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Training clipping of intracranial aneurysms is challenging due to less frequent interventions because of minimalinvasive methods, ethical aspects regarding cadaver training and consumption of resources when using 3D printed models. By proposing an immersive virtual reality training system, we make use of increased motivation, engagement and realism when using a virtual operating room. In this simulation, a selected microsurgical clip can be applied at the aneurysm neck. Before closing the clip and deforming the vessels, the affected area is visualized to assess the clip position. Our qualitative evaluation with two neurosurgeons with different levels of experience indicates benefits such as increased motivation, presence, and the possibility to try out different strategies. However, some surgical steps can be refined to increase realism and learning effect, and interactions can be further improved. The proposed training system benefits from training by trial and error in an engaging environment leading to an improved training experience.

Purpose Intracranial aneurysms are local dilations of brain vessels. Their rupture, as well as their treatment, is associated with high risk of morbidity and mortality. In this work, we propose shape indices for aneurysm ostia for the rupture risk assessment of intracranial aneurysms. Methods We analyzed 84 middle cerebral artery bifurcation aneurysms (27 ruptured and 57 unruptured) and their ostia, with respect to their size and shape. We extracted 3D models of the aneurysms and vascular trees. A semi-automatic approach was used to separate the aneurysm from its parent vessel and to reconstruct the ostium. We used known indices to quantitatively describe the aneurysms. For the ostium, we present new shape indices: the 2D Undulation Index (UI$$_\mathrm{2D}$$ 2 D ), the 2D Ellipticity Index (EI$$_\mathrm{2D}$$ 2 D ) and the 2D Noncircularity Index (NCI$$_\mathrm{2D}$$ 2 D ). Results were analyzed using the Student t test, the Mann–Whitney U test and a correlation analysis between indices of the aneurysms and their ostia. Results Of the indices, none was significantly associated with rupture status. Most aneurysms have an NCI$$_\mathrm{2D}$$ 2 D below 0.2. Of the aneurysms that have an NCI$$_\mathrm{2D}$$ 2 D above 0.5, only one is ruptured, which indicates that ruptured aneurysms often have a circular-shaped ostium. Furthermore, the ostia of ruptured aneurysms tend to have a smaller area, which is also correlated with the aneurysm’s size. While also other variables were significantly correlated, strong linear correlations can only be seen between the area of the ostium with the aneurysm’s volume and surface. Conclusion The proposed shape indices open up new possibilities to quantitatively describe and compare ostia, which can be beneficial for rupture risk assessment and subsequent treatment decision. Additionally, this work shows that the ostium area and the size of the aneurysm are correlated. Further longitudinal studies are necessary to analyze whether stable and unstable aneurysms can be distinguished by their ostia.

In light of our own experiences, we value the existing literature to critically point out possible “near” future applications of optical coherence tomography (OCT) as an intraoperative neurosurgical guidance tool. “Pub Med”, “Cochrane Library”, “Crossref Metadata Search”, and “IEEE Xplore” databases as well as the search engine “Google Scholar” were screened for “optical coherence tomography + neurosurgery”, “optical coherence tomography + intraoperative imaging + neurosurgery”, and “microscope integrated optical coherence tomography + neurosurgery”. n = 51 articles related to the use of OCT as an imaging technique in the field of neurosurgery or neurosurgical research. n = 7 articles documented the intraoperative use of OCT in patients. n = 4 articles documented the use of microscope-integrated optical coherence tomography as a neurosurgical guidance tool. The Results demonstrate that OCT is the first imaging technique to study microanatomy in vivo. Postoperative analysis of intraoperative scans holds promise to enrich our physiological and pathophysiological understanding of the human brain. No data exists to prove that OCT-guided surgery minimizes perioperative morbidity or extends tumor resection. But results suggest that regular use of microscope-integrated OCT could increase security during certain critical microsurgical steps like, e.g., dural dissection at cavernous sinus, transtentorial approaches, or aneurysm clip placement. Endoscopy integration could aid surgery in regions which are not yet accessible to real-time imaging modalities like the ventricles or hypophysis. Theranostic instruments which combine OCT with laser ablation might gain importance in the emerging field of minimal invasive tumor surgery. OCT depicts vessel wall layers and its pathologies uniquely. Doppler OCT could further visualize blood flow in parallel. These abilities shed light on promising future applications in the field of vascular neurosurgery.

We present an analysis tool for subgroup identification in medical research based on feature analysis. Our use case is intracranial aneurysms. In the tool, an aneurysm-of-interest’s most similar aneurysms within a database are found. Similarity is defined via user-selected parameters, which can be entirely arbitrary. Different interactive outputs and visualizations include a heatmap view and a graph, which give an intuitive feedback to support researchers in the consideration of research questions, which in the present use case often relate to rupture risk analysis. The tool was evaluated with a pilot study and phantom database and received favorable results for its requirements of reliability and appropriate and clear outputs.

Purpose Evaluation of extravascular, microscope integrated OCT (iOCT) as an in vivo imaging modality of cerebral blood vessels and as an intraoperative imaging method. Methods Microscope integrated optical coherence tomography of major cerebral arteries (n = 13) and superficial sylvian veins (n = 5) and one incidental cerebral vasospasm (n = 1) in (n = 10) patients. Post procedural analysis of OCT volume scans, microscopic images and videos during the time of scan as well as measurements of the diameter of vessel walls and its layers with an accuracy of 7.5 μm. Results iOCT was feasible during vascular microsurgical procedures. In all scanned arteries a clear delineation of the physiological three layered vessel wall composition could be achieved. Pathological arteriosclerotic alterations of cerebral artery walls could precisely be demonstrated. Major superficial cortical veins conversely presented a mono layered composition. First in vivo measurements of vascular mean diameters were possible. Cerebral artery walls showed a diameter of 296 μm, tunica externa 78 μm, media 134 μm and interna 84 μm. Conclusion For the first time the microstructural composition of cerebral blood vessels could be illustrated in vivo. Due to an outstanding spatial resolution a clear definition of physiological and pathological characteristics was possible. Therefore, microscope integrated optical coherence tomography holds promise for basic research in the field of cerebrovascular arteriosclerotic diseases and for intraoperative guidance during microvascular surgery.

There has been an increase in the use of acetylsalicylic acid (ASA, Aspirin®) among patients with stroke and heart disease as well as in aging populations as a means of primary prevention. The potentially life-threatening consequences of a postoperative hemorrhagic complication after neurosurgical operative procedures are well known. In the present study, we evaluate the risk of continued ASA use as it relates to postoperative hemorrhage and cardiopulmonary complications in patients undergoing cerebral aneurysm surgery. We retrospectively analyzed 200 consecutive clipping procedures performed between 2008 and 2018. Two different statistical models were applied. The first model consisted of two groups: (1) group with No ASA impact - patients who either did not use ASA at all as well as those who had stopped their use of the ASA medication in time (> = 7 days prior to operation); (2) group with ASA impact - all patients whose ASA use was not stopped in time. The second model consisted of three groups: (1) No ASA use; (2) Stopped ASA use (> = 7 days prior to operation); (3) Continued ASA use (did not stop or did not stop in time, ASA impact group vs. No ASA impact group: OR = 1.0516 [0.1187; 9.3132], p = 1.000; RR = 1.0015 [0.9360; 1.0716]). Cardiopulmonary complications were significantly more frequent in the group with ASA impact than in the group without ASA impact (p = 0.030). In this study continued ASA use was not associated with an increased risk of a postoperative hemorrhage. However, cardiopulmonary complications were significantly more frequent in the ASA impact group than in the No ASA impact group. Thus, ASA might relatively safely be continued in patients with increased cardiovascular risk and cases of emergency cerebrovascular surgery.

Purpose Medical case-based reasoning solves problems by applying experience gained from the outcome of previous treatments of the same kind. Particularly for complex treatment decisions, for example, incidentally found intracranial aneurysms (IAs), it can support the medical expert. IAs bear the risk of rupture and may lead to subarachnoidal hemorrhages. Treatment needs to be considered carefully, since it may entail unnecessary complications for IAs with low rupture risk. With a rupture risk prediction based on previous cases, the treatment decision can be supported. Methods We present an interactive visual exploration tool for the case-based reasoning of IAs. In presence of a new aneurysm of interest, our application provides visual analytics techniques to identify the most similar cases with respect to morphology. The clinical expert can obtain the treatment, including the treatment outcome, for these cases and transfer it to the aneurysm of interest. Our application comprises a heatmap visualization, an adapted scatterplot matrix and fully or partially directed graphs with a circle- or force-directed layout to guide the interactive selection process. To fit the demands of clinical applications, we further integrated an interactive identification of outlier cases as well as an interactive attribute selection for the similarity calculation. A questionnaire evaluation with six trained physicians was used. Result Our application allows for case-based reasoning of IAs based on a reference data set. Three classifiers summarize the rupture state of the most similar cases. Medical experts positively evaluated the application. Conclusion Our case-based reasoning application combined with visual analytic techniques allows for representation of similar IAs to support the clinician. The graphical representation was rated very useful and provides visual information of the similarity of the k most similar cases.

Objectives Meningiomas are the most frequent primary brain tumours. Recently, knowledge about the molecular drivers underlying aggressive meningiomas has been expanded. A hotspot mutation in the AKT1 gene (AKT1E17K ), which is found in meningiomas at the convexity and especially at the skull base, has been associated with earlier tumour recurrence. Materials and methods Here we analysed the effects of the AKT1E17K mutation and treatment response to the Akt inhibitor AZD5363 in transgenic meningioma cell clones and mouse xenografts modelling convexity or skull base meningiomas. Results We show that the AKTE17K mutation significantly enhances meningioma cell proliferation and colony size in vitro, resulting in significantly shortened survival times of mice carrying convexity or skull base AKT1E17K xenografts. Treatment of mutant cells or xenografts (150 mg/kg/d) with AZD5363 revealed a significant decrease in cell proliferation and colony size and a prolongation of mouse survival. Western blots revealed activation of AKT1 kinase (phosphorylation at Ser273 and Thr308) by the E17K mutation in human meningioma samples and in our in vitro and in vivo models. Conclusion Our data suggest that AKT1E17K mutated meningiomas are a promising selective target for AZD5363.

Meningiomas are the most frequent primary intracranial tumors. The considerable variety of histological subtypes has been expanded by the definition of molecular alterations, which can improve both diagnostic accuracy and determination of individual patient's outcome. According to the upcoming WHO classification of brain tumors, the in-time analysis of frequent molecular events in meningiomas may become mandatory to define meningioma subtypes. We have compiled a custom-made amplicon-based next generation sequencing (NGS) meningioma panel covering the most frequent known recurrent mutations in 15 different genes. In an unselected consecutive meningioma cohort (109 patients) analyzed over a period of 12 months, we detected mutations in 11 different genes, with most frequent alterations in NF2 (43%), AKT1

Purpose Intracranial aneurysms can be treated micro-surgically. This procedure involves an appropriate head position of the patient and a proper craniotomy. These steps enable a proper access, facilitating the subsequent steps. To train the access planning process, we propose a VR-based training system. Method We designed and implemented an immersive VR access simulation, where the user is surrounded by a virtual operating room, including medical equipment and virtual staff. The patient’s head can be positioned via hand rotation and an arbitrary craniotomy contour can be drawn. The chosen access can be evaluated by exposing the aneurysm using a microscopic view. Results The evaluation of the simulation took place in three stages: testing the simulation using the think-aloud method, conducting a survey and examining the precision of drawing the contour. Although there are differences between the virtual interactions and their counterparts in reality, the participants liked the immersion and felt present in the operating room. The calculated surface dice similarity coefficient, Hausdorff distance and feedback of the participants show that the difficulty of drawing the craniotomy is appropriate. Conclusion The presented training simulation for head positioning and access planning benefits from the immersive environment. Thus, it is an appropriate training for novice neurosurgeons and medical students with the goal to improve anatomical understanding and to become aware of the importance of the right craniotomy hole.

Brain metastases frequently occur during the course of disease in patients suffering from lung cancer. Occasionally, neurological symptoms caused by brain metastases (BM) might represent the first sign of systemic tumor disease (so called precocious metastases), leading to the detection of the primary lung tumor. The biological basis of precocious BM is largely unknown, and treatment options are not well established for this subgroup of patients. Therefore, we retrospectively analyzed 33 patients (24 non-small cell lung cancer (NSCLC)), 9 small cell lung cancer (SCLC)) presenting with precocious BM focusing on molecular alterations potentially relevant for the tumor's biology and treatment. We found five FGFR1 amplifications (4 adenocarcinoma, 1 SCLC) among 31 analyzed patients (16.1%), eight MET amplifications among 30 analyzed tumors (7 NSCLC, 1 SCLC; 26.7%), three EGFR mutations within 33 patients (all adenocarcinomas, 9.1%), and five KRAS mutations among 32 patients (all adenocarcinomas; 15.6%). No ALK, ROS1 or RET gene rearrangements were detected. Our findings suggest that patients with precocious BM of lung cancer harbor EGFR mutations, MET amplifications or FGFR1 amplifications as potential targeted treatment options.

Objective: The present study explores three-dimensional microscope integrated extravascular OCT as the first suitable intraoperative imaging modality of cerebral aneurysm (CA) and parent vessel wall morphology. Methods: Incidental CAs (n=16) of the anterior circulation with indication for [for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

To exploit the potential of virtual reality (VR) in medicine, the input devices must be selected carefully due to their different benefits. In this work, input devices for common interaction tasks in medical VR planning and training are compared. Depending on the specific purpose, different requirements exist. Therefore, an appropriate trade-off between meeting task-specific requirements and having a widely applicable device has to be found. We focus on two medical use cases, liver surgery planning and craniotomy training, to cover a broad medical domain. Based on these, relevant input devices are compared with respect to their suitability for performing precise VR interaction tasks. The devices are standard VR controllers, a pen-like VR Ink, data gloves and a real craniotome, the medical instrument used for craniotomy. The input devices were quantitatively compared with respect to their performance based on different measurements. The controllers and VR Ink performed significantly better than the remaining two devices regarding precision. Qualitative data concerning task load, cybersickness, and usability and appropriateness of the devices were assessed. Although no device stands out for both applications, most participants preferred using the VR Ink, followed by the controller and finally the data gloves and craniotome. These results can guide the selection of an appropriate device for future medical VR applications.

Objective: High resolution vessel wall imaging plays an increasingly important role in assessing the risk of aneurysm rupture. We aim to introduce an approach towards the validation of the wall enhancement as a direct surrogate parameter for aneurysm stability. Methods: 19 patients harboring 22[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

Background and purpose The evaluation of a suspected malfunction of a ventricular shunt is a common procedure in neurosurgery. The evaluation relies on either the interpretation of the ventricular width using cranial imaging or invasive techniques. Several attempts have been made to measure the flow velocity of cerebrospinal fluid (CSF) utilizing different phase-contrast magnet resonance imaging (PC MRI) techniques. In the present study, we evaluated 3 T (Tesla) MRI scanners for their effectiveness in determining of flow in the parenchymal portion of ventricular shunt systems with adjustable valves containing magnets. Methods At first, an MRI phantom was used to measure the phase-contrasts at different constant low flow rates. The next step was to measure the CSF flow in patients treated with ventricular shunts without suspected malfunction of the shunt under observation. Results The measurements of the phantom showed a linear correlation between the CSF flow and corresponding phase values. Despite many artifacts resulting from the magnetic valves, the ventricular catheter within the parenchymal portion of shunt was not superimposed by artifacts at each PC MRI plane and clearly distinguishable in 9 of 12 patients. Three patients suffering from obstructive hydrocephalus showed a clear flow signal. Conclusion CSF flow detected within the parenchymal portion of the shunt by PC MRI may reliably provide information about the functional status of a ventricular shunt. Even in patients whose hydrocephalus was treated with magnetic adjustable valves, the CSF flow was detectable using PC MRI sequences at 3 T field strength.

Genetically modified T cells expressing chimeric antigen receptors (CARs) so far have mostly failed in the treatment of solid tumors owing to a number of limitations, including an immunosuppressive tumor microenvironment and insufficient CAR T cell activation and persistence. Next-generation approaches using CAR T cells that secrete transgenic immunomodulatory cytokines upon CAR signaling, known as TRUCKs (&ldquo, T cells redirected for universal cytokine-mediated killing&rdquo, ), are currently being explored. As TRUCKs were engineered by the transduction of T cells with two separate vectors, we developed a lentiviral modular &ldquo, all-in-one&rdquo, vector system that combines constitutive CAR expression and inducible nuclear factor of activated T cells (NFAT)-driven transgene expression for more efficient production of TRUCKs. Activation of the GD2-specific CAR via GD2+ target cells induced NFAT promoter-driven cytokine release in primary human T cells, and indicated a tight linkage of CAR-specific activation and transgene expression that was further improved by a modified NFATsyn promoter. As proof-of-concept, we showed that T cells containing the &ldquo, vector system secrete the immunomodulatory cytokines interleukin (IL)12 or IL18 upon co-cultivation with primary human GD2+ tumor cells, resulting in enhanced effector cell properties and increased monocyte recruitment. This highlights the potential of our system to simplify application of TRUCK-modified T cells in solid tumor therapy.

Genetically modified T cells expressing chimeric antigen receptors (CARs) so far have mostly failed in the treatment of solid tumors owing to a number of limitations, including an immunosuppressive tumor microenvironment and insufficient CAR T cell activation and persistence. Next-generation approaches using CAR T cells that secrete transgenic immunomodulatory cytokines upon CAR signaling, known as TRUCKs (“T cells redirected for universal cytokine-mediated killing”), are currently being explored. As TRUCKs were engineered by the transduction of T cells with two separate vectors, we developed a lentiviral modular “all-in-one” vector system that combines constitutive CAR expression and inducible nuclear factor of activated T cells (NFAT)-driven transgene expression for more efficient production of TRUCKs. Activation of the GD2-specific CAR via GD2+ target cells induced NFAT promoter-driven cytokine release in primary human T cells, and indicated a tight linkage of CAR-specific activation and transgene expression that was further improved by a modified NFATsyn promoter. As proof-of-concept, we showed that T cells containing the “all-in-one” vector system secrete the immunomodulatory cytokines interleukin (IL)12 or IL18 upon co-cultivation with primary human GD2+ tumor cells, resulting in enhanced effector cell properties and increased monocyte recruitment. This highlights the potential of our system to simplify application of TRUCK-modified T cells in solid tumor therapy.

Background Due to improvements in both the quality and availability of intracranial imaging as well as the evolution of surgical and endovascular techniques during the last decade, the number of treatments of unruptured intracranial aneurysms (UIA) has increased steadily. However, it is not generally known that vasospasm can arise after an uneventful clipping. Case presentation We present a case of a 69-year-old woman who suffered from vasospasm and delayed cerebral ischemia that occurred after an uneventful clipping of a UIA. The aneurysm of the right middle cerebral artery was found incidentally via magnetic resonance imaging ordered after the patient complained of a short period of slight gait disturbances. To avoid a subarachnoid hemorrhage and consecutive complications like vasospasms, the patient elected microsurgical treatment. Clipping was managed by keyhole approach. Temporal clipping of the M1 was not necessary. After clip placement, appropriate flow in all distal segments was confirmed by indocyanine green video-angiography and micro-Doppler. The patient was discharged seven days after surgery without neurological deficits. After 12 days, the patient developed at home a sudden drooping on the left side of the face. Upon admission to the emergency room, the patient was alert but slightly confused. Neurological examination revealed a left-sided hemiparesis and motor speech disorder. In contrast to the preoperative transfemoral catheter angiography, the subsequent right internal carotid angiogram showed clear signs of vasospasm along the M1 and M2 segments of the right middle cerebral artery. Antithrombotic treatment with acetylsalicylic acid was begun. In accordance with guidelines for the treatment of subarachnoid hemorrhage and vasospasm, nimodipine was added. After 11 days the patient was discharged with no symptoms. Conclusion Cerebral vasospasm as a cause of ischemic stroke after uneventful surgery for a UIA seems to be a rare but possibly underestimated etiology that demands particular attention with respect to providing appropriate treatment. In future, it may be prudent to perform follow-up transcranial ultrasonography testing after the clipping of a UIA, especially considering the availability of potentially neuroprotective medications like nimodipine.

Ruptured middle cerebral artery (MCA) aneurysms are one of the causes of subarachnoid (SAH) or intracerebral hemorrhage (ICH) but the factors associated with the bleeding type are unknown. The aim of the study was to analyze the association of the morphological variations of the Sylvian fissure (SF) and vascular parameters on occurrence of different bleeding patterns in patients with ruptured MCA aneurysms.The data of consecutive 202 patients with ruptured MCA aneurysm of two centers were included for analysis. Patients were divided into three groups: Group 1 with SAH, Group 2 with accompanying ICH and Group 3 with intrasylvian hemorrhage (ISH). The SF was divided into five types according to the previously described classification. Analyzed vascular parameters were aneurysm size, localization, presence of a daughter aneurysm, shape, and angulation of the aneurysm sac.A total of 202 patients (141 female, 61 male, mean age 52.4 yr) were included in this study. 67 patients (33.2%) had a SAH, 122 (60.4%) an ICH and 13 (6.4%) presented with ISH. Statistical analysis showed a significant association of narrow and twisted SF types 4 and 5 (p 0.001) and temporal angulation of the aneurysm (p = 0.030) for occurrence of ICH. All other vascular parameters showed no significant association for any kind of hemorrhage.Our results allow the conclusion that the complex SF types 4 and 5, as well as the temporal angulation of the aneurysm sac are associated with the occurrence of ICH in ruptured MCA aneurysms.

Glioblastoma (GBM) is the most malignant brain tumor and one of the deadliest types of solid cancer overall. Despite aggressive therapeutic approaches consisting of maximum safe surgical resection and radio-chemotherapy, more than 95% of GBM patients die within 5 years after diagnosis. Thus, there is still an urgent need to develop novel therapeutic strategies against this disease. Accumulating evidence indicates that cannabinoids have potent anti-tumor functions and might be used successfully in the treatment of GBM. This review article summarizes the latest findings on the molecular effects of cannabinoids on GBM, both in vitro and in (pre-) clinical studies in animal models and patients. The therapeutic effect of cannabinoids is based on reduction of tumor growth via inhibition of tumor proliferation and angiogenesis but also via induction of tumor cell death. Additionally, cannabinoids were shown to inhibit the invasiveness and the stem cell-like properties of GBM tumors. Recent phase II clinical trials indicated positive results regarding the survival of GBM patients upon cannabinoid treatment. Taken together these findings underline the importance of elucidating the full pharmacological effectiveness and the molecular mechanisms of the cannabinoid system in GBM pathophysiology.

Objectives Cerebral arterio-venous malformations (AVM) are considered congenital lesions, emerging as an important cause of haemorrhagic stroke in children. The potential influence of age on clinical presentation and angio-architecture have been analysed extensively in the last years. Yet, comparative studies comprising ascending age groups may be limited in their conclusions, especially when comparing young children and adults. It is the aim of this study to evaluate characteristic clinical and angiographic features of AVM within a paediatric subgroup and their correlation to age at presentation. Patients and methods Between 1990–2015, 46 children harbouring AVMs were treated at our institution. Clinical presentation, radiological data, treatment strategies and outcome were evaluated retrospectively. Results Of 46 consecutive patients, 18 were male and 28 female patients. Mean age was 11.6 ± 4.3 years, ranging from 2 to 17 years. 35 patients (76%) presented with haemorrhage. Seizures were found in 6 patients (13%) and progressive or transient focal neurological deficits in 4 individuals (9%). There was one incidental patient, only. Mean age of children presenting with haemorrhage was significantly lower as compared to those without a history of intracranial bleeding (p = 0.1). The size of the AVM was small (n = 27, 59%), corresponding a grade I AVM in the majority of patients (N = 28, 61%). 41 patients (89%) underwent treatment of their AVM by an interdisciplinary approach achieving complete elimination of the lesion in 34 patients (83%). 34 patients (83%) showed at least a favourable outcome (mRS ≤ 2) at last follow-up. An excellent recovery (mRS 0–1) was noted in 28 patients (68%). Conclusion From our data we suggest that patients’ age impacts the clinical presentation. Particularly young children seem to bear a higher risk for haemorrhage from their AVM. Treatment of paediatric AVMs can be achieved safely in experienced hands with a high rate of complete elimination and good clinical outcome.

Spinal injuries are rarely seen in pediatric patients and therapeutic options are still poorly defined. The present study is aimed to present our experience with a rather large series of children and young adults suffering from traumatic spinal injury. Between 1990 and 2010, 75 consecutive pediatric patients with spinal injuries were treated in our institution. Mean age was 15 years, ranging from 3 months to 21 years. Radiological findings, treatment strategies, and clinical outcome were evaluated retrospectively and compared with literature. Forty (53.3 %) patients were treated conservatively and 35 patients (47 %) surgically using anterior or posterior approaches. Subgroup analysis was performed depending on age groups, severity of neurological symptoms, and localization. Main trauma mechanisms were fall in 24 patients (38 %) and motor vehicle accidents in 21 patients (28 %). Complete neurological deficits were present in 17 individuals (23 %) and incomplete in 36 patients (48 %). Fractures were most frequently localized at the cervical region (56 %) with predilection of the C 5/6 segment. Odontoid fractures were seen in 10 (13 %) patients. Fractures of the lumbar and thoracic region were rare. Level of injury or clinical course did not differ between the subgroups (≤15 years versus >15 years). Nearly three fourths of all radiologically detected spinal injuries are located at the cervical spine. Complete neurological deficits after trauma was associated with a poor outcome, in particular for patients with injuries of the upper cervical spine. The use of autologous bone graft was associated with favorable long-term results and should be considered as the material of first choice for vertebral body and disc replacement.

Background: Associated aneurysms (AAs) are presumed to represent an additional risk factor for intracranial haemorrhage from cerebral arterio-venous malformations (AVMs). To date, efforts to capture their natural history, as well as to identify aneurysms with the potential capability of regression after AVM treatment remain incomprehensive. As the aneurysm size represents an important aspect for the treatment indication of incidental saccular aneurysms, this factor has rarely been encountered for the treatment of AAs so far. The present study aims to determine the angiographic and clinical characteristics of AAs with special focus on aneurysm size and their consequences for treatment. Methods: Patients with cerebral AVMs, treated in our department between 1990 and 2013, were analyzed retrospectively. Only patients with supratentorial AVMs and flow-related AAs of the feeding arteries were evaluated. Thus, patients harboring AVMs of the cerebellum and the brain stem and patients with intranidal, venous or remote aneurysms were excluded. Treatment strategies were assessed with special attention on bleeding source and on AA size. Results: In 59 of 409 patients (14%) with supratentorial AVMs, a total of 85 AAs of the feeding arteries were identified. 14 of 59 individuals (24%) presented with multiple AAs. Of 85 AA, 58 aneurysms (68%) were classified as proximal and 27 aneurysms (32%) as distal. The most common location of AAs was the middle cerebral artery (MCA, 39%), followed by the internal carotid artery (ICA, 27%) and the anterior cerebral artery (ACA, 21%). The mean AA size was 4.4 mm ± 3.4 mm. Intracranial haemorrhage was found in 21 of 59 patients (36%) with coexisting AAs. Among these, 10 individuals (17%) suffered from rupture of an AA, accounting for nearly half of all bleedings in this subgroup. Among those patients bearing a single AA, the size of ruptured aneurysms differed significantly from those unruptured (6.6 mm vs. 4.4 mm, p = 0.0046). Nineteen patients (32%) received treatment of 22 AAs, whereas sole AVM treatment was adopted in 26 patients (44%) and conservative management in 14 patients (24%). The main reasons to leave AAs untreated were the small AA size (Conclusions: The aneurysm size of AAs in AVM influences the risk of haemorrhage. Therefore, the treatment of larger (diameter ≥5 mm) AAs should be considered, even if a treatment indication of the associated AVM is not given.

In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.

The rupture of an intracranial aneurysm leads to subarachnoid hemorrhage (SAH). To prevent SAH, unruptured lesions can be treated by either endovascular or microsurgical approach. Due to their complex anatomy, middle cerebral artery (MCA) aneurysms represent a unique subgroup of intracranial aneurysms. Primary objective was to determine radiological and clinical outcomes in patients with middle cerebral artery aneurysms who were interdisciplinary treated by either endovascular or microsurgical approach in a single center. Secondary objective was to determine the impact of the lesions' angiographic characteristics on treatment outcome. Clinical and radiological data of 103 patients interdisciplinary treated for unruptured MCA aneurysms over a 5-year period were analyzed in endovascular (n = 16) and microsurgical (n = 87) cohorts. Overall morbidity (Glasgow Outcome Score

The present study aimed to determine the clinical presentation, the multimodal interdisciplinary treatment strategies and outcome of posterior fossa arterio-venous malformations (AVMs) in our neurovascular centre. Fifty-three patients with a posterior fossa AVM were seen between 1998 and 2012 and analysed retrospectively. Patients were either managed conservatively or treated with endovascular, microsurgical or radiosurgical procedures or in combination. Thirty-nine patients (74 %) presented with intracranial haemorrhage and 14 patients (26 %) with unspecific symptoms. In 22 cases with haemorrhage (56 %), an intracerebellar haematoma was found, whereas 17 patients (44 %) suffered from subarachnoid haemorrhage. AVMs were located in the cerebellum in 44 patients (83 %), in the brainstem in four patients (7.5 %) and the cerebello-pontine angle in another four individuals (7.5 %). Forty-two patients (79 %) were treated either by emboliziation (n = 12, 29 %), surgical resection (n = 16, 38 %), surgical resection with preoperative embolization (n = 12, 29 %) or radiotherapy alone (n = 2, 4 %). A total of eleven patients did not receive any treatment (21 %). Both, morbidity and mortality related to treatment were 12 %, whereas overall morbidity and mortality was 26 and 15 %, respectively. Complete AVM elimination was achieved in 81 % of the treated lesions. A multimodal treatment sequence nowadays represents the gold standard for posterior fossa AVMs. Patients are at high risk for morbidity and mortality, due to the impact of haemorrhage and treatment. Therefore, treatment has to be thoroughly indicated, especially for those patients without bleeding. The initial neurological condition seems to be crucial in terms of clinical outcome.

Objective The aim of this study was to analyze our clinical and neurological results of surgically treated patients suffering from cervical spondylodiscitis with focusing particularly on the surgical methods used and to review the literature. Patients and methods We present a series of 21 patients operated with cervical spondylodiscitis between 1998 and 2011. Basic demographic data, comorbidities, the radiological segments involved, the surgical strategy with special consideration of the material used and the clinical outcome were evaluated retrospectively. Results The mean age of 6 female and 12 male patients was 65 years (range 28–89 years). The mean follow-up was 3.7 years ranging between 4 weeks and 9 years. The leading symptom was neurological deficits rather than pain. The segments C 5/6 (n = 8) and C 6/7 (n = 7) were most frequently involved. Different surgical methods depending on the location, anatomical and pathological condition and extension of the lesion were performed. Conclusion In conclusion, cervical spondylodiscitis could effectively be treated in the presented patient cohort by surgical decompression, debridement and PMMA or bone graft implants followed by long term antibiotic therapy. The presented surgical reconstruction technique with PMMA might be a feasible alternative to the use of bone graft or cages. The promising clinical results warrant future prospective studies to further investigate this technique.

Multiple AVMs are exceptionally rare lesions and only a few larger series have been published, including other vascular pathologies, such as arterio-venous fistulae (AVF) or patients with hereditary syndromes. Our study presents clinical, angiographic, and therapeutic characteristics of patients harboring sporadic multiple AVMs. Basic demographic data, vascular architecture, clinical presentation, treatment strategies, and treatment outcome were analyzed retrospectively from patients with cerebral AVMs treated in our department between 1990 and 2015. Six out of 539 patients (1.1 %) harbored 15 multiple and distinct cerebral lesions. Nidus size was predominantly small, consequently determining a Spetzler–Martin grade °I–°II (three-tier grading system). In three patients, AVMs shared a proximal feeding artery supply, whereas each AVM displayed its own venous drainage. Five of six patients (83 %) presented with hemorrhage. Four patients received therapy of the AVMs with complete elimination in 3/4 patients (75 %) and 8/9 treated AVMs (89 %). All patients with treatment of the AVM showed good-to-excellent recovery (n = 4, mRS ≤ 2). Multiple cerebral AVMs are complex vascular lesions. The multiplicity of hemodynamic and malformation-related variables influence treatment strategy and sequence. Thus, awareness of these parameters (of various malformations before and during treatment) is important. The high number of hemorrhagic events in the present series might justify a more aggressive treatment of multiple AVMs than previously thought.

To evaluate prospectively 7 Tesla time-of-flight (TOF) magnetic resonance angiography (MRA) and 7 Tesla non-contrast-enhanced magnetization-prepared rapid acquisition gradient-echo (MPRAGE) for delineation of intracerebral arteriovenous malformations (AVMs) in comparison to 1.5 Tesla TOF MRA and digital subtraction angiography (DSA). Twenty patients with single or multifocal AVMs were enrolled in this trial. The study protocol comprised 1.5 and 7 Tesla TOF MRA and 7 Tesla non-contrast-enhanced MPRAGE sequences. All patients underwent an additional four-vessel 3D DSA. Image analysis of the following five AVM features was performed individually by two radiologists on a five-point scale: nidus, feeder(s), draining vein(s), relationship to adjacent vessels, and overall image quality and presence of artefacts. A total of 21 intracerebral AVMs were detected. Both sequences at 7 Tesla were rated superior over 1.5 Tesla TOF MRA in the assessment of all considered AVM features. Image quality at 7 Tesla was comparable with DSA considering both sequences. Inter-observer accordance was good to excellent for the majority of ratings. This study demonstrates excellent image quality for depiction of intracerebral AVMs using non-contrast-enhanced 7 Tesla MRA, comparable with DSA. Assessment of untreated AVMs is a promising clinical application of ultra-high-field MRA. • Non-contrast-enhanced 7 Tesla MRA demonstrates excellent image quality for intracerebral AVM depiction. • Image quality at 7 Tesla was comparable with DSA considering both sequences. • Assessment of intracerebral AVMs is a promising clinical application of ultra-high-field MRA.

Lesions of the anterior skull base often require sufficient closure in order to prevent cerebrospinal fluid (CSF) leak, ascending infection and/or brain tissue prolapse. The transfer of devitalized autologous, allogenic or xenogeneic material is not always sufficient particularly not in larger defects or in the recurrent situation. Here the transfer of vascularised tissue seems to be more appropriate. The anterior skull base with various complex defects of 41 patients was reconstructed in an interdisciplinary setting by vascularised, autologous tissue transfer. Minor defects (2.5 cm in max. diameter), generally occurring after extended endoscopic skull base approaches (n = 26, among those meningiomas, recurrent CSF fistulas, chordoma, chondroblastoma, metastasis, nasal fistula), were reconstructed by a local, vascularized pedicled mucosal flap of the lower turbinate (n = 3) or septum (n = 23). Patients with major defects (2.5 cm in max. diameter, n = 15), comprising those with malignoma, meningoencephalocele, aneurysmatic bone cyst and trauma, were repaired by a "sandwich technique" with a combination of calvarian split and galea periosteum flap in 10 patients, in one case with a temporalis muscle flap, while in 4 further patients free vascularised radial forearm flaps were used for revision after multiple unsuccessful operations elsewhere. After a mean follow-up time of 30.5 months 38 of the 41 cases were successfully repaired with respect to prevention and treatment of CSF leakage or brain tissue prolapse, only 3 cases needed surgical revision. The reconstruction of the anterior skull base bearing complex lesions is feasible using vascularised, autologous local and also distal tissue transfer in a close interdisciplinary cooperation.

Background Cerebral cavernous malformation (CCM) is mainly a disorder of endothelial cells. Although the endothelial function of CCM genes has been characterized in familial CCMs, little attention has been paid to the pathological alterations of the endothelium in sporadic CCMs. Objective We assumed that the endothelia derived from sporadic CCMs present genotypic and/or phenotypic alterations and exhibit unique responses to the pathogenic stimuli. Methods Endothelial cells were prepared from fresh operative specimens of sporadic CCMs with a single lesion (CCM-ECs, n = 20). The expression of VEGF and its receptors and CCM1-3 genes were detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Endothelial cell proliferation, migration, sprouting, and tube formation were compared between CCM-ECs and control endothelial cells after different angiogenic stimuli and after silencing CCM1. Results RT-PCR revealed a highly activated VEGF system in CCM-ECs without significant alteration in CCM1-3 gene expression. Accordingly, CCM-ECs exhibited great growth potential under normal culture conditions and a significantly high proliferation activity in response to various angiogenic stimuli including hypoxia, fetal calf serum, and vascular endothelial growth factor treatment. A considerably higher mobility, spontaneous sprouting and extensive tube-branching were exclusively detected in CCM-ECs. In comparison with control endothelia, CCM-EC resisted apoptotic stimuli and showed distinct responses to activating angiogenesis after silencing CCM1. Conclusion Distinct genotypic and phenotypic features occur in CCM-EC independently from the deficiency in CCM1-3 gene expression. The distinct responses of CCM-EC to different pathogenic stimuli suggest that CCM-EC is a valuable in vitro model for further study of CCMs.

The treatment of spontaneous cerebellar hemorrhage is still discussed controversially. We analyzed a series of 57 patients who underwent surgical evacuation of a cerebellar hematoma at our department. Preoperative clinical and radiological parameters were assessed and correlated with the clinical outcome in order to identify factors with impact on outcome. The overall clinical outcome according to the Glasgow Outcome Scale at the last follow-up was good (GOS 4-5) in 27 patients (47%) and poor (GOS 2-3) in 16 patients (28%). Fourteen patients (25%) died. The initial neurological condition and the level of consciousness proved to be significant factors determining clinical outcome (p = 0.0032 and p = 0.0001, respectively). Among radiological parameters, brain stem compression and a tight posterior fossa solely showed to be predictive for clinical outcome (p = 0.0113 and p = 0.0167, respectively). Overall, our results emphasize the predictive impact of the initial neurological condition on clinical outcome confirming the grave outcome of patients in initially poor state as reported in previous studies. The hematoma size solely, in contrast to previous observations, showed not to be predictive for clinical outcome. Especially for the still disputed treatment of patients in good initial neurological condition, a suggestion can be derived from the present study. Based on the excellent outcome of patients with good initial clinical condition undergoing surgery due to secondary deterioration, we do not recommend preventive evacuation of a cerebellar hematoma in these patients.

This study was undertaken to analyze the functional outcome of surgically treated spinal meningiomas and to determine factors for surgical morbidity. Between January 1990 and December 2006 a total of 131 patients underwent surgical resection of a spinal menigioma. There were 114 (87%) female and 17 (13%) male patients. Age ranged from 17 to 88 years (mean 69 years). The mean follow-up period was 61 months (range 1–116 months) including a complete neurological examination and postoperative MRI studies. The pre- and postoperative neurological state was graded according to the Frankel Scale. Surgery was performed under standard microsurgical conditions with neurophysiological monitoring. In 73% the lesion was located in the thoracic region, in 16% in the cervical region, in 5% at the cervico-thoracic junction, in 4.5% at the thoraco-lumbar junction and in 1.5% in the lumbar region. Surgical resection was complete in 127 patients (97%) and incomplete in 4 patients (3%). At the last follow-up the neurological state was improved or unchanged in 126 patients (96.2%) and worse in 4 patients (3%). Permanent operative morbidity and mortality rates were 3 and 0.8%, respectively. Extensive tumour calcification proved to be a significant factor for surgical morbidity (P

Aneurysm growth appears to be associated with an increased risk of rupture. Therefore, it may be of interest to identify mechanisms contributing to aneurysm growth. Angiogenic factors, particularly vascular endothelial growth factor (VEGF), appear to play an important role in the pathogenesis and growth of cerebrovascular malformations. We aimed to study systemic VEGF levels as a potential systemic marker in patients with non-ruptured intracranial aneurysms compared with healthy controls. Mean VEGF plasma concentrations were found to be increased in patients with non-ruptured intracranial aneurysms compared with healthy controls (85.2 pg/ml versus 44.1 pg/ml). This difference did not reach significance in the analyzed study cohort (p=0.05) but only when the analysis was restricted to male patients (p=0.04). Female patients and controls demonstrated significantly increased VEGF plasma levels only on correlation with age but not with the presence of aneurysms. Neither the presence of multiple aneurysms nor aneurysm location were correlated with VEGF levels. Although overall VEGF plasma difference was not statistically significant, we found significantly increased levels in male patients. Furthermore, we identified a distinct group of female patients with intracranial aneurysms who presented excessively increased VEGF plasma levels to an amount that was not observed in the controls. Further studies may clarify the relationship of aneurysm growth and VEGF.

Summary Objective To describe the interdisciplinary surgical approach in spheno-orbital meningiomas and to evaluate the operative results regarding resectability and functional outcome. Patients and methods A series of 16 patients underwent surgical resection of spheno-orbital meningiomas followed by bony reconstruction. Four patients presented with a recurrent meningioma and had undergone surgical resection previously. Radical tumour removal was attempted in all cases, although no aggressive effort was made to remove tumour tissue infiltrating the cavernous sinus or soft tissues deep in the orbit to avoid severe functional disturbances. All patients but one were female (mean age 53 years). Mean follow-up period was 68 months (range 4–155 months). Results The leading symptom was proptosis in 14 patients, accompanied in 7 cases by progressive visual impairment. Surgical resection was thought to have been complete in 11 patients (69%) and incomplete in 5 (31%). Residual tumour was deliberately left when there was infiltration of the cavernous sinus \( n = 4 \) , the pterygopalatine fossa \( n = 2 \) and/or the deep intraorbital soft tissues \( n = 1 \) . Tumour recurrence was observed in 9 patients, among whom were 6 patients with an initially "completely" resected meningioma. Eight patients underwent re-operation. Complete resection was achieved in 3 of these latter patients with an isolated exclusively intraorbital tumour manifestation. Conclusion By means of combined skull base approaches, spheno-orbital meningiomas are grossly resected totally with a long-term survival free of recurrence and an acceptable quality of life. In some cases, deliberate subtotal tumour resection is useful to avoid severe neurological damage with sufficient tumour control and a valuable progression-free survival.

Objective:The objective of this study was to analyse our initial experience using an interdisciplinary angio suite approach to neurosurgical treatment of complex neurovascular lesions and expound technical feasibility and possible applications.Subjects:Six out of 451 patients with cranial or spinal neurovascular lesions were surgically treated in the angio suite (biplane angiographic system) during a 28-month observation period. Clinical baseline data, radiological and intraoperative findings as well as clinical and radiological outcome were assessed.Results:A ventral spinal perimedullary arteriovenous malformation, a ventral spinal perimedullary fistula, two diffuse frontal dural arteriovenous fistulas, a multifocal temporal arteriovenous malformation and a partially embolized fronto-temporo-basal dural arteriovenous fistula were successfully treated with angiographically confirmed complete occlusion and unimpaired neurological condition of the patients at the 12-month follow up.Conclusion:This study demonstrates the feasibility of this approach and points out possible indications, namely ventrally located spinal lesions and diffuse, deep seated cranial lesions.

Objective Dens fractures are common cervical injuries in advanced aged patients. The presented study was undertaken to analyze the clinical results and risks of surgically treated patients with dens fractures over 70 years. Methods Data of 28 patients (17 female, 11 male) over 70 years treated from September 2004 to October 2009 were recorded. Clinical and radiological parameters were obtained including type of fracture, associated cervical and/or other injuries, comorbidities, symptoms, neurological condition, surgical strategy, postoperative course and complications. Results 89% were in a good neurological condition before surgery (ASIA E or D). In most cases, surgery was performed at an early stage after trauma (21 patients within 5 days). Ventral screw fixation was the preferred surgical strategy (64%). A slight worsening of neurological functions immediately after operation was only seen in one patient. Five patients died in the early and 2 in the late postoperative course which means a treatment mortality of 25%. Among the surviving patients two had general medical complications. Conclusion Type II dens fractures are a common fracture of elderly patients. Our results are good concerning the neurological functions. Surgical and general medical complications were acceptable. However, the study also underlines that mortality rate is high and therefore treatment options should be well-considered in this high risk group.