Trends in frailty in brain tumor care during the COVID-19 pandemic in a nationwide hospital network in Germany.

PURPOSE: Among brain tumor patients, frailty is associated with poor outcomes. The COVID-19 pandemic has led to increased frailty in the general population. To date, evidence on changes in frailty among brain tumor patients during the pandemic is lacking. We aimed to compare frailty among brain tumor patients in Germany during the COVID-19 pandemic to the pre-pandemic era and to assess potential effects on brain tumor care. METHODS: In this retrospective observational study, we compared frailty among brain tumor patients hospitalized during the COVID-19 pandemic in years 2020 through 2022 to pre-pandemic years 2016 through 2019 based on administrative data from a nationwide network of 78 hospitals in Germany. Using the Hospital Frailty Risk Score (HFRS), frailty was categorized as low, intermediate, or high. We examined changes in frailty, patient demographics, the burden of comorbidity, rates of surgery, and mortality rates for different frailty groups during the pandemic and compared them to pre-pandemic levels. RESULTS: Of the 20,005 included hospitalizations for brain tumors, 7979 were during the pandemic (mean age 60.0 years (± 18.4); females: 49.8%), and 12,026 in the pre-pandemic period (mean age: 59.0 years [± 18.4]; females: 49.2%). Average daily admissions decreased from 8.2 (± 5.1) during pre-pandemic years to 7.3 (± 4.5) during the pandemic (p < 0.01). The overall median HFRS decreased from 3.1 (IQR: 0.9-7.3) during the pre-pandemic years to 2.6 (IQR: 0.3-6.8) during the pandemic (p < 0.01). At the same time, the Elixhauser Comorbidity Index (ECI) decreased from 17.0 (± 12.4) to 16.1 (± 12.0; p < 0.01), but to a larger degree among high compared to low frailty cases (by 1.8 vs. 0.3 points; p = 0.04). In the entire cohort, the mean length of stay was significantly shorter in the pandemic period (9.5 days [± 10.7]) compared with pre-pandemic levels (10.2 days [± 11.8]; p < 0.01) with similar differences in the three frailty groups. Rates of brain tumor resection increased from 29.9% in pre-pandemic years to 36.6% during the pandemic (p < 0.001) without differences between frailty levels. Rates of in-hospital mortality did not change during the pandemic (6.1% vs. 6.7%, p = 0.07), and there was no interaction with frailty. CONCLUSION: Even though our findings are limited in that the HFRS is validated only for patients ≥ 75 years of age, our study among patients of all ages hospitalized for brain tumors in Germany suggests a marked decrease in levels of frailty and in the burden of comorbidities during the COVID-19 pandemic.

Proinflammatory Macrophage Activation by the Polysialic Acid-Siglec-16 Axis Is Linked to Increased Survival of Patients with Glioblastoma.

PURPOSE: Interactions with tumor-associated microglia and macrophages (TAM) are critical for glioblastoma progression. Polysialic acid (polySia) is a tumor-associated glycan, but its frequency of occurrence and its prognostic value in glioblastoma are disputed. Through interactions with the opposing immune receptors Siglec-11 and Siglec-16, polySia is implicated in the regulation of microglia and macrophage activity. However, due to a nonfunctional SIGLEC16P allele, SIGLEC16 penetrance is less than 40%. Here, we explored possible consequences of SIGLEC16 status and tumor cell-associated polySia on glioblastoma outcome. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded specimens of two independent cohorts with 70 and 100 patients with newly diagnosed glioblastoma were retrospectively analyzed for SIGLEC16 and polySia status in relation to overall survival. Inflammatory TAM activation was assessed in tumors, in heterotypic tumor spheroids consisting of polySia-positive glioblastoma cells and Siglec-16-positive or Siglec-16-negative macrophages, and by exposing Siglec-16-positive or Siglec-16-negative macrophages to glioblastoma cell-derived membrane fractions. RESULTS: Overall survival of SIGLEC16 carriers with polySia-positive tumors was increased. Consistent with proinflammatory Siglec-16 signaling, levels of TAM positive for the M2 marker CD163 were reduced, whereas the M1 marker CD74 and TNF expression were increased, and CD8+ T cells enhanced in SIGLEC16/polySia double-positive tumors. Correspondingly, TNF production was elevated in heterotypic spheroid cultures with Siglec-16-expressing macrophages. Furthermore, a higher, mainly M1-like cytokine release and activating immune signaling was observed in SIGLEC16-positive as compared with SIGLEC16-negative macrophages confronted with glioblastoma cell-derived membranes. CONCLUSIONS: Collectively, these results strongly suggest that proinflammatory TAM activation causes the better outcome in patients with glioblastoma with a functional polySia-Siglec-16 axis.

Changes in nationwide in-hospital stroke care during the first four waves of COVID-19 in Germany.

Introduction: In the early stages of the global COVID-19 pandemic hospital admissions for acute ischemic stroke (AIS) decreased substantially. As health systems have become more experienced in dealing with the pandemic, and as the proportion of the population vaccinated rises, it is of interest to determine whether the prevalence of AIS hospitalization and outcomes from hospitalization have returned to normal. Patients and methods: In this observational, retrospective cohort study, we compared the prevalence and outcomes of AIS during the first four waves of the pandemic to corresponding pre-pandemic periods in 2019 using administrative data collected from a nationwide network of 76 hospitals that manages 7% of all in-hospital cases in Germany. Results: We included 25,821 AIS cases in the study period (2020/2021) and used 26,295 AIS cases as controls (2019). Compared to pre-pandemic numbers, mean daily AIS admissions decreased only during wave 1 (from 39.6 to 34.1; p < 0.01) and wave 2 (from 39.9 to 38.3; p = 0.03) and returned to normal levels during waves 3 and 4. AIS case fatality increased in wave 1 only (from 6.0% to 7.6%; p = 0.03). We observed a consistent decrease in the prevalences of arterial hypertension, diabetes, and obesity among AIS cases throughout the pandemic and no changes in rates of systemic thrombolysis, mechanical thrombectomy, or decompressive craniectomy. The rate of transfer to stroke units increased only during waves 2 (by 4.6%; p < 0.01) and 3 (by 3.0%; p < 0.01). The proportion of patients with coinciding SARS-CoV-2 and AIS was low, peaking at 3.4% in wave 2 and subsequently decreasing to 0.4% in wave 4. Conclusion: In Germany, the COVID-19 pandemic seems to have had a larger effect on nationwide in-hospital AIS care during the early pandemic stages, in which AIS case numbers decreased and case fatality rose. This may reflect a nationwide "learning curve" within health care systems in providing AIS care in times of a pandemic.

Rare germline variants in the E-cadherin gene CDH1 are associated with the risk of brain tumors of neuroepithelial and epithelial origin.

The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced ß-catenin binding resulting in increased cytosolic and nuclear ß-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/ß-catenin signaling.

Primary and secondary gliosarcoma: differences in treatment and outcome.

INTRODUCTION: There are only few studies comparing differences in the outcome of primary versus secondary gliosarcoma. This study aimed to review the outcome and survival of patients with primary or secondary gliosarcoma following surgical resection and adjuvant treatment. The data were also matched with data of patients with primary and secondary glioblastoma (GBM). PATIENTS AND METHODS: Treatment histories of 10 patients with primary gliosarcoma and 10 patients with secondary gliosarcoma were analysed and compared. Additionally, data of 20 patients with primary and 20 patients with secondary GBM were analysed and compared. All patients underwent surgical resection of the tumour in our department. Follow-up data, progression-free survival (PFS), and median overall survival (mOS) were evaluated. RESULTS: The median PFS in patients with primary gliosarcoma was significantly higher than in patients with secondary gliosarcoma (p = 0.037). The 6-month PFS rates were 80.0% in patients with primary and 30.0% in patients with secondary gliosarcoma. Upon recurrence, five patients with primary gliosarcoma and four patients with secondary gliosarcoma underwent repeat surgical resection. The mOS of patients with primary gliosarcoma was significantly higher than that of patients with secondary gliosarcoma (p = 0.031). The percentage of patients surviving at 1-year/2-year follow-up in primary gliosarcoma was 70%/20%, while it was only 10%/10% in secondary gliosarcoma. When PFS and mOS of primary gliosarcoma was compared to primary GBM, there were no statistically differences (p = 0.509; p = 0.435). The PFS and mOS of secondary gliosarcoma and secondary GBM were also comparable (p = 0.290 and p = 0.390). CONCLUSION: Patients with primary gliosarcoma have a higher PFS and mOS compared to those with secondary gliosarcoma. In the case of tumour recurrence, patients with secondary gliosarcoma harbour an unfavourable prognosis with limited further options. The outcome of patients with primary or secondary gliosarcoma is comparable to that of patients with primary or secondary GBM.

Effect of a bundle approach on external ventricular drain-related infection.

BACKGROUND: Emergency placement of an external ventricular drain (EVD) is one of the most frequently performed neurosurgical procedures. EVD-related infection continues to be a major challenge causing significant morbidity and costs. Bundle approaches have been shown to reduce infection rates; however, they are still not widely used, and observation periods often were rather short. METHODS: The present study evaluated the effect of a multi-item bundle approach for EVD placement and care on the occurrence of EVD-related infection. A before/after approach was used to compare groups of consecutive patients over 5-year epochs to control for bias and secondary confounding variables. RESULTS: The number of patients in the group before implementation of the bundle approach was 141 and 208 thereafter. There were no statistical differences in demographic and other variables. While 41/141 patients (29.1%) had an EVD-related infection before, this was the case in only 10/208 patients (4.8%) thereafter (p < 0.0001). The EVD-related infection rate was reduced from 13.7/1000 catheter days to 3.2/1000, and the 50% probability of an EVD-related infection in correlation to the mean duration of EVD placement was significantly lower (p < 0.0001). Routine EVD replacement was not helpful to reduce EVD-related infection. EVD-related infection rates remained low also over the next 8 years after the study was finished. CONCLUSIONS: The introduction of a multi-item bundle approach for EVD insertion and care resulted in a marked reduction of EVD-related infection. Long observation periods over 5 years and beyond confirm that short-term changes are sustained with continued use of such protocols.

The prognostic significance of clinicopathological features in meningiomas: Microscopic brain invasion can predict patient outcome in otherwise benign meningiomas.

AIMS: Brain invasion (BI) was firstly defined as a single criterion of atypia in otherwise benign meningiomas in the revised fourth edition of 2016 WHO classification of brain tumours after being previously inconsistently addressed. However, recent studies have raised doubts about the prognostic significance of BI in otherwise benign meningiomas. In our study, we investigate the reproducibility of such a prognostic effect. METHODS: We identified two cohorts one consisting of 483 patients with meningioma WHO grade I (M°I) or atypical meningioma WHO grade II (M°II) from Hannover Medical School and the other including atypical meningiomas defined according to the classical WHO criteria (M°IIb) from the University Hospital Heidelberg. Follow-up data with a median observation time of 38.2 months were available from 308 cases. These included 243 M°I and 65 M°II patients with the latter group consisting of 25 patients with otherwise benign meningiomas with BI (M°IIa) and 40 with M°IIb. RESULTS: A significant difference of progression-free interval (PFI) was found between patients with M°I and M°II, M°I and M°IIa and those with M°I and M°IIb of both cohorts and each separately. However, PFI of M°IIa and M°IIb patients showed no significant difference. In the multivariate regression analysis adjusted for M°I/M°IIa versus M°IIb, sex, age, extent of resection and tumour location, BI exhibited the strongest risk of relapse (Hazard ratio: 4.95) serving as an independent predictor of PFI (p = 0.002). CONCLUSIONS: Our results clearly support the definition of BI as a single criterion of atypia in WHO classification of 2016.

Diagnostic reliability of the Berlin classification for complex MCA aneurysms-usability in a series of only giant aneurysms.

BACKGROUND AND OBJECTIVE: The main challenge of bypass surgery of complex MCA aneurysms is not the selection of the bypass type but the initial decision-making of how to exclude the affected vessel segment from circulation. To this end, we have previously proposed a classification for complex MCA aneurysms based on the preoperative angiography. The current study aimed to validate this new classification and assess its diagnostic reliability using the giant aneurysm registry as an independent data set. METHODS: We reviewed the pretreatment neuroimaging of 51 patients with giant (> 2.5 cm) MCA aneurysms from 18 centers, prospectively entered into the international giant aneurysm registry. We classified the aneurysms according to our previously proposed Berlin classification for complex MCA aneurysms. To test for interrater diagnostic reliability, the data set was reviewed by four independent observers. RESULTS: We were able to classify all 51 aneurysms according to the Berlin classification for complex MCA aneurysms. Eight percent of the aneurysm were classified as type 1a, 14% as type 1b, 14% as type 2a, 24% as type 2b, 33% as type 2c, and 8% as type 3. The interrater reliability was moderate with Fleiss's Kappa of 0.419. CONCLUSION: The recently published Berlin classification for complex MCA aneurysms showed diagnostic reliability, independent of the observer when applied to the MCA aneurysms of the international giant aneurysm registry.

Infratentorial IDH-mutant astrocytoma is a distinct subtype.

Diffuse IDH-mutant astrocytic tumors are rarely diagnosed in the cerebellum or brainstem. In this multi-institutional study, we characterized a series of primary infratentorial IDH-mutant astrocytic tumors with respect to clinical and molecular parameters. We report that about 80% of IDH mutations in these tumors are of non-IDH1-R132H variants which are rare in supratentorial astrocytomas. Most frequently, IDH1-R132C/G and IDH2-R172S/G mutations were present. Moreover, the frequencies of ATRX-loss and MGMT promoter methylation, which are typically associated with IDH mutations in supratentorial astrocytic tumors, were significantly lower in the infratentorial compartment. Gene panel sequencing revealed two samples with IDH1-R132C/H3F3A-K27M co-mutations. Genome-wide DNA methylation as well as chromosomal copy number profiling provided further evidence for a molecular distinctiveness of infratentorial IDH-mutant astrocytomas. Clinical outcome of patients with infratentorial IDH-mutant astrocytomas is significantly better than that of patients with diffuse midline gliomas, H3K27M-mutant (p < 0.005) and significantly worse than that of patients with supratentorial IDH-mutant astrocytomas (p = 0.028). The presented data highlight the very existence and distinctiveness of infratentorial IDH-mutant astrocytomas that have important implications for diagnostics and prognostication. They imply that molecular testing is critical for detection of these tumors, since many of these tumors cannot be identified by immunohistochemistry applied for the mutated IDH1-R132H protein or loss of ATRX.

Intracranial emergencies during pregnancy requiring urgent neurosurgical treatment.

OBJECTIVE: Despite contemporary diagnostic and therapeutic techniques intracranial emergencies in the obstetric setting pose still a major challenge for the clinicians. There are limited guidelines and differing ethical views. Multidisciplinary teams are needed to support the pregnant woman in a way that she can deliver a viable and healthy child. The aim of the present study was to scrutinize the management of intracranial emergencies during pregnancy which needed urgent neurosurgical treatment. PATIENTS AND METHODS: Data of all pregnant women who presented with newly diagnosed intracranial pathologies and neurological symptoms caused by these pathologies in an emergency setting were collected over a 10-year period (2008-2018). Patient characteristics including maternal age, gestational age, and preoperative work-up of both mother and fetus were recorded. Furthermore, the surgical treatment, mode of delivery, and neonatal and maternal outcomes were analysed. RESULTS: The mean maternal age was 32.7 years and most patients were in their third trimester. There was one twin pregnancy (total of 12 fetuses). Five out of eleven pregnant women suffered from intracerebral haemorrhage (epidural haematoma (1), arteriovenous malformation (1), subarachnoid haemorrhage (2) and intracerebral haemorrhage (1)) and the other six patients had intracranial neoplasms (primary meningeal sarcoma (1), trigeminal schwannoma (1), anaplastic astrocytoma (2), glioblastoma (1) and sphenoid wing meningioma (1)).Neurosurgical procedures were performed via craniotomies in eight patients. A stereotactic biopsy via a frontal burr hole was achieved one patient. The two other patients with subarachnoid haemorrhage due to rupture of PICA aneurysms were treated with coil embolization. Depending on the gestational age and the clinical condition of the pregnant women it was decided to perform an emergency Caesarean section prior to further therapeutic measures in seven patients. Two out of 12 fetuses were unviable. Six women survived, while five women succumbed to the intracranial pathology. CONCLUSION: The individualized treatment approach in this peculiar obstetric scenario needs to consider various issues such as the clinical condition of the pregnant woman, prognosis of the disease, gestational age and the status of the pregnancy. The primary concern in this context must be the mother`s health and safety. Caesarean section is the primary mode of delivery in most cases. While contemporary care can insure survival for the majority of infants, maternal mortality still poses an extraordinary challenge. Interdisciplinary consulting of the patient and/or her family is necessary to develop a treatment strategy for both the expectant woman and her offspring.

Spinal Emergency Surgery During Pregnancy: Contemporary Strategies and Outcome.

BACKGROUND: Low back pain is a common complaint during pregnancy. However, spinal pathologies, which manifest with severe pain, radiculopathy, and acute neurologic deficits because of disk herniation or mass lesions require special attention. Here, we present our interdisciplinary experience in the surgical management of spinal emergencies during pregnancy. METHODS: The data of pregnant women who underwent surgery for spinal pathologies over a 10-year period were collected. Patient-related characteristics such as maternal age, gestational age, preoperative workup, signs and symptoms of mothers, and diagnostic procedures were evaluated. After an interdisciplinary conference, individualized treatment plans regarding available options were developed. Fetal Doppler and cardiotocography were obtained before and after surgery. RESULTS: Nine pregnant women presented with spinal disorders and underwent spinal emergency surgery within the study period. The mean maternal age was 32.2 years. Six women presented with lumbar disk herniations manifesting as severe sciatica or foot drop and 3 patients had thoracic mass lesions resulting in cauda equine syndrome and/or ataxia. The mean gestational age at the time of presentation was 26.5 weeks. Caesarean sections were performed in 3 women prior to the neurosurgical procedure, whereas the pregnancies were maintained in the 6 other patients. Eight infants who were healthy at birth had an unremarkable development. CONCLUSIONS: Surgery for spinal emergencies in pregnancy can be performed safely according to individual treatment plans developed by an interdisciplinary team taking into account the expectant mother's decision. Maintenance of pregnancy is possible and feasible in most patients.

Giant intracranial aneurysms: natural history and 1-year case fatality after endovascular or surgical treatment.

OBJECTIVE: Clinical evidence on giant intracranial aneurysms (GIAs), intracranial aneurysms with a diameter of at least 25 mm, is limited. The authors aimed to investigate the natural history, case fatality, and treatment outcomes of ruptured and unruptured GIAs. METHODS: In this international observational registry study, patients with a ruptured or unruptured GIA received conservative management (CM), surgical management (SM), or endovascular management (EM). The authors investigated rupture rates and case fatality. RESULTS: The retrospective cohort comprised 219 patients with GIAs (21.9% ruptured GIAs and 78.1% unruptured GIAs) whose index hospitalization occurred between January 2006 and November 2016. The index hospitalization in the prospective cohort (362 patients with GIAs [17.1% ruptured and 82.9% unruptured]) occurred between December 2008 and February 2017. In the retrospective cohort, the risk ratio for death at a mean follow-up of 4.8 years (SD 2.2 years) after CM, compared with EM and SM, was 1.63 (95% CI 1.23-2.16) in ruptured GIAs and 3.96 (95% CI 2.57-6.11) in unruptured GIAs. In the prospective cohort, the 1-year case fatality in ruptured GIAs/unruptured GIAs was 100%/22.0% during CM, 36.0%/3.0% after SM, and 39.0%/12.0% after EM. Corresponding 1-year rupture rates in unruptured GIAs were 25.0% during CM, 1.2% after SM, and 2.5% after EM. In unruptured GIAs, the HR for death within the 1st year in patients with posterior circulation GIAs was 6.7 (95% CI 1.5-30.4, p < 0.01), with patients with a GIA at the supraclinoid internal carotid artery as reference. Different sizes of unruptured GIAs were not associated with 1-year case fatality. CONCLUSIONS: Rupture rates for unruptured GIAs were high, and the natural history and treatment outcomes for ruptured GIAs were poor. Patients undergoing SM or EM showed lower case fatality and rupture rates than those undergoing CM. This difference in outcome may in part be influenced by patients in the CM group having been found poor candidates for SM or EM.Clinical trial registration no.: NCT02066493 (clinicaltrials.gov).

Detection of bacterial DNA on neurostimulation systems in patients without overt infection.

OBJECTIVE: Hardware-related infection remains a major problem in patients with neurostimulation systems. The role of bacterial colonization and the formation of biofilm on the surface of implanted devices remain unclear. Here, we analysed the incidence of bacterial DNA on the surface of implantable pulse generators (IPGs) using 16S rRNA gene sequencing in a consecutive series of patients who underwent routine IPG replacement without clinical signs of infection. PATIENTS AND METHODS: We included 36 patients who underwent scheduled replacement surgery of 44 IPGs. The removed IPGs were processed and whole genomic DNA was extracted. The detection of bacterial DNA was carried out by Polymerase Chain Reaction (PCR) using universal bacterial primers targeting the 16S rRNA gene. The DNA strands were analysed by single-strand conformation polymorphism (SSCP) analysis. RESULTS: Indications for chronic neurostimulation were Parkinson disease, tremor, dystonia, neuropathic pain and peripheral artery occlusion disease. Mean age of patients at the time of implantation was 48 ±â€¯17.6 years. The mean interval between implantation and replacement of the IPG was 24.8 months. PCR/SSCP detected bacterial DNA of various species in 5/36 patients (13.9%) and in 5/44 pacemakers (11.4%), respectively. There was no evidence of clinical infection or wound healing impairment during follow-up time of 45.6 ±â€¯19.6 months. CONCLUSION: Bacterial DNA can be detected on the surface of IPGs of neurostimulation systems in patients without clinical signs of infection by using PCR techniques. It remains unclear, similar to other permanently implanted devices, which mechanisms and processes promote progression to the point of overt infection.

Clinical implications and radiographic characteristics of the relation between giant intracranial aneurysms of the posterior circulation and the brainstem.

BACKGROUND: Giant intracranial aneurysms of the posterior circulation (GPCirA) are rare entities compressing the brainstem and adjacent structures. Previous evidence has shown that the amount of brainstem shift away from the cranial base is not associated with neurological deficits. This raises the question whether other factors may be associated with neurological deficits. METHODS: All data were extracted from the Giant Intracranial Aneurysm Registry, an international multicenter prospective study on giant intracranial aneurysms. We grouped GPCirA according to the mass effect on the brainstem (lateral versus medial). Brainstem compression was evaluated with two indices: (a) brainstem compression ratio (BCR) or diameter of the compressed brainstem to the assumed normal diameter of the brainstem and (b) aneurysm to brainstem ratio (ABR) or diameter of the aneurysm to the diameter of the compressed brainstem. We examined associations between neurological deficits and GPCirA characteristics using binary regression analysis. RESULTS: Twenty-eight GPCirA were included. Twenty GPCirA showed medial (71.4%) and 8 lateral compression of the brainstem (28.6%). Baseline characteristics did not differ between the groups for patient age, aneurysm diameter, aneurysm volume, modified Rankin Scale (mRS), motor deficit (MD), or cranial nerve deficits (CND). Mean BCR was 53.0 in the medial and 54.0 in the lateral group (p = 0.92). The mean ABR was 2.9 in the medial and 2.3 in the lateral group (p = 0.96). In the entire cohort, neither BCR nor ABR nor GPCirA volumes were associated with the occurrence of CND or MD. In contrast, disability (mRS) was significantly associated with ABR (OR 1.94 (95% CI 1.01-3.70; p = 0.045) and GPCirA volumes (OR 1.21 (95% CI 1.01-1.44); p = 0.035), but not with BCR. CONCLUSION: In this cohort of patients with GPCirA, neither the degree of lateral projection nor the amount of brainstem compression predicted neurological deficits. Disability was associated only with aneurysm volume. When designing treatment strategies for GPCirA, aneurysm laterality or the amount of brainstem compression should be viewed as less relevant while the high risk of rupture of such giant lesions should be emphasized. TRIAL REGISTRATION: The registry is listed at clinicaltrials.gov under the registration no. NCT02066493.

Secondary extradural spinal manifestation of esthesioneuroblastoma.

Secondary spinal manifestations of esthesioneuroblastoma are rare. A 67-year-old woman was presented with an extradural spinal manifestation at the vertebra Th7 within 8 weeks after resection of an esthesioneuroblastoma. Subtotal removal of the epidural tumour was achieved combined with dorsal transpedicular stabilization. Early screening for distant metastases may be considered in patients with esthesioneuroblastoma.

Cerebellar glioblastoma: a clinical series with contemporary molecular analysis.

BACKGROUND: Glioblastomas (GBM) are localized in only less than 1% of patients in the cerebellum. Therefore, tumor characteristics, survival, and the efficacy of therapies are not yet well defined. The present study aims to characterize the molecular features of cerebellar GBM (GBMc) in 8 patients treated with contemporary modality in our institution. METHODS: Patients' treatment history, progression-free survival (PFS), and overall survival (OS) were analyzed. All histopathological specimens were re-investigated. EGFR amplification was determined by FISH, H3F3A, and HIST1H3B mutation status and MGMT promoter methylation after bisulfite treatment by pyrosequencing and BRAF V600E by pyrosequencing and immunohistochemistry. TERT promoter mutations were analyzed by Sanger sequencing, CDKN2A/B deletions by digital PCR. The expression of IDH1 R132H, ATRX, and p53 was determined through immunohistochemistry. RESULTS: Six adults and two children (mean age 36 years) underwent tumor resection via medial or lateral suboccipital craniotomy. The median overall survival (mOS) of the adult patients was 7 months. GBMc from two children demonstrated a H3F3A K27M mutation. One of these also harbored a BRAF V600E mutation and has already had a PFS of 74 months. Mutated IDH1 R132H protein was expressed in 2 GBM from adult patients with previous supratentorial anaplastic astrocytoma. One patient carried a TERT promoter mutation. Another patient initially presented with a thalamic pilocytic astrocytoma. The cerebellar tumor revealed neither a BRAF V600E nor a H3F3A mutation but a homozygous CDKN2A/B deletion. CONCLUSIONS: GBM located in the cerebellum can be found in all age groups. We provide novel molecular genetic data on these rare tumors. Mutated IDH1 R132H protein and H3F3A K27M mutations indicate that a substantial number of GBMc are "metastatic" or "diaschismatic" lesions. Mutation of BRAF V600E may have a stronger biological significance than H3F3A K27M alterations. In a subset of patients, GBM may arise primarily as a distinct entity in the cerebellum.

Giant intracranial aneurysms of the posterior circulation and their relation to the brainstem: analysis of risk factors for neurological deficits.

OBJECTIVE: Giant posterior circulation aneurysms (GPCirAs) usually cause substantial mass effect on the brainstem, which may lead to neurological deficits. So far, there has been no systematic investigation of factors associated with such deficits in GPCirA. The authors aim to examine the risk factors for cranial nerve deficit (CND), motor deficit, and disability in patients with GPCirA. METHODS: Using MR images obtained in 30 patients with unruptured GPCirA, the authors examined GPCirA volume, presence of hydrocephalus or partial thrombosis (PT) of the aneurysm, and the degree of brainstem displacement measured by the distance between the McRae line and the tip of the GPCirA (∆MT). They evaluated associations between these factors and neurological deficits. RESULTS: Thirty GPCirAs in 30 patients were included. The prevalence of CNDs was 50%. Patients with CNDs significantly differed from those without CNDs in terms of age (mean 51.0 years [SD 15.0 years] vs 69.0 years [SD 21.0 years], p = 0.01) and in ∆MT (median 50.7 mm [IQR 39.2-53.9 mm] vs 39.0 mm [IQR 32.3-45.9 mm], p = 0.02). The prevalence of motor deficits was 33.3%. Patients with motor deficits showed a larger ∆MT (median 50.5 mm [IQR 40.8-54.6 mm]) compared with those without (∆MT: median 39.1 mm [IQR 32.8-50.5 mm], p = 0.04). GPCirA volume was larger in patients with poor modified Rankin Scale (mRS) scores (median 14.9 cm3 [IQR 8.6-18.7 cm3]) than in those with mRS scores of 0-2 (median 6.8 cm3 [IQR 4.4-11.7 cm3], p = 0.03). After adjusting for patient age and the occurrence of hydrocephalus or PT, the authors found that higher degrees of disability were significantly associated with aneurysm volume (OR 1.13, 95% CI 1.0-1.3; p = 0.04), but not with ∆MT. The occurrence of CND or motor deficit was not associated with any of the examined variables. There was no correlation between GPCirA volume and ∆MT (rs = 0.01, p = 0.96). The prevalence of neurological deficits did not differ between GPCirA at the basilar apex, the basilar trunk, the vertebrobasilar junction, or the vertebral artery. CONCLUSIONS: In this study, the neurological condition of the patients was associated only with GPCirA volume and not with the degree of brainstem displacement, the occurrence of PT or hydrocephalus, or the exact location of the GPCirA. These findings highlight the clinical relevance of GPCirA volume and suggest that factors such as brainstem displacement or PT should play less of a role when finding arguments for or against treatment of GPCirA.Clinical trial registration no.: NCT02066493 (clinicaltrials.gov).

Challenges in cerebrospinal fluid shunting in patients with glioblastoma.

BACKGROUND: Cerebrospinal fluid (CSF) circulation disturbances may occur during the course of disease in patients with glioblastoma. Ventriculoperitoneal shunting has generally been recommended to improve symptoms in glioblastoma patients. Shunt implantation for patients with glioblastoma, however, presents as a complex situation and produces different problems to shunting in other contexts. Information on complications of shunting glioma patients has rarely been the subject of investigation. In this retrospective study, we analysed restropectively the course and outcome of glioblastoma-related CSF circulation disturbances after shunt management in a consecutive series of patients within a period of over a decade. METHODS: Thirty of 723 patients with histopathologically-confirmed glioblastoma diagnosed from 2002 to 2016 at the Department of Neurosurgery, Hannover Medical School, underwent shunting for CSF circulation disorders. Treatment history of glioblastoma and all procedures associated with shunt implementation were analyzed. Data on follow-up, time to progression and survival rates were obtained by review of hospital charts and supplemented by phone interviews with the patients, their relations or the primary physicians. RESULTS: Mean age at the time of diagnosis of glioblastoma was 43 years. Five types of CSF circulation disturbances were identified: obstructive hydrocephalus (n = 9), communicating hydrocephalus (n = 15), external hydrocephalus (n = 3), trapped lateral ventricle (n = 1), and expanding fluid collection in the resection cavity (n = 2). All patients showed clinical deterioration. Procedures for CSF diversion were ventriculoperitoneal shunt (n = 21), subduroperitoneal shunt (n = 3), and cystoperitoneal shunt (n = 2). In patients with lower Karnofsky Performance Score (KPS) (< 60), there was a significant improvement of median KPS after shunt implantation (p = 0.019). Shunt revision was necessary in 9 patients (single revision, n = 6; multiple revisions, n = 3) due to catheter obstruction, catheter dislocation, valve defect, and infection. Twenty-eight patients died due to disease progression during a median follow-up time of 88 months. The median overall survival time after diagnosis of glioblastoma was 10.18 months. CONCLUSIONS: CSF shunting in glioblastoma patients encounters more challenge and is associated with increased risk of complications, but these can be usually managed by revision surgeries. CSF shunting improves neurological function temporarily, enhances quality of life in most patients although it is not known if survival rate is improved.

Surgical Treatment of Spinal Ependymomas: Experience in 49 Patients.

BACKGROUND: Ependymomas are rare central nervous system tumors. Local tumor distribution in the central nervous system depends on age: among adults, ependymomas occur mostly in the spinal cord, whereas among children, intracranial manifestations are more common. To date, there are no prospective studies about treatment strategies for ependymomas. In most cases, complete tumor resection is recommended. The role of radiation therapy in low-grade ependymomas is unclear. METHODS: We report the results of 49 patients over an 18-year-period. Patients' clinical and radiologic data were analyzed retrospectively. RESULTS: Mean age of patients at time of surgery was 46.4 years. There were 29 women (59%) and 20 men (41%). Gross total resection was achieved in 72% of patients. Tumors affected cervical spinal cord in 14 patients (29%), cauda equina and filum terminale in 10 (21%), conus medullaris in 8 (16%), thoracic spinal cord in 7 (14%), and cervicolumbar or thoracolumbar junction in 10 (20%). Postoperative radiation therapy was performed in 6 cases. Long-term follow-up was available for 39 patients (mean 50.7 months). High preoperative McCormick grade correlated with high risk for clinical deterioration postoperatively. On long-term follow-up, clinical status was the same as preoperatively in 51% of patients, worse in 21%, and improved in 28%. We found no differences in progression-free survival with regard to histology. Four tumors relapsed after progression-free survival of a mean of 21 months. CONCLUSIONS: Gross total resection is considered the first choice in treatment of spinal ependymomas. The most important predictor of clinical outcome is preoperative neurologic functioning. The role of postoperative radiation needs further clarification.

Early Ectopic Recurrence of Craniopharyngioma in the Cerebellopontine Angle.

Ectopic recurrence of craniopharyngioma in the cerebellopontine angle after surgical resection of a suprasellar craniopharyngioma is rare. Thus, only 5 cases were reported with a delay ranging between 4 and 26 years after removal of the primary tumor. We report a unique case of ectopic recurrence of craniopharyngioma in the cerebellopontine angle, which occurred at only 4 months after surgical resection of the primary tumor. A 24-year-old man underwent resection of a suprasellar craniopharyngioma via a right pterional approach four months earlier. During follow-up, cerebral magnetic resonance imaging (MRI) showed a round homogeneous contrast-enhancing tumor in the right cerebellopontine angle with neither relation to the internal auditory canal nor to the dura mater. After microsurgical resection, histopathological findings revealed ectopic recurrence of craniopharyngioma with similar tumors like the primary tumor. Although infrequent, craniopharyngioma may disseminate via the cerebrospinal fluid during surgical resection and grow in an ectopic place. Early follow-up and MRI scan following resection of a craniopharyngioma is recommended.