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Objective: This review article describes the characteristics of published literature using the cisterna magna blood injection mouse model of subarachnoid hemorrhage (SAH) with the aim to define particular standards and identify moderators of mortality rate, SAH grade, and large artery vasospasm. Methods: We searched for English-original peer-reviewed studies which reported the induction of SAH in mice via single or multiple blood injections into the cisterna magna. The search included studies published until 13th February 2023 on PubMed, Embase and Web of Science. Furthermore, we investigated the reporting of mortality rate, vasospasms by measuring large arteries, and SAH grade in cisterna magna blood injection mouse model. Results: Seven articles out of 136 identified records matched our inclusion criteria and were therefore included in descriptive analysis. Four articles reported the mortality rate which varied between zero and 22 percent. Five articles displayed vasospasms of large cerebral arteries including basilar artery (BA), anterior cerebral artery (ACA), and middle cerebral artery (MCA). Interestingly, the diameters of the observed arteries started to decrease already within the first hour after blood injection and achieved the lowest values at different times, but mainly between six and twelve hours after SAH induction. The artery diameters reached nearly their pre-SAH (control group) diameters approximately after four to seven days after SAH. However, the SAH severity grade was reported in none of these publications. No uniform model characteristics were observed in current literature. Conclusion: A systemic overview of the cisterna magna blood injection mouse model of SAH is presented. An important heterogeneity was observed. Hence, standardized model features and study endpoints have to be defined in order to improve reporting frequency and quality to enhance the reproducibility of preclinical SAH research in the future.

BACKGROUND: Non-vestibular schwannomas are relatively rare, with trigeminal and jugular foramen schwannomas being the most common. This is a heterogenous group which requires detailed investigation and careful consideration to management strategy. The optimal management for these tumours remains unclear, and there are several controversies. The aim of this paper is to provide insight into the main principles defining management and surgical strategy, in order to formulate a series of recommendations. METHODS: A task force was created by the EANS skull base section committee along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumours on a European perspective. To achieve this, the task force performed an extensive systematic review in this field and had discussions within the group. This article is the third of a three-part series describing non-vestibular schwannomas (IX, X, XI, XII). RESULTS: A summary of literature evidence was proposed after discussion within the EANS skull base section. The constituted task force dealt with the practice patterns that exist with respect to preoperative radiological investigations, ophthalmological assessments, optimal surgical and radiotherapy strategies and follow-up management. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the treatment of non-vestibular schwannomas. For each of these tumours, the management paradigm is shifting towards the compromise between function preservation and progression free survival.

ZusammenfassungAusgewertet wurden 86 Patienten mit einem retrosigmoidal mikrochirurgisch resezierten Vestibularisschwannom im Tumorstadium Koos II–IV. Es zeigte sich, dass im Bereich des inneren Gehörgangs in über 2/3 der Fälle der Nervus cochlearis dem elektroneurographisch leicht zu identifizierenden Nervus facialis in immer wiederkehrenden ähnlichen Verlaufsmustern folgte. Ausgehend vom Fundus erleichterte dies die frühzeitige Identifizierung und damit den Kontinuitätserhalt des Nervus cochlearis im Verlauf des inneren Gehörgangs. Dies war vor allem dann von Bedeutung, wenn ein sicherer Funktionserhalt aufgrund der Tumorgröße oder -formation trotz intraoperativer Ableitung somatosensorischer Potenziale nicht sicher gewährleistet werden konnte, aber die Möglichkeit einer späteren Hörrehabilitation mit einem Cochleaimplantat bestehen bleiben sollte. Präoperative Magnetresonanztomographie(MRT)-Sequenzen ergaben zwar in einigen Fällen einen Hinweis auf die möglichen Nervenverläufe, die intraoperative Darstellung im inneren Gehörgang war der MRT aber überlegen.

Robust preclinical models are inevitable for researchers to unravel pathomechanisms of subarachnoidal hemorrhage (SAH). For the mouse perforation model of SAH, the goal of this meta-review was the determination of variances in mortality, SAH severity grade, and vasospasm, and their experimental moderators, as many researchers are facing with incomparable results. We searched on the databases PubMed, Embase, and Web of Science for articles describing in vivo experiments using the SAH perforation mouse model and measuring mortality, SAH grade, and/or vasospasm. After screening, 42 articles (total of 1964 mice) were included into systematic review and meta-analysis. Certain model characteristics were insufficiently reported, e.g., perforation location (not reported in six articles), filament (material (n = 15) and tip texture (n = 25)), mouse age (n = 14), and weight (n = 10). Used injective anesthetics and location of perforation showed large variation. In a random-effects meta-analysis, the overall animal mortality following SAH was 21.3% [95% CI: 17.5%, 25.7%] and increased with longer observational periods. Filament material significantly correlated with animal mortality (p = 0.024) after exclusion of hyperacute studies (time after SAH induction

Zusammenfassung Hintergrund Die Schädelbasis stellt eine chirurgisch hochkomplexe Einheit dar und ist häufig nur über kombinierte Zugangswege erreichbar. Neu entwickelte Operationstechniken mit Verwendung von mikrochirurgischen Visualisierungsverfahren und aktiven Instrumenten („powered instruments“) sowie „Multi-Port-Zugänge“ ermöglichen neue, weniger traumatische Operationskorridore. Hierfür ist eine enge interdisziplinäre Zusammenarbeit zwischen dem Chirurgen aus dem Fachgebiet der Hals-Nasen-Ohren-Heilkunde sowie dem Neurochirurgen notwendig. Die aktuell etablierten Zugangsverfahren zur zentralen Schädelbasis werden aufgrund eigener klinischer Erfahrungen und unter Berücksichtigung der Entität systematisiert und in Bezug auf die aktuelle Studienlage erörtert. Material und Methode Es erfolgte eine retrospektive, qualitative und deskriptive Auswertung der Operationsberichte einzelner Patienten, die in der Zeit zwischen 2006 und 2019 mit Pathologien an der zentralen Schädelbasis chirurgisch gemeinsam von der Neurochirurgie und der Hals-Nasen-Ohren-Heilkunde/Kopf- und Halschirurgie behandelt wurden. Ergebnisse Die chirurgischen Zugangswege zur zentralen Schädelbasis ließen sich nachfolgend kategorisieren, teilweise auch in Kombination derselben, als sog. Multi-Port-Zugänge: transnasal-transsphenoidal, subfrontal, subtemporal, transzygomatisch, transpterygonal, transpetrös, translabyrinthär und subokzipital. Maßgebend für die Wahl des Zugangswegs waren die Lokalisation und Art der Pathologie, sowie der mögliche Anspruch auf Funktionserhalt und Komplettentfernung. Schlussfolgerung Aufgrund der Komplexität der Strukturen der zentralen Schädelbasis, der unterschiedlichsten Tumorentitäten und der benötigten Fachkompetenz unterschiedlicher Facharztdisziplinen bleibt die Chirurgie der zentralen Schädelbasis eine Herausforderung, der man sich nur an speziellen, nach den Kriterien der Gesellschaft für Schädelbasischirurgie e. V. zertifizierten Kompetenzzentren stellen sollte.

The optimal management of petroclival meningiomas (PCMs) continues to be debated along with several controversies that persist. A task force was created by the EANS skull base section along with its members and other renowned experts in the field to generate recommendations for the management of these tumors. To achieve this, the task force reviewed in detail the literature in this field and had formal discussions within the group. The constituted task force dealt with the existing definitions and classifications, pre-operative radiological investigations, management of small and asymptomatic PCMs, radiosurgery, optimal surgical strategies, multimodal treatment, decision-making, and patient’s counselling. This article represents the consensually derived opinion of the task force with respect to the management of PCMs.

OBJECTIVEAneurysm wall enhancement (AWE) on 3D vessel wall MRI (VWMRI) has been suggested as an imaging biomarker for intracranial aneurysms (IAs) at higher risk of rupture. While computational fluid dynamics (CFD) studies have been used to investigate the association between hemodynamic forces and rupture status of IAs, the role of hemodynamic forces in unruptured IAs with AWE is poorly understood. The authors investigated the role and implications of abnormal hemodynamics related to aneurysm pathophysiology in patients with AWE in unruptured IAs.METHODSTwenty-five patients who had undergone digital subtraction angiography (DSA) and VWMRI studies from September 2016 to September 2017 were included, resulting in 22 patients with 25 IAs, 9 with and 16 without AWE. High-resolution CFD models of hemodynamics were created from DSA images. Univariate and multivariate analyses were performed to investigate the association between AWE and conventional morphological and hemodynamic parameters. Normalized MRI signal intensity was quantified and quantitatively associated with wall shear stresses (WSSs) for the entire aneurysm sac, and in regions of low, intermediate, and high WSS.RESULTSThe AWE group had lower WSS (p < 0.01) and sac-averaged velocity (p < 0.01) and larger aneurysm size (p < 0.001) and size ratio (p = 0.0251) than the non-AWE group. From multivariate analysis of both hemodynamic and morphological factors, only low WSS was found to be independently associated with AWE. Sac-averaged normalized MRI signal intensity correlated with WSS and was significantly different in regions of low WSS compared to regions of intermediate (p = 0.018) and high (p < 0.001) WSS.CONCLUSIONSThe presence of AWE was associated with morphological and hemodynamic factors related to rupture risk. Low WSS was found to be an independent predictor of AWE. Our findings support the hypothesis that low WSS in IAs with AWE may indicate a growth and remodeling process that may predispose such aneurysms to rupture; however, a causality between the two cannot be established.

Objective Lately, morphological parameters of the surrounding vasculature aside from aneurysm size, specific for the aneurysm location, e.g., posterior cerebral artery angle for basilar artery tip aneurysms, could be identified to correlate with the risk of rupture. We examined further image-based morphological parameters of the aneurysm surrounding vasculature that could correlate with the growth or the risk of rupture of basilar artery tip aneurysms. Methods Data from 83 patients with basilar tip aneurysms (27 not ruptured; 56 ruptured) and 100 control patients were assessed (50 without aneurysms and 50 with aneurysms of the anterior circle of Willis). Anatomical parameters of the aneurysms were assessed and analyzed, as well as of the surrounding vasculature, namely the asymmetry of P1 and the vertebral arteries. Results Patients with basilar tip aneurysm showed no significant increase in P1 or vertebral artery asymmetry compared with the control patients or patients with aneurysms of the anterior circulation, neither was there a significant difference in asymmetry between cases with ruptured and unruptured aneurysms. Furthermore, we observed no significant correlations between P1 asymmetry and the aneurysm size or number of lobuli in the aneurysms. Conclusion We observed no significant difference in aneurysm size, rupture, or lobulation associated with P1 or vertebral artery (surrounding vasculature) asymmetry. Therefore, the asymmetry of the surrounding vessels does not seem to be a promising morphological parameter for the evaluation of probability of rupture and growth in basilar tip aneurysms in future studies.

•OGM surgery is much more complex than a simple debate of "from above or from below" (transcranial vs endoscopic).•Lateral Sub-frontal and Superior Interhemispheric seem the most effective, superior and versatile approaches for OGM.•Minimally Invasive Transcranial approaches showed no inferiority in OGM sized

Background The optimal management of clinoidal meningiomas (CMs) continues to be debated. Methods We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of these tumors. The data from the literature along with contemporary practice patterns were discussed within the task force to generate consensual recommendations. Results and conclusion This article represents the consensus opinion of the task force regarding pre-operative evaluations, patient’s counselling, surgical classification, and optimal surgical strategy. Although this analysis yielded only Class B evidence and expert opinions, it should guide practitioners in the management of patients with clinoidal meningiomas and might form the basis for future clinical trials.

INTRODUCTION Dorsal root ganglion stimulation (DRG) is a new but well-established neuromodulation technique allowing new indications and superiority to pre-existing stimulation techniques such as spinal cord stimulation in selected pain etiologies. Previous surgical procedures in the implantation area pose a challenge for the percutaneous technique and are therefore considered contraindications for DRG stimulation surgery. We describe the successful open DRG electrode placement in two patients with previous surgeries suffering from severe radiculopathy due to foraminal stenosis. METHODS Percutaneous implantation attempts failed and an open laminotomy/foraminotomy followed by open lead placement was performed. Leads and loops were placed under the microscope, lead location was verified by x-ray during surgery. Leads and loops were kept in position with fibrin glue and fibrin sealant patches. No special tool was required for open lead placement. RESULTS In both patients, surgery resulted in lead and loop placement resembling the results seen in percutaneous technique. Programming and stimulation results are similar to observations made following percutaneous techniques in one patient significantly lower stimulation amplitudes were necessary. In 18 and 12 months follow-up, respectively, lead location and paresthesia coverage were stable. CONCLUSION The option of open electrode placement should be taken into account following unsuccessful percutaneous lead placement. A combination of fibrin sealant patch and fibrin glue may be a good option for stabilization of the lead and specially of the strain relief loops in open placement. Knowledge of basic spinal surgery techniques and experience in percutaneous DRG stimulation is necessary to perform this procedure.

Background Patients with aneurysmal subarachnoid hemorrhage (aSAH) are at risk of the development of chronic shunt-dependent hydrocephalus. However, identification of shunt-dependent patients remains challenging. We sought to develop a prognostic model to identify patients with aSAH at risk of chronic shunt-dependent hydrocephalus. In addition to the well-known prognostic variables, blood clearance in the cerebrospinal fluid (CSF) spaces was considered. Methods We retrospectively analyzed the data from 227 patients treated at our institution from January 2012 to January 2016. The outcome was ventriculoperitoneal shunt placement within 30 days after aSAH. The candidate prognostic variables were patient age, World Federation of Neurological Surgeons grade and Fisher grade, external ventricular drainage, ventricular and intracerebral hemorrhage, and interval to blood clearance in the peripheral/basal CSF spaces. Adjustment for multiple testing was performed. Multivariable logistic regression analysis was used for model development. Bootstrapping was applied for internal validation. The model performance measures included indexes for explained variance (R2), calibration (graphic plot, Hosmer-Lemeshow test), and discrimination (c-statistic). Results Of the 227 patients, 90 (39.6%) required a ventriculoperitoneal shunt. The constructed prognostic model combined external ventricular drainage placement, the presence of ventricular blood, and the duration of blood clearance in the basal cisterns. The model performance was promising, with an R2 of 33% (20% after bootstrapping), the calibration plot was adequate, the Hosmer-Lemeshow test result was not significant, and the c-statistic was 0.85 (0.84 as assessed after bootstrapping) indicating a good discriminating prognostic model. Conclusions Our prognostic model could help identify patients requiring permanent CSF diversion after aSAH, although additional modification and external validation are needed. Interventions aimed at accelerating the clearance of blood in the basal cisterns might have the potential to prevent the development of chronic hydrocephalus after aSAH.

Decompressive craniectomy (DC) is rarely required in infants, but when performed several aspects should be considered: These youngest patients are vulnerable to blood loss and cranial reconstruction can be challenging due to skull growth and bone flap resorption. On the other hand, infants have thin and flexible bone and osteogenic potential. The authors propose a technique which makes use of these unique aspects by achieving decompression with the craniofacial method of barrel stave osteotomy, aiming to achieve adequate DC, limit perioperative risks and facilitate subsequent cranial reconstruction.

Background De novo aneurysm formation after completely occluded aneurysms via clipping or coiling has not been well studied. Although known to occur several years after initial aneurysm management, the natural history of de novo aneurysms is obscure. We investigated the formation of new aneurysms in patients who had previously undergone treatment of intracranial aneurysms. Methods In a retrospective, single-institutional series, eligible patients who had undergone treatment of ruptured cerebral aneurysms from 2000 to 2011 were included. The primary outcome measure was the development of de novo aneurysms during long-term follow-up. Results Overall, 130 patients (63% women) who had undergone microsurgical clipping (n = 63; 48.5%) or endovascular coiling (n = 67%; 51.5%) for ruptured aneurysms were included. The average follow-up time for our cohort was 10 ± 2.7 years. De novo aneurysms occurred in 10 of 130 patients (7.7%), with a mean time of 7.9 years for aneurysm detection. No association between the formation of de novo aneurysms and the location of the treated aneurysms, smoking status, hypertension, age, or gender was found. Follow-up imaging studies were performed every 2 years. De novo aneurysms had formed in 2 patients within 2–5 years, 7 patients after 5–10 years, and 1 patient after 10 years of follow-up. In 2 of 10 patients, the de novo aneurysm had ruptured and led to subarachnoid haemorrhage. Conclusion The rate of de novo aneurysm occurrence was 7.6%, with a mean time to development of 7.9 years. This underscores the significance of long-term monitoring of patients with intracranial aneurysms. In our series, most new aneurysms had occurred after 5 years of follow-up.

Bow hunter's syndrome is a rare clinical condition. It is caused by dynamic compression of the vertebral artery (VA) either at the level of the transverse foramina (V2 segment) or at the atlantoaxial level (V3 segment). We report a 54-year-old man with typical bow hunter's syndrome caused by compression at the level of C6/C7. He was successfully treated by anterolateral VA decompression without a need for stabilization. We present preoperative imaging (magnetic resonance imaging, computed tomographic angiography, and dynamic angiography) and a high-quality intraoperative video detailing each step of the surgical technique (high-definition video with annotations and audio track of the Doppler ultrasound used as intraoperative control). Furthermore, postoperative imaging and a video of the clinical outcome are presented. Adequate management of bow hunter's syndrome requires good pathophysiologic understanding of the disease and careful clinical examination. Dynamic angiography confirms the exact site of VA compression. Surgical decompression is the treatment of the cause. Surgical techniques include VA decompression by an anterolateral approach (V2 or V3) or a posterior approach (V3). Some authors advocate stand-alone stabilization, which is, however, only an indirect treatment and results in significant loss of head motion. Other nonsurgical treatments such as orthesis, medical therapy, or endovascular stenting have been only anecdotally reported. Bow hunter's syndrome is best treated by VA decompression. This may safely be achieved by good anatomic knowledge and a straightforward surgical technique. Here, the anterolateral approach is presented in detail in a high-definition surgical instruction video.

Objective To evaluate a new surgical tool combining suction and monopolar neurostimulation (stimulation sucker) for cerebellopontine angle (CPA) tumors. The usefulness for continuous (time) and dynamic (space) facial nerve mapping was studied. Methods Patients operated on with the stimulation sucker for a CPA tumor between April 2016 and May 2017 in a tertiary care center were identified. Clinical charts were retrospectively evaluated. The minimum follow-up time of patients was 12 months. Results The study population included 17 patients with tumor (6 women and 11 men). The age range was from 2 to 77 years (mean age, 45.7 years; standard error of the mean, 22.7 years). Most CPA tumors were large (Koos grade 4) vestibular schwannomas (n = 10); other pathologies included petrous meningioma (n = 1), metastasis (n = 1), medulloblastoma (n = 2), ependymoma (n = 2), and pilocytic astrocytoma (n = 1). One patient with trigeminal neuralgia served as the normal control subject. No complications because of the stimulation sucker were encountered. Clinical and radiologic outcomes compared favorably with institutional experience and literature. The stimulation sucker allowed for continuous (time) mapping of the facial nerve at the site of resection (space). This real-time feedback allowed early identification of the facial nerve. Handling and ergonomy were excellent and workflow improved. The shortcomings compared with a bayonet-shaped bipolar probe were decreased visibility of neurovascular structures and lower spatial discrimination. The new device did not simplify delicate at the brainstem and on the nerve. We think it should be considered as a complementary tool in the surgeon's armamentarium. Conclusions Until now, nerve damage as assessed by neuromonitoring (e.g., facial nerve electromyography, motor evoked potential) served as surrogate for nerve function. This concept should be challenged. The studied stimulation sucker detected the facial nerve earlier than conventional techniques, preventing harm by surgical trauma. A larger, prospective study is warranted to better define its role in CPA surgery.

In patients with aneurysmal subarachnoid hemorrhage (aSAH) and multiple aneurysms, there is a need to objectively identify the ruptured aneurysm. Additionally, studying the intra-individual rupture risk of multiple aneurysms eliminates extrinsic risk factors and allows a focus on anatomical factors, which could be extrapolated to patients with single aneurysms too. Retrospective bi-center study (Department of Neurosurgery of the University Hospital Duesseldorf and Bern) on patients with multiple aneurysms and subarachnoid hemorrhage caused by the rupture of one of them. Parameters investigated were height, width, neck, shape, inflow angle, diameter of the proximal and distal arteries, width/neck ratio, height/width ratio, height/neck ratio, and localization. Statistical analysis and logistic regressions were performed by the R program, version 3.4.3. N = 186 patients with aSAH and multiple aneurysms were treated in either department from 2008 to 2016 (Bern: 2008-2016, 725 patients and 100 multiple aneurysms, Duesseldorf: 2012-2016, 355 patients, 86 multiple aneurysms). The mean age was 57 years. N = 119 patients had 2 aneurysms, N = 52 patients had 3 aneurysms, N = 14 had 4 aneurysms and N = 1 had 5 aneurysms. Eighty-four percent of ruptured aneurysms were significantly larger than the largest unruptured. Multilobularity of ruptured aneurysms was significantly higher than in unruptured. Metric variables describing the geometry (height, width, etc.) and shape are the most predictive for rupture. One or two of them alone are already reliable predictors. Ratios are completely redundant in saccular aneurysms.

Background There are controversies concerning the natural history of arteriovenous malformations (AVMs) in literature and it is not clear which AVMs should be treated and which should be just observed. Objective criteria beyond growth in serial MRIs or angiographies are needed. The use of black blood MRI is currently under investigation for evaluating the rupture risk of cerebral aneurysms, however its use for assessment of AVMs has yet to be evaluated. We therefore conducted a feasibility study on the application of black blood MRI (bbMRI) in AVMs to assess rupture risk. Methods Retrospective study of 10 patients with intracranial AVMs and 4 patients with arteriovenous fistulas who received a black blood MRI before treatment. Results AVM niduses (9/10) show contrast enhancement irrespective of rupture or size. All arteriovenous fistulas (4 / 4) were contrast enhancing irrespective of rupture. Conclusion High flow malformations are in a permanent stage of inflammation which does not seem to allow conclusions on their rupture risk at the current stage. BbMRI is a feasible method of identifying inflammation in AVMs and arteriovenous fistulas. However, future prospective studies are needed to evaluate whether bbMRI contrast enhancement correlates with rupture risk.

Objective To compare fluorescence intensity of tumor specimens, as measured by a fluorescence-guided surgery microscope and a spectrometer, to evaluate tumor infiltration of dura mater around meningiomas with help of these 2 different 5-aminolevulinic acid (5-ALA)-based fluorescence tools, and to correlate fluorescence intensity with histopathologic data. Material and Methods In a clinical series, meningiomas were resected by 5-ALA fluorescence-guided surgery. Fluorescence intensity was semiquantitatively rated by the surgeon at predefined points. Biopsies were harvested and fluorescence intensity measured by a spectrometer and histopathologically analyzed. Sampling was realized at the level of the dura in a centrifugal direction. Results A total of 104 biopsies (n = 13 tumors) were analyzed. Specificity and sensitivity of the microscope were 0.96 and 0.53 and of the spectrometer 0.95 and 0.93, respectively. Fluorescence intensity as measured by the spectrometer was correlated to histologically confirmed tumor burden. In a centrifugal direction, tumor burden and fluorescence intensity continuously decreased (along the dural tail). Below a threshold value of 639 arbitrary units no tumor was histologically detectable. Conclusions At the level of the dura the spectrometer was highly sensitive for detection of meningioma cells. The surgical microscope showed false negative results and missed residual tumor cells in more than one half of the cases. The complementary use of both fluorescence tools may improve resection quality.

Chordomas are very rare tumors of the skull base and the sacrum. They show infiltrating and destructive growth and are known to be chemo- and radio-resistant. After surgical resection, the recurrence rate is high and overall survival limited. As current adjuvant treatments are ineffective, new treatment concepts are urgently needed. 5-aminolevulinic acid-based photodynamic therapy (5-ALA based PDT) showed promising results for malignant gliomas. However, it is unknown so far, whether chordomas accumulate protoporphyrin IX (PPIX) after application of 5-ALA and whether they are sensitive to subsequent 5-ALA based PDT.The immortalized human chordoma cells U-CH2 were used as in vitro model. After incubation for 4h or 6h with different 5-ALA concentrations, PPIX accumulation was determined by flow cytometry. To assess sensitivity to PDT, chordoma cells were incubated at 30.000cells/well (high cell density) or 15.000cells/well (low cell density) with graded doses of 5-ALA (0-50μg/ml) in 96-well plates and subsequently exposed to laser light of 635nm wavelength (18.75J/cmU-CH2 cells dose-dependently accumulated PPIX (ANOVA; p0.0001). PPIX fluorescence was significantly higher, when cells were incubated with 5-ALA for 6h compared to 4h at higher 5-ALA concentrations (ANOVA/Bonferroni; p≤0.05 for≥30μg/ml 5-ALA). For both cell densities, a 5-ALA dose-dependent decline in viability was observed (ANOVA; p0.0001). Viability was significantly lower at higher 5-ALA concentrations, when 30.000 cells/wells were treated compared to 15.000cells/well (ANOVA/Bonferroni; p≤0.001 for≥30μg/ml 5-ALA). LD50 was 30.25μg/ml 5-ALA.The human UCH-2 cell line was a very useful in vitro model to study different effects of 5-ALA based PDT. For the first time, it could be shown that human chordoma cells may be destroyed by 5-ALA/PDT.

Objectives The pathophysiology of traumatic brain injury (TBI) largely involves the brains vascular structural integrity. We analyzed the value of an intraoperative cortical indocyanine green (ICG) angiography in patients with severe TBI and acute subdural hematoma who underwent decompressive craniectomy. Methods ICG-derived fluorescence curves of cortex and cerebral vessels were recorded by the use of software integrated into a surgical microscope in 10 patients. The maximum intensity, rise time (RT), time to peak, and residual fluorescence intensity (FI) were estimated from cortical arteries, the parenchyma, and veins. Results ICG-derived fluorescence parameters were correlated with the short-term outcome 3 months after discharge. Five patients had a favorable and 5 an unfavorable outcome. Patients with a favorable outcome showed a significant longer RT in the arteries and a trend towards a significant longer RT in the veins. Overall mean residual FI was 47.5 ± 6.8% for the arteries, 45.0 ± 7% for the parenchyma and 57.6 ± 6% for the veins. The residual FI of the parenchyma and the veins was significantly greater in patients with an unfavorable clinical outcome. Conclusions Patients with an unfavorable clinical outcome showed an altered shape of the ICG-derived fluorescence curve, a shorter increase of the ICG-derived fluorescence intensity in the cortical arteries, and significantly greater residual fluorescence intensity. These observations are likely a correlate of an increased intracranial pressure, a capillary leak, and venous congestion. Intraoperative quantification of the ICG-derived fluorescence might help to appreciate the clinical outcome in patients with severe TBI.

Background and objective: The optimal management of large vestibular schwannomas continues to be debated. We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of this problem from a European perspective. Material and methods: A systematic review of MEDLINE database, in compliance with the PRISMA guidelines, was performed. A subgroup analysis screening all surgical series published within the last 20 years (January 2000 to March 2020) was performed. Weighted summary rates for tumor resection, oncological control, and facial nerve preservation were determined using meta-analysis models. This data along with contemporary practice patterns were discussed within the task force to generate consensual recommendations regarding preoperative evaluations, optimal surgical strategy, and follow-up management. Results: Tumor classification grades should be systematically used in the perioperative management of patients, with large vestibular schwannomas (VS) defined as > 30 mm in the largest extrameatal diameter. Grading scales for pre- and postoperative hearing (AAO-HNS or GR) and facial nerve function (HB) are to be used for reporting functional outcome. There is a lack of consensus to support the superiority of any surgical strategy with respect to extent of resection and use of adjuvant radiosurgery. Intraoperative neuromonitoring needs to be routinely used to preserve neural function. Recommendations for postoperative clinico-radiological evaluations have been elucidated based on the surgical strategy employed. Conclusion: The main goal of management of large vestibular schwannomas should focus on maintaining/improving quality of life (QoL), making every attempt at facial/cochlear nerve functional preservation while ensuring optimal oncological control, thereby allowing to meet patient expectations. Despite the fact that this analysis yielded only a few Class B evidences and mostly expert opinions, it will guide practitioners to manage these patients and form the basis for future clinical trials., SCOPUS: re.j, info:eu-repo/semantics/published

Introduction: There is still controversial discussion of the value of transcranial Doppler (TCD) in predicting vasospasms in patients with aneurysmal SAH (aSAH). A newer method of predicting a delayed ischemic deficit (DCI) is CT perfusion (CTP), although it is not quite understood which kind of perfusion deficit is detected by this method since it seems to also identifying microcirculatory disturbances. We compared the TCD and CTP values with angiography and evaluated TCD and CTP changes before and after patients received intra-arterial spasmolytic therapy.

Background Incomplete resection of pituitary adenomas may result in recurrence. As adjuvant irradiation is not riskless, alternative treatment options should be investigated. 5-aminolevulinic acid based photodynamic therapy (5-ALA based PDT) showed promising results for malignant gliomas. The present study examined the efficacy of 5-ALA PDT in vitro on benign pituitary adenoma cell cultures. Methods In group I experiments were performed on immortalized rat pituitary adenoma cells (GH3). The cultured cells were treated with different 5-ALA concentrations ranging from 7.5–16.5 μg/ml. In Group II human pituitary adenoma cell cultures were obtained from surgically resected adenoma tissue ( n = 15). These were incubated with 5-ALA concentrations from 12.5–100 μg/ml. The concentration ranges had been determined in preliminary dose-finding tests. For both groups incubation time was four hours and PDT was performed by exposition to laser light (635 nm, 625 s, 18.75 J/cm 2 ). Cell viability was examined by WST-1 assay. Results In both groups PDT showed a 5-ALA concentration-dependent effect on cell death. In group I lower 5-ALA concentrations were necessary to destroy all cells as compared to group II. Moreover, in group II, the different subtypes of human adenomas showed different sensitivities to 5-ALA-based PDT (secreting vs . non-secreting). Especially corticotroph adenomas were highly sensitive to 5-ALA PDT. Conclusions The GH3 cell line was an useful in vitro model to optimize different PDT parameters. Human pituitary adenoma cells could also be killed by 5-ALA PDT, however this required higher 5-ALA concentrations. Furthermore, the results suggested different 5-ALA sensitivities between different human adenoma cell types. More experiments are necessary to confirm these preliminary results.

5-Aminolevulinic acid (5-ALA)-fluorescence-guided resection is well established in many neuro-oncologic centers. Different classifications of 5-ALA-induced fluorescence have been reported. The aim of the systematic analysis was to evaluate the frequency of graduations, definitions, and designations of 5-ALA-induced fluorescence qualities. A systematic database search of PubMed was performed to identify studies reporting (1) on 5-ALA fluorescence-guided either spinal or cranial surgery, (2) on qualitative estimation and/or categorization of 5-ALA-induced fluorescence, (3) in English, and (4) were published as peer-reviewed original studies. Totally, 93 studies were identified. Different classification systems of 5-ALA-induced fluorescence were found. Over 60 % of the included studies used a dichotomized categorization of 5-ALA-induced fluorescence and 27.5 % of studies distinguished two different intensities of 5-ALA fluorescent tissue in addition to non-fluorescing tissue. More than 50 % of studies explicitly defined criteria for categorization of 5-ALA-induced fluorescence. The major limitation of the present analysis might be that it mainly comprises data from retrospective, uncontrolled, non-randomized trials. However, a precise definition of each 5-ALA-induced fluorescence quality is essential. Although dichotomized classification is the most common and simple graduation system, it may not be suitable for every clinical or scientific task. A three-level 5-ALA-induced fluorescence classification with precise definition of each fluorescence quality and their correlation with histological features would be more useful and reproducible in these cases.

Background Integrity of intervertebral disks may influence, and be influenced by, the maintenance of hydrostatic pressures inside the nucleus pulposus. Disk degeneration causes decreased pressures, leading to overload and injury of the annulus fibrosus, increasing the risk of disk herniation. Diskectomies to treat disk herniation can cause further loss of hydrostatic pressures resulting in worsening degeneration. This study investigated the impact of opening the annulus on intradiscal pressure and whether implantation of an annular closure device (ACD) can restore physiologic pressures. Methods The pressure responses under unconstrained moments in concert with axial compressive loads of nine human cadaver lumbar disks were biomechanically tested at baseline, immediately following posterior annulotomy, and immediately following implantation of the ACD. Results The analysis of variance indicated a significant difference in the pressure response (p = 0.0001) among the three rounds of testing. Specifically, the post hoc Bonferroni test revealed that the pressure response after diskectomy was significantly different when compared with baseline (p Conclusion Our findings suggest that restoration of annular integrity during diskectomy with implantation of the tested ACD may restore pressures closer to preoperative levels. Whether or not restoring pressures to preoperative levels has any clinical benefit or effect on the rate of degeneration is an area for further clinical research.

Intracranial metastases are the most frequent brain tumor with recurrence rates after treatment of around 40–60%. Age is still considered a determinant of treatment and prognosis in this pathology. Recent studies analyzing the impact of metastasectomy in elderly patients focused on reporting perioperative mortality and morbidity rates but not on the evaluation of oncological outcome parameters. Aim of this study is to determine risk factors for in-brain local recurrence after brain surgery in this sub-population. From October 2009 until September 2016 all patients aged 65 years and above with histopathologically confirmed metastasis after surgical resection were retrospectively studied. Clinical, radiological and perioperative information was collected and statistically analysed. Follow-up consisted of clinical and radiological assessment every 3-months following surgery. 78 patients were included, of these 50% were female (39 patients). Median age was 71 years (66–83). Early postoperative-MRI verified a complete surgical resection in 41 patients (52.6%) and showed a tumor-remnant in 15 patients (19.2%). In 22 patients the MRI result was inconclusive (28.2%). None of the patients experienced severe complications due to surgery. The median postoperative NIHSS was adequate 1 ± 1.4 (0–6), nonetheless, insignificantly improved in comparison to the preoperative NIHSS (p = 0.16). A total of 20 patients (25.6%) presented local recurrence. The only statistically significant factor for development of local in-brain recurrence after resection of cerebral metastases in patients above 65 years of age was a tumor-remnant in the early postoperative MRI (p = 0.00005). Median overall survival was 13 months. Local in-brain recurrence after surgical resection of a cerebral metastasis in patients above 65 years of age was 25.6%. In our analysis, tumor-remnant in early postoperative MRI is the only risk factor for local in-brain recurrence. Oncological parameters in the present cohort do not seem to differ from recent phase III studies with non-geriatric patients. Nevertheless, controlled studies on the impact of metastasectomy in elderly patients delivering high quality reliable data are required.

Compression syndromes of the vertebral artery that occur at the craniocervical junction are extremely rare causes of haemodynamic insufficiency of the posterior cerebral circulation. The aetiology of the compression syndrome may be a malformation, trauma, tumour, infection or degenerative pathology. This may lead to dynamic vertebral artery occlusion where the vessel courses around the atlas and the axis-the so-called V3 segment. This in turn may result in insufficient collateral flow to the posterior fossa. The clinical picture is a vertebrobasilar insufficiency syndrome of variable expression ranging from vertigo to posterior fossa stroke. The typical clinical presentation is syncope occurring during rotation of the head, also known as 'bow hunter's syndrome'. The workup is based on dynamic angiography and computed tomography angiography. The treatment of choice is surgical vascular decompression, resulting in a good clinical outcome. However, in some instances, atlantoaxial fusion may be indicated. Alternatively, conservative and endovascular options have to be considered in inoperable patients.

Compression syndromes of the vertebral artery that occur at the craniocervical junction are extremely rare causes of haemodynamic insufficiency of the posterior cerebral circulation. The aetiology of the compression syndrome may be a malformation, trauma, tumour, infection or degenerative pathology. This may lead to dynamic vertebral artery occlusion where the vessel courses around the atlas and the axis—the so-called V3 segment. This in turn may result in insufficient collateral flow to the posterior fossa. The clinical picture is a vertebrobasilar insufficiency syndrome of variable expression ranging from vertigo to posterior fossa stroke. The typical clinical presentation is syncope occurring during rotation of the head, also known as ‘bow hunter’s syndrome’. The workup is based on dynamic angiography and computed tomography angiography. The treatment of choice is surgical vascular decompression, resulting in a good clinical outcome. However, in some instances, atlantoaxial fusion may be indicated. Alternatively, conservative and endovascular options have to be considered in inoperable patients.

Background Minimally invasive surgery of small skull base meningiomas is technically challenging. We report the role of endoscopic 5-aminolevulinic acid fluorescence guidance (e-5-ALA-FGS) for small and deep-seated anterior skull base meningiomas. Methods We report the cases of 2 patients. The first case was a small olfactory groove meningioma resected via a trans-eyebrow, subfrontal approach. The second case was a clinoid meningioma with invasion of the optic canal resected via a small frontolateral approach. Intraoperative documentation demonstrated the usefulness of 5-ALA endoscopy. In either case, residual fluorescing tumor tissue was detected. No complication was encountered. The clinical and radiological outcomes were good. No regrowth had occurred after 54 and 17 months of follow-up, respectively. Results Residual meningioma tissue on the far side of a keyhole approach (e.g., in the olfactory groove or at the optic canal) can be difficult to visualize. Visualization can be improved by use of an endoscope. To date, fluorescence guidance with a microscope was limited by insufficient fluorescence signals in deep corridors. With a specially equipped 5-ALA fluorescence endoscope, one can combine the advantages of both endoscopic vision and fluorescence guidance. The results of present report have demonstrated the usefulness of 5-ALA endoscopy for difficult to visualize areas. Conclusion Endoscopic 5-ALA fluorescence guidance was shown to be feasible when resecting small and deep-seated skull base meningiomas via minimally invasive approaches. Based on this proof of principle, we encourage its evaluation for the middle or posterior fossa (e.g., internal auditory canal) and other difficult areas (e.g., behind neurovascular structures or the brainstem). The sensitivity and specificity of this method should be prospectively and systematically investigated.