM. The assessment of the isocitrate dehydrogenase-1 (IDH1) R132H mutation was performed by immunohistochemical staining. Results Forty-five patients with sGBM were included within our analysis (median age, 41 years). Mutated IDH1 (R132H) protein was present within the gliomas of 24 patients and was absent in 17. Immunohistochemistry assessment could not be performed for 4 patients. The median time between first diagnosis of glioma and sGBM was 158.9 weeks. Median overall survival (OS) after a diagnosis of sGBM was 63.6 weeks. When assessing patient-specific (i.e., therapy-independent) factors, mutated IDH1 (R132H) protein ( P = 0.01; hazard ratio (HR), 0.54; confidence interval (CI) 0.33–0.87), WHO grade II tumor as precursor lesion ( P = 0.05; HR, 0.49; CI 0.25–0.97), and a frontal tumor location ( P = 0.04; HR, 0.48; CI 0.23–0.99) were found to be associated with better OS by multivariate analysis. Our data further indicate that complete tumor removal is associated with better patient survival in sGBM patients within certain risk groups (time period to development of sGBM, >104 weeks; initial WHO grade II tumor, IDH1 mutation, and time period to development of sGBM, >104 weeks; initial WHO grade II or III tumor, IDH1 wild type, frontal lobe localization). Conclusions Our retrospective analysis suggested that the presence of an IDH1 (R132H) mutation, frontal tumor location, and WHO grade of the initial tumor are associated with OS after progression to sGBM. In addition, some patients with sGBM may benefit from complete tumor resection depending on these patient-specific parameters. This is a finding that will ultimately need prospective validation.

Central nervous system lymphomas (CNSL) are traditionally regarded as non-surgically treated tumors with a poor prognosis. Usually, only stereotactic biopsy is performed to establish the diagnosis, and most patients show disease progression within half a year. A recent study questioned this view, since patients who had surgical resection of CNSL manifestations prior to adjuvant therapy reportedly had a better outcome than patients who had biopsy only. We performed a retrospective analysis of our patient database to identify patients with CNSL who had undergone "accidental" tumor removal in our department between 2002 and 2013. Four patients had CNSL specific therapy following surgery. One patient received no further therapy because of his bad clinical status. Five patients with CNSL were treated surgically. Three patients were in complete remission at nine, thirteen and 45 months postoperatively, while two others had disease progression at 45 months, respectively. The median survival was 22.6 months. Gross total removal of CNSL may improve outcome. We present a series of five patients who had surgical resection of CNSL. While the importance of chemotherapy is beyond doubt, more data on the effect of surgery on the prognosis of patients with CNSL are needed. However, the paradigm of medical treatment only for CNSL is being challenged.

Several methods have been introduced to improve the extent of resection in glioma surgery. Yet, radical tumor resections must not be attempted at the cost of neurological deterioration. We sought to assess whether the use of an intraoperative MRI (iMRI) in combination with multimodal neurophysiological monitoring is suitable to increase the extent of resection without endangering neurological function in patients with eloquently located gliomas. Fifty-four patients were included in this study. In 21 patients (38.9 %), iMRI led to additional tumor resection. A radiologically complete resection was achieved in 31 patients (57.4 %), while in 12 of these, iMRI had depicted residual tumor tissue before resection was continued. The mean extent of resection was 92.1 % according to volumetric analyses. Postoperatively, 13 patients (24.1 %) showed new or worsening of pre-existing sensory motor deficits. They were severe in 4 patients (7.4 %). There was no correlation between the occurrence of either any new (P = 0.77) or severe (P = 1.0) sensory motor deficit and continued resection after intraoperative image acquisition. Likewise, tumor location, histology, and tumor recurrence did not influence complication rate on uni- and multivariate analysis. We conclude that the combination of iMRI guidance with multimodal neurophysiological monitoring allows for extended resections in glioma surgery without inducing higher rates of neurological deficits, even in patients with eloquently located tumors.

For intra-operative subcortical electrical stimulation of the corticospinal tract, two techniques - originally described for cortical stimulation - have evolved: the 50-Hz-stimulation first described by Penfield in 1937 and the high-frequency multipulse train stimulation technique first described by Taniguchi in 1993. Motor thresholds of both methods in combination with a bipolar and monopolar stimulation technique and their reliability for eliciting motor evoked potentials (MEPs) were studied.Data were obtained in 20 patients (50±17 years; 10 females) undergoing tumour resection under general anaesthesia. Both 50-Hz-stimulation of 1-s duration and a multipulse stimulation (5 pulses interstimulus interval 4 ms, 0.5-Hz repetition rate) were applied with a bipolar probe (1.5-mm ball tip, 8-mm interelectrode distance) and a monopolar probe (1.5-mm-diameter tip). MEPs were recorded in muscles contralateral to the stimulated hemisphere. Comparison of different stimulation modalities was performed at the site where monopolar multipulse stimulation technique elicited MEPs with the lowest stimulation intensity (constant current monophasic cathodal stimulation, individual pulse width 0.5 ms, max. 25 mA).MEPs were elicited by monopolar multipulse stimulation with an intensity of 8±3.9 mA (21/21 stimulation sites); monopolar 50-Hz stimulation with 12±5.4 mA (18/21 stimulation sites); bipolar multipulse stimulation with 14±8.1 mA (12/21 stimulation sites) and bipolar 50-Hz stimulation with 15±6.3 mA (11/21 stimulation sites).Stimulation intensities for eliciting MEPs are significantly lowest for the monopolar multipulse stimulation (p0.025). Monopolar compared to bipolar stimulation resulted in eliciting MEPs in a higher number of tested patients (Fisher's p0.0001).Subcortical stimulation with a monopolar probe and a multipulse stimulation is most efficient for the purpose of identifying the corticospinal tract. This is explained by the more radiant electric field properties of the monopolar probe compared to the bipolar probe.

BACKGROUND: Data about the influence of pregnancy on progression free survival and overall survival of glioma patients are sparse and controversial. We aimed at providing further evidence on this relation. MATERIAL AND METHODS: The course of 18 glioma patients giving birth to 23 children after tumor surgery was reviewed. Results were compared to the course of 18 nulliparous female patients matched for tumor diagnosis including molecular markers, extent of resection and tumor location. RESULTS: Tumor pathology was astrocytoma in 9 patients, oligodendroglioma in 6 patients and ependymoma in 3 patients. Time interval between tumor resection and delivery was 5.3 ± 4.4 years, and all newborns were healthy after uneventful deliveries. Tumor progression was diagnosed during pregnancy in 1 patient, and 4 patients displayed progressive disease 31.0 ± 11 months after delivery. Three of these patients underwent second surgery after delivery, whereas resection of recurrent tumor was performed in two women before pregnancy. Among nulliparous patients 9 women suffered from tumor progression, resulting in re-operation in 7 patients and/or further adjuvant treatment in 6 cases. Progression-free survival did not differ between patients with children and patients without children (6.0 ± 4.2 vs. 7.5 ± 3.2 years; p=0.4). Moreover, in both groups, median overall survival was not reached after a mean follow-up period of 9.7 ± 5.7 years in glioma patients who gave birth to a child and 8.9 ± 4.2 years in nulliparous glioma patients. CONCLUSION: Pregnancy has neither a positive nor a negative influence on the clinical course of glioma patients. Likewise, glioma has no impact on delivered children’s health.

BACKGROUND: Surgery of brain tumors aims, in general, at complete tumor resection. However, persuing this aim, neuropsychological deficits cannot be considered all the time. Due to its importance regarding quality of life and further professional ability, we analysed the influence of left frontal and left temporal brain tumor surgery on patients′ neuro-cognitive performance. MATERIAL AND METHODS: Neuropsychological evaluation was performed pre-operatively in 33 patients who underwent awake surgery for brain tumors in the left inferior frontal gyrus (IFG), the left anterior frontal lobe (ATL) or the left supramarginal gyrus (SMG). Twelve of these patients underwent additional postoperative neuropsychological examination. Evaluation focused on aspects of language, attention, execution as well as working, verbal and visual memory. Results were analysed descriptive. RESULTS: While first testing was carried out in all patients within 1 month before awake surgery, postoperative evaluation was realized in 12 patients 6.47 ± 3.07 months after surgery. Defining test performances within the 25(th) and the 75(th) percentile as normal, patients with tumors involving the IFG or SMG showed unimpaired. However, in patients suffering from lesions involving the ATL, reduced verbal memory and impaired interference ability was noted preoperatively, recovering to normal after surgery. Thus, removal by awake surgery of lesions involving the IFG, SMG or ATL did not result in long-term neuropsychological impairments. CONCLUSION: Our results underline the importance of considering cognitive outcome by evaluating neuropsychological deficits in brain tumor patients.

BACKGROUND: Classification as well as treatment of patients with lower grade gliomas (°II+°III) have changed fundamentally during the last years. Molecular markers have augmented diagnostic workup and combined radiochemotherapy was established for most of the subgroups. However, molecular markers have not been part of the inclusion criteria of most of the relevant clinical trials. Larger analyses outside of clinical trials are rare. MATERIAL AND METHODS: We screened our clinical cancer database for patients with lower grade glioma newly diagnosed from 1995 to 2015. We identified 774 patients of whom 345 had to be excluded, resulting in an evaluable cohort of 423 patients. We evaluated general characteristics, morphological diagnosis, molecular markers, treatment, time-to-treatment-failure (TTF; initiation of a new treatment or death) and overall survival (OS). RESULTS: According to the 2007 WHO classification our cohort included 145 (34.3%) Astrocytoma WHO °II, 56 (13.3%) Oligoastrocytoma/Oligodendroglioma WHO °II, 129 (52.5%) Astrocytoma WHO °III and 93 (22.0%) Oligoastrocytoma/Oligodendroglioma WHO °III. In 235 patients we were able to molecularly classify the tumors based on the 2017 WHO classification using IDH status and 1p/19q or ATRX status. Patients with a molecularly defined Oligodendroglioma showed a median TTF of 5.2, 4.2 and 7.8 years for radiotherapy, chemotherapy and radiochemotherapy, respectively. Patients with a molecularly defined Astrocytoma showed a median TTF of 1.6, 2.9 and 6.7 years for radiotherapy, chemotherapy and radiochemotherapy, respectively. In IDH wildtype tumors TTF was below 12 months without relevant differences. Treatment with combined radiochemotherapy resulted in markedly improve TTF in molecular defined oligodendroglioma and astrocytoma compared with either radiotherapy or chemotherapy alone. Due to the short follow-up of 5.3 years (mean) median OS has not been reached for any of the IDH mutant subgroups. CONCLUSION: Combined treatment with radiotherapy and chemotherapy resulted in markedly improved TTF in patients with molecularly defined oligodendroglioma and astrocytoma.

Acute subdural hematomas (aSDHs) are found in up to one-third of patients with severe traumatic brain injury and are associated with an unfavorable outcome in the majority of cases. Mortality ranges between 40 and 60%, but was reported to be even higher in patients undergoing oral anticoagulation therapy (OAT) at the time of injury. The objective of this study is to specifically report on the peri-operative management and outcome of patients with aSDH and pre-injury OAT.From June 2002 to June 2006, all patients with OAT who underwent surgical treatment of aSDH were retrospectively analysed. Results of pre-operative blood tests, the peri-operative and surgical management and the clinical courses were assessed. Patient outcome is reported according to the Glasgow Outcome Scale (GOS) at 6 months.Eleven (10.3%) out of 107 patients with aSDH were on OAT. Patients with OAT were significantly older than patients without OAT (72.4 +/- 9.3 versus 59.9 +/- 17.5 years; p0.05, Mann-Whitney U-test). Intensity of head trauma was moderate in four and severe in seven patients with a median pre-operative Glasgow Coma Scale (GCS) of 8. Median pre-treatment prothrombin time and international normalized ratio were 23% (range: 10-65%) and 3.3 (range: 1.5-10.6), respectively. Replacement therapy consisted of administration of prothrombin complex concentrates, vitamin K and FFP (fresh frozen plasma). In four patients, antithrombin was additionally given to prevent disseminated intravascular coagulation. Surgical treatment consisted of craniotomy (n=10) or craniectomy (n=1) and hematoma evacuation with intracranial pressure probe placement. Low molecular weight heparin was administered as pharmacological prophylaxis of thrombembolic events in an increasing dose post-operatively. At 6 months, six out of 11 patients survived with a median GOS of 4. All-cause mortality was 45.5%. A pre-operative GCS ofor = 8 was not associated with an increased risk of mortality (p0.5, Fisher's exact test). No relevant rebleedings or thrombembolic complications were observed. The mortality rate of patients who did not undergo OAT was 50%.A large number of patients with aSDH are on pre-injury OAT. Specific replacement therapy facilitates successful clot evacuation without bleeding complications. The overall outcome of these patients does not seem to differ from historical cohorts with aSDH without OAT, but a large prospective multicenter study is warranted to answer that question.

Objective: Tumor resection plays a role in the initial treatment but also in the setting of recurrent glioblastoma (rGBM). In order to achieve maximum resection, 5-aminolaevulinic acid (5’ALA) and intraoperative MRI (iMRI) can be used as surgical tools. 5’ALA is a very helpful fluorescent[for full text, please go to the a.m. URL], 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

BACKGROUND Tractography based on diffusion tensor imaging has become a popular tool for delineating white matter tracts for neurosurgical procedures. OBJECTIVE To explore whether navigated transcranial magnetic stimulation (nTMS) might increase the accuracy of fiber tracking. METHODS Tractography was performed according to both anatomic delineation of the motor cortex (n = 14) and nTMS results (n = 9). After implantation of the definitive electrode, stimulation via the electrode was performed, defining a stimulation threshold for eliciting motor evoked potentials recorded during deep brain stimulation surgery. Others have shown that of arm and leg muscles. This threshold was correlated with the shortest distance between the active electrode contact and both fiber tracks. Results were evaluated by correlation to motor evoked potential monitoring during deep brain stimulation, a surgical procedure causing hardly any brain shift. RESULTS Distances to fiber tracks clearly correlated with motor evoked potential thresholds. Tracks based on nTMS had a higher predictive value than tracks based on anatomic motor cortex definition (P < .001 and P = .005, respectively). However, target site, hemisphere, and active electrode contact did not influence this correlation. CONCLUSION The implementation of tractography based on nTMS increases the accuracy of fiber tracking. Moreover, this combination of methods has the potential to become a supplemental tool for guiding electrode implantation.