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Background Pyogenic spondylodiskitis affects a fragile patient population frequently fraught with severe comorbidities. Data on long-term outcomes, especially for patients undergoing surgery, are scarce. The aim of this study was to assess the long-term quality of life after surgical instrumentation. Methods Data of 218 patients who were treated for spondylodiskitis at our institution between January 2008 and July 2017 were reviewed. In-hospital death and mortality rates at 1 year and follow-up were assessed. A survey was conducted using the following questionnaires: Oswestry Disability Index (ODI), Short Form Work Ability Index (SF-WAI), 36-Item Short Form Health Survey (SF-36), and Short Form McGill Pain Questionnaire (SF-MPQ). We investigated the correlation between the assessed variables and clinical data including patient age, comorbidity score at admission, number of operated levels, corpectomy, and length of hospital stay. Results In-hospital mortality rate was 1.8% and 1-year mortality rate was 5.5%. At the final follow-up (mean 7 ± 6 years), the mortality rate was 45.4%. Seventy-four patients were lost to follow-up or refused to participate in the study. Forty-four patients responded to the survey and had a mean age of 73 years and mean follow-up of 7 ± 2 years. In the ODI questionnaire, disability grades were classified as minimal (23%), moderate (21%), severe (19%), complete (33%), and bed bound (4%). We found a significant correlation between inability to return to work and severe disability on ODI (p Conclusion Despite low in-hospital and 1-year mortality rates, patients with surgically treated pyogenic spondylodiskitis are prone to long-term limitation in all domains of quality of life, especially in physical health and work ability.

OBJECTIVE Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient’s risk of experiencing any functional impairment. METHODS The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69–0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69–0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.

Background Surgery for pyogenic Spondylodiscitis as an adjunct to antibiotic therapy is an established treatment. However, the technique and extent of surgical debridement remains a matter of debate. Some propagate diskectomy in all cases. Others maintain that stand-alone instrumentation is sufficient. Methods We reviewed charts of patients who underwent instrumentation for pyogenic Spondylodiscitis with a minimum follow-up of 1 year. Patients were stratified according to whether they underwent diskectomy plus instrumentation or posterior instrumentation alone. Outcome measures included the need for surgical revision due to recurrent epidural intraspinal infection, wound revision, and construct failure. Results In all, 257 patients who underwent surgery for pyogenic Spondylodiscitis were identified. Diskectomy and interbody procedure (group A) was performed in 102 patients, while 155 patients underwent instrumentation surgery for Spondylodiscitis without intradiskal debridement (group B). The mean age was 67 ± 12 years, and 102 patients (39.7%) were females. No significant differences were found in the need for epidural abscess recurrence therapy (group A [2.0%] and 5 cases in group B [3%; p = 0.83]) and construct failure (p = 0.575). The need for wound revisions showed a tendency toward higher rates in the posterior instrumentation–only group, which failed to reach significance (p = 0.078). Conclusions Overall, intraspinal relapse of surgically treated pyogenic diskitis was low in our retrospective series. The choice of surgical technique was not associated with a significant difference. However, a somewhat higher rate of wound infections requiring revision in the group where no diskectomy was performed has to be weighed against a longer duration of surgery in an already ill patient population.

Background Infectious Spondylodiscitis is a heterogeneous disease usually affecting a fragile patient population with multiple comorbidities. Therefore, surgical and medical complications are important considerations before initiating treatment. Methods This retrospective analysis included data of 218 patients who underwent surgical treatment for pyogenic Spondylodiscitis between 2008 and 2016. Groups were divided into length of hospital stay (LOS) (group I ≤21 days and group II>21 days). Analysis included patient age, gender, Charlson comorbidity index, smoking, obesity, osteoporosis, colonization with multidrug-resistant bacteria, preoperative neurologic deficit, pre- and postoperative inflammation markers (CRP and WBC), duration of surgery, number of operated segments, vertebrectomy, and postoperative medical and surgical complications. The case value for each patient expressed in Euro was retrieved from hospital records and included in the analysis. Results Duration of stay after surgical treatment of Spondylodiscitis was ≤21 days (range: 4–21 days; mean: 16 days) in 41% of patients and >21 days (range: 22–162 days; mean: 41 days) in 59% of the patients. Multivariate analysis showed that both medical complications (odds ratio [OR]: 2.62; 95% confidence interval [CI]: 1.24–5.56; p=0.012) and surgical site infection (OR: 6.04; 95% CI: 2.35–15.51; p Conclusions This study provides benchmark data for patients treated surgically for Spondylodiscitis. Surgical site infection and medical complications are the main drivers of prolonged hospital stays and cost of care.

Background Radiooncological scores are used to stratify patients for radiation therapy. We assessed their ability to predict overall survival (OS) in patients undergoing surgery for metastatic brain disease. Methods We performed a post-hoc single-center analysis of 175 patients, prospectively enrolled in the MetastaSys study data. Score index of radiosurgery (SIR), graded prognostic assessment (GPA), and recursive partitioning analysis (RPA) were assessed. All scores consider age, systemic disease, and performance status prior to surgery. Furthermore, GPA and SIR include the number of intracranial lesions while SIR additionally requires metastatic lesion volume. Predictive values for case fatality at 1 year after surgery were compared among scoring systems. Results All scores produced accurate reflections on OS after surgery (p ≤ 0.003). Median survival was 21–24 weeks in patients scored in the unfavorable cohorts, respectively. In cohorts with favorable scores, median survival ranged from 42 to 60 weeks. Favorable SIR was associated with a hazard ratio (HR) of 0.44 [0.29, 0.66] for death within 1 year. For GPA, the HR amounted to 0.44 [0.25, 0.75], while RPA had a HR of 0.30 [0.14, 0.63]. Overall test performance was highest for the SIR. Conclusions All scores proved useful in predicting OS. Considering our data, we recommend using the SIR for preoperative prognostic evaluation and counseling.

OBJECTIVE Fluorescence-guided resection of cerebral metastases has been proposed as an approach to visualize residual tumor tissue and maximize the extent of resection. Critics have argued that tumor cells at the resection margins might be overlooked under microscopic visualization because of technical limitations. Therefore, an endoscope, which is capable of inducing fluorescence, has been applied with the aim of improving exposure of fluorescent tumor tissue. In this retrospective analysis, authors assessed the utility of endoscope assistance in 5-aminolevulinic acid (5-ALA) fluorescence–guided resection of brain metastases. METHODS Between June 2013 and December 2016, a standard 20-mg/kg dose of 5-ALA was administered 4 hours prior to surgery in 26 patients with suspected single brain metastases. After standard neuronavigated microsurgical tumor resection, a microscope capable of inducing fluorescence was used to examine tumor margins. The authors classified the remaining fluorescence into 3 grades (0 = none, 1 = weak, and 2 = strong). Endoscopic assistance was employed if no or only weak fluorescence was visualized at the resection margins under the microscope. Endoscopically identified fluorescent tissue at the margins was resected and evaluated separately via histological examination to prove or disprove tumor infiltration. RESULTS Under the microscope, weakly fluorescent tissue was seen at the margins of the resection cavity in 15/26 (57.7%) patients. In contrast, endoscopic inspection revealed strongly fluorescent tissue in 22/26 (84.6%) metastases. In 11/26 (42.3%) metastases no fluorescence at the tumor margins was detected by the microscope; however, strong fluorescence was visualized under the endoscope in 7 (63.6%) of these 11 metastases. In the 15 metastases with microscopically weak fluorescence, strong fluorescence was seen when using the endoscope. Neither microscopic nor endoscopic fluorescence was found in 4/26 (15.4%) cases. In the 26 patients, 96 histological specimens were obtained from the margins of the resection cavity. Findings from these specimens were in conjunction with the histopathological findings, allowing identification of metastatic infiltration with a sensitivity of 95.5% and a specificity of 75% using endoscope assistance. CONCLUSIONS Fluorescence-guided endoscope assistance may overcome the technical limitations of the conventional microscopic exposure of 5-ALA–fluorescent metastases and thereby increase visualization of fluorescent tumor tissue at the margins of the resection cavity with high sensitivity and acceptable specificity.

Introduction A subpopulation of patients with hydrocephalus and idiopathic intracranial hypertension (IIH) treated for elevated intracranial pressure (ICP) with a cerebrospinal fluid (CSF) shunt may continue to suffer from symptoms or develop new symptoms despite valve adjustments. The use of telemetric ICP measurements may help confirm a clinical suspicion of CSF under- or overdrainage in these patients. However, point in time, duration and activity during the measurements, which may influence the results, have never been standardized. We devised a simple and repeatable maneuver for outpatient telemetric ICP recording. The aim of this study is to evaluate its test-retest reliability. Methods Data of patients who underwent ventriculoperitoneal or ventriculoatrial shunt placement and subsequent telemetric ICP sensor implantation were retrospectively reviewed. Telemetric ICP recordings in these patients were conducted in a standardized manner: The standing-supine-sitting-paradigm requires postural changes in 10-minute intervals over 30 minutes. First, the patient is requested to walk (upright body position), secondly to lay down (supine body position), and lastly to sit down with a headrest elevation of 60°. All ICP measurements were analyzed using a dedicated freeware tool developed by the first author ( www.icp-analyzer.org ). ICP data were given as mean values (SD) in mmHg. Test-retest validity was assessed using Pearson´s correlation analysis. Results We evaluated 66 ICP data sets obtained repeatedly with a time difference of at least 24 hours under condition of unchanged valve settings in seven patients (1 male, 6 female). Implantation diagnoses were IIH (n=2), congenital hydrocephalus (n=2), normal pressure hydrocephalus (NPH) (n=1) and malresorptive hydrocephalus (n=2). Overall test re-test reliability was excellent (Pearsons correlation coefficient 0.99, p Conclusions We confirmed the high test-retest reliability of the standing-supine-sitting-paradigm for telemetric ICP measurements in the outpatient setting. The high test-retest reliability should be considered as pre-requisite for clinical decision making. We advocate the implementation and further testing of this method to validate its utility in guiding treatment decisions.

BACKGROUND AND PURPOSE Aneurysms of the posterior inferior cerebellar artery (PICA) are relatively uncommon and evidence is sparse about patients presenting with ruptured PICA aneurysms. We performed an analysis of the Swiss SOS national registry to describe clinical presentation, treatment pattern, and neurological outcome of patients with ruptured PICA aneurysms compared with other ruptured posterior circulation (PC) aneurysms. METHODS This was a retrospective analysis of anonymized data from the Swiss SOS registry (Swiss Study on Aneurysmal Subarachnoid Hemorrhage; 2009-2014). Patients with ruptured PC aneurysms were subdivided into a PICA and non-PICA group. Clinical, radiological, and treatment-related variables were identified, and their impact on the neurological outcome was determined in terms of modified Rankin score at discharge and at 1 year of follow-up for the two groups. RESULTS Data from 1864 aneurysmal subarachnoid hemorrhage patients were reviewed. There were 264 patients with a ruptured PC aneurysm. Seventy-four PICA aneurysms represented 28% of the series; clinical and radiological characteristics at admission were comparable between the PICA and non-PICA group. Surgical treatment was accomplished in 28% of patients in the PICA group and in the 4.8% of patients in the non-PICA group. No statistically significant difference was found between the two groups in terms of complications after treatment. Hydrocephalus requiring definitive shunt was needed in 21.6% of PICA patients (p = 0.6); cranial nerve deficit was present in average a quarter of the patients in both PICA and non-PICA group with no statistical difference (p = 0.3). A more favorable outcome (66.2%) was reported in the PICA group at discharge (p

Brain metastases (BMs) are the most frequent malignancy of the central nervous system. Previous research suggested that some metastases show infiltrative behavior rather than sharp demarcation. We hypothesized that three magnetic resonance (MR) imaging parameters—(a) tumor size, (b) extent of peritumoral edema, and (c) presence of multiple BMs—are predictors of cellular invasion beyond the surgically identifiable tumor margins. We performed a post hoc analysis on prospectively collected data of patients with BMs. Biopsies beyond the resection margin and immunohistochemistry were performed to assess infiltration status. The three MR imaging parameters were dichotomized into diameters ≤ 30 mm (“small”) and > 30 mm (“large”), amount of peritumoral edema “extended” and “limited,” and “multiple BMs” and “single BMs,” respectively. The association between infiltration status and imaging parameters was calculated using chi-square test. Biopsy beyond the resection margin was performed in 77 patients; 49 (63.6%) had supramarginal infiltration and 28 patients (36.4%) showed no infiltration. Histological evidence of tumor infiltration was found in 25/41 patients with smaller lesions (61%) and in 24/36 with larger lesions (66.7%, p = 0.64), in 28/44 patients with limited (63.6%) and in 21/33 patients with extended edema (63.6%, p = 1.0), in 28/45 patients (62.2%) with single BM and in 21/32 patients (65.6%) with multiple BMs (p = 0.81). Based on the post hoc analysis of our prospective trial data, we could not confirm the hypothesis that infiltration of brain parenchyma beyond the glial pseudocapsule is associated with the MR imaging parameters tumor size, extent of edema, or multiplicity of metastases.

BACKGROUND Current prognostic tools in aneurysmal subarachnoid hemorrhage (aSAH) are constrained by being primarily based on patient and disease characteristics on admission. OBJECTIVE To develop and validate a complication- and treatment-aware outcome prediction tool in aSAH. METHODS This cohort study included data from an ongoing prospective nationwide multicenter registry on all aSAH patients in Switzerland (Swiss SOS [Swiss Study on aSAH]; 2009-2015). We trained supervised machine learning algorithms to predict a binary outcome at discharge (modified Rankin scale [mRS] ≤ 3: favorable; mRS 4-6: unfavorable). Clinical and radiological variables on admission ("Early" Model) as well as additional variables regarding secondary complications and disease management ("Late" Model) were used. Performance of both models was assessed by classification performance metrics on an out-of-sample test dataset. RESULTS Favorable functional outcome at discharge was observed in 1156 (62.0%) of 1866 patients. Both models scored a high accuracy of 75% to 76% on the test set. The "Late" outcome model outperformed the "Early" model with an area under the receiver operator characteristics curve (AUC) of 0.85 vs 0.79, corresponding to a specificity of 0.81 vs 0.70 and a sensitivity of 0.71 vs 0.79, respectively. CONCLUSION Both machine learning models show good discrimination and calibration confirmed on application to an internal test dataset of patients with a wide range of disease severity treated in different institutions within a nationwide registry. Our study indicates that the inclusion of variables reflecting the clinical course of the patient may lead to outcome predictions with superior predictive power compared to a model based on admission data only.

Background and Purpose: The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level. Methods: All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded. Results: We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0–2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3–5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year. Conclusions: The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03245866.

Introduction The postoperative functional status of patients with intracranial tumors is influenced by patient-specific factors, including age. Research question This study aimed to elucidate the association between age and postoperative morbidity or mortality following the resection of brain tumors. Material and methods A multicenter database was retrospectively reviewed. Functional status was assessed before and 3–6 months after tumor resection by the Karnofsky Performance Scale (KPS). Uni- and multivariable linear regression were used to estimate the association of age with postoperative change in KPS. Logistic regression models for a ≥10-point decline in KPS or mortality were built for patients ≥75 years. Results The total sample of 4864 patients had a mean age of 56.4 ​± ​14.4 years. The mean change in pre-to postoperative KPS was −1.43. For each 1-year increase in patient age, the adjusted change in postoperative KPS was −0.11 (95% CI -0.14 - - 0.07). In multivariable analysis, patients ≥75 years had an odds ratio of 1.51 to experience postoperative functional decline (95%CI 1.21–1.88) and an odds ratio of 2.04 to die (95%CI 1.33–3.13), compared to younger patients. Discussion Patients with intracranial tumors treated surgically showed a minor decline in their postoperative functional status. Age was associated with this decline in function, but only to a small extent. Conclusion Patients ≥75 years were more likely to experience a clinically meaningful decline in function and about two times as likely to die within the first 6 months after surgery, compared to younger patients.

Breast cancer has been associated with activation of the WNT signaling pathway, although the underlying molecular mechanisms are still unclear. Here, we found the WNT receptor ROR2 to be highly expressed in aggressive breast tumors and associated with worse metastasis-free survival. In order to understand the molecular basis of these observations, we overexpressed ROR2 in human breast cancer cell lines, inducing a BRCAness-like phenotype and rendering them resistant to PARP inhibition. High levels of ROR2 were associated with defects in cell morphology and cell-cell-contacts leading to increased tumor invasiveness. Using gene expression analysis we demonstrated an upregulation of several non-canonical WNT ligands in ROR2-overexpressing breast cancer cells, in particular WNT11. Co-immunoprecipitation confirmed that WNT11 is indeed a novel ligand for ROR2 that interacts with its cysteine-rich domain and triggers the invasion-promoting signaling via RHO/ROCK. Knockdown of WNT11 reversed the pro-invasive phenotype and the cellular changes in ROR2-overexpressing cells. Taken together, our studies revealed a novel auto-stimulatory loop in which ROR2 triggers the expression of its own ligand, WNT11, resulting in enhanced tumor invasion associated with breast cancer metastasis.

Background Metastatic brain disease continues to have a dismal prognosis. Previous studies achieved a reduction of local recurrence rates by aggressively resecting the peritumoral zone (supramarginal resection) or using 5-aminolaevulinic acid (5-ALA) fluorescence. The aim of the present study is to assess whether the use of 5-ALA has an impact on local recurrence or survival compared to conventional white light microscopic tumor resection. Materials and methods We included consecutive patients who underwent surgical resection of brain metastases. Two groups were compared: In the "white light" group, resection was performed with conventional microscopy. In the 5-ALA group, fluorescence guided peritumoral resection was additionally performed after standard microscopic resection. In-brain recurrence and mortality were compared between groups. Results N = 175 patients were included in the study. All baseline parameters were similarly distributed with no significant difference between surgical groups. Local in-brain recurrence occurred in 21/175 patients (12%) with a rate of 15/119 (12.6%) in the white light and 6/56 (10.7%) in the 5-ALA group (p = 0.720). The use of 5-ALA influenced neither in-brain recurrence (OR 0.59 [CI = 95% 0.18; 1.99], p = 0.40) nor mortality (OR 0.71 [CI = 95% 0.27; 1.85], p = 0.49). Conclusions The use of 5-ALA did not result in lower in-brain recurrence or mortality compared to the use of white light microscopy. The most prominent predictors of survival remain favorable preoperative performance status, a low tumor diameter and the absence of multiple cerebral lesions.

Unresectable malignant intramedullary tumors and metastases usually require radiotherapy which intensifies spinal cord edema and might result in neurological decline. Spinal expansion duroplasty before radiotherapy enlarges the intrathecal volume and might thus prevent neurological deficits. The study aims to evaluate the clinical course of patients undergoing expansion duroplasty. This retrospective analysis (2007-2016) included all patients with unresectable intramedullary tumors who underwent spinal expansion duroplasty. To assess the degree of preoperative cord enlargement, we calculated the "diameter ratio": diameter of the spinal cord below and above the tumor / diameter of the tumor × 2. The presence of perimedullary cerebrospinal fluid (CSF) at the affected levels was analyzed on the preoperative magnetic resonance imaging (MRI). We recorded the occurrence of neurological deficits, wound breakdown, and CSF fistula. We screened 985 patients, 11 of which were included. Eight patients had an intramedullary metastasis, three patients a spinal malignant glioma. A diameter ratio ≤ 0.8 representing a significant preoperative intramedullary enlargement was seen in 10 cases (90.9%). Postoperative imaging was available in 9 patients, demonstrating successful decompression in 8 of the 9 patients (88.9%). The postoperative course was uneventful in 9 patients (81.8%). Mean overall survival was 13.4 (SD 16.2) months. Spinal expansion duroplasty prior to radiotherapy is a previously undescribed concept. Despite neoadjuvant radiation, no wound breakdown or CSF fistula occurred. In unresectable intramedullary tumors and metastases, spinal expansion duroplasty seems to be a safe procedure with the potential to prevent neurological decline due to radiation-induced cord swelling.

It was suggested that D, L-Methadone might improve the clinical course of glioma patients. Owing to massive press coverage, patients demand the prescription of D, L-Methadone, but regarding its adjunctive use in glioma therapy there is no standard medication plan. Furthermore, it is not known which side effects the administration of D, L-Methadone might harbor, especially if the patients are opioid-naive and if D, L-Methadone therapy was managed by the patients themselves or their general practitioners. Opioid-naive patients with high-grade glioma (new diagnosis or recurrent) receiving D, L-Methadone were included in this retrospective observational analysis. Side effects were assigned if the condition deteriorated in conjunction with the initiation of D, L-Methadone and resolved/ ameliorated after cessation of the intake/reduction of the dosage. Side effects were categorized according to the common toxicity criteria (CTC). Twenty-four patients were included. All patients were opioid-naive and received D, L-Methadone from their general practitioners. Sixteen patients experienced side effects. The median dosage when side effects began to occur was 15.8 mg/ 24 h. Fatigue and mood changes were reported most frequently (14 of 24 patients). Five patients had severe side effects related to relatively high doses. In all cases, symptoms resolved after cessation or dose reduction. Our results show that D/L M intake lead to frequent occurrence of side effects in opioid-naive patients especially when not handled with caution and close supervision. Patients, their relatives, their GPs and neuro-oncologists need to be informed about the broad spectrum of side effects in order to thoroughly counsel glioma patients.

IntroductionRobotic guidance (RG) and computer-assisted navigation (NV) have seen increased adoption in instrumented spine surgery over the last decade. Although there exists some evidence that these techniques increase radiological pedicle screw accuracy compared with conventional freehand (FH) surgery, this may not directly translate to any tangible clinical benefits, especially considering the relatively high inherent costs. As a non-randomised, expertise-based study, the European Robotic Spinal Instrumentation Study aims to create prospective multicentre evidence on the potential comparative clinical benefits of RG, NV and FH in a real-world setting.Methods and analysisPatients are allocated in a non-randomised, non-blinded fashion to the RG, NV or FH arms. Adult patients that are to undergo thoracolumbar pedicle screw instrumentation for degenerative pathologies, infections, vertebral tumours or fractures are considered for inclusion. Deformity correction and surgery at more than five levels represent exclusion criteria. Follow-up takes place at 6 weeks, as well as 12 and 24 months. The primary endpoint is defined as the time to revision surgery for a malpositioned or loosened pedicle screw within the first postoperative year. Secondary endpoints include patient-reported back and leg pain, as well as Oswestry Disability Index and EuroQOL 5-dimension questionnaires. Use of analgesic medication and work status are recorded. The primary analysis, conducted on the 12-month data, is carried out according to the intention-to-treat principle. The primary endpoint is analysed using crude and adjusted Cox proportional hazards models. Patient-reported outcomes are analysed using baseline-adjusted linear mixed models. The study is monitored according to a prespecified monitoring plan.Ethics and disseminationThe study protocol is approved by the appropriate national and local authorities. Written informed consent is obtained from all participants. The final results will be published in an international peer-reviewed journal.Trial registration numberClinical Trials.gov registryNCT03398915; Pre-results, recruiting stage.

OBJECTIVEAlthough several studies have suggested that the incidence of intracranial aneurysms (IAs) is higher in smokers, the higher prevalence of subarachnoid hemorrhage (SAH) in smokers remains uncertain. It is unclear whether smoking additionally contributes to the formation of multiple aneurysms and the risk of rupture. The aim of this study was to determine whether smoking is associated with IA formation, multiplicity, or rupture.METHODSPatients from the prospective multicenter @neurIST database (n = 1410; 985 females [69.9%]) were reviewed for the presence of SAH, multiple aneurysms, and smoking status. The prevalence of smokers in the population of patients diagnosed with at least one IA was compared with that of smokers in the general population.RESULTSThe proportion of smokers was higher in patients with IAs (56.2%) than in the reference population (51.4%; p < 0.001). A significant association of smoking with the presence of an IA was found throughout group comparisons (p = 0.01). The presence of multiple IAs was also significantly associated with smoking (p = 0.003). A trend was found between duration of smoking and the presence of multiple IAs (p = 0.057). However, the proportion of smokers among patients suffering SAH was similar to that of smokers among patients diagnosed with unruptured IAs (p = 0.48).CONCLUSIONSSmoking is strongly associated with IA formation. Once an IA is present, however, smoking does not appear to increase the risk of rupture compared with IAs in the nonsmoking population. The trend toward an association between duration of smoking and the presence of multiple IAs stresses the need for counseling patients with IAs regarding lifestyle modification.

The online version of the original article can be found at https://doi.org/10.1007/s00701-019-03812-9

OBJECTIVEThe objective of this study was to determine patterns of care and outcomes in ruptured intracranial aneurysms (IAs) of the middle cerebral artery (MCA) in a contemporary national cohort.METHODSThe authors conducted a retrospective analysis of prospective data from a nationwide multicenter registry of all aneurysmal subarachnoid hemorrhage (aSAH) cases admitted to a tertiary care neurosurgical department in Switzerland in the years 2009–2015 (Swiss Study on Aneurysmal Subarachnoid Hemorrhage [Swiss SOS]). Patterns of care and outcomes at discharge and the 1-year follow-up in MCA aneurysm (MCAA) patients were analyzed and compared with those in a control group of patients with IAs in locations other than the MCA (non-MCAA patients). Independent predictors of a favorable outcome (modified Rankin Scale score ≤ 3) were identified, and their effect size was determined.RESULTSAmong 1866 consecutive aSAH patients, 413 (22.1%) harbored an MCAA. These MCAA patients presented with higher World Federation of Neurosurgical Societies grades (p = 0.007), showed a higher rate of concomitant intracerebral hemorrhage (ICH; 41.9% vs 16.7%, p < 0.001), and experienced delayed cerebral ischemia (DCI) more frequently (38.9% vs 29.4%, p = 0.001) than non-MCAA patients. After adjustment for confounders, patients with MCAA were as likely as non-MCAA patients to experience DCI (aOR 1.04, 95% CI 0.74–1.45, p = 0.830). Surgical treatment was the dominant treatment modality in MCAA patients and at a significantly higher rate than in non-MCAA patients (81.7% vs 36.7%, p < 0.001). An MCAA location was a strong independent predictor of surgical treatment (aOR 8.49, 95% CI 5.89–12.25, p < 0.001), despite statistical adjustment for variables traditionally associated with surgical treatment, such as (space-occupying) ICH (aOR 1.73, 95% CI 1.23–2.45, p = 0.002). Even though MCAA patients were less likely to die during the acute hospitalization (aOR 0.52, 0.30–0.91, p = 0.022), their rate of a favorable outcome was lower at discharge than that in non-MCAA patients (55.7% vs 63.7%, p = 0.003). At the 1-year follow-up, 68.5% and 69.6% of MCAA and non-MCAA patients, respectively, had a favorable outcome (p = 0.676).CONCLUSIONSMicrosurgical occlusion remains the predominant treatment choice for about 80% of ruptured MCAAs in a European industrialized country. Although patients with MCAAs presented with worse admission grades and greater rates of concomitant ICH, in-hospital mortality was lower and long-term disability was comparable to those in patients with non-MCAA.

Obstruction is a common cause of ventriculo-peritoneal shunt failure. Head computed tomography and plain x-ray examinations of shunt tubing (“shunt series”) are routinely used in patients readmitted for reemerging symptoms but are of limited value. The validity of shunt series can be improved by applying contrast agent into the system (contrast-enhanced shunt series, a.k.a. a “shuntogram” or “shuntography”). We hypothesized that contrast-enhanced shunt series have a high predictive value for shunt revision surgeries. We retrospectively re-evaluated 107 contrast-enhanced shunt series and reviewed the patient histories. We defined outcome parameters for calculating the utility of a pathological contrast-enhanced shunt series in predicting revision surgery. Of 107 contrast-enhanced shunt series, 41 examinations were positive for obstruction, mainly of the ventricular (36.5 %) and the peritoneal catheter (48.8 %). Within 30 days, 35 successful revision surgeries and 3 revision surgeries without resolution of symptoms were performed. In two cases the shunt tubing was found to be patent. Sixty-six negative examinations resulted in two revision surgeries, in addition to ten surgeries not attempting to restore patency. After 30 days, the specificity of contrast-enhanced shunt series for shunt failure identification was calculated at 92.8 %, the sensitivity at 94.7 %, the positive predictive value at 87.8 %, and the negative predictive value at 97.0 %. The contrast-enhanced shunt series method is a highly specific examination with a negative predictive value exceeding that of head computed tomography and plain shunt series. Compared to radionuclide marker studies, contrast-enhanced shunt series demonstrate better spatiotemporal resolution, enabling focused local surgical repair.

OBJECTIVEPyogenic spondylodiscitis affects a fragile patient population. Surgical treatment in cases of instability entails instrumentation, and loosening of this instrumentation is a frequent occurrence in pyogenic spondylodiscitis. The authors therefore attempted to investigate whether low bone mineral density (BMD)—which is compatible with the diagnosis of osteoporosis—is underdiagnosed in patients with pyogenic spondylodiscitis. How osteoporosis was treated and how it affected implant stability were further analyzed.METHODSCharts of patients who underwent operations for pyogenic spondylodiscitis were retrospectively reviewed for clinical data, prior medical history of osteoporosis, and preoperative CT scans of the thoracolumbar spine. In accordance with a previously validated high-fidelity opportunistic CT assessment, average Hounsfield units (HUs) in vertebral bodies of L1 and L4 were measured. Based on the validation study, the authors opted for a conservative cutoff value for low BMD, being compatible with osteoporosis ≤ 110 HUs. Baseline and outcome variables, including implant failure and osteoporosis interventions, were entered into a multivariate logistic model for statistical analysis.RESULTSOf 200 consecutive patients who underwent fusion surgery for pyogenic spondylodiscitis, 64% (n = 127) were male and 66% (n = 132) were older than 65 years. Seven percent (n = 14) had previously been diagnosed with osteoporosis. The attenuation analysis revealed HU values compatible with osteoporosis in 48% (95/200). The need for subsequent revision surgery due to implant failure showed a trend toward an association with estimated low BMD (OR 2.11, 95% CI 0.95–4.68, p = 0.067). Estimated low BMD was associated with subsequent implant loosening (p < 0.001). Only 5% of the patients with estimated low BMD received a diagnosis and pharmacological treatment of osteoporosis within 1 year after spinal instrumentation.CONCLUSIONSRelying on past medical history of osteoporosis is insufficient in the management of patients with pyogenic spondylodiscitis. This is the first study to identify a substantially missed opportunity to detect osteoporosis and to start pharmacological treatment after surgery for prevention of implant failure. The authors advocate for routine opportunistic CT evaluation for a better estimation of bone quality to initiate diagnosis and treatment for osteoporosis in these patients.

Background: In glioma surgery, 5-aminolevulinic acid (5-ALA) fluorescence reflects tumor infiltration, and fluorescence-assisted resection correlates with higher removal rates and improved progression-free survival. Recent studies report that a sizable proportion of brain metastases exhibit peritumoral infiltration on the cellular level. There is little information regarding whether 5-ALA is useful to guide surgery in the peritumoral zone in metastases. The aim of this study was to assess histologically whether 5-ALA fluorescence accurately reflects metastatic brain infiltration. Methods and Materials: Fluorescence-assisted tumor resection was performed in 27 patients with brain metastases. Patients received 20 mg/kg 5-ALA 3 hours before anesthesia. After resection, biopsy specimens of the surrounding parenchyma were analyzed for 5-ALA fluorescence and histologic evidence of infiltrating tumor cells. The correlation between 5-ALA positivity and immunohistochemical evidence of tumor in the peritumoral zone was also assessed. Results: Of 27 metastases, 23 (85%) were 5-ALA positive. For qualitative tissue analysis, 110 of 125 samples were collected. Metastatic infiltration was present in 49 samples with faint or red fluorescence; 33 samples without fluorescence were tumor-free. The presence of metastatic infiltration correlated with fluorescence (P < 0.001). Tumor infiltration correlated with fluorescence (blue fluorescence 0.09% ± 0.04% and red or faint fluorescence 3.26%; P = 0.003). Conclusions: Infiltration of surrounding brain tissue is a common finding in brain metastases in selected primary tumors. 5-ALA fluorescence correlates with tumor cell infiltration and might guide more radical resection. Key words: 5-ALA, Brain metastasis, Brain tumor, Fluorescence-guided surgery, Histology, Tumor infiltration

Background/aim Glioblastoma multiforme (GBM) is a malignant primary brain tumor with high rates of recurrence. This study aimed to investigate the effect of repurposed drug combinations on GBM. Materials and methods Viability of U87 MG and 11ST patient-derived GMB cell lines, after valproic acid, tranylcypromine or riluzole alone, in different combinations, as well as combined with standard temozolomide chemotherapy was examined using the MTT assay. Proliferation, mRNA level of tissue factor pathway inhibitor 2 (TFPI2), and cell invasion were evaluated using anti-Ki-67 antibody staining, reverse transcriptase-polymerase chain reaction and xCELLigence system. Results The strongest effect on cell viability was achieved by the combination of riluzole with valproic acid (U87MG: 27.2%, 11ST: 25.99%). Tranylcypromine significantly enhanced the effect of temozolomide when used in combination, as did valproic acid. The normally high proliferation of GBM significantly declined under treatment with valproic acid with tranylcypromine (p=0.01). Finally, we observed reduction of invasion comparing single tranylcypromine to its combination with valproic acid or riluzole. Conclusion These results support the idea that combinations of drugs could increase the treatment efficiency of GBM.

Somatic single nucleotide variants (SNVs) are genomic events with increasing implications in cancer treatment. The clinical standard for SNVs detection is whole genome/exome sequencing (WGS/WES) in matched tumor-normal samples. Yet, this is a very costly approach both economically and biologically and very often only tumor samples are sequenced. On the other hand, RNA sequencing (RNA-Seq) is the most popular technology to study gene expression, and has also the potential for a cost-effective identification of SNVs as an alternative to tumor-only WES. Here we present a method for the identification of SNVs in tumor-only RNA-Seq data putting a special focus on a small panel of clinically relevant SNVs. For evaluation purposeswe analyzed matched tumor-normal WEStumor-only RNA-Seq data from 14 cancer patients. We compared SNVs detected in i) RNA-Seq by our method, ii) WES tumor-only by Mutect2 and iii) WES matched tumor-normal by Mutect2. We did a detailed evaluation for a reduced panel of clinically relevant SNVs and reliably identified in RNA-Seq data a subset of mutations for which we had pathological annotation. Hence, RNA-Seq rises as a cost-effective option to detect in parallel gene expression as well as a small panel of clinically relevant SNVs in research.

Dear Editor, Oxidized regenerated cellulose (ORC, Surgicel®, Ethicon Inc.) is widely used as a hemostatic fleece. The manufacturer recommends removing as much ORC as possible before closure. As one of the possible complications of its use, postoperative neurological compression symptoms caused by so-called “surgiceloma” have been described in the spine [1] and brain [2, 4]. Since this entity regularly occurs despite better knowledge, we would like to share our experience with a catastrophic complication following the inappropriate use of ORC in spinal surgery. A 54-year-old male underwent posterolateral thoracotomy for a Pancoast tumor T4N0M0 of the right upper pulmonary lobe with infiltration of the vertebral body of Th2 at another institution. The patient awoke from surgery without neurological deficits. On postoperative day 1, he fell asleep in the afternoon and woke up with paraplegia and complete sensory loss in his right leg. An emergencyMRI showed a mass lesion within the spinal canal at the Th2 level (Fig. 1a) whereupon the patient was transferred to our department for neurosurgical treatment. After a Th2-Th3 laminectomy (Fig. 1b), we found ORC material compressing the spinal cord from the right side and penetrating the dura, creating a cerebrospinal fluid (CSF) leak. A postoperative MRI showed the sequelae of the compression as an intramedullary hyperintense signal on T2-weighted imaging at the Th2-Th3 level (Fig. 1c). The patient was sent to rehabilitation with some recovery in the left leg. He died 1 year later because of the progression of the underlying oncological disease. We found 17 (N=17) reports of delayed neural compression due to ORC after a comprehensive MEDLINE search, and we would like to summarize the most salient features. Almost half of the described procedures (8/17=47 %) were thoracotomies at vertebral levels Th3 to Th8 for resection of neoplasms in adults. Three pediatric cases of thoracic surgery that resulted in neural compression syndromes due to ORC were also reported. Median time to symptom discovery was at 30 h postoperatively. The delayed occurrence of symptoms indicates that neurological deficits were not due to inadequate application of pressure on neural structures, but due to delayed swelling of the hemostatic material that was left in place and subsequent migration of material into the spinal canal via the neuroforamen. Eleven out of 17 patients (64 %) already had complete paraplegia at the time of reoperation. This indicates that by the time of symptom onset, the damage to the spinal cord is almost irreversible and decompression—if at all—only partly attenuates the damage. Hemostatic agents can be hypointense on T1and T2weighted imaging and may therefore be indistinguishable from (1) epidural hematoma or (2) a herniated disc on MRI [3]. In most of the literature, the “surgiceloma” was described as an extradural mass. While careful hemostasis during spinal and thoracic procedures is mandatory, it is also necessary to remain mindful of the amount of hemostatic materials we leave in situ. Removal of hemostatic fabric after successful hemostasis can prevent debilitating complications.

Background and Purpose— To identify predictors of in-hospital mortality in patients with aneurysmal subarachnoid hemorrhage and to estimate their impact. Methods— Retrospective analysis of prospective data from a nationwide multicenter registry on all aneurysmal subarachnoid hemorrhage cases admitted to a tertiary neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]; 2009–2015). Both clinical and radiological independent predictors of in-hospital mortality were identified, and their effect size was determined by calculating adjusted odds ratios (aORs) using multivariate logistic regression. Survival was displayed using Kaplan–Meier curves. Results— Data of n=1866 aneurysmal subarachnoid hemorrhage patients in the Swiss SOS database were available. In-hospital mortality was 20% (n=373). In n=197 patients (10.6%), active treatment was discontinued after hospital admission (no aneurysm occlusion attempted), and this cohort was excluded from analysis of the main statistical model. In the remaining n=1669 patients, the rate of in-hospital mortality was 13.9% (n=232). Strong independent predictors of in-hospital mortality were rebleeding (aOR, 7.69; 95% confidence interval, 3.00–19.71; P P P =0.003), and new infarction post-treatment (aOR, 2.57; 95% confidence interval, 1.43–4.62; P =0.002). Conclusions— Several—and among them modifiable—factors seem to be associated with in-hospital mortality after aneurysmal subarachnoid hemorrhage. Our data suggest that strategies aiming to reduce the risk of rebleeding are most promising in patients where active treatment is initially pursued. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT03245866.

Mutations and activation of the PI3K signaling pathway in breast cancer cells have been linked to brain metastases. However, here we describe that in some breast cancer brain metastases samples the protein expression of PI3K signaling components is restricted to the metastatic microenvironment. In contrast to the therapeutic effects of PI3K inhibition on the breast cancer cells, the reaction of the brain microenvironment is less understood. Therefore we aimed to quantify the PI3K pathway activity in breast cancer brain metastasis and investigate the effects of PI3K inhibition on the central nervous system (CNS) microenvironment. First, to systematically quantify the PI3K pathway activity in breast cancer brain metastases, we performed a prospective biomarker study using a reverse phase protein array (RPPA). The majority, namely 30 out of 48 (62.5%) brain metastatic tissues examined, revealed high PI3K signaling activity that was associated with a median overall survival (OS) of 9.41 months, while that of patients, whose brain metastases showed only moderate or low PI3K activity, amounted to only 1.93 and 6.71 months, respectively. Second, we identified PI3K as a master regulator of metastasis-promoting macrophages/microglia during CNS colonization; and treatment with buparlisib (BKM120), a pan-PI3K Class I inhibitor with a good blood-brain-barrier penetrance, reduced their metastasis-promoting features. In conclusion, PI3K signaling is active in the majority of breast cancer brain metastases. Since PI3K inhibition does not only affect the metastatic cells but also re-educates the metastasis-promoting macrophages/microglia, PI3K inhibition may hold considerable promise in the treatment of brain metastasis and the respective microenvironment.

BACKGROUND The Barrow Neurological Institute (BNI) scale is a novel quantitative scale measuring maximal subarachnoid hemorrhage (SAH) thickness to predict delayed cerebral ischemia (DCI). This scale could replace the Fisher score, which was traditionally used for DCI prediction. OBJECTIVE To validate the BNI scale. METHODS All patient data were obtained from the prospective aneurysmal SAH multicenter registry. In 1321 patients, demographic data, BNI scale, DCI, and modified Rankin Scale (mRS) score up to the 1-yr follow-up (1FU) were available for descriptive and univariate statistics. Outcome was dichotomized in favorable (mRS 0-2) and unfavorable (mRS 3-6). Odds ratios (OR) for DCI of Fisher 3 patients (n = 1115, 84%) compared to a control cohort of Fisher grade 1, 2, and 4 patients (n = 206, 16%) were calculated for each BNI grade separately. RESULTS Overall, 409 patients (31%) developed DCI with a high DCI rate in the Fisher 3 cohort (34%). With regard to the BNI scale, DCI rates went up progressively from 26% (BNI 2) to 38% (BNI 5) and corresponding OR for DCI increased from 1.9 (1.0-3.5, 95% confidence interval) to 3.4 (2.1-5.3), respectively. BNI grade 5 patients had high rates of unfavorable outcome with 75% at discharge and 58% at 1FU. Likelihood for unfavorable outcome was high in BNI grade 5 patients with OR 5.9 (3.9-8.9) at discharge and OR 6.6 (4.1-10.5) at 1FU. CONCLUSION This multicenter external validation analysis confirms that patients with a higher BNI grade show a significantly higher risk for DCI; high BNI grade was a predictor for unfavorable outcome at discharge and 1FU.

The exploration of applications of robots for spine surgery has begun! The quest to improve safety and invasiveness of surgical procedures has been a driving force in surgical innovation. In view of the continual evolution of technology, the spinal surgery is also trying to take advantage of this improvement which may be particularly useful in patients with challenging anatomy. Nowadays, robotic assistance systems are mainly used to guide thoracolumbar pedicle screw placement, because surgeons’ interest in robotic guidance for spinal implant placement is increasing. Potential benefits of robotic application include improving safety, accuracy, and clinical outcome. This chapter describes the principles of the current available spine robotic systems in the market, their indications, and usefulness.

BACKGROUND Literature on multiple intracranial aneurysms (MIA) in patients with aneurysmal subarachnoid hemorrhage (aSAH) largely focuses on risk factor analysis and consists essentially of retrospective cohort studies of limited sample size, or else studies in populations outside Europe and North America. OBJECTIVE The purpose of this cohort study was to determine the predictors for aneurysm multiplicity and to investigate the anatomical distribution of MIA in a representative Western cohort of aSAH patients. METHODS The Swiss Study of Subarachnoid Hemorrhage (SOS) database includes anonymized data from all tertiary neurovascular facilities in Switzerland. The dataset 2009-2014 was used to compare characteristics of aSAH patients with MIA and aSAH patients with a single intracranial aneurysm (SIA) by means of descriptive and multivariate regression analysis. RESULTS Out of 1689 unselected aSAH patients, 467 had MIA (prevalence: 27.6%). The location of the ruptured index aneurysm was correlated with the probability of finding bystander aneurysm(s) and predicted their likely anatomical distribution. Patients with a ruptured basilar artery (OR 2.08, 95%CI 1.28-3.37) or a ruptured middle cerebral artery (OR 1.86, 95%CI 1.36-2.55) aneurysm had the highest likelihood for MIA. Larger size of the index aneurysm (OR per 1mm 1.03, 95%CI 1.01-1.06) was also positively correlated with aneurysm multiplicity. Males compared to females were less likely to have MIA (OR 0.78, 95%CI 0.61-1.01). CONCLUSION In patients suffering from aSAH the location of the ruptured index aneurysm correlates with the probability of finding bystander aneurysm(s) and predicts the sites where bystander aneurysm(s) are the most likely found.

Background Anatomic shape of the spinal canal (oval, round, trefoil) has been reported to predict outcome of bilateral decompression performed in an undercutting technique via unilateral laminotomy in monosegmental lumbar spinal stenosis, with poorest results observed in a trefoil spinal canal, leading to the proposal of using bilateral instead of unilateral laminotomy. The aim of this study was to assess whether this anatomic classification into oval, round, and trefoil shapes is relevant to surgical treatment of lumbar spinal stenosis. Methods Retrospective chart review of patients undergoing lumbar decompression surgery was performed. Spinal canal configuration was assessed on preoperative computed tomography based on maximal transverse and anteroposterior diameter, and shapes were classified into oval, round, and trefoil. Associations between spinal canal shape and outcome improvement (aggregate of walking distance and leg pain) were tested. Results Decompression of 236 lumbar levels was performed in 159 patients (mean age, 73 ± 8 years; mean body mass index, 29 ± 6). Average number of operated segments was 1.3 ± 0.6. Oval configurations were detected in 155 (65%) levels, round configurations were detected in 11 (5%) levels, and trefoil configurations were detected in 70 (30%) levels. Postoperative improvement was recorded in 91.7% of patients. Spinal canal shape had no influence on surgical outcome (oval, area under the curve 0.529, P = 0.672; trefoil, area under the curve 0.500, P = 0.997; round, area under the curve 0.471, P = 0.670). Conclusions Spinal canal configuration varies in frequency with lumbar segment. Our results do not support the idea that this anatomic classification, particularly the nomenclature of oval, round, and trefoil, should influence surgical decision making.