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Ischemic stroke is a very frequent neurological disorder. It's incidence is increasing as western societies are aging. Effective therapies that reduce mortality and increase the chances of living symptom-free or, at least, in independence are available. Intravenous or intraarterial thrombolysis is an effective treatment with a number needed to treat of 6 if given within 4.5 hours after symptom onset. The safe use of thrombolysis requires an effective and repeatedly trained workflow established within a team of a neurologist and specialized nursing staff in an optimized environment (admission, imaging facility, laboratory, stroke unit). After peracute treatment, the patient should be transferred to a stroke unit. This unit is a spatially defined intermediate care unit with specifically trained personnel (physicians, nurses, therapists). Treating the patient in a stroke unit is as effective in improving outcome as thrombolysis and also reduces the length of hospital stay. In contrast to thrombolysis, which can be provided, on average, to only 5% of stroke patients, stroke unit care is applicable to most. The organization of medical care in most European countries and in Switzerland separate the acute phase from subacute rehabilitation and chronic stroke treatment. This can be highly confusing for the patient who, during the course of the disease, meets different physicians, nurses and therapists with often diverging opinions about prognosis and therapies. Consistent treatment approaches and patient/ caregiver information is necessary and can only be implemented by providing a homogeneous pathway for continuous stroke care. [ABSTRACT FROM AUTHOR]

Purpose: There is limited information on treatment recommendations for glioblastoma patients with poor performance status. Here, we aim to evaluate the association of radiotherapy on survival in glioblastoma patients presenting with poor postoperative performance status in first-line setting., Methods: We retrospectively analyzed data of 93 glioblastoma patients presenting with poor postoperative performance status (ECOG 2-4) at the University Hospital Zurich, Switzerland, in the years 2005-2019. A total of 43 patients received radiotherapy with or without systemic therapy in the first-line setting, whereas 50 patients received no additive local or systemic treatment after initial biopsy or resection. Overall survival was calculated from primary diagnosis and from the end of radiotherapy. In addition, factors influencing survival were analyzed., Results: Median overall survival from primary diagnosis was 6.2 months in the radiotherapy group (95% CI 6.2-14.8 weeks, range 2-149 weeks) and 2.3 months in the group without additive treatment (95% CI 1.3-7.4 weeks, range 0-28 weeks) (p < 0.001). This survival benefit was confirmed by landmark analyses. Factors associated with overall survival were extent of resection and administration of radiotherapy with or without systemic treatment. Median survival from end of radiotherapy was 3 months (95% CI 4.3-21.7 weeks, range 0-72 weeks), with 25.6% (n = 11) early termination of treatment and 83.7% (n = 36) requiring radiotherapy as in-patients. Performance status improved in 27.9% (n = 12) of patients after radiotherapy., Conclusion: In this retrospective single-institution analysis, radiotherapy improved overall survival in patients with poor performance status, especially in patients who were amendable to neurosurgical resection., (© 2021. The Author(s).)

Background: Glioblastoma is the most common malignant primary brain tumour in adults and driven by various genomic alterations. Next generation sequencing (NGS) provides timely information about the genetic landscape of tumours and might detect targetable mutations. To date, differences exist in the application and NGS assays used as it remains unclear to what extent these variants may affect clinical decision making. In this survey-based study, we investigated the use of NGS in adult patients with glioblastoma in Switzerland., Methods: All eight primary care centres for Neuro-Oncology in Switzerland participated in this survey. The NGS assays used as well as the criteria for the application of NGS in newly diagnosed glioblastoma were investigated. Decision trees were analysed for consensus and discrepancies using the objective consensus methodology., Results: Seven out of eight centres perform NGS in patients with newly diagnosed glioblastoma using custom made or commercially available assays. The criteria most relevant to decision making were age, suitability of standard treatment and fitness. NGS is most often used in fitter patients under the age of 60 years who are not suitable for standard therapy, while it is rarely performed in patients in poor general health., Conclusion: NGS is frequently applied in glioblastomas in adults in Neuro-Oncology centres in Switzerland despite seldom changing the course of treatment to date., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Delirium is a common severe complication of stroke. We aimed to determine the cost-of-illness and risk factors of poststroke delirium (PSD)., Methods: This prospective single-center study included n=567 patients with acute stroke from a hospital-wide delirium cohort study and the Swiss Stroke Registry in 2014. Delirium was determined by Delirium Observation Screening Scale or Intensive Care Delirium Screening Checklist 3 times daily during the first 3 days of admission. Costs reflected the case-mix index and diagnosis-related groups from 2014 and were divided into nursing, physician, and total costs. Factors associated with PSD were assessed with multiple regression analysis. Partial correlations and quantile regression were performed to assess costs and other factors associated with PSD., Results: The incidence of PSD was 39.0% (221/567). Patients with delirium were older than non-PSD (median 76 versus 70 years; P<0.001), 52% male (115/221) versus 62% non-PSD (214/346) and hospitalized longer (mean 11.5 versus 9.3 days; P<0.001). Dementia was the most relevant predisposing factor for PSD (odds ratio, 16.02 [2.83–90.69], P=0.002). Moderate to severe stroke (National Institutes of Health Stroke Scale score 16–20) was the most relevant precipitating factor (odds ratio, 36.10 [8.15–159.79], P<0.001). PSD was a strong predictor for 3-month mortality (odds ratio, 15.11 [3.33–68.53], P<0.001). Nursing and total costs were nearly twice as high in PSD (P<0.001). There was a positive correlation between total costs and admission National Institutes of Health Stroke Scale (correlation coefficient, 0.491; P<0.001) and length of stay (correlation coefficient, 0.787; P<0.001) in all patients. Quantile regression revealed rising nursing and total costs associated with PSD, higher National Institutes of Health Stroke Scale, and longer hospital stay (all P<0.05)., Conclusions: PSD was associated with greater stroke severity, prolonged hospitalization, and increased nursing and total costs. In patients with severe stroke, dementia, or seizures, PSD is anticipated, and additional costs are associated with hospitalization.

Aim of the Study: Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O 6 -methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma., Methods: MGMT promoter methylation and TERT promoter mutation status were retrospectively assessed in a prospective cohort of patients with IDH-wild-type glioblastoma of the German Glioma Network (GGN) (n = 298) and an independent retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n = 302)., Results: In the GGN cohort, but not in the Düsseldorf/Zurich cohort, TERT promoter mutation was moderately associated with inferior outcomes in patients with MGMT promoter-unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07-2.82; p = 0.026). TERT promoter mutations were not associated with better outcomes in patients with MGMT promoter-methylated tumours in either cohort. The two different TERT promoter hotspot mutations (C228T and C250T) were not linked to distinct outcomes., Conclusions: Analysis of two independent cohorts of patients with glioblastoma did not confirm previous data, suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in patients with IDH-wild-type glioblastoma., Competing Interests: Conflict of interest statement P.R. has received honoraria for advisory board participation and lectures from Bristol-Myers Squibb (BMS), Debiopharm, Medac, Merck, MSD, Novocure, QED and Roche. T.P. has received honoraria for lectures from Chugai, Tokyo, and Mayo Clinic, Rochester. M.S. has received honoraria for consulting from Novocure and Integra. Mi.W. has received research grants from AbbVie, Adastra, Dracen, Merck Sharp & Dohme (MSD), Merck (EMD) and Novocure and honoraria for lectures or advisory board participation or consulting from AbbVie, Basilea, BMS, Celgene, Medac, MSD, Merck (EMD), Nerviano Medical Sciences, Orbus, Roche and Tocagen. G.R. has received honoraria for advisory board participations from AbbVie. The other authors report no disclosures., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Several preclinical and epidemiologic studies have indicated tumour-promoting effects of thyroid hormones (THs). However, very limited knowledge exists on the prognostic impact of thyroid function in metastatic cancer., Methods: We compiled a discovery cohort of 1692 patients with newly diagnosed brain metastases (BMs) of solid cancers treated at the Medical University of Vienna and an independent validation cohort of 191 patients with newly diagnosed BMs treated at the University Hospital Zurich., Results: Hypothyroidism before diagnosis of cancer was evident in 133 of 1692 (7.9%) patients of the discovery, and in 18 of 191 (9.4%) patients of the validation cohort. In the discovery cohort, hypothyroidism was statistically significantly associated with favourable survival prognosis from diagnosis of cancer (31 vs. 21 months; p = 0.0026) and with survival prognosis from diagnosis of BMs (12 vs. 7 months; p = 0.0079). In multivariate analysis including the diagnosis-specific graded prognostic assessment score, primary tumour type and sex, hypothyroidism was an independent factor associated with survival after diagnosis of BMs (hazard ratio: 0.76; 95% confidence interval [CI]: (0.63; 0.91; p = 0.0034). In the validation cohort, the association of hypothyroidism and favourable survival prognosis from diagnosis of cancer (55 vs. 11 months; p = 0.00058), as well as from diagnosis of BMs (40 vs. 10 months; p = 0.0036) was confirmed., Conclusion: Pre-existing hypothyroidism was strongly and independently associated with prognosis in patients with newly diagnosed BMs, supporting the evidence from preclinical data that THs may indeed have a tumour-promoting effect. Further investigation of the underlying pathobiological mechanism and potential therapeutic implications are required., Competing Interests: Conflict of interest statement A.S.B. has received research support from Daiichi Sankyo (≤10000€), Roche (>10000€); has received honoraria for lectures;has been a member of the consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo (all < 5000€), has received travel support from Roche, Amgen and AbbVie. M.K. has received research support from Sanofi, AstraZeneca and Ipsen; served as a speaker and received consulting fees from AstraZeneca, Novartis, Novo Nordisk, Lilly, Merck, Böhringer, Roche and Sanofi. M.W. has received research grants from Abbvie, Adastra, Bristol Meyer Squibb (BMS), Dracen, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Piqur and Roche; has received honoraria for lectures or served as a member of advisory board participation or consulting from Abbvie, Basilea, Bristol Meyer Squibb (BMS), Celgene, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Orbus, Roche and Tocagen. M.P. has received research support from Böhringer-Ingelheim, GlaxoSmithKline, Merck Sharp & Dome and Roche; has received honoraria for lectures; served as a member of the consultation or advisory board participation (all < 5000€) from Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp & Dome. All the other authors have no conflicts of interest to declare., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In 30% of patients with brain metastasis (BM), neurological symptoms are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). Here, we define the diagnostic value of 18 F-fluordesoxyglucose positron emission tomography (FDG-PET/CT) in the workup of BM-CUPS., Methods: We screened 565 patients operated for BM at the University Hospital Zurich and identified 64 patients with BM-CUPS with data on both FDG-PET/CT and contrast-enhanced chest/abdomen computed tomography (CT) available at BM diagnosis. A cohort of 125 patients with BM-CUPS from Lille and Vienna was used for validation., Results: FDG-PET/CT was not superior to chest/abdomen CT in localising the primary lesion in the discovery cohort, presumably because most primary tumours were lung cancers. However, FDG-PET/CT identified additional lesions suspicious of extracranial metastases in 27 of 64 patients (42%). The inclusion of FDG-PET/CT findings shifted the graded prognostic assessment (GPA) score from 3 with CT alone to 2.5 for PET/CT (p = 3.8 × 10 -5 , Wilcoxon's test), resulting in a predicted survival of 5.3 versus 3.8 months (p = 6.1 × 10 -5 ; Wilcoxon's test). All observations were confirmed in the validation cohort., Conclusions: Lung cancers are the most common primary tumour in BM-CUPS; accordingly, CT alone shows similar overall sensitivity for detecting the primary tumour as FDG-PET/CT. Yet, FDG-PET/CT improves the accuracy of staging by detecting more metastases, reflected by decreased GPA scores and decreased predicted survival. Therefore, randomised trials on patients with BM should standardise methods of staging, notably when stratifying for GPA., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Despite moderate improvements in outcome of glioblastoma after first-line treatment with chemoradiation recent clinical trials failed to improve the prognosis of recurrent glioblastoma. In the absence of a standard of care we aimed to investigate institutional treatment strategies to identify similarities and differences in the pattern of care for recurrent glioblastoma. We investigated re-treatment criteria and therapeutic pathways for recurrent glioblastoma of eight neuro-oncology centres in Switzerland having an established multidisciplinary tumour-board conference. Decision algorithms, differences and consensus were analysed using the objective consensus methodology. A total of 16 different treatment recommendations were identified based on combinations of eight different decision criteria. The set of criteria implemented as well as the set of treatments offered was different in each centre. For specific situations, up to 6 different treatment recommendations were provided by the eight centres. The only wide-range consensus identified was to offer best supportive care to unfit patients. A majority recommendation was identified for non-operable large early recurrence with unmethylated MGMT promoter status in the fit patients: here bevacizumab was offered. In fit patients with late recurrent non-operable MGMT promoter methylated glioblastoma temozolomide was recommended by most. No other majority recommendations were present. In the absence of strong evidence we identified few consensus recommendations in the treatment of recurrent glioblastoma. This contrasts the limited availability of single drugs and treatment modalities. Clinical situations of greatest heterogeneity may be suitable to be addressed in clinical trials and second opinion referrals are likely to yield diverging recommendations.

Background: In 2005, findings of the first "cost of disorders of the brain in Europe" study of the European Brain Council (EBC) showed that these costs cause a substantial economic burden to the Swiss society. In 2010 an improved update with a broader range of disorders has been analysed. This report shows the new findings for Switzerland and discusses changes., Methods: Data are derived from the EBC 2010 census study that estimates 12-month prevalence of 12 groups of disorders of the brain and calculates costs (direct health-care costs, direct non-medical costs and indirect costs) by combining top-down and bottom up cost approaches using existing data., Results: The most frequent disorder was headache (2.3 million). Anxiety disorders were found in 1 million persons and sleep disorders in 700,000 persons. Annual costs for all assessed disorders total to 14.5 billion Euro corresponding to about 1,900 EUR per inhabitant per year. Mood, psychotic disorders and dementias (appr. 2 billion EUR each) were most costly. Costs per person were highest for neurological/neurosurgery-relevant disorders, e.g. neuromuscular disorders, brain tumour and multiple sclerosis (38,000 to 24,000 EUR)., Conclusion: The estimates of the EBC 2010 study for Switzerland provide a basis for health care planning. Increase in size and costs compared to 2005 are mostly due to the inclusion of new disorders (e.g., sleep disorders), or the re-definition of others (e.g., headache) and to an increase in younger cohorts. We suggest coordinated research and preventive measures coordinated between governmental bodies, private health-care and pharmaceutical companies.

Objectives: Therapy for relapsing-remitting multiple sclerosis with natalizumab (Tysabri; Biogen Idec) has been shown to be effective in the reduction of the clinical relapse rate and disability progression. However, real-life longitudinal data, including years before baseline, are rare., Methods: An observational single-center study was carried out. We analyzed data from 64 consecutive patients with multiple sclerosis., Results: After 1 year of treatment (n = 64), score on the Expanded Disability Status Scale (EDSS) decreased by 0.47 points (P = 0.047) and the annualized relapse rate (ARR) decreased by 82% (P < 0.001). After 2 years (n = 41), EDSS score was still reduced by 0.28 (not significant) and ARR was reduced by 69% (P < 0.001). After 3 years (n = 23), EDSS score was reduced by 0.26 (not significant), and ARR was reduced by 77% (P < 0.001). Reduction of EDSS score and ARR did not depend on baseline ARR (1-2 vs >2) or EDSS score and was not biased by exceptional high disease activity or relapses around baseline., Conclusions: These real-life data reinforce that natalizumab is effective over years, reduces ARR, and stabilizes EDSS score independent of baseline ARR, baseline EDSS score, or baseline treatment.