The effectiveness of temozolomide (TMZ) dosing schemes and the "rechallenge" of recurrent glioblastoma (GBM) with TMZ are controversial. We therefore compared the efficacy of different TMZ dosing schemes against GBM cancer stem cell (CSC) lines in vitro. In O(6)-methyl-guanidine-methyl-transferase (MGMT)-negative CSC lines, all schedules (1 day on/27 days off, 5 days on/23 days off, 7 days on/7 days off, 21 days on/7 days off, continuous low-dose TMZ) depleted clonogenic cells. In TMZ-resistant CSC lines, the 7 days on/7 days off scheme showed higher toxicity as compared with the other schemes. However, clinically feasible concentrations remained ineffective in highly resistant CSC lines. In addition, none of the schedules induced long-term depletion of clonogenic cells even at the highest concentrations (up to 250 μM). After sublethal TMZ treatment for 5 days, TMZ rechallenge of recovering CSC lines remained effective. Our data advocate CSC lines as in vitro model to address clinical questions. Using this model, our data suggest the effectiveness of TMZ in MGMT-negative CSC lines and support the concept of TMZ rechallenge. The 7 days on/7 days off scheme consistently showed the best activity of all schedules in TMZ-resistant CSC lines.

Aim:Recently, D,L-methadone has been put forward as adjuvant treatment in glioblastoma (GBM).Methods:We analyzed the μ-opioid receptor expression in a set of GBM cell lines and investigated the efficacy of D,L-methadone alone and in combination with temozolomide (TMZ).Results & conclusion:Expression of the μ-opioid receptor was similar in the tested cell lines. High concentrations of D,L-methadone induced apoptosis in all cell lines and showed treatment interaction with TMZ. However, in lower dosages, reflecting clinically attainable concentrations, D,L-methadone alone showed no efficacy, and induced even higher proliferation in one specific cell line. Also, no interaction with TMZ was observed. These results suggest caution to the premature use of D,L-methadone in the treatment of GBM patients.

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OBJECTIVEDecision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient’s risk of experiencing any functional impairment.METHODSThe authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated.RESULTSIn the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69–0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69–0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/.CONCLUSIONSFunctional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.

Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th–April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017–2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017–2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

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Background Patients with intervertebral disc herniation undergo surgical removal of herniated disc material in cases of persisting symptoms and/or neurologic deficits. While motor deficits often prompt surgery, little is known about the optimal timing of surgery in these cases. The aim of this study was to prospectively evaluate the impact of timing of disc surgery on motor recovery. Does postponing surgical treatment worsen outcome? Method In total, 120 patients with sciatica and/or sensorimotor deficits due to a lumbar disc herniation were surgically treated at the authors’ center within a 3-month period. In 60 patients, motor deficits were present at the time of admission. Motor function was assessed using manual muscle testing and subdivided according to the Medical Research Council (MRC) scale. Patient demographics, neurologic deficits, duration of motor deficits, treatment characteristics, and outcome were assessed. At a minimum follow-up of 1 year, functional recovery and complications were collated. Patients were subdivided into groups according to the severity of the paresis (MRC ≤ 3/5 vs. MRC 4/5). Intra-group differences were compared based on the duration of the neurologic deficits. Results Patients with moderate and severe paresis (MRC ≤ 3/5) benefit from treatment within 72 h as they were shown to have a significantly higher complete recovery rate at 1-year follow-up (75% vs. 0%; p < 0.001). Conclusion Immediate surgery should be offered to patients with moderate and severe motor deficits to increase the likelihood of neurologic recovery. This prospective data may have an impact on emergency triage in these patients.