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Glioblastoma (GBM) is one of the most frequent primary brain tumors. Limited therapeutic options and high recurrency rates lead to a dismal prognosis. One frequent, putative driver mutation is the genomic amplification of the oncogenic receptor tyrosine kinase EGFR. Often accompanied by variants like EGFRvIII, heterogenous expression and ligand independent signaling render this tumor subtype even more difficult to treat, as EGFR-directed therapeutics show only weak effects at best. So EGFR-amplified GBM is considered to have an even worse prognosis, and therefore, deeper understanding of molecular mechanisms and detection of potential targets for novel therapeutic strategies is urgently needed. In this study, we looked at the level of microRNAs (miRs), small non-coding RNAs frequently deregulated in cancer, both acting as oncogenes and tumor suppressors. Comparative analysis of GBM with and without EGFR amplification should give insight into the expression profiles of miRs, which are considered both as potential targets for directed therapies or as therapeutic reagents. Comparison of miR profiles of EGFR-amplified and EGFR-normal GBM revealed an upregulation of the miR-183/96/182 cluster, which is associated with oncogenic properties in several tumor entities. One prominent target of this miR cluster is FOXO1, a pro-apoptotic factor. By observing FOXO1 downregulation in EGFR-amplified tumors, we can see a significant correlation of EGFR amplification, miR-183/96/182 cluster upregulation, and repression of FOXO1. Although no significant difference in overall survival is shown, these data may contribute to the molecular understanding of this tumor subtype and offer potential targets for miR-based therapies.

Glioblastoma is one of the most frequent primary brain tumors with a poor prognosis. Nevertheless, some patients show a prolonged survival. The aim of the present study was to compare the expression profiles of tumor derived microRNA (miR) of long‑term survivors with those of short‑term survivors in order to identify differentially expressed miRs as well as their target genes, which may elucidate mechanisms that play a role in varying tumor progression and, therefore, may influence survival. Formalin‑fixed paraffin‑embedded samples of 23 patients with glioblastoma were classified according to overall survival. Profiles of miR expression were determined using Nanostring technology. Expression levels of potential target genes of differentially expressed miRs were assessed using immunohistochemistry. MiR profiles of long‑term survivors differed from those of short‑term survivors. A total of three prominent differentially expressed miRs were highlighted: MiR‑130b‑3p, which is downregulated in long‑term survivors, and miR‑146b‑5p and miR‑148a‑3p, which are upregulated in long‑term survivors. Known tumor suppressor genes are among targets potentially affected by miR‑130b‑3p, whereas targets of miR‑146b‑5p and miR‑148a‑3p consist of several genes known to have a role in tumor invasion and aggressiveness. In conclusion, it was revealed that a type of miR‑signature was associated with short‑ and long‑term survival, potentially serving as biomarker for disease progression and providing a base for further functional studies.

ZusammenfassungErkrankungen der Hirnhäute gehen mit einem pathologischen Signal auf T2w und nativen T1w Aufnahmen einher und zeigen eine pathologische (durale oder leptomeningeale) Mehranreicherung. In diesem Beitrag werden typische Erkrankungen der Meningen vor allem anhand der MRT dargestellt: Die Veränderungen selbst zeigen sich am besten auf kontrastmittelverstärkten T1w und die extrazerebrale Lage am besten auf hochauflösenden T2w Aufnahmen.

Frakturen des Kopfes und der Halswirbelsaule (HWS) sind haufige Traumafolgen. Die rechtzeitige Diagnose ist von entscheidender Bedeutung fur eine adaquate Therapie und die Verhinderung neurologischer Komplikationen. Die verschiedenen bildgebenden Verfahren zur Diagnostik von Kalotten- und Halswirbelsaulenfrakturen werden beurteilt. Die Bildgebung wird im Kontext mit der aktuellen Literatur diskutiert. In diesem Beitrag werden haufige Frakturen der Kalotte und der Halswirbelsaule sowie deren Indikationen und Klassifikationen beschrieben. Frakturen des Kopfes konnen die Kalotte, die Schadelbasis und das Felsenbein betreffen. Verletzungen der Dura fuhren zu einem offenen Schadel-Hirn-Trauma. Frakturen der Halswirbelsaule konnen in subaxiale und in Frakturen des kraniozervikalen Ubergangs unterteilt werden. Untersuchungsmodalitat der Wahl bei Frakturen des Kopfes oder der Halswirbelsaule ist die Computertomographie (CT). Bei Frakturen des Kopfes mussen ein offenes und geschlossenes Schadel-Hirn-Trauma unterschieden und begleitende intrakranielle Traumafolgen erfasst werden. Bei Felsenbeinfrakturen ist immer auf die Mittel- und Innenohrstrukturen zu achten. Bei Frakturen der Halswirbelsaule ist entscheidend, ob es sich um eine stabile oder instabile Fraktur handelt und ob eine begleitende Verletzung des Myelons vorliegt.

Background Despite optimal drug-conservative therapy, a relevant percentage of patients with vertebral compression fractures (WKF) do not experience any relevant improvement in their pain symptoms. Vertebroplasty (VP) and kyphoplasty (KP) are described in the literature as percutaneous interventional procedures for the treatment of WKF. Objective Assessment of the effectiveness of the VP and KP in the treatment of WKF and discussion of the procedures in the context of the current literature. Material and methods Presentation of the fundamentals of VP and KP and their further developments. Description of indications and contraindications. Discussion of the current literature and recommendations of the individual professional associations. Results In patients with vertebral compression fractures, VP or KP of the affected vertebral body leads to a pain reduction in more than 90% of cases. Clinically relevant complications occur in less than 1% of interventions. Conclusion VP and KP are a safe and effective method for treating painful WKF. Optimal patient selection improves the clinical outcome.

The objective of this study was to evaluate the morphology of glioblastoma on structural pretreatment magnetic resonance imaging (MRI), defining imaging prognostic factors. We conducted a retrospective analysis of MR images from 114 patients harboring a primary glioblastoma, derived from two neurosurgical departments. Tumor segmentation was carried out in a semi-automated fashion. Tumor compartments comprised contrast-enhancing volume (CEV+), perifocal hyperintensity on fluid-attenuated inversion recovery (FLAIR) images (FLAIR+) excluding CEV+, and a non-enhancing area within the CEV+ lesion (CEV−). Additionally, two ratios were calculated from these volumes, the edema-tumor ratio (ETR) and necrosis-tumor ratio (NTR). All patients received surgical resection, followed by concomitant radiation and chemotherapy. Tumor segmentation revealed the strongest correlation between the CEV+ volume and the CEV−, presenting intratumoral necrosis (p

Objective Previous research has shown a strong correlation between the Ki-67 proliferation index and grade of malignancy in astrocytoma. Ki-67 has also shown encouraging results as a prognostic marker for patients' overall survival (OS). We focus on whether the index is linked to the appearance of glioblastoma on pretreatment magnetic resonance imaging (MRI) or to OS. Methods In our retrospective study, only isocitrate dehydrogenase IDH wild-type glioblastoma was included (n = 152). Ki-67 index was quantified via immunohistochemistry. On all pretreatment MRI, tumor compartments (tumor, necrosis, and edema) were volumetrically assessed. An OS subpopulation was filtered from the total cohort (residual tumor volume ≤2 cm3). In addition, a propensity score matching was executed. Results All volumetric assessed tumor volumes correlated with each other (P ≤ 0.011), although the Ki-67 index showed no correlation with any of the measured volumes. Concerning the OS, a cutoff value of 20% for the Ki-67 index showed a significant influence on patients' OS in multivariate analysis (P = 0.043). Conclusions The unique appearance of every glioblastoma on MRI seems to be independent of the Ki-67 index. Furthermore, the Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 20% for Ki-67.

OBJECTIVE Cranioplasty (CP) is a crucial procedure after decompressive craniectomy and has a significant impact on neurological improvement. Although CP is considered a standard neurosurgical procedure, inconsistent data on surgery-related complications after CP are available. To address this topic, the authors analyzed 502 patients in a prospective multicenter database (German Cranial Reconstruction Registry) with regard to early surgery-related complications. METHODS Early complications within 30 days, medical history, mortality rates, and neurological outcome at discharge according to the modified Rankin Scale (mRS) were evaluated. The primary endpoint was death or surgical revision within the first 30 days after CP. Independent factors for the occurrence of complications with or without surgical revision were identified using a logistic regression model. RESULTS Traumatic brain injury (TBI) and ischemic stroke were the most common underlying diagnoses that required CP. In 230 patients (45.8%), an autologous bone flap was utilized for CP; the most common engineered materials were titanium (80 patients [15.9%]), polyetheretherketone (57 [11.4%]), and polymethylmethacrylate (57 [11.4%]). Surgical revision was necessary in 45 patients (9.0%), and the overall mortality rate was 0.8% (4 patients). The cause of death was related to ischemia in 2 patients, diffuse intraparenchymal hemorrhage in 1 patient, and cardiac complications in 1 patient. The most frequent causes of surgical revision were epidural hematoma (40.0% of all revisions), new hydrocephalus (22.0%), and subdural hematoma (13.3%). Preoperatively increased mRS score (OR 1.46, 95% CI 1.08–1.97, p = 0.014) and American Society of Anesthesiologists Physical Status Classification System score (OR 2.89, 95% CI 1.42–5.89, p = 0.003) were independent predictors of surgical revision. Ischemic stroke, as the underlying diagnosis, was associated with a minor rate of revisions compared with TBI (OR 0.18, 95% CI 0.06–0.57, p = 0.004). CONCLUSIONS The authors have presented class II evidence–based data on surgery-related complications after CP and have identified specific preexisting risk factors. These results may provide additional guidance for optimized treatment of these patients.

Injuries of the skull and the cervical spine are common trauma sequelae and prompt diagnosis is of utmost importance to prevent neurologic complications.The different imaging modalities for the diagnosis of skull and cervical spine fractures are presented and discussed in the context of the current literature.Common fractures of the skull and cervical spine and their classification systems are described. Indications for imaging are discussed within the context of the literature.Fractures of the head can affect the cranial vault, the base of the skull, and the petrous bone. Injuries to the dura are associated with an open craniocerebral trauma. Fractures of the cervical spine can be subdivided into fractures of the craniocervical junction and subaxial fractures.The imaging modality of choice in the acute setting is computed tomography (CT). Skull fractures can be differentiated into open and closed craniocerebral traumas and accompanying intracranial trauma sequelae must be recognized. In the case of petrous bone fractures, attention must always be paid to the middle and inner ear structures. In cervical spine fractures, decisive is whether the fracture is stable or unstable and whether there has been an accompanying injury to the myelon.

Gliomas are the most common primary brain tumors and often become apparent through symptomatic epileptic seizures. Glial cells express the inwardly rectifying K+ channel Kir4.1 playing a major role in K+ buffering, and are presumably involved in facilitating epileptic hyperexcitability. We therefore aimed to investigate the molecular and functional expression of Kir4.1 channels in cultured rat and human glioma cells. Quantitative PCR showed reduced expression of Kir4.1 in rat C6 and F98 cells as compared to control. In human U-87MG cells and in patient-derived low-passage glioblastoma cultures, Kir4.1 expression was also reduced as compared to autopsy controls. Testing Kir4.1 function using whole-cell patch-clamp experiments on rat C6 and two human low-passage glioblastoma cell lines (HROG38 and HROG05), we found a significantly depolarized resting membrane potential (RMP) in HROG05 (-29 ± 2 mV, n = 11) compared to C6 (-71 ± 1 mV, n = 12, P < 0.05) and HROG38 (-60 ± 2 mV, n = 12, P < 0.05). Sustained K+ inward or outward currents were sensitive to Ba2+ added to the bath solution in HROG38 and C6 cells, but not in HROG05 cells, consistent with RMP depolarization. While immunocytochemistry confirmed Kir4.1 in all three cell lines including HROG05, we found that aquaporin-4 and Kir5.1 were also significantly reduced suggesting that the Ba2+-sensitive K+ current is generally impaired in glioma tissue. In summary, we demonstrated that glioma cells differentially express functional inwardly rectifying K+ channels suggesting that impaired K+ buffering in cells lacking functional Ba2+-sensitive K+ currents may be a risk factor for increased excitability and thereby contribute to the differential epileptogenicity of gliomas.

With a rising number of cranioplasty (CP) procedures and an increasing percentage of patients with a good clinical outcome and prolonged survival after CP, looking at the functional and aesthetic outcome of these patients becomes more and more important. The aim of our study was to evaluate a novel score, combining functional and cosmetics aspects after CP, created at our institution: the Rostock Functional and Cosmetic Cranioplasty (RFCC-) Score. A total of 27 patients were enrolled, representing all indications for a secondary CP after decompressive craniectomy or extended temporal trephination with a complete separation of the temporalis muscle. Besides the clinical evaluation, five different already established clinical rating systems were tested and compared with our score. For reasons of objectivity, the score was also tested against the patient's own rating. Our findings showed that the RFCC-Score, derived from a health professional, is superior to other scoring systems, which only display a facet of the functional state of the patient. Our score is objective and independent of a disposition for a depression of the patient. It can be obtained without the need of a verbal communication, making it applicable for nearly all patients after CP. The score is time-saving, clearly arranged, and reliable, which are inevitable requirements for the comparing and evaluation of different surgical techniques and associated complications of CP.

The potential impact of different radiological features of glioblastoma multiforme (GBM) on overall survival (OS) like tumor volume, peritumoral edema (PTE), necrosis volume, necrosis-tumor ratio (NTR) and edema-tumor ratio (ETR) is still very controversial. To determine the influence of volumetric data on OS und to compare different measuring techniques described in literature. We prospectively evaluated preoperative MR images from 30 patients harboring a primary supratentorial GBM. All patients received gross-total tumor resection followed by standard radiation and chemotherapy (temozolomide). By 3D semi-automated segmentation, we measured tumor volume, necrosis volume, PTE, postoperative residual tumor volume and calculated ETR, NTR and the extent of resection. After critical review of the existing literature we compared alternative measuring techniques with the gold standard of 3D segmentation. Statistical analysis showed a significant impact of the preoperative tumor and necrosis volumes on OS (p = 0.041, respectively p = 0.039). Furthermore, NTR also showed a significant association with OS (p = 0.005). Comparison of previously described measuring techniques and scorings with our results showed that no other technique is reliable and accurate enough as a predictive tool. The critical review of previously published studies revealed mainly inaccurate measurement techniques and patient selection as potential reasons for inconsistent results. Preoperatively measured necrosis volume and NTR are the most important radiological features of GBM with a strong influence on OS. No other measuring techniques are specific enough and comparable with 3D segmentation.

Despite optimal drug-conservative therapy, a relevant percentage of patients with vertebral compression fractures (WKF) do not experience any relevant improvement in their pain symptoms. Vertebroplasty (VP) and kyphoplasty (KP) are described in the literature as percutaneous interventional procedures for the treatment of WKF.Assessment of the effectiveness of the VP and KP in the treatment of WKF and discussion of the procedures in the context of the current literature.Presentation of the fundamentals of VP and KP and their further developments. Description of indications and contraindications. Discussion of the current literature and recommendations of the individual professional associations.In patients with vertebral compression fractures, VP or KP of the affected vertebral body leads to a pain reduction in more than 90% of cases. Clinically relevant complications occur in less than 1% of interventions.VP and KP are a safe and effective method for treating painful WKF. Optimal patient selection improves the clinical outcome.

BACKGROUND Seizures are a common initial symptom of malignant brain tumors such as glioblastoma (GBM). However, why some of these tumors are epileptogenic and others never trigger seizures remains controversial. OBJECTIVE To identify potential clinical and radiological features of epileptogenic tumors and the effect of initial seizures on survival. METHODS The analyzed patient cohort was retrospectively compiled (bicentric), only isocitrate dehydrogenase wild-type GBMs were included. Volumetric assessment was performed on pretreatment magnetic resonance imaging with the aid of a semi-automated 3D measurement (tumor, necrosis, and edema volume). Two ratios were calculated, reflecting the proportion of peritumoral edema and necrosis (NTR) toward the tumor volume. For overall survival analyses, only patients after a surgical resection (residual tumor volume

There is a distinct diversity between the appearance of every glioblastoma multiforme (GBM) on pretreatment magnetic resonance imaging (MRI) with a potential impact on clinical outcome and survival of the patients. The object of this study was to determine the impact of 10 different single nucleotide polymorphisms (SNPs) on various volumetric parameters in patients harboring a GBM. We prospectively analyzed 20 steroid-naïve adult patients who had been treated for newly diagnosed GBM. The volumetry was performed using MRI with the help of a semiautomated quantitative software measuring contrast enhancing tumor volume including necrosis, central necrosis alone and peritumoral edema (PTE). We calculated ratios between the tumor volume and edema (ETR), respectively necrosis (NTR). SNP analysis was done using genomic DNA extracted from peripheral blood genotyped via PCR and sequencing. There was a strong correlation between tumor volume and PTE (p0.001), necrosis (p0.001) and NTR (p = 0.003). Age and sex had no influence on volumetric data. The Aquaporin 4-31GA SNP had a significant influence on the ETR (p = 0.042) by decreasing the measured edema compared with the tumor volume. The Interleukin 8-251AT SNP was significantly correlated with an increased tumor (p = 0.048), PTE (p = 0.033) and necrosis volume (p = 0.028). We found two SNPs with a distinct impact on pretreatment tumor characteristics, presenting a potential explanation for the individual diversity of GBM appearance on MRI and influence on survival.

INTRODUCTION: Owing to increasing numbers of decompressive craniectomies in patients with malignant middle cerebral artery infarction, cranioplastic surgery becomes more relevant. However, the current literature mainly consists of retrospective single-centre (evidence class III) studies. This leads to a wide variability of technical approaches and clinical outcomes. To improve our knowledge about the key elements of cranioplasty, which may help optimising clinical treatment and long-term outcome, a prospective multicentre registry across Germany, Austria and Switzerland will be established. METHODS: All patients undergoing cranioplastic surgery in participating centres will be invited to join the registry. Technical methods, materials, medical history, adverse events and clinical outcome measures, including modified Rankin scale and EQ-5D, will be assessed at several time points. Patients will be accessible to inclusion either at initial decompressive surgery or when cranioplasty is planned. Scheduled monitoring will be carried out at time of inclusion and subsequently at time of discharge, if any readmission is necessary, and at follow-up presentation. Cosmetic results and patient satisfaction will also be assessed. Collected data will be managed and statistically analysed by an independent biometric institute. The primary endpoint will be mortality, need for operative revision and neurological status at 3 months following cranioplasty. ETHICS AND DISSEMINATION: Ethics approval was obtained at all participating centres. The registry will provide reliable prospective evidence on surgical techniques, used materials, adverse events and functional outcome, to optimise patient treatment. We expect this study to give new insights in the treatment of skull defects and to provide a basis for future evidence-based therapy regarding cranioplastic surgery. TRIAL REGISTRATION NUMBER: This trial is indexed in the German Clinical Trials Register (DRKS-ID: DRKS00007931). The Universal Trial Number (UTN) is U1111-1168-7425. peerReviewed

Preoperative differentiation between primary central nervous system lymphoma (PCNSL) and high grade astrocytoma (HGA) on conventional magnetic resonance imaging (MRI) can be difficult and even impossible. However, differentiation is important to guide therapeutic strategy. Several authors have reported the leakage pattern in dynamic susceptibility-contrast (DSC)-MRI in PCNSL. It describes the shape of the signal intensity curve which does not return to the baseline after the first pass of the bolus of contrast agent but crosses above it and sometimes even slopes up. In this retrospective study, our goal was to define the sensitivity and specificity of this sign.Patients with first ever diagnosed PCNSL and HGA who were treatment naive and received DSC-MRI were included. In all patients, a histological specimen was available. Patients did not receive corticosteroids prior to imaging and were HIV negative. The presence of a leakage pattern was assessed by two neuroradiologists working in consensus and correlated with the histological diagnosis.Nine patients with PCNSL (2 women, 7 men, age 59 ± 10 years) and 14 patients with HGA (3 women, 11 men, age 58 ± 17 years) were included. Six of the patients with PCNSL exhibited a leakage pattern, while only two patients with HGA did (P = 0.0227, Fischer's exact test). Sensitivity was 0.67, and specificity was 0.86.Although the leakage pattern does not prove PCNSL, it is an important diagnostic clue and can be easily assessed.

The endothelial nitric oxide (eNOS) gene T-786C polymorphism may influence as a genetic risk factor cardiovascular diseases and shows association with cardiovascular mortality. We hypothesized that this polymorphism may lead to increase mortality and morbidity after cardiac surgery with cardiopulmonary bypass (CPB).In 500 patients who underwent cardiac surgery with CPB we investigated the eNOS T-786C polymorphism by DNA-sequencing. The patients were grouped according to their genotype in three groups (TT, TC, and CC).The overall genotype distribution of T-786C polymorphism was TT=41.6%, TC=51.2%, and CC=7.2% respectively. The groups did not differ in age and gender. No significance was shown in preoperative risk factors, excluding peripheral disease (P=0.03). No difference was shown in Euroscore, APACHE II, and SAPS II. The usage of norepinephrine (P=0.03) and nitroglycerine (P=0.01) was significant higher in TC allele carrier. The mortality was quite uniform across elective and urgent subgroup. However, we found a significant difference concerning mortality and emergency cardiac procedures in homozygous C-allele carrier (P=0.014).The present study demonstrates that this polymorphism contributes to a higher prevalence of postoperative mortality after emergency cardiac surgery. Thus, the eNOS T-786C polymorphism could serve as a possibility to differentiate high risk subgroups in heterogeneous population of individuals with cardiac diseases who need cardiac surgery with CPB.