Virtual Reality vs Phantom Model: Benefits and Drawbacks of Simulation Training in Neurosurgery.

BACKGROUND AND OBJECTIVES: Traditional neurosurgical education has relied heavily on the Halstedian "see one, do one, teach one" approach which is increasingly perceived as inefficient in contemporary settings marked by a steady decline in surgical caseload. In recent years, simulation training has emerged as an effective and accessible training alternative. To date, however, there is no standardized criterion pertaining to the quality and implementation of simulators in neurosurgical education and training. This research aims to compare the efficacy of virtual reality (VR) and Phantom-based simulation training in the context of neurosurgical skill acquisition, with a focus on middle cerebral artery aneurysm clipping. METHODS: An immersive VR clipping tool and a haptic clipping simulator incorporating 3-dimensional printing, additive manufacturing, and rheological analyses were developed. Twenty-two participants, comprising 12 medical students, 6 neurosurgical residents, and 4 experienced neurosurgeons, tested and evaluated both simulators for face and content validity. Construct and predictive validity of the simulators were assessed using an objective structured assessment scale for aneurysm clipping, measuring participants' performances and progress. RESULTS: Both modalities were deemed highly advantageous for educational purposes. Objective evaluations, however, revealed measurable differences in usability, efficacy, and transferability of the learned skills with VR excelling in procedural planning and visualization while Phantom simulation being noticeably superior in conveying surgical skills. CONCLUSION: Simulation training can accelerate the neurosurgical learning curve. The results of this study highlight the importance of establishing standardized criteria for the implementation and assessment of simulation modalities, ensuring consistent quality and efficacy in neurosurgical education.

Lactococcus garviae in Lumbar Spondylodiscitis With Spinal Epidural Abscess Causing Paraparesis: A Case Report.

Spinal epidural abscess (SEA) can lead to a subacute onset of neurological deficits of the extremities and is commonly accompanied by spondylodiscitis if located anterior to the dura. Lactococcus garviae is a fish pathogen that is occasionally found in poultry, cattle, and swine. It is a rare cause of infection in humans. Most commonly it is associated with endocarditis. Until 2019, less than 30 cases of human Lactoccous garviae infection have been published. To the best of our knowledge, we present the second reported case of SEA with spondylodiscitis caused by Lactococcus garviae. How Lactococcus garviae caused SEA, remains unclear in this case.

Enlarged tumefactive perivascular, or Virchow-Robin, spaces and hydrocephalus: do we need to treat? Illustrative cases.

BACKGROUND: Perivascular spaces (PVSs) are spaces in brain parenchyma filled with interstitial fluid surrounding small cerebral vessels. Massive enlargements of PVSs are referred to as "giant tumefactive perivascular spaces" (GTPVSs), which can be classified into three types depending on their localization. These lesions are rare, predominantly asymptomatic, and often initially misinterpreted as cystic tumor formations. However, there are several reported cases in which GTPVSs have induced neurological symptoms because of their size, mass effect, and location, ultimately leading to obstructive hydrocephalus necessitating neurosurgical intervention. Presented here are three diverse clinical presentations of GTPVS. OBSERVATIONS: Here, the authors observed an asymptomatic case of type 1 GTPVS and two symptomatic cases of type 3 GTPVS, one causing local mass effect and the other hydrocephalus. LESSONS: GTPVSs are mostly asymptomatic lesions. Patients without symptoms should be closely monitored, and biopsy is discouraged. Hydrocephalus resulting from GTPVS necessitates surgical intervention. In these cases, third ventriculostomy, shunt implantation, or direct cyst fenestration are surgical options. For patients presenting with symptoms from localized mass effect, a thorough evaluation for potential neurosurgical intervention is imperative. Follow-up in type 3 GTPVS is recommended, particularly in untreated cases. Given the infrequency of GTPVS, definitive guidelines for neurosurgical treatment and subsequent follow-up remain elusive.

Unveiling rupture risk and clinical outcomes in midline aneurysms: A matched cohort analysis investigating the impact of localization within the anterior or posterior circulation.

Intracranial aneurysms (IAs) located in the anterior and posterior circulations of the Circle of Willis present differential rupture risks. This study aimed to compare the rupture risk and clinical outcomes of anterior communicating artery aneurysms (AcomA) and basilar tip aneurysms (BAs); two IA types located along the midline within the Circle of Willis. We retrospectively collected data from 1026 patients presenting with saccular IAs. Only AcomA and BAs with a 3D angiography were included. Out of 186 included IAs, a cohort of 32 BAs was matched with AcomA based on the patients' pre-existing conditions and morphological parameters of IAs. Clinical outcomes, including rupture risk, hydrocephalus development, vasospasm incidence, and patients' outcome, were compared. The analysis revealed no significant difference in rupture risk, development of hydrocephalus, need for ventricular drainage, or vasospasm incidence between the matched AcomA and BA cohorts. Furthermore, the clinical outcomes post-rupture did not significantly differ between the two groups, except for a higher Fisher Grade associated with BAs. Once accounting for morphological and patient factors, the rupture risk between AcomA and BAs is comparable. These findings underscore the importance of tailored management strategies for specific IA types and suggest that further investigations should focus on the role of individual patient and aneurysm characteristics in IA rupture risk and clinical outcomes.

Concept of a fully-implantable system to monitor tumor recurrence.

Current treatment for glioblastoma includes tumor resection followed by radiation, chemotherapy, and periodic post-operative examinations. Despite combination therapies, patients face a poor prognosis and eventual recurrence, which often occurs at the resection site. With standard MRI imaging surveillance, histologic changes may be overlooked or misinterpreted, leading to erroneous conclusions about the course of adjuvant therapy and subsequent interventions. To address these challenges, we propose an implantable system for accurate continuous recurrence monitoring that employs optical sensing of fluorescently labeled cancer cells and is implanted in the resection cavity during the final stage of tumor resection. We demonstrate the feasibility of the sensing principle using miniaturized system components, optical tissue phantoms, and porcine brain tissue in a series of experimental trials. Subsequently, the system electronics are extended to include circuitry for wireless energy transfer and power management and verified through electromagnetic field, circuit simulations and test of an evaluation board. Finally, a holistic conceptual system design is presented and visualized. This novel approach to monitor glioblastoma patients is intended to early detect recurrent cancerous tissue and enable personalization and optimization of therapy thus potentially improving overall prognosis.

Extravascular optical coherence tomography of cerebral vessel walls in vivo.

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.

[Intracerebral Hemorrhage]. / Intrazerebrale Blutungen.

Intracerebral hemorrhage (ICB) causes approximately 12% of all strokes in Germany and 9-27% of all strokes worldwide 1 2. Epidemiological studies show a decrease in younger individuals mainly due to better antihypertensive management, but there is also an increase in incidence in older individuals due to cerebral amyloid angiopathy and increasing use of anticoagulants 3.

Spinal Meningioma Surgery through the Ages-Single-Center Experience over Three Decades.

Background and Objectives: Spinal meningiomas, which are well characterized and are most frequently intradural extramedullary tumors, represent 25% of all intradural spinal tumors. The goal of this study was to compare the outcomes of surgically treated patients with spinal meningiomas in two time intervals with special emphasis on postoperative functional outcomes. Methods: Patients with spinal meningiomas admitted to our department between 1990 and 2020 were enrolled and divided into a historic cohort (HC; treated 1990−2007) and a current cohort (CC; treated 2008−2020). Patients' clinical data and surgical and radiological reports were retrospectively analyzed up to 5 years. Preoperative and postoperative neurological function were assessed using the modified McCormick Scale (mMCS). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities on the preoperative status and postoperative outcome. Results: We included 300 patients. Participants in the CC (n = 144) were significantly younger compared to those in the HC (n = 156), with twice as many patients <50 years of age (p < 0.001). The most common tumor location was the thoracic spine (n = 204). The median follow-up was 38.1 months (±30.3 standard deviation). A symptom duration until surgery <12 months was significantly associated with an earlier improvement in the mMCS (p = 0.045). In the CC, this duration was shorter and patients' neurological function at the first and last follow-ups was significantly better than for those in the HC (p < 0.001 for both). Conclusions: Our study results suggested that the impact of surgical management and postoperative rehabilitation on spinal meningioma patients' long-term neurological outcome has reached important milestones over the last decades. An earlier diagnosis led to earlier surgical treatment and improved patients' postoperative neurological recovery. Our results exposed that surgical therapy for spinal meningioma should be performed within 12 months after appearance of symptoms to achieve a better recovery.

Angiosarcoma on Top of a Meningioma Mimicking a Transosseous Meningioma: an Interdisciplinary Point of View.

Cutaneous angiosarcoma is a rare type of sarcoma with poor prognosis. Meningioma is the most frequent benign intracranial tumor. Despite the fact that meningiomas are mostly benign, bone and skin can be infiltrated. We report the rare case of an angiosarcoma on top of a meningioma with hyperostosis at exactly the same location mimicking a transosseous growth of a meningioma. An 84-year-old man presented with progressive swelling and ulcerous lesion of the forehead. The patient underwent surgery in an interdisciplinary setting together with a plastic surgeon, including resection of the intracranial tumor and infiltrated bone and skin. To the best of our knowledge, this is the only reported case of a meningioma and angiosarcoma in direct neighborhood. A preoperative biopsy of the skin tumor would have led initially to the correct diagnosis of an angiosarcoma and would have allowed a better planning of the operation and extent of resection.

Overcoming Barriers in Neurosurgical Education: A Novel Approach to Practical Ventriculostomy Simulation.

BACKGROUND: In the high-risk, high-stakes specialty of neurosurgery, traditional teaching methods often fail to provide young residents with the proficiency needed to perform complex procedures in stressful situations, with direct effects on patient outcomes. Physical simulators provide the freedom of focused, hands-on training in a more controlled environment. However, the adoption of simulators in neurosurgical training remains a challenge because of high acquisition costs, complex production processes, and lack of realism. OBJECTIVE: To introduce an easily reproducible, cost-effective simulator for external ventricular drain placements through various ventriculostomy approaches with life-like tactile brain characteristics based on real patients' data. METHODS: Whole brain and skull reconstruction from patient's computed tomography and MRI data were achieved using freeware and a desktop 3-dimensional printer. Subsequently, a negative brain silicone mold was created. Based on neurosurgical expertise and rheological measurements of brain tissue, gelatin in various concentrations was tested to cast tactilely realistic brain simulants. A sample group of 16 neurosurgeons and medical students tested and evaluated the simulator in respect to realism, haptics, and general usage, scored on a 5-point Likert scale. RESULTS: We saw a rapid and significant improvement of accuracy among novice medical students. All participants deemed the simulator as highly realistic, effective, and superior to conventional training methods. CONCLUSION: We were able to demonstrate that building and implementing a high-fidelity simulator for one of the most important neurosurgical procedures as an effective educational and training tool is achievable in a timely manner and without extensive investments.

Life and death of molecular subclones in recurrent meningioma: A case study.

Meningiomas are the most common primary intracranial tumors, of which atypical meningiomas account for ~ 20%. A loss of NF2 has been proven to be an initial step for meningioma development; however, the role of non-NF2 alterations is unknown. Here we report a case of an atypical meningioma with a NF2 splice donor mutation and four recurrences. Using a custom NGS panel, further complex heterogenic molecular alterations were discovered. At first, one subclone of the initial tumor showed an additional PIK3CA variant, most likely of no pathogenic relevance. Then, the first and second recurrences no longer harbored the PIK3CA variant and no tumor heterogeneity was found. The tumor-driving NF2 mutation persisted, however. The latest, third recurrence showed a remarkable genetic heterogeneity with multiple, additional non-NF2 variants and a pathogenic PIKC3A mutation. In detail, one subclone showed a SUFU and two SMARCE1 variants. Another, geographically separate tumor subclone, in contrast, showed several different non-NF2 variants in SMO, PIK3CA and SUFU. Most important, one of the newly acquired PIK3CA alterations in the kinase domain (L1006F) is likely to be an additional tumor-driving mutation, which activates the PI3K-AKT-mTOR pathway. The reported genetic heterogeneity in meningiomas has been addressed in only a few studies. Although some of the detected variants in our case are expected to have biochemical consequences, these consequences are usually not likely to promote tumor development, when taking into account the suggested role of the altered proteins in tumorigenic pathways. However, the occurrence of a single oncogenic missense mutation in a subclone of the third recurrence may indicate a clonal change towards enhanced aggressiveness. Taken together, our case supports the need to perform in-depth studies to clarify the role of non-NF2 mutations for meningioma growth and development.

A comparison of input devices for precise interaction tasks in VR-based surgical planning and training.

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.

A new amplicon-based gene panel for next generation sequencing characterization of meningiomas.

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%), AKT1E17K (15%), and TRAF7 (13%). In 39 tumors (36%), two different mutations were detected, with NF2 and SUFU (n = 5) and KLF4 and TRAF7 (n = 5) being the most frequent combinations. No alterations were found in POLR2A, CDKN2A, CDKN2B, and BAP1, and no homozygous CDKN2A/B deletion was detected. NF2 mutations were found in tumors of all WHO grades, whereas mutations in KLF4, TRAF7, and SMO were restricted to WHO grade I meningiomas. In contrast, SMARCE1 and TERT mutations were associated with WHO grade II meningiomas (according to the WHO classification 2016). The distribution of mutations across histological subtypes or tumor localization was in line with the existing literature, with typical combinations like KLF4K409Q /TRAF7 for secretory meningiomas and preferential skull base localization of meningiomas harboring SMO and AKT1E17K mutations. Thus, we present a custom-made NGS meningioma panel providing a time and cost-efficient reliable detection of relevant somatic molecular alterations in meningiomas suitable for daily routine.

Brain biopsy in patients with CLIPPERS syndrome: why and when.

CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an inflammatory disorder of the central nervous system (CNS), predominantly involving the brainstem with a characteristic magnetic resonance imaging (MRI) appearance and clinical and radiological responsiveness to glucocorticosteroids. Yet diagnostic biomarkers are missing and other immune-mediated, (para-) infectious and malignant causes mimic CLIPPERS-like MRI presentations. We report the case of a 51-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. After 7 months, however, treatment failed, and he had a biopsy-confirmed diagnosis of a CNS B-cell lymphoma. Clinical and MRI signs of CLIPPERS include a wide spectrum of differential diagnoses which often arise only later during the course of disease. Similar to the case presented here, delayed diagnosis and specific therapy may contribute to an unfavorable outcome. Hence, we propose that in the absence of other diagnostic markers, brain biopsy should be performed as early as possible in CLIPPERS patients.

Theranostic applications of optical coherence tomography in neurosurgery?

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.

AKT1E17K -mutated meningioma cell lines respond to treatment with the AKT inhibitor AZD5363.

AIMS: 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. 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. CONCLUSIONS: Our data suggest that AKT1E17K mutated meningiomas are a promising selective target for AZD5363.

VR-based training of craniotomy for intracranial aneurysm surgery.

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.

Generation of an NFκB-Driven Alpharetroviral "All-in-One" Vector Construct as a Potent Tool for CAR NK Cell Therapy.

Immune cell therapeutics are increasingly applied in oncology. Especially chimeric antigen receptor (CAR) T cells are successfully used to treat several B cell malignancies. Efforts to engineer CAR T cells for improved activity against solid tumors include co-delivery of pro-inflammatory cytokines in addition to CARs, via either constitutive cytokine expression or inducible cytokine expression triggered by CAR recognition of its target antigen-so-called "T cells redirected for universal cytokine-mediated killing" (TRUCKs) or fourth-generation CARs. Here, we tested the hypothesis that TRUCK principles could be expanded to improve anticancer functions of NK cells. A comparison of the functionality of inducible promoters responsive to NFAT or NFκB in NK cells showed that, in contrast to T cells, the inclusion of NFκB-responsive elements within the inducible promoter construct was essential for CAR-inducible expression of the transgene. We demonstrated that GD2CAR-specific activation induced a tight NFκB-promoter-driven cytokine release in NK-92 and primary NK cells together with an enhanced cytotoxic capacity against GD2+ target cells, also shown by increased secretion of cytolytic cytokines. The data demonstrate biologically relevant differences between T and NK cells that are important when clinically translating the TRUCK concept to NK cells for the treatment of solid malignancies.

Definition and extraction of 2D shape indices of intracranial aneurysm necks for rupture risk assessment.

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[Formula: see text]), the 2D Ellipticity Index (EI[Formula: see text]) and the 2D Noncircularity Index (NCI[Formula: see text]). 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[Formula: see text] below 0.2. Of the aneurysms that have an NCI[Formula: see text] 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.