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The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to health-care systems around the world. As approximately one-third of the world´s population is living under \"lockdown\" conditions, medical resources are being reallocated and hospital admissions are limited to emergencies. We examined the decision-making impact of these actions and their effects on access to hospital treatment in patients with neurosurgical conditions. This retrospective cohort study analyzes hospital admissions of two major neurosurgical services in Germany during the nationwide lockdown period (March 16th to April 16th, 2020). Spinal or cranial conditions requiring immediate hospital admission and treatment constituted emergencies. A total of 243 in-patients were treated between March 16th and April 16th 2020 (122 patients at the University Medical Center Mainz, 121 patients at the University Medical Center Göttingen). Of these, 38.0±16% qualified as emergency admission. Another 1,688 admissions were reviewed during the same periods in 2018 and 2019, providing a frame of reference. Overall, emergency admissions declined by 44.7±0.7% during lockdown. Admissions for cranial emergencies fell by 48.1±4.44%, spinal emergencies by 30.9±14.6%. Above findings indicate that in addition to postponing elective procedures, emergency admissions were dramatically curtailed during the COVID-19 lockdown. As this surely is unexpected and unintended, reasons are undoubtedly complex. As consequences in morbidity and mortality are still unpredictable, efforts should be made to accommodate all patients in need of hospital access going forward.

Brain metastases are common in non-small cell lung cancer (NSCLC) and affect prognosis and survival. While frailty and sarcopenia are associated with the overall survival in NSCLC the impact on outcome and survival after surgery for brain metastasis is unknown. We therefore analyzed 179 patients (81 women) with NSCLC undergoing resection for brain metastasis between 2011 and 2020 retrospectively. Frailty was measured using the Clinical Frailty Scale (CFS). Temporal Muscle Volume (TMV) was assessed in preoperative T1w MRI. The median age was 63 years. Clinical frailty was present in about 20.6%. Mean follow-up was 11 months. Frailty correlated significantly with age ( r  = 0.36, p  < 0.001) and smaller TMV ( r =-0.24, p  = 0.002). However, only measurement of TMV predicted impaired survival (median OS 34.5 vs. 10.3 months, p  < 0.001). Physical performance after surgery was negatively affected by frailty ( r =-0.72, p  < 0.001) and positively by TMV ( r  = 0.2, p  = 0.038). Major postoperative complications were more strongly associated with sarcopenia rather than frailty. Treatment response towards immunotherapy improved in the absence of sarcopenia (B = 2.48, p  = 0.031). TMV is a predictor for survival after resection of brain metastasis and an indicator of treatment response to immunotherapy in patients with NSCLC. Accounting for sarcopenia in surgical decision making could improve patient selection for different treatment modalities.

Preoperative identification of intracranial meningiomas with aggressive behaviour may help in choosing the optimal treatment strategy. Radiomics is emerging as a powerful diagnostic tool with potential applications in patient risk stratification. In this study, we aimed to compare the predictive value of conventional, semantic based and radiomic analyses to determine CNS WHO grade and early tumour relapse in intracranial meningiomas. We performed a single-centre retrospective analysis of intracranial meningiomas operated between 2007 and 2018. Recurrence within 5 years after Simpson Grade I-III resection was considered as early. Preoperative T1 CE MRI sequences were analysed conventionally by two radiologists. Additionally a semantic feature score based on systematic analysis of morphological characteristics was developed and a radiomic analysis were performed. For the radiomic model, tumour volume was extracted manually, 791 radiomic features were extracted. Eight feature selection algorithms and eight machine learning methods were used. Models were analysed using test and training datasets. In total, 226 patients were included. There were 21% CNS WHO grade 2 tumours, no CNS WHO grade 3 tumour, and 25 (11%) tumour recurrences were detected in total. In ROC analysis the best radiomic models demonstrated superior performance for determination of CNS WHO grade (AUC 0.930) and early recurrence (AUC 0.892) in comparison to the semantic feature score (AUC 0.74 and AUC 0.65) and conventional radiological analysis (AUC 0.65 and 0.54). The combination of human classifiers, semantic score and radiomic analysis did not markedly increase the model performance. Radiomic analysis is a promising tool for preoperative identification of aggressive and atypical intracranial meningiomas and could become a useful tool in the future.

Purpose The patients’ burden with asymptomatic meningiomas and patients with good clinical outcome after meningioma resection often remains neglected. In this study, we aimed to investigate the longitudinal changes of psychological distress and quality of life in these patient groups. Methods Patients with conservatively managed (CM) or operated (OM) meningiomas and excellent neurological status, who were screened for psychological distress during the follow-up visit (t1), were included. We performed a follow-up mail/telephone-based survey 3–6 months (t2) after t1. Distress was measured using Hospital Anxiety and Depression Scale (HADS), Distress Thermometer (DT), 36-item Short Form (SF-36), and Brief Fatigue Inventory (BFI). Results Sixty-two patients participated in t1 and 47 in t2. The number of patients reporting increased or borderline values remained high 3 months after initial presentation, with n  = 25 (53%) of patients reporting increased anxiety symptom severity and n  = 29 (62%) reporting increased depressive symptom severity values. The proportion of distressed patients according to a DT score remained similar after 3 months. Forty-four percent of patients reported significant distress in OM and 33% in CM group. The most common problems among distressed patients were fatigue (t2 75%) and worries (t2 50%), followed by pain, sleep disturbances, sadness, and nervousness. Tumor progress was associated with increased depression scores ( OR 6.3 (1.1–36.7)). Conclusion The level of psychological distress in asymptomatic meningiomas and postoperative meningiomas with excellent outcome is high. Further investigations are needed to identify and counsel the patients at risk.

Objectives Gender differences have been reported to influence medical training. We investigated gender differences encountered during training in interventional radiology maneuvers. Methods Catheter handling was analyzed under standardized conditions in 64 participants naïve to endovascular procedures (26 women, 38 men). Objective (e.g., catheter pathway, catheter movements, required time) and subjective parameters (stress level) were recorded. The NASA-Task Load Index (NASA-TLX; 1–20 points) was used to assess participants’ stress levels and perceived workload. Results In the easier tasks, no significant differences between male and female participants regarding catheter handling were observed. In the most complex task, female participants took themselves more time (688 ± 363 vs. 501 ± 230 s; p  = 0.02), asked for help more frequently ( n  = 19 vs. n  = 8) and earlier than men (203 ± 94 vs. 305 ± 142 s; p  = 0.049), whereas men stood out by more agitated catheter handling (6.0 ± 1.8 vs. 4.8 ± 1.6 movements/s; p  = 0.005). Overall, female participants perceived tasks to be more difficult (11.5 ± 4.2 vs. 9.6 ± 3.3; p  = 0.016), perceived higher stress levels (8.9 ± 4.9 vs. 6.3 ± 4.4; p  = 0.037), and rated their own performance lower (9.12 ± 3.3 vs. 11.3 ± 3.3; p  = 0.009). However, female participants were able to correlate self-assessed with objective parameters correctly ( r between −0.555 and −0.469; p  = 0.004–0.018), whereas male participants failed to correctly rate their performance ( p between 0.34 and 0.73). Stress levels correlated with objective parameters in males ( r between 0.4 and 0.587; p  < 0.005), but not in female participants. Conclusion Perceived stress levels, self-evaluation skills, and catheter handling differ greatly between untrained male and female participants trying to solve interventional radiological tasks. These gender-specific differences should be considered in interventional radiology training. Clinical relevance statement As psychological aspects may influence individual working strategies gender-specific differences in self-perception while learning interventional radiology maneuvers could be essential regarding success in teaching and treatment outcomes. Key Points • After performing standardized training, 38 male and 26 female volunteers showed significant differences regarding objective and self-assessed performance, as well as in perceived workload while performing simulated endovascular catheter maneuvers. • After solving simulated endovascular radiological tasks, female participants were able to self-assess their objective performance much more accurately than male participants. • Women took more time to solve simulated endovascular tasks and asked earlier and more frequently for help than men.

The first therapeutical goal followed by neurooncological surgeons dealing with prefrontal gliomas is attempting supramarginal tumor resection preserving relevant neurological function. Therefore, advanced knowledge of the frontal aslant tract (FAT) functional neuroanatomy in high-order cognitive domains beyond language and speech processing would help refine neurosurgeries, predicting possible relevant cognitive adverse events and maximizing the surgical efficacy. To this aim we performed the recently developed correlational tractography analyses to evaluate the possible relationship between FAT’s microstructural properties and cognitive functions in 27 healthy subjects having ultra-high-field (7-Tesla) diffusion MRI. We independently assessed FAT segments innervating the dorsolateral prefrontal cortices (dlPFC-FAT) and the supplementary motor area (SMA-FAT). FAT microstructural robustness, measured by the tract’s quantitative anisotropy (QA), was associated with a better performance in episodic memory, visuospatial orientation, cognitive processing speed and fluid intelligence but not sustained selective attention tests. Overall, the percentual tract volume showing an association between QA-index and improved cognitive scores (pQACV) was higher in the SMA-FAT compared to the dlPFC-FAT segment. This effect was right-lateralized for verbal episodic memory and fluid intelligence and bilateralized for visuospatial orientation and cognitive processing speed. Our results provide novel evidence for a functional specialization of the FAT beyond the known in language and speech processing, particularly its involvement in several higher-order cognitive domains. In light of these findings, further research should be encouraged to focus on neurocognitive deficits and their impact on patient outcomes after FAT damage, especially in the context of glioma surgery.

The cerebral thrombin system is activated in the early stage after intracerebral hemorrhage (ICH). Expression of thrombin leads to concentration dependent secondary neuronal damage and detrimental neurological outcome. In this study we aimed to investigate the impact of thrombin concentration and activity in the cerebrospinal fluid (CSF) of patients with ICH on clinical outcome. Patients presenting with space-occupying lobar supratentorial hemorrhage requiring extra-ventricular drainage (EVD) were included in our study. The CSF levels of thrombin, its precursor prothrombin and the Thrombin-Antithrombin complex (TAT) were measured using enzyme linked immune sorbent assays (ELISA). The oxidative stress marker Superoxide dismutase (SOD) was assessed in CSF. Initial clot size and intraventricular hemorrhage (IVH) volume was calculated based on by computerized tomography (CT) upon admission to our hospital. Demographic data, clinical status at admission and neurological outcome were assessed using the modified Rankin Scale (mRS) at 6-weeks and 6-month after ICH. Twenty-two consecutive patients (9 females, 11 males) with supratentorial hemorrhage were included in this study. CSF concentrations of prothrombin (p < 0.005), thrombin (p = 0.005) and TAT (p = 0.046) were statistical significantly different in patients with ICH compared to non-hemorrhagic CSF samples. CSF concentrations of thrombin 24h after ICH correlated with the mRS index after 6 weeks (r2 = 0.73; < 0.005) and 6 months (r2 = 0.63; < 0.005) after discharge from hospital. Thrombin activity, measured via TAT as surrogate parameter of coagulation, likewise correlated with the mRS at 6 weeks (r2 = 0.54; < 0.01) and 6 months (r2 = 0.66; < 0.04). High thrombin concentrations coincide with higher SOD levels 24h after ICH (p = 0.01). In this study we found that initial thrombin concentration and activity in CSF of ICH patients did not correlate with ICH and IVH volume but are associated with a poorer functional neurological outcome. These findings support mounting evidence of the role of thrombin as a contributor to secondary injury formation after ICH.

BackgroundAtypical meningiomas (WHO grade II) have high recurrence rate. However, data on the effect of radiotherapy (RT) is still conflicting. The aim of this study was to evaluate the influence of postoperative RT on the recurrence of primary atypical intracranial meningiomas.MethodsThe medical records of all patients who underwent surgery (2007–2017 in 4 neurosurgical departments) for a histologically diagnosed primary atypical meningioma were reviewed to assess progression-free survival (PFS) and prognostic factors.ResultsThis analysis included 258 patients with a median age of 60 years (54.7% female). The predominant tumor locations were convexity and falx (60.9%) followed by the skull base (37.2%). Simpson grade I–II resection was achieved in 194 (75.2%) patients, Simpson grade III–IV in 53 patients (20.5%). Tumor progressed in 54 cases (20.9%). Postoperative RT was performed in 46 cases (17.8%). RT was more often applied after incomplete resection (37.7% vs. 13.4% Simpson III–IV vs. I–II). A multivariate analysis showed a significantly shorter PFS associated with Simpson III–IV [HR 1.19, (95% CI) 1.09–1.29, p < 0.001] and age > 65 years [HR 2.89, (95% CI) 1.56–5.33, p = 0.001]. A subgroup analysis with a minimal follow-up of 36 months revealed that Simpson III–IV [HR 3.01, 95% CI 1.31–6.931.03–1.24, p = 0.009] and age > 65 years [HR 2.48, 95% CI 1.20–5.13, p = 0.014] reduced PFS. The impact of postoperative RT on PFS remained statistically insignificant, even in a propensity-score matched survival analysis [n = 46; p = 0.438; OR 0.710 (0.299–1.687)].ConclusionsIn the present study, postoperative RT did not improve PFS. The most important prognostic factors remain the extent of resection and age.

Immune evasion and suppression lead to unchecked tumor growth in glioblastoma. Cytomegalovirus (CMV) has been implicated in tumor progression and modulation in glioblastoma. To investigate this potential connection, CMV-associated changes in the glioblastoma immune landscape were characterized in vitro and in a murine glioblastoma model. Infection of mouse glioblastoma cells (GL261Luc2) with mCMV resulted in a short period of viral replication. MHC-I cell surface expression was reduced after mCMV infection by approximately 40% compared with non-infected tumor cells ( p  < 0.0001). Viral regulators of antigen presentation (vRAP) were shown to be responsible for MHC-I downregulation using a recombinant mCMV (ΔvRAP) lacking the known immune evasion genes. RNA sequencing of mCMV infected GL261Luc cells revealed 2711 differentially expressed genes ( p  < 0.005). Of particular interest was the downregulation of MHC-I-associated genes H2-Q1-10 and Tap1 fter CMV infection. In vivo, the mCMV immediate early gene (IE1) was detected in brains of mCMV + animals after tumor implantation and increased during tumor growth. mCMV + mice had significantly shorter survival than controls, depending on initial tumor size ( P  < 0.001). Tumor immune infiltrates in mCMV infection were characterized by B cell infiltrates and low levels of NK cell infiltration. Here, the landscape of immune cell infiltrates is shifted toward B cell infiltration and reduced numbers of NK cells. CMV leads to immune evasion mediated MHC-I downregulation in murine glioblastoma. Thus, CMV infection in glioblastoma may contribute to unchecked tumor growth in glioblastoma by increasing immune evasion.

Background Isocitrate dehydrogenase ( IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown. Methods Patients undergoing surgery (between 2016–2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2–3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors. Results This multi-center study included 157 patients (mean age 58 years (20–87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response. Conclusions WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.