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Background The impact of extent of resection (EOR), residual tumor volume (RTV), and gross-total resection (GTR) in glioblastoma subgroups is currently unknown. This study aimed to analyze their impact on patient subgroups in relation to neurological and functional outcomes. Methods Patients with tumor resection for eloquent glioblastoma between 2010 and 2020 at 4 tertiary centers were recruited from a cohort of 3919 patients. Results One thousand and forty-seven (1047) patients were included. Higher EOR and lower RTV were significantly associated with improved overall survival (OS) and progression-free survival (PFS) across all subgroups, but RTV was a stronger prognostic factor. GTR based on RTV improved median OS in the overall cohort (19.0 months, P Conclusions Maximum resection was especially beneficial in the subgroups aged

Background: Awake mapping has been associated with decreased neurological deficits and increased extent of resection in eloquent glioma resections. However, its effect within clinically relevant glioblastoma subgroups remains poorly understood. We aimed to assess the benefit of this technique in subgroups of patients with glioblastomas based on age, preoperative neurological morbidity, and Karnofsky Performance Score (KPS). Methods: In this propensity score-matched analysis of an international, multicentre, cohort study (GLIOMAP), patients were recruited at four tertiary centres in Europe (Erasmus MC, Rotterdam and Haaglanden MC, The Hague, Netherlands, and UZ Leuven, Leuven, Belgium) and the USA (Brigham and Women's Hospital, Boston, MA). Patients were eligible if they were aged 18–90 years, undergoing resection, had a histopathological diagnosis of primary glioblastoma, their tumour was in an eloquent or near-eloquent location, and they had a unifocal enhancing lesion. Patients either underwent awake mapping during craniotomy, or asleep resection, as per treating physician or multidisciplinary tumour board decision. We used propensity-score matching (1:3) to match patients in the awake group with those in the asleep group to create a matched cohort, and to match patients from subgroups stratified by age (

Background: Traditionally, surgical removal of glioblastoma is performed with general anaesthesia but a recent meta-analysis revealed that awake surgery in glioblastoma resulted in better surgical outcomes than non-awake surgery. Preoperative severe aphasia is one of the exclusion criteria for awake surgery because of difficulties in intraoperative interpretation of language deterioration and the distinction between preoperative vs. intraoperative induced paraphasias. As severe aphasia is common in glioblastoma patients, many potential patients who may benefit from awake surgery are excluded. Aims: We aim to investigate the feasibility of awake surgery in glioblastoma patients with severe aphasia using a patient-tailored approach with adapted intraoperative language tasks. We also examined the effect of awake surgery on language outcomes. Methods & Procedures: We discuss five case studies of patients elected for awake surgery with presumed glioblastoma in eloquent language areas and severe aphasia. Pre- and postoperatively, an extensive test-protocol was administered at different linguistic levels and modalities. A patient-tailored intraoperative language test-protocol was applied. Outcomes & Results: Preoperatively, all patients had severe impairments on all language and cognitive tests. Intraoperative language tasks for direct electrical stimulation and resection were selected and adapted to patients’ preoperative level. Despite preoperative severe aphasia, functional boundaries for critical language areas could be identified in each patient. Postoperatively, all patients had stable or improved language outcome. One of the patients recovered to maximum scores on nearly all language tests. Conclusions: Our cases demonstrate that awake surgery in severely aphasic glioblastoma patients is feasible and did not cause further deterioration of aphasia. An extensive preoperative neurolinguistic examination is necessary for adequate patient-tailored intraoperative monitoring with maximal tumour resection and to consequently increase the chance of language preservation and quality of life.

There is no consensus on a target definition and optimal dose in radiotherapy for atypical meningioma (AM). Insight into the postradiotherapy recurrence pattern is needed for optimal target definition and local control. The objective was to describe the patterns of recurrence after postoperative or salvage radiotherapy in patients with AM.A retrospective analysis was conducted of patients treated for intracranial AM with (fractionated) stereotactic radiotherapy (FSRT). The relationships between postradiotherapy recurrences, the dura and irradiated volume were established. Moreover, the dose prescriptions and fractionation schedules were converted to a reference to determine the relationship between dose and local control.The included patients received 57 (F)SRT treatments and 73 surgeries. Recurrent disease was found in 21 of 29 patients (72%) and after 39 of 57 (F)SRTs (68%). The median interval to first recurrence was 39.7 months. Of these recurrences, 25 were in-field, 11 were marginal, and 3 were out of field. In-field recurrence rates after biological equivalent doses60 Gy or AM frequently recurs after radiotherapy. All postradiotherapy recurrences were connected to the dura. Most marginal recurrences occurred within 3 cm of the irradiated abnormal dura. The lowest rate of in-field recurrences occurred after equivalent doses of least 60 Gy in 2 Gy fractions suggesting a dose-effect relationship.

Background and objectives:Few prospective well-designed diagnostic accuracy studies have been performed to study the parameters of infection in patients suspected for external ventricular catheter-associated infection. Our objective was to analyze the diagnostic accuracy of clinical characteristics and biochemical and microbiological parameters in diagnosing external ventricular cerebrospinal fluid (CSF) catheter-associated infection.Methods:From 2014 to 2017 we performed a single-center cohort study in consecutive patients at the intensive care unit who required an external ventricular CSF catheter in the Hague, the Netherlands. CSF was sampled and analyzed daily. Ventricular catheter-associated infection was defined according to the 2017 Infectious Diseases Society of America's Clinical Practice Guidelines. We compared clinical characteristics and biochemical parameters between patients with and without infection from 3 days prior to 3 days after the day the CSF sample was collected that grew bacteria.Results:103 patients were included of whom 15 developed a catheter-associated infection (15%). The median day cultures were positive was 3 days after CSF collection (IQR +2 to +4). On day 0, none of the tests could differentiate between patients with and without infection. CSF leukocyte count was increased in patients with ventricular catheter-associated infection as compared to patients without on day +2 and +3. The difference was most prominent on day +2 (1,703 × 106/L [IQR 480-6296] vs. 80 × 106/L [IQR 27-251]; p < 0.001; AUC 0.87 [CI 0.71-1.00]). Sensitivity for CSF leukocyte count at a cut off level >1,000 × 106/L was 67% (95% CI 30-93) and specificity was 100% (95% CI 90-100), the positive predictive value was 100% and the negative predictive value was 92% (95% CI 83-97). The percentage polymorphonuclear cells was higher in patients with infection on day +1 and +2 (day +2 89% [IQR 78-94] vs 59% [IQR 39-75]; p < 0.01; AUC 0.91 [95% CI 0.81-1.0]).Discussion:An elevated CSF leukocyte count and increased percentage polymorphonuclear cells are the strongest indicators for external catheter-associated infections on the days prior to culture positivity. New CSF markers of drain-associated infection should be studied to enable earlier diagnosis and treatment in patients with an infection, and reduce antibiotic treatment in those with no infection.Classification of Evidence:This study provides Class I evidence that in individuals requiring an external ventricular CSF catheter, elevated CSF leukocyte count and an increased percentage polymorphonuclear cells are the strongest indicators of catheter-associated infections in the days prior to CSF culture positivity.

OBJECTIVE Patients with glioblastoma are often scheduled for urgent elective surgery. Currently, the impact of the waiting period until glioblastoma surgery is undetermined. In this national quality registry study, the authors determined the wait times until surgery for patients with glioblastoma, the risk factors associated with wait times, and the risk-standardized variation in time to surgery between Dutch hospitals. The associations between time to surgery and patient outcomes were also explored. METHODS Data from all 4589 patients who underwent first-time glioblastoma surgery between 2014 and 2019 in the Netherlands were collected by 13 hospitals in the Quality Registry Neuro Surgery. Time to surgery comprised 1) the time from first MR scan to surgery (MTS), and 2) the time from first neurosurgical consultation to surgery (CTS). Long MTS was defined as more than 21 days and long CTS as more than 14 days. Potential risk factors were analyzed in multivariable logistic regression models. The standardized rate of long time to surgery was analyzed using funnel plots. Patient outcomes including Karnofsky Performance Scale (KPS) score change, complications, and survival were analyzed by multivariable logistic regression and proportional hazards models. RESULTS The median overall MTS and CTS were 18 and 9 days, respectively. Overall, 2576 patients (56%) had an MTS within 3 weeks and 3069 (67%) had a CTS within 2 weeks. Long MTS was significantly associated with older age, higher preoperative KPS score, higher American Society of Anesthesiologists comorbidity class, season, lower hospital case volume, university affiliation, and resection. Long CTS was significantly associated with higher baseline KPS score, university affiliation, resection, more recent year of treatment, and season. In funnel plots, considerable practice variation was observed between hospitals in patients with long times to surgery. Fewer patients with KPS score improvement were observed after a long time until resection. Long CTS was associated with longer survival. Complications and KPS score decline were not associated with time to surgery. CONCLUSIONS Considerable between-hospital variation among Dutch hospitals was observed in the time to glioblastoma surgery. A long time to resection impeded KPS score improvement, and therefore, patients who may improve should be identified for more urgent resection. Longer survival was observed in patients selected for longer time until surgery after neurosurgical consultation (CTS).

Few prospective well-designed diagnostic accuracy studies have been performed to study the parameters of infection in patients suspected for external ventricular catheter-associated infection. Our objective was to analyze the diagnostic accuracy of clinical characteristics and biochemical and microbiological parameters in diagnosing external ventricular CSF catheter-associated infection.From 2014 to 2017, we performed a single-center cohort study in consecutive patients at the intensive care unit who required an external ventricular CSF catheter in the Hague, the Netherlands. CSF was sampled and analyzed daily. Ventricular catheter-associated infection was defined according to the 2017 Infectious Diseases Society of America's Clinical Practice Guidelines. We compared clinical characteristics and biochemical parameters between patients with and without infection from 3 days before to 3 days after the day the CSF sample was collected that grew bacteria.A total of 103 patients were included of whom 15 developed a catheter-associated infection (15%). The median day cultures were positive was 3 days after CSF collection (interquartile range [IQR] +2 to +4). On day 0, none of the tests could differentiate between patients with and without infection. The CSF leukocyte count was increased in patients with ventricular catheter-associated infection as compared with patients without on days +2 and +3. The difference was most prominent on day +2 (1,703 × 10An elevated CSF leukocyte count and increased percentage of PMNs are the strongest indicators for external catheter-associated infections on the days before culture positivity. New CSF markers of drain-associated infection should be studied to enable earlier diagnosis and treatment in patients with an infection and reduce antibiotic treatment in those with no infection.This study provides Class I evidence that in individuals requiring an external ventricular CSF catheter, an elevated CSF leukocyte count and an increased percentage of PMNs are the strongest indicators of catheter-associated infections in the days before CSF culture positivity.

Purpose The present study aims to conduct a systematic review of literature reporting on the dose and dosing schedule of dexamethasone (DXM) in relation to clinical outcomes in malignant brain tumor patients, with particular attention to evidence-based practice. Methods A systematic search was performed in PubMed, Embase, Web of Science, Cochrane, Academic Search Premier, and PsycINFO to identify studies that reported edema volume reduction, symptomatic relief, adverse events and survival in relation to dexamethasone dose in glioma or brain metastasis (BM) patients. Results After screening 1812 studies, fifteen articles were included for qualitative review. Most studies reported a dose of 16 mg, mostly in a schedule of 4 mg four times a day. Due to heterogeneity of studies, it was not possible to perform quantitative meta-analysis. For BMs, best available evidence suggests that higher doses of DXM may give more adverse events, but may not necessarily result in better clinical condition. Some studies suggest that higher DXM doses are associated with shorter survival in the palliative setting. For glioma, DXM may lead to symptomatic improvement, yet no studies directly compare different doses. Results regarding edema reduction and survival in glioma patients are conflicting. Conclusions Evidence on the safety and efficacy of different DXM doses in malignant brain tumor patients is scarce and conflicting. Best available evidence suggests that low DXM doses may be noninferior to higher doses in certain circumstances, but more comparative research in this area is direly needed, especially in light of the increasing importance of immunotherapy for brain tumors. Electronic supplementary material The online version of this article (10.1007/s11060-019-03238-4) contains supplementary material, which is available to authorized users.

Introduction For decisions on glioblastoma surgery, the risk of complications and decline in performance is decisive. In this study, we determine the rate of complications and performance decline after resections and biopsies in a national quality registry, their risk factors and the risk-standardized variation between institutions. Methods Data from all 3288 adults with first-time glioblastoma surgery at 13 hospitals were obtained from a prospective population-based Quality Registry Neuro Surgery in the Netherlands between 2013 and 2017. Patients were stratified by biopsies and resections. Complications were categorized as Clavien-Dindo grades II and higher. Performance decline was considered a deterioration of more than 10 Karnofsky points at 6 weeks. Risk factors were evaluated in multivariable logistic regression analysis. Patient-specific expected and observed complications and performance declines were summarized for institutions and analyzed in funnel plots. Results For 2271 resections, the overall complication rate was 20 % and 16 % declined in performance. For 1017 biopsies, the overall complication rate was 11 % and 30 % declined in performance. Patient-related characteristics were significant risk factors for complications and performance decline, i.e. higher age, lower baseline Karnofsky, higher ASA classification, and the surgical procedure. Hospital characteristics, i.e. case volume, university affiliation and biopsy percentage, were not. In three institutes the observed complication rate was significantly less than expected. In one institute significantly more performance declines were observed than expected, and in one institute significantly less. Conclusions Patient characteristics, but not case volume, were risk factors for complications and performance decline after glioblastoma surgery. After risk-standardization, hospitals varied in complications and performance declines.

INTRODUCTION Steroids are commonly used for treatment of peritumoral edema and increased intracranial pressure in brain tumor patients. However, despite the widespread use of steroids, relatively little evidence is available about the optimal dosing scheme in brain tumor patients. PURPOSE The aim of this study is to increase insight in the practice variation of steroid dosing and tapering schedules among the neuro-oncology community. METHODS An electronic survey consisting of 27 questions regarding dosing and tapering schedules and adverse events of steroids was conducted among neurosurgeons internationally between 6 December 2019 and 1 June 2020. The survey was distributed by the electronic mailing lists of the Europeans Association of Neurosurgical Societies and via social media platforms. Collected data was assessed for quantitative and qualitative analysis using the Kruskal-Wallis test. RESULTS The survey obtained 175 responses. 87% of respondents answered all questions. Steroids are prescribed routinely perioperatively by 80% of respondents. Prescribed doses range from 2 to 64 mg/day in dosing schedule ranging from one to four times a day. The most prescribed steroid is dexamethasone in a dose of 16 mg/day. No significant association is seen between the prescribed dose and frequency of adverse events, years of experience, country, type of institution or having an institutional guideline. CONCLUSION Steroids are routinely prescribed perioperatively in brain tumor patients. However, there is a great practice variation in steroid dosing and tapering schedules among neurosurgeons. Future investigation is needed to identify an optimal dosing scheme and implement (inter)national guidelines for the dosing of steroids.

Despite profound diagnostics, the aetiology of spinal epidural haematoma (SEH) often remains unknown. In this case, diagnostics revealed an SEH at the fifth and sixth thoracic levels due to a subclavian steal syndrome with a tortuous vascular loop between the sixth thoracic intercostal artery and the costocervical arteries deriving from the left subclavian artery with plump arteries in the epidural space. The patient underwent decompression surgery and a percutaneous transluminal angioplasty. The patient showed good recovery at follow-up. The SEH was a result of secondary formed thoracic collateral circuits with epidural involvement due to a subclavian steal syndrome.