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Background Entrustable professional activities (EPAs) represent an assessment framework with an increased focus on competency-based assessment. Originally developed and adopted for undergraduate medical education, concerns over resident ability to practice effectively after graduation have led to its implementation in residency training but yet not in vascular neurosurgery. Subjective assessment of resident or fellow performance can be problematic, and thus, we aim to define core EPAs for neurosurgical vascular training. Methods We used a nominal group technique in a multistep interaction between a team of experienced neurovascular specialists and a medical educator to identify relevant EPAs. Panel members provided feedback on the EPAs until they reached consent. Results The process produced seven core procedural EPAs for vascular residency and fellowship training, non-complex aneurysm surgery, complex aneurysm surgery, bypass surgery, arteriovenous malformation resection, spinal dural fistula surgery, perioperative management, and clinical decision-making. Conclusion These seven EPAs for vascular neurosurgical training may support and guide the neurosurgical society in the development and implementation of EPAs as an evaluation tool and incorporate entrustment decisions in their training programs.

Considerable progress has been made over the past years to better understand the genetic nature and pathophysiology of brain AVM. For the actual review, a PubMed search was carried out regarding the embryology, inflammation, advanced imaging, and fluid dynamical modeling of brain AVM. Whole-genome sequencing clarified the genetic origin of sporadic and familial AVM to a large degree, although some open questions remain. Advanced MRI and DSA techniques allow for better segmentation of feeding arteries, nidus, and draining veins, as well as the deduction of hemodynamic parameters such as flow and pressure in the individual AVM compartments. Nonetheless, complete modeling of the intranidal flow structure by computed fluid dynamics (CFD) is not possible so far. Substantial progress has been made towards understanding the embryology of brain AVM. In contrast to arterial aneurysms, complete modeling of the intranidal flow and a thorough understanding of the mechanical properties of the AVM nidus are still lacking at the present time.

Isocitrate dehydrogenase (IDH)-wildtype glioblastoma is the most common primary malignant brain tumor. It is associated with a particularly poor prognosis, as reflected by an overall median survival of only 15 months in patients who undergo a supramarginal surgical reduction of the tumor mass followed by combined chemoradiotherapy. The highly malignant nature of IDH-wildtype glioblastoma is thought to be driven by glioblastoma stem-like cells (GSCs) that harbor the ability of self-renewal, survival, and adaptability to challenging environmental conditions. The wingless (WNT) signaling pathway is a phylogenetically highly conserved stemness pathway, which promotes metabolic plasticity and adaptation to a nutrient-limited tumor microenvironment. To unravel the reciprocal regulation of the WNT pathway and the nutrient-limited microenvironment, glioblastoma cancer stem-like cells were cultured in a medium with either standard or reduced glucose concentrations for various time points (24, 48, and 72 h). Glucose depletion reduced cell viability and facilitated the survival of a small population of starvation-resistant tumor cells. The surviving cells demonstrated increased clonogenic and invasive properties as well as enhanced chemosensitivity to pharmacological inhibitors of the WNT pathway (LGK974, berberine). Glucose depletion partially led to the upregulation of WNT target genes such as CTNNB1, ZEB1, and AXIN2 at the mRNA and corresponding protein levels. LGK974 treatment alone or in combination with glucose depletion also altered the metabolite concentration in intracellular compartments, suggesting WNT-mediated metabolic regulation. Taken together, our findings suggest that WNT-mediated metabolic plasticity modulates the survival of GSCs under nutrient-restricted environmental conditions.

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.

OBJECTIVEThe objective of this study was to measure the concentration of nimodipine in CSF and plasma after intraventricular injection of a sustained-release formulation of nimodipine (EG-1962) in patients with aneurysmal subarachnoid hemorrhage (SAH).METHODSPatients with SAH repaired by clip placement or coil embolization were randomized to EG-1962 or oral nimodipine. Patients were classified as grade 2–4 on the World Federation of Neurosurgical Societies grading scale for SAH and had an external ventricular drain inserted as part of their standard of care. Cohorts of 12 patients received 100–1200 mg of EG-1962 as a single intraventricular injection (9 per cohort) or they remained on oral nimodipine (3 per cohort). Plasma and CSF were collected from each patient for measurement of nimodipine concentrations and calculation of maximum plasma and CSF concentration, area under the concentration-time curve from day 0 to 14, and steady-state concentration.RESULTSFifty-four patients in North America were randomized to EG-1962 and 18 to oral nimodipine. Plasma concentrations increased with escalating doses of EG-1962, remained stable for 14 to 21 days, and were detectable at day 30. Plasma concentrations in the oral nimodipine group were more variable than for EG-1962 and were approximately equal to those occurring at the EG-1962 800-mg dose. CSF concentrations of nimodipine in the EG-1962 groups were 2–3 orders of magnitude higher than in the oral nimodipine group, in which nimodipine was only detected at low concentrations in 10% (21/213) of samples. In the EG-1962 groups, CSF nimodipine concentrations were 1000 times higher than plasma concentrations.CONCLUSIONSPlasma concentrations of nimodipine similar to those achieved with oral nimodipine and lasting for 21 days could be achieved after a single intraventricular injection of EG-1962. The CSF concentrations from EG-1962, however, were at least 2 orders of magnitude higher than those with oral nimodipine. These results supported a phase 3 study that demonstrated a favorable safety profile for EG-1962 but yielded inconclusive efficacy results due to notable differences in clinical outcome based on baseline disease severity.Clinical trial registration no.: NCT01893190 (ClinicalTrials.gov).

Objective Isocitrate dehydrogenase (IDH)-wildtype glioblastomas are the most malignant glial tumours. Median survival is only 14–16 months after diagnosis, with patients aged ≥ 65 years reportedly showing worse outcome. This study aimed to further evaluate the prognostic role of age in a homogenously treated patient cohort. Methods The study includes 132 IDH-wildtype glioblastoma patients treated between 2013 and 2017 with open resection followed by radiotherapy with concomitant and maintenance temozolomide. Patients were dichotomized into a non-elderly (MGMT) promoter methylation status were determined for each tumour. Clinical and radiological follow-up data were obtained at 6 weeks after the end of radiation therapy and thereafter in 3-month intervals. Progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate cox regression analyses. Results The elderly group consisted of 58 patients (median age: 70.5 years) and the non-elderly group of 74 patients (median age: 55 years). Median pre- and postoperative operative Karnofsky Performance Scale (KPS), Eastern Cooperative Oncology Group (ECOG) score and National Institutes of Stroke Scale (NIHSS) were not significantly different between the groups, but KPS and ECOG scores became significantly worse in the elderly group at 6 weeks after termination of radiation therapy. Neither PFS nor OS differed significantly between the age groups. Patients with MGMT promoter-methylated tumours survived longer. Conclusion Elderly patients in good pre- and postoperative clinical conditions may show similar outcome as younger patients when treated according to standard of care. However, elderly patients may suffer more frequently from clinical deterioration following chemoradiotherapy. In both age groups, MGMT promoter methylation was linked to longer PFS and OS.

Background Prior studies have suggested an association between patient socioeconomic status and brain tumors. In the present study we attempt to indirectly validate the findings, using health insurance status as a proxy for socioeconomic status. Methods There are 2 types of health insurance in Germany: statutory and private. Owing to regulations, low- and middle-income residents are typically statutory insured, whereas high-income residents have the option of choosing a private insurance. We compared the frequencies of privately insured patients suffering from malignant neoplasms of the brain with the corresponding frequencies among other neurosurgical patients at our hospital and among the German population. To correct for age, sex, and distance from the hospital, we included these variables as predictors in logistic and binomial regression. Results A significant association (odds ratio [OR] = 1.59, CI = 1.45-1.74, P < .001) between health insurance status and brain tumors was found. The association is independent of patients’ sex or age. Whereas privately insured patients generally tend to come from farther away, such a relationship was not observed for patients suffering from brain tumors. Comparing the out of house and in-house brain tumor patients showed no selection bias on our side. Conclusion Previous studies have found that people with a higher income, level of education, or socioeconomic status are more likely to suffer from malignant brain tumors. Our findings are in line with these studies. Although the reason behind the association remains unclear, the probability that our results are due to some random effect in the data is extremely low.

Background We report the first case of a purely intraventricular calcifying pseudoneoplasm of neuraxis (CAPNON) in the posterior third ventricle. Case Description A 63-year-old male without any previous medical history presented with Hakim triad. Imaging showed a calcified lesion of the posterior third ventricle with hydrocephalus. An endoscopic third ventriculostomy was performed. Endoscopic removal or debulking of the lesion was impossible due to its rock-hard consistency, and thus the procedure was aborted after biopsy. Conclusions When encountering such calcified lesions within the ventricular system, especially in proximity to eloquent regions, the decision making process should include the hard consistency and parenchymal adhesions as obstacles to neuroendoscopic removal. Even for biopsy, a higher morbidity rate compared with typical soft tumors should be assumed. Although data on intraventricular CAPNON is limited, biopsy of the lesion and treatment of associated hydrocephalus appear to be the primary neurosurgical goals, followed by imaging surveillance.

In 1999 a visionary short article by The Wall Street Journal writers Robert Langreth and Michael Waldholz popularized the new term “personalized medicine,” that is to say, the targeting of drugs to each unique genetic profile. From today’s perspective, targeted approaches have clearly found the widest use in the antineoplastic domain. The current review was initiated to review the progress that has been made regarding the treatment of patients with advanced cancer and brain metastases. PubMed was searched for the terms brain metastasis, brain metastases, or metastatic brain in the Title/Abstract. Selection was limited to randomized controlled trial (RCT) and publication date January 2010 to February 2022. Following visual review, 51 papers on metastatic lung cancer, 12 on metastatic breast cancer, and 9 on malignant melanoma were retained and underwent full analysis. Information was extracted from the papers giving specific numbers for intracranial response rate and/or overall survival. Since most pharmacological trials on advanced cancers excluded patients with brain metastases and since hardly any information on adjuvant radiotherapy and radiosurgery is available from the pharmacological trials, precise assessment of the effect of targeted medication for the subgroups with brain metastases is difficult. Some quantitative information regarding the success of targeted pharmacological therapy is only available for patients with breast and lung cancer and melanoma. Overall, targeted approaches approximately doubled the lifespan in the subgroups of brain metastases from tumors with targetable surface receptors such as anaplastic lymphoma kinase (ALK) fusion receptor in non-small cell lung cancer or human epidermal growth factor receptor 2 (HER2)–positive breast cancer. For these types, overall survival in the situation of brain metastases is now more than a year. For receptor-negative lung cancer and melanoma, introduction of immune checkpoint blockers brought a substantial advance, although overall survival for melanoma metastasized to the brain appears to remain in the range of 6 to 9 months. The outlook for small cell lung cancer metastasized to the brain apparently remains poor. The introduction of targeted therapy roughly doubled survival times of advanced cancers including those metastasized to the brain, but so far, targeted therapy does not differ essentially from chemotherapy, therefore also facing tumors developing escape mechanisms. With the improved perspective of patients suffering from brain metastases, it becomes important to further optimize treatment of this specific patient group within the framework of randomized trials.

Predictive analytics are increasingly reported by clinicians. These tools aim to improve patient outcomes in terms of quality, safety, and efficiency. However, deploying predictive analytics in clinical practice remains challenging today. We highlight several advantages and disadvantages of the application of predictive analytics in clinical practice. To flourish and reach its potential, predictive analytics need data that is of adequate quantity and quality, ideally tailored to clinical scenarios in equipoise regarding optimal management. Adequate reporting of predictive analytic tools is incumbent for uptake into clinical workflows. At least for now, the clinicians' knowledge, experience, and vigilance remain imperative for applying predictive analytics in clinical practice.

Purpose Intravenous and intra-arterial milrinone as a rescue measure for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been adopted by several groups, but so far, evidence for the clinical benefit is unclear and effect on brain perfusion is unknown. The aim of the actual analysis was to define cerebral hemodynamic effects and outcome of intravenous milrinone plus norepinephrine supplemented by intra-arterial nimodipine as a rescue strategy for DCI following aneurysmal SAH. Methods Of 176 patients with aneurysmal SAH treated at our neurosurgical department between April 2016 and March 2021, 98 suffered from DCI and were submitted to rescue therapy. For the current analysis, characteristics of these patients and clinical response to rescue therapy were correlated with hemodynamic parameters, as assessed by CT angiography (CTA) and perfusion CT. Time to peak (TTP) delay in the ischemic focus and the volume with a TTP delay of more than 4 s (T4 volume) were used as hemodynamic parameters. Results The median delay to neurological deterioration following SAH was 5 days. Perfusion CT at that time showed median T4 volumes of 40 cc and mean focal TTP delays of 2.5 ± 2.1 s in these patients. Following rescue therapy, median T4 volume decreased to 10 cc and mean focal TTP delay to 1.7 ± 1.9 s. Seventeen patients (17% of patients with DCI) underwent additional intra-arterial spasmolysis using nimodipine. Visible resolution of macroscopic vasospasm on CTA was observed in 43% patients with DCI and verified vasospasm on CTA, including those managed with additional intra-arterial spasmolysis. Initial WFNS grade, occurrence of secondary infarction, ischemic volumes and TTP delays at the time of decline, the time to clinical decline, and the necessity for additional intra-arterial spasmolysis were identified as the most important features determining neurological outcome at 6 months. Conclusion The current analysis shows that cerebral perfusion in the setting of secondary cerebral ischemia following SAH is measurably improved by milrinone and norepinephrine–based hyperdynamic therapy. A long-term clinical benefit by the addition of milrinone appears likely. Separation of the direct effect of milrinone from the effect of induced hypertension is not possible based on the present dataset.

Purpose A possible disadvantage of endovascular occlusion outside work hours is that complex procedures might expose patients to additional risk when performed in a suboptimal setting. In this prospective cohort study, we evaluated whether treatment during out of office hours is a risk factor for per-procedural complications and clinical outcome. Methods We included 471 endovascular-treated, consecutive aneurysmal subarachnoid hemorrhage patients (56.6 ± 13.1, 69% female), from two prospective observational databases which were retrospectively analyzed. Primary outcome was the occurrence of per-procedural complications. Secondary outcomes were good clinical outcome (modified ranking scale ≤ 2) and death at 6-month follow-up. We determined odds ratios (OR) with 95% confidence intervals (CI) by ordered polytomous logistic regression analysis and adjusted odds ratios (aOR) for age, World Federation of Neurosurgical Societies grade, and time to treatment. Results Most patients were treated during office hours (363/471; 77.1%). Treatment during out of office hours did not result in an increased risk of per-procedural complications (OR 0.85 (95% CI 0.53–1.37; p = 0.51). Patients treated during out of office hours displayed similar odds of good clinical outcome and death after 6 months (OR 1.14, 95% CI 0.68–1.97 and 1.16 95% CI 0.56–2.29, respectively) compared to patients treated during office hours. Conclusion In our study, endovascular coil embolization during out of office hours did not expose patients to an increased risk of procedural complications or affect functional outcome after 6 months.

The cerebellum is historically implicated in motor coordination, but accumulating modern evidence indicates involvement in non-motor domains, including cognition, emotion, and language. This correlates with the symptoms observed in postoperative cerebellar mutism syndrome (CMS). Profound knowledge of cerebellar functional topography and tractography is important when approaching cerebellar tumors, as surgical trauma to relevant structures of cerebellar pathways plays a role in the pathogenesis of CMS. The aim of this systematic review is to provide a concise overview of relevant modern neuroimaging data and cerebellar functional tracts with regard to neurosurgical procedures.

Objective Symptomatic spine metastases are found in about 10% of patients with cancer. As the long-term survival of patients with carcinoma rises, the number of patients with symptomatic spine metastases is also increasing. In our tertiary referral center, patients usually present rapidly progressive neurologic disorders, which require an urgent treatment decision. Treatment options include extensive 360° stabilizations. These complex interventions are not always readily available. We examined the extent to which the patient population benefited from decompressive surgery without stabilization. We hypothesize that patients benefit from merely dorsal decompression, which preserves stability when they experience symptomatic spine metastases. Methods We performed a retrospective analysis of electronic patient data from 19 patients, who were treated for symptomatic spine metastases by hemilaminectomy between 2009 and 2017. We evaluated the preoperative and postoperative neurologic functions using the American Spinal Injury Association (ASIA) Impairment Scale. A comparative literature analysis was carried out to assess the Spinal Neoplastic Instability Score, Tokuhashi score, and Tomita score. Results Nine participants had prostate cancer, 4 had mammary carcinoma, 3 had bronchial carcinoma, and 3 had other cancers. The median preoperative ASIA score was C, postoperatively, the score significantly improved to D (sign test P = 0.002). None of the patients needed stabilization within the follow-up period of up to 56 months. Conclusions In our patient population, minimal intervention could significantly improve neurologic disorders. This outcome was seen over the whole study period. Even though different scoring systems suggest stabilization, our results show that spinal decompression alone might be indicated as well.

Objective With the introduction of the 5-aminolevulinic acid (5-ALA) technique, surgical neuro-oncology has made a major advance. 5-ALA fluorescence–guided resection of malignant glioma results in more complete surgical resections and subsequently prolonged survival. However, it remains uncertain how light intensities of the blue light source and 5-ALA–derived fluorescence intensities of the illuminated tissue are connected. The aim of the present study was to compare light intensities of different blue light sources and protoporphyrin (PpIX) fluorescence intensities of PpIX solutions with defined concentrations after illumination with different light sources. Material and Methods The light spectrum of 7 different blue light sources and the fluorescence intensity of 2 PpIX solutions (0.15 μg/mL and 5 μg/mL) were quantified after illumination. We compared the Zeiss OPMI Pentero microscope, the Zeiss OPMI Pentero 900 microscope, the Leica M530 OH6 microscope, an endoscope equipped with the 5-ALA technique, a mini-spectrometer equipped with a multi-channel light-emitting diode (LED) source emitting monochromatic light, a modified commercially available LED head lamp, and a commercially available unmodified UV-LED lamp. PpIX fluorescence was quantified in a standardized setup using a mini-spectrometer. Results Maximum light intensities of the evaluated light sources were reached at different wavelengths. All tested devices were able to detect PpIX-induced fluorescence. However, the intensity of PpIX fluorescence of the differently concentrated PpIX solutions (0.15 μg/mL and 5 μg/mL) was significantly dependent on the light source used. Conclusions Intensity of the 5-ALA–derived fluorescence is related to the light source used.

5-ALA fluorescence-guided surgery (FGS) is a major advance in neuro-oncological surgery. So far, Protoporphyrin IX (PpIX)-fluorescence has been observed in about half of cerebral metastases resected with routinely equipped microscopes during 5-ALA FGS. The aim of the present pilot study was to quantify PpIX-induced fluorescence of cerebral metastases with a spectrometer. We hypothesize that non-fluorescing metastases under the operating microscope may have spectrometrically measurable levels of fluorescence. A second aim was to analyze correlations between quantified 5-ALA fluorescence and histology or primary tumor type, respectively. Standard FGS was performed in all patients. The fluorescence intensity of the metastasis was semi-quantitatively determined in vivo by a senior surgeon using a special surgical microscope equipped for FGS. A systematic spectrometric ex vivo evaluation of tumor specimens and PpIX-induced fluorescence was performed using a spectrometer connected by optic fibers to a handheld probe. Quantification of 5-ALA-derived fluorescence was measured in a standardized manner with direct contact between mini-spectrometer and metastasis. The difference between the maximum PpIX-fluorescence at 635 nm and the baseline fluorescence was defined as the PpIX fluorescence intensity of the metastasis and given in arbitrary units (AU). Diagnosis of a cerebral metastasis was confirmed by histopathological analysis. A total of 29 patients with cerebral metastases were included. According to neuropathological analysis, 11 patients suffered from non-small cell lung cancer, 10 patients from breast cancer, 6 patients from cancer originating in the gastro-intestinal tract, 1 patient suffered from a malignant melanoma and one patient from renal cancer. The mean age was 63 years (37–81 years). 15 patients were female, 14 patients male. 13 cerebral metastases were considered as ALA-positive by the surgeon. In nine metastases, 5-ALA fluorescence was not visible to the naked eye and could only be detected using the spectrometer. The threshold for an ALA signal rated as “positive” by the surgeon was PpIX fluorescence above 1.1 × 106 AU. The mean PpIX fluorescence of all analyzed cerebral metastases was 1.29 × 106 ± 0.23 × 106 AU. After quantification, we observed a significant difference between the mean 5-ALA-derived fluorescence in NSCLC and breast cancer metastases (Mean Diff: − 1.2 × 106; 95% CI of difference: − 2.2 × 106 to − 0.15 × 106; Sidak-adjusted p = 0.026). In our present pilot series, about half of cerebral metastases showed a 5-ALA fluorescence invisible to the naked eye. Over 50% of these non-fluorescent metastases show a residual 5-ALA fluorescence which can be detected and quantified using a spectrometer. Moreover, the quantified 5-ALA signal significantly differed with respect to the primary tumor of the corresponding cerebral metastasis. Further studies should evaluate the predictive value of the 5-ALA signal and if a quantified 5-ALA signal enables a reliable intraoperative differentiation between residual tumor tissue and edematous brain—in particular in metastases with a residual fluorescence signal invisible to the naked eye.

Study design Retrospective analysis of anonymized malpractice claims. Summary of background data Spine surgery is considered a high-risk specialty with regards to malpractice claims. However, limited data is available for Germany. We analyzed the rate, subject, and legal outcome of malpractice claims faced by spine surgeons in one of the largest Medical Council coverage areas in Germany, representing 60,000 physicians and a population of 10 million. Methods Analysis of all malpractice claims regarding spinal surgeries completed by the Review Board of the North Rhine Medical Council (NRMC) from 2012 to 2016. Claim merit, content, and actual treatment errors were reviewed. Severity of damage was graded from negligible (1) to death (6). Results A total of 8,381 malpractice cases were reviewed by the NRMC from 2012 to 2016. Four percent (340 cases: 181 females, 159 males) pertained to patients undergoing spinal surgery with 94.7% of patients undergoing inhospital treatment and 5.3% as outpatients. Malpractice claims most frequently involved neurosurgery (48.5%) and orthopedic surgery (37.6%). Trauma surgery was involved in 9.1% and other specialties in 4.8%. Actual treatment errors were found in 89 of 340 cases (26.2%).Of those, 81 resulted in treatment-associated health impairment. Negligible and/or temporary impairment was found in 49.3%. Negligible to moderate but permanent damage was observed in 39.5%. Nine patients suffered severe permanent damage or death (11.1%). The treated diagnosis was degenerative disc disease in 34 patients (41.9%), spinal canal stenosis in 13 (16%), vertebral body fractures in 10 (12.3%), spondylolisthesis in 6 (7.4%), and other diagnoses accounting for the remaining 18 (22.2%). Errors involved actual surgical treatment in 40.7%, surgical indication and preoperative workup in 28.4%, postoperative treatment in 25.9%, and patient consent in 4.9%. Conclusions Spinal surgery claims account for 4% of all claims reviewed by the NRMC in the 5-year period from 2012 to 2016. Eighty-nine (26.2%) were deemed justified. The majority of treatment errors (59.3%) occurred during workup, indication and consent, or during postoperative care. Errors during actual surgery were responsible for 40.7% of all treatment-associated damages. Understanding the distribution and content of claims is key to improving patient satisfaction not only by honing surgical skills, but also by improving pre- and postoperative communication and care.

Malignant stroke occurs in a subgroup of patients suffering from ischemic cerebral infarction and is characterized by neurological deterioration due to progressive edema, raised intracranial pressure, and cerebral herniation. Decompressive craniectomy (DC) is a surgical technique aiming to open the “closed box” represented by the non-expandable skull in cases of refractory intracranial hypertension. It is a valuable modality in the armamentarium to treat patients with malignant stroke: the life-saving effect has been proven for both supratentorial and infratentorial DC in virtually all age groups. This leaves physicians with the difficult task to decide who will require early or preemptive surgery and who might benefit from postponing surgery until clear evidence of deterioration evolves. Together with the patient’s relatives, physicians also have to ascertain whether the patient will have acceptable disability and quality of life in his or her presumed perception, based on preoperative predictions. This complex decision-making process can only be managed with interdisciplinary efforts and should be supported by continued research in the age of personalized medicine.

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.

Elevated levels of unbound unconjugated bilirubin (UCB) can lead to bilirubin encephalopathy and kernicterus. In spite of a large number of studies demonstrating UCB-induced changes in central neurotransmission, it is still unclear whether these effects involve alterations in the function of specific ion channels. To assess how different UCB concentrations and UCB:albumin (U/A) molar ratios affect neuronal R-type voltage-gated Ca2+ channels, we evaluated their effects on whole-cell currents through recombinant Cav2.3 + β3 channel complexes and ex-vivo electroretinograms (ERGs) from wildtype and Cav2.3-deficient mice. Our findings show that modestly elevated levels of unbound UCB (U/A = 0.5) produce subtle but significant changes in the voltage-dependence of activation and prepulse inactivation, resulting in a stimulation of currents activated by weak depolarization and inhibition at potentials on the plateau of the activation curve. Saturation of the albumin binding capacity (U/A = 1) produced additional suppression that became significant when albumin was omitted completely and might involve a complete loss of channel function. Acutely administered UCB (U/A = 0.5) has recently been shown to affect transsynaptic signaling in the isolated vertebrate retina. The present report reveals that sustained exposure of the murine retina to UCB significantly suppresses also late responses of the inner retina (b-wave) from wildtype compared to Cav2.3-deficient mice. In addition, recovery during washout was significantly more complete and faster in retinae lacking Cav2.3 channels. Together, these findings show that UCB affects cloned and native Cav2.3 channels at clinically relevant U/A molar ratios and indicate that supersaturation of albumin is not required for modulation but associated with a loss of channel functional that could contribute to chronic neuronal dysfunction.

Background Randomized trials on spontaneous lobar intracerebral hemorrhage (ICH) provided no convincing evidence of the superiority of surgical treatment. Since recruitment in the trials was under the premise of equipoise, a selection bias toward patients who did not need surgery or were in hopeless condition must be suspected. The aim of the actual analysis was to compare outcome and patient profile of an unselected hospital series with recent randomized trials and to develop a prognostic model. Methods Of 821 patients with spontaneous ICH managed at the neurosurgical department of the University Hospital Düsseldorf between 2013 and 2018, 159 had lobar bleedings. Patient characteristics, hematoma volume, treatment modality, and 6-month survival were compared with STICH II and the subset of lobar hemorrhage in the MISTIE III trial. In addition, a prognostic model for 6-month survival in our patients was developed using a random forest classifier. Results One hundred and seven patients were managed by surgical evacuation of the hematoma and 52 without surgical evacuation. Median hemorrhage volume in our surgical cohort was 66 and 42 mL in the conservative cohort, compared with 38 and 36 mL in the STICH II trial, and 46 and 47 mL in the surgical and conservative MISTIE III lobar hemorrhage subset. Median initial Glasgow Coma Scale (GCS) score was 12 in our surgical group and 11 in the conservative group, compared with 13 in the STICH II cohorts and 12 in the MISTIE III lobar hemorrhage subset. Median age in our surgical and conservative cohorts was 73 and 74 years, respectively, compared with 65 years in both STICH II cohorts and 68 years in the MISTIE II subsets. Twenty-nine percent of our surgical cohort and 55% of our conservatively managed patients deceased within the first 6 months, compared with 18 and 24%, respectively, in STICH II and 17 and 24% in the MISTIE III subset. Our prognostic model identified large hemorrhage volumes and low admission GCS score as main unfavorable prognostic factors for 6-month survival. The random forest classifier achieved a predictive accuracy of 78% and an area under curve (AUC)- value of 88% regarding survival at 6 months, on a test set independent of the training set. Conclusions In comparison with our surgical group, the STICH II and MISTIE III cohorts, recruited under the premise of physician equipoise, underrepresented patients with large ICHs. The cohorts in the randomized trials were therefore biased toward patients with a favorable perspective under conservative management. Initial hematoma volume and admission GCS were the main prognostic factors in our patients.

Simple Summary Glioblastoma (GBM) is the most aggressive form of glioma (WHO grade IV), and mounting evidence suggests that glioblastoma stem-like cells (GSCs) play an important role in tumor growth and response to therapy. In the current study, we sought to understand the metabolic dependencies of GSCs using high-resolution proton magnetic resonance spectroscopy (1H-NMR). In a defined experimental setting, we stratified in vitro GSC models into two subtypes (Gln/GluHigh, Gln/GluLow) and used diverse molecular approaches to perform comprehensive analyses in GSC neurosphere cultures and primary GBM samples. Abstract Cancer stem-like cells mediate tumor initiation, progression, and therapy resistance; however, their identification and selective eradication remain challenging. Herein, we analyze the metabolic dependencies of glioblastoma stem-like cells (GSCs) with high-resolution proton nuclear magnetic resonance (1H-NMR) spectroscopy. We stratify our in vitro GSC models into two subtypes primarily based on their relative amount of glutamine in relationship to glutamate (Gln/Glu). Gln/GluHigh GSCs were found to be resistant to glutamine deprivation, whereas Gln/GluLow GSCs respond with significantly decreased in vitro clonogenicity and impaired cell growth. The starvation resistance appeared to be mediated by an increased expression of the glutamate/cystine antiporter SLC7A11/xCT and efficient cellular clearance of reactive oxygen species (ROS). Moreover, we were able to directly correlate xCT-dependent starvation resistance and high Gln/Glu ratios with in vitro clonogenicity, since targeted differentiation of GSCs with bone morphogenic protein 4 (BMP4) impaired xCT expression, decreased the Gln/Glu ratio, and restored the sensitivity to glutamine starvation. Moreover, significantly reduced levels of the oncometabolites lactate (Lac), phosphocholine (PC), total choline (tCho), myo-inositol (Myo-I), and glycine (Gly) were observed in differentiated GSCs. Furthermore, we found a strong association between high Gln/Glu ratios and increased expression of Zinc finger E-box-binding homeobox 1 (ZEB1) and xCT in primary GBM tumor tissues. Our analyses suggest that the inhibition of xCT represents a potential therapeutic target in glioblastoma; thus, we could further extend its importance in GSC biology and stress responses. We also propose that monitoring of the intracellular Gln/Glu ratio can be used to predict nutrient stress resistance.

Objective: Vaccination therapy using tumour antigen-loaded, autologous dendritic cells (DC) is a promising therapeutic approach alongside standard treatment for glioblastoma (GBM). However, reliable diagnostic criteria regarding therapy monitoring are not established. Here, we analysed the impact of additional 18F-fluoroethyl-tyrosine positron emission tomography (18F-FET PET) imaging following DC vaccination therapy.Methods: We analysed data of GBM patients who received DC vaccination therapy. Following MRI diagnosis of tumour recurrence, additional static and dynamic 18F-FET PET imaging was performed. Vaccination was performed five times by intradermal injections, either weekly between concomitant radio/-chemotherapy and intermittent chemotherapy or after tumour recurrence, before re-radiation therapy. MRI and 18F-FET PET results were compared and correlated with clinical data.Results: Between 2003 and 2016, 5 patients were identified who received DC vaccination and 18F-FET PET imaging (1 female/4 males; mean age: 44 ± 14 y). 3/5 patients showed congruent results of tumour progression. In three patients 18F-FET PET indicated treatment related changes, which was in contrast to MRI findings that indicated tumour progression. In these patients 18F-FET PET results could be confirmed by either neuropathological diagnosis or according to the RANO criteriaConclusions: Despite the small patients number our results indicate an additional impact of 18F-FET PET for monitoring outcome following vaccination therapy.

Objectives: Lennox-Gastaut syndrome (LGS) is among the most severe epileptic and developmental encephalopathies. A meta-analysis was performed to evaluate the effectiveness of adjunctive vagus nerve stimulation (VNS Therapy) in patients with LGS. Materials & Methods: PubMed database was queried (January 1997 to September 2018) to identify publications reporting on the efficacy of VNS Therapy in patients with LGS, with or without safety findings. Primary endpoint of the meta-analysis was the proportion of responders (≥50% reduction in seizure frequency). Random-effects analysis was used to calculate weighted mean estimates and confidence intervals. Heterogeneity was evaluated by statistical tests including I2. Results: Of 2752 citations reviewed, 17 articles (480 patients) were eligible including 10 retrospective studies and seven prospective studies. A random-effects model produced a pooled proportion of 54% (95% confidence intervals [CI]: 45%, 64%) of patients with LGS who responded to adjunctive VNS Therapy (p for heterogeneity

Contains fulltext : 225137.pdf (Publisher’s version ) (Open Access) Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for the failed translational results. The present article proposes a standardized definition for DCI in experimental mouse models, which can be used as outcome measure in future animal studies. We used a consensus-building approach to propose a definition for "experimental secondary ischemia" (ESI) in experimental mouse subarachnoid hemorrhage that can be used as an outcome measure in preclinical studies. We propose that the outcome measure should be as follows: occurrence of focal neurological impairment or a general neurological impairment compared with a control group and that neurological impairment should occur secondarily following subarachnoid hemorrhage (SAH) induction compared with an initial assessment following SAH induction. ESI should not be used if the condition can be explained by general anesthesia or if other means of assessments sufficiently explain function impairment. If neurological impairment cannot reliably be evaluated, due to scientific setup. Verification of a significant secondary impairment of the cerebral perfusion compared with a control group is mandatory. This requires longitudinal examination in the same animal. The primary aim is that ESI should be distinguished from intervention-related ischemia or neurological deficits, in order establish a uniform definition for experimental SAH in mice that is in alignment with outcome measures in human studies.

Surgery of single cerebral metastases is standard but frequently fails to achieve local tumour control. Reliable predictors for local tumour progression and overall survival are unknown. MRI-based apparent diffusion coefficients (ADC) correlate with tumour cellularity and invasion. The present study analysed a potential relation between the MRI based apparent diffusion coefficients local recurrence and outcome in patients with brain metastases.A retrospective analysis was performed for patients with cerebral metastases and complete surgical resection evaluated by an early postoperative MRI72h. Minimal ADC and mean ADC were assessed in preoperative 1,5T-MRI scans by placing regions of interests in the tumour and the peritumoural tissue.Analysis of the relation between ADC values, local progression and outcome was performed in 86 patients with a mean age of 59 years (range 33-83 years). Primary site was NSCLC in 37.2% of all cases. Despite complete resection 33.7% of all patients suffered from local in-brain-progression. There were no significant differences in ADC values in groups based on histology. In the present cohort, the mean ADCmin and the mean ADCmean within the metastasis did not differ significantly between patients with and without a later local in-brain progression (634 × 10In the present study analysed ADC values had no significant impact on local in brain progression and survival parameters.

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.

Limitations in genetic stability and recapitulating accurate physiological disease properties challenge the utility of patient-derived (PD) cancer models for reproducible and translational research. A portfolio of isogenic human induced pluripotent stem cells (hiPSCs) with different pan-cancer relevant oncoprotein signatures followed by differentiation into lineage-committed progenitor cells was genetically engineered. Characterization on molecular and biological level validated successful stable genetic alterations in pluripotency state as well as upon differentiation to prove the functionality of our approach. Meanwhile proposing core molecular networks possibly involved in early dysregulation of stem cell homeostasis, the application of our cell systems in comparative substance testing indicates the potential for cancer research such as identification of augmented therapy resistance of stem cells in response to activation of distinct oncogenic signatures.

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.

Journal Impact Factors (JIFs) appear to increase for the majority of scientific journals. The current analysis was initiated to better define the dynamics of JIFs. Original data from the Journal Citation Reports, from 1997 to 2016, were analysed. The number of citations referring to publications of the previous two years was correlated with the number of articles and the increase in the number of articles. A model was calculated by smoothing the correlation curves. The mean JIF increased from 1.1 to 2.2 almost continuously. The model suggested that the mean JIF will asymptotically reach a maximum value of 2.6. The number of publications has been growing annually by a factor of 1.048. Correlating the overall number of countable citations with the number of published articles revealed a stable relationship of 6.3 citations referring to the previous two years. Validation of the model with a sample of forty-nine journals that have been published since 1961 showed that their recent JIF dynamics are well reflected in the data, but extrapolation of the current dynamics did not reflect the JIFs of these journals in the past. Average JIF is likely to reach a plateau in the future.

// Marion Rapp 1, * , Stephanie Schipmann 2, * , Kira Hoffmann 1 , Rainer Wiewrodt 3 , Hans-Jakob Steiger 1 , Marcel Kamp 1 , Walter Stummer 2 , Dorothee Wiewrodt 2, * and Michael Sabel 1, * 1 Department of Neurosurgery, Heinrich-Heine-University, Duesseldorf, Germany 2 Department of Neurosurgery, University Hospital Muenster, Muenster, Germany 3 Pulmonary Division, Dpt. of Medicine A, University Hospital Muenster, Muenster, Germany * These authors have contributed equally to this work Correspondence to: Marion Rapp, email: marion.rapp@med.uni-duesseldorf.de Keywords: psychooncology; distress; brain surgery; screening; algorithm Received: April 11, 2018 Accepted: June 09, 2018 Published: August 03, 2018 ABSTRACT Background: Cerebral tumors are associated with high rates of anxiety, depression and reduced health related quality of life. Nevertheless psychooncological screening instruments are neither implemented nor well defined in the daily routine of neurosurgical departments. Therefore, we tried (1) to identify a suitable screening algorithm for neurosurgical patients, (2) to define clinical risk factors for increased distress and (3) to analyze the optimal screening time point. Results: Between October 2013 and January 2015 472 elective neurosurgical in-patients (median age 55.85 years) of the neurosurgical departments of the University Hospitals Duesseldorf and Muenster were prospectively included into this study. Regarding their diagnosis 244 (51.7%) patients were identified with malignant lesions and 228 (48.3%) patients with benign lesions. Increased distress was diagnosed in 63.1% of all patients via DT, in 13.6% via HADS and 27.8% via PO-Bado. Combining the cut-off criteria with the problem list increased sensitivity (90%) and specificity (70%) of the DT assessment. Regarding risk factors pre-existing psychiatric disorders, ataractic medication and a decreased clinical performance status were associated with increased distress. Patients and methods: Patients with diagnosis of an intracranial lesion with elective surgical indication were screened for psychological distress via three assessment-instruments the Hospital Anxiety and Depression Scale (HADS), the Distress Thermometer (DT), and the Basic Documentation for Psycho-Oncology (PO-Bado). Screening results were correlated with clinical and demographic data. Conclusion: Postoperative distress screening for neurosurgical patients is important independent from the neurosurgical diagnosis. The DT represents a suitable, non time-consuming instrument for daily routine in a neurosurgical department.

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.