Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

COveRs to impRove EsthetiC ouTcome after Surgery for Chronic subdural hemAtoma by buRr hole trepanation-Results of a Swiss Single-Blinded, Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Burr hole trepanation to evacuate chronic subdural hematoma (cSDH) results in bony skull defects that can lead to skin depressions. We intend to study the effect of burr hole covers to prevent skin depressions and improve the esthetic result. METHODS: In a randomized trial, we enrolled adult patients with symptomatic cSDH. Patients received burr hole trepanation with (intervention) vs without burr hole covers (control) in a 1:1 ratio. Patients requiring evacuation of bilateral cSDHs served as their internal control. Primary outcome was satisfaction with the esthetic result of the scar, measured from 0 (dissatisfied) to 10 (very satisfied) on the Esthetic Numeric Analog (ANA) scale at 90 days. Secondary outcomes included ANA scale, rates of skin depression, complications, as well as neurological, disability, and health-related quality of life outcomes until 12 months. RESULTS: We included 78 patients (55 with unilateral and 23 with bilateral cSDH; median age 78 years, 83% male) between 03/2019 and 05/2021, 50 trepanations for the intervention and 51 for the control group. In an intention-to-treat analysis, the ANA scale scores were 9.0 (intervention) and 8.5 (control arm) at 90 days (P = .498). At 12 months, the ANA scale scores were 9.0 and 8.0 for the intervention and control groups, respectively (P = .183). Skin depressions over the frontal burr hole were noted by 35% (intervention) and 63% (control) of patients at 90 days (P = .009) and by 35% and 79% (P < .001) at 12 months, respectively. There were no differences in complications, neurological, disability, and health-related quality of life outcomes. CONCLUSION: Satisfaction with the esthetic result of the scar was inherently high. This study does not show evidence for improvement on the ANA scale by applying a burr hole cover. The application of burr hole covers resulted in less skin depressions and did not negatively affect complication rates or outcomes.

A T-cell antigen atlas for meningioma: novel options for immunotherapy.

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.

Impact of Long-Term Antithrombotic and Statin Therapy on the Clinical Outcome in Patients with Cavernous Malformations of the Central Nervous System: A Single-Center Case Series of 428 Patients.

INTRODUCTION: Literature regarding the safety and efficacy of antithrombotic (antiplatelet or anticoagulant) therapy and statins in patients with cavernous malformations (CMs) of the central nervous system is sparse, resulting in uncertainty about its use in clinical practice. The aim of this study was to analyze the impact of antithrombotic therapy and statins on the risk of hemorrhage and focal neurological deficit in patients with CMs. METHODS: The authors' institutional database was screened for all patients with CMs of the central nervous system treated at their institution between 2006 and 2018. Patients with radiological and/or histological diagnosis of CMs, clinical baseline characteristics, available patient's medication history, and follow-up data were included in this study. Time-to-event probability (hemorrhage or focal neurological deficit) as well as the number of events (hemorrhage or focal neurological deficit) during follow-up were assessed in patients who were categorized according to their medical treatment (antithrombotic therapy, statins, combined therapy, or no treatment). RESULTS: Four hundred twenty-eight patients with CMs were eligible and included in the final analysis. Sixty-nine (16.1%) patients were on long-term antithrombotic therapy and 46 (10.6%) on long-term statins, of whom 31 patients were on a combination of both. The probability of experiencing first hemorrhage or focal neurological deficit was less likely in patients on antiplatelet therapy (HR 0.09, 95% CI 0.021-0.39, p = 0.001), anticoagulant therapy (HR 0.12, 95% CI 0.016-0.85, p = 0.034), or the combination thereof (HR 0.12, 95% CI 0.016-0.93, p = 0.043) compared to patients with no antithrombotic treatment. The number of hemorrhages and focal neurological deficits were significantly lower in patients on antithrombotic therapy compared to patients on no treatment during follow-up. In patients on statins alone, the time-to-event probability was comparable to that of patients on no treatment (HR 0.91, 95% CI 0.438-1.91, p = 0.812), and the number of events was similar to patients on no treatment. CONCLUSION: The results of our study provide further evidence that antithrombotic therapy alone or in combination with statins in patients with CMs of the central nervous system does not increase the risk of hemorrhage or focal neurological deficit but, on the contrary, may have some benefit.

Association of perioperative adverse events with subsequent therapy and overall survival in patients with WHO grade III and IV gliomas.

Background: Maximum safe resection followed by chemoradiotherapy as current standard of care for WHO grade III and IV gliomas can be influenced by the occurrence of perioperative adverse events (AE). The aim of this study was to determine the association of AE with the timing and choice of subsequent treatments as well as with overall survival (OS). Methods: Prospectively collected data of 283 adult patients undergoing surgery for WHO grade III and IV gliomas at the University Hospital Zurich between January 2013 and June 2017 were analyzed. We assessed basic patient characteristics, KPS, extent of resection, and WHO grade, and we classified AE as well as modality, timing of subsequent treatment (delay, interruption, or non-initiation), and OS. Results: In 117 patients (41%), an AE was documented between surgery and the 3-month follow-up. There was a significant association of AE with an increased time to initiation of subsequent therapy (p = 0.005) and a higher rate of interruption (p < 0.001) or non-initiation (p < 0.001). AE grades correlated with time to initiation of subsequent therapy (p = 0.038). AEs were associated with shorter OS in univariate analysis (p < 0.001). Conclusion: AEs are associated with delayed and/or altered subsequent therapy and can therefore limit OS. These data emphasize the importance of safety within the maximum-safe-resection concept.

Mapping and Monitoring of the Corticospinal Tract by Direct Brainstem Stimulation.

BACKGROUND: Direct stimulation and diffusion tensor imaging/tractography are established techniques that assist in complex surgery for lesions in the eloquent area of the central nervous system. OBJECTIVE: To continuously map the corticospinal tract (CST) by direct stimulation during brainstem surgery and to explore the association between direct brainstem stimulation and the shortest distance from the stimulation point to the CST (DS-to-T). METHODS: We prospectively enrolled 30 consecutive patients for microsurgical resection of lesions within or in proximity to the brainstem between January 2019 and August 2021. Direct stimulation with initially 2 mA was performed for mapping and monitoring the motor fiber tracts. To evaluate CST status and measure DS-to-T, postoperative diffusion tensor imaging/tractography was used. Preoperative and postoperative modified Ranking Scale and motor function were evaluated to assess the clinical outcome. RESULTS: Intraoperative direct brainstem stimulation was successfully performed in all patients with a total of 909 stimulation points. One patient experienced a temporary neurological deficit postoperatively. Mapping of the CST was achieved in 5 patients. DS-to-T was ≤4 mm when motor-evoked potential responses were positive under 2 mA stimulation and ≤2 mm under 1 mA. Overall sensitivity and specificity for this association were 84.7% and 100%, respectively. CONCLUSION: This study further supports the paradigm for continuous CST monitoring and mapping through direct brainstem stimulation. The relationship between stimulation intensity and DS-to-T in brainstem surgery could help surgeon's better estimate the safe edge intraoperatively.

Pediatric brainstem cavernous malformations: 2-center experience in 40 children.

OBJECTIVE: Brainstem cavernous malformations (BSCMs) are relatively uncommon, low-flow vascular lesions in children. Given the paucity of data, guidelines regarding the clinical management of BSCMs in children are lacking and the surgical indication is most commonly based on an individual surgeon's judgment and experience. The goal in this study was to evaluate the clinical behavior of BSCMs in childhood and the long-term outcome in children managed conservatively and surgically. METHODS: This was an observational, retrospective study including all children with BSCMs who were followed at 2 institutions between 2008 and 2020. RESULTS: The study population consisted of 40 children (27 boys, 67.5%) with a mean age of 11.4 years. Twenty-three children (57.5%) were managed conservatively, whereas 17 children (42.5%) underwent resection of BSCMs. An aggressive clinical course was observed in 13 children (32.5%), who experienced multiple hemorrhages with a progressive pattern of neurological decline. Multiple BSCMs were observed in 8 patients, of whom 3 patients presented with a complex of multiple tightly attached BSCMs and posed a significant therapeutic challenge. The overall long-term outcome was favorable (modified Rankin Scale [mRS] scores 0-2) in 36 patients (90%), whereas an unfavorable outcome (mRS scores 3 and 4) was seen in 4 children (10%). An mRS score of 5 or 6 was not observed. The mean (± SD) follow-up was 88.0 (± 92.6) months. CONCLUSIONS: The clinical course of BSCMs in children is highly variable, with benign lesions on the one hand and highly aggressive lesions with repetitive hemorrhages on the other. Given the greater life expectancy and the known higher functional recovery in children, surgical treatment should be considered early in young patients presenting with surgically accessible lesions and an aggressive clinical course, and it should be performed in a high-volume center.

The BSCM score: a guideline for surgical decision-making for brainstem cavernous malformations.

Microsurgical resection of brainstem cavernous malformations (BSCMs) can be performed today with acceptable morbidity and mortality. However, in this highly eloquent location, the indication for surgery remains challenging. We aimed to elaborate a score system that may help clinicians with their choice of treatment in patients with BSCMs in this study. A single-center series of 88 consecutive BSCMs patients with 272 follow-up visits were included in this study. Univariable and multivariable generalized estimating equations (GEE) were constructed to identify the association of variables with treatment decisions. A score scale assigned points for variables that significantly contributed to surgical decision-making. Surgical treatment was recommended in 37 instances, while conservative treatment was proposed in 235 instances. The mean follow-up duration was 50.4 months, and the mean age at decision-making was 45.9 years. The mean BSCMs size was 14.3 ml. In the multivariable GEE model, patient age, lesion size, hemorrhagic event(s), mRS, and axial location were identified as significant factors for determining treatment options. With this proposed score scale (grades 0-XII), non-surgery was the first option at grades 0-III. The crossover point between surgery and non-surgery recommendations lay between grades V and VI while surgical treatment was found in favor at grades VII-X. In conclusion, the proposed BSCM operating score is a clinician-friendly tool, which may help neurosurgeons decide on the treatment for patients with BSCMs.

Anatomical phenotyping and staging of brain tumours.

Unlike other tumours, the anatomical extent of brain tumours is not objectified and quantified through staging. Staging systems are based on understanding the anatomical sequence of tumour progression and its relationship to histopathological dedifferentiation and survival. The aim of this study was to describe the spatiotemporal phenotype of the most frequent brain tumour entities, to assess the association of anatomical tumour features with survival probability and to develop a staging system for WHO grade 2 and 3 gliomas and glioblastoma. Anatomical phenotyping was performed on a consecutive cohort of 1000 patients with first diagnosis of a primary or secondary brain tumour. Tumour probability in different topographic, phylogenetic and ontogenetic parcellation units was assessed on preoperative MRI through normalization of the relative tumour prevalence to the relative volume of the respective structure. We analysed the spatiotemporal tumour dynamics by cross-referencing preoperative against preceding and subsequent MRIs of the respective patient. The association between anatomical phenotype and outcome defined prognostically critical anatomical tumour features at diagnosis. Based on a hypothesized sequence of anatomical tumour progression, we developed a three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma. This staging system was validated internally in the original cohort and externally in an independent cohort of 300 consecutive patients. While primary CNS lymphoma showed highest probability along white matter tracts, metastases enriched along terminal arterial flow areas. Neuroepithelial tumours mapped along all sectors of the ventriculocortical axis, while adjacent units were spared, consistent with a transpallial behaviour within phylo-ontogenetic radial units. Their topographic pattern correlated with morphogenetic processes of convergence and divergence of radial units during phylo- and ontogenesis. While a ventriculofugal growth dominated in neuroepithelial tumours, a gradual deviation from this neuroepithelial spatiotemporal behaviour was found with progressive histopathological dedifferentiation. The proposed three-level staging system for WHO grade 2 and 3 gliomas and glioblastoma correlated with the degree of histological dedifferentiation and proved accurate in terms of survival upon both internal and external validation. In conclusion, this study identified specific spatiotemporal phenotypes in brain tumours through topographic probability and growth pattern assessment. The association of anatomical tumour features with survival defined critical steps in the anatomical sequence of neuroepithelial tumour progression, based on which a staging system for WHO grade 2 and 3 gliomas and glioblastoma was developed and validated.

Natural History of Brainstem Cavernous Malformations: On the Variation in Hemorrhage Rates.

BACKGROUND: Hemorrhage rates of conservatively managed brainstem cavernous malformations (BSCMs) vary widely in the literature. We aimed to elucidate the reason for the variation and to add the results of our experience of BSCMs management over the past decade. METHODS: We performed a review of consecutive patients with BSCMs referred to our department in the period 2006-2018. A hemorrhagic event was defined as a radiographically verified intralesional and extralesional hemorrhage. Both retrospective and prospective hemorrhage rates were calculated based on the patient age in years, counted either from birth or from the time of initial presentation until the last contact (or until surgical resection). In addition, we retrieved and reviewed publications with a clear definition of hemorrhagic event and a detailed description of BSCM hemorrhage rate. RESULTS: In total, 118 patients with BSCMs were reviewed, and 78 patients (mean age on admission 45.9 years) were included in the final analysis. The retrospective and prospective hemorrhage rates were 1.9% (95% confidence interval 1.6%-2.3%) per year and 11.9% (95% confidence interval 7.5%-17.8%), respectively. The retrospective hemorrhage rate in the literature review ranged from 1.9% to 6.8% per year with a median value of 3.8%, whereas the prospective hemorrhage rate ranged between 4.1% and 21.5%, with a median value of 10.2%. CONCLUSIONS: The reported hemorrhage rates are calculated in 2 different ways. In our patient cohort, both the retrospective and prospective hemorrhage rates were in accordance with those in the literature. The long-term hemorrhage rate lies between the prospective and retrospective rate.

Preoperative risk factors associated with new focal neurological deficit and other major adverse events in first-time intracranial meningioma neurosurgery.

BACKGROUND: Neurosurgical resection is the mainstay of meningioma treatment. Adverse event (AE) rates of meningioma resections are significant, but preoperative risk factors for major AEs in patients undergoing first-time meningioma surgery are largely unknown. The aim of this study was to explore major AEs and identify preoperative risk factors in patients undergoing first-time meningioma surgery. METHODS: Data on all meningioma resections performed at the University Hospital Zurich from 1 January 2013 to 31 December 2018 were collected in a prospective registry. All AEs that occurred within 3 months of surgery were documented in detail and classified as "minor" or "major." Statistical analysis included initial individual bivariate analyses of all preoperative factors and the occurrence of major AEs. Statistically significant variables were then included in a logistic regression model to identify predictors. RESULTS: Three hundred forty-five patients were included in the study. Mean age was 58.1 years, and 77.1% of patients were female. The overall major AE rate was 20.6%; the most common of which was a new focal neurological deficit (12.8% of patients). Six preoperative factors showed a significant association with the occurrence of major AEs in bivariate analysis. All variables included in the logistic regression model showed increased odds of occurrence of major AE, but only tumor complexity as measured by the Milan Complexity Scale was a statistically significant predictor, with a score of 4 or more having twice the odds of major AEs (OR: 2.00, 95% CI: 1.15-3.48). CONCLUSION: High tumor complexity is an independent predictor of the occurrence of major AEs following meningioma resection. Preoperative assessment of tumor complexity using the Milan Complexity Scale is warranted and can aid communication with patients about AE rates and surgical decision-making.

Mortality in Patients with Brainstem Cavernous Malformations.

OBJECTIVE: Brainstem cavernous malformations (BSCM)-associated mortality has been reported up to 20% in patients managed conservatively, whereas postoperative mortality rates range from 0 to 1.9%. Our aim was to analyze the actual risk and causes of BSCM-associated mortality in patients managed conservatively and surgically based on our own patient cohort and a systematic literature review. METHODS: Observational, retrospective single-center study encompassing all patients with BSCM that presented to our institution between 2006 and 2018. In addition, a systematic review was performed on all studies encompassing patients with BSCM managed conservatively and surgically. RESULTS: Of 118 patients, 54 were treated conservatively (961.0 person years follow-up in total). No BSCM-associated mortality was observed in our conservatively as well as surgically managed patient cohort. Our systematic literature review and analysis revealed an overall BSCM-associated mortality rate of 2.3% (95% CI: 1.6-3.3) in 22 studies comprising 1,251 patients managed conservatively and of 1.3% (95% CI: 0.9-1.7) in 99 studies comprising 3,275 patients with BSCM treated surgically. CONCLUSION: The BSCM-associated mortality rate in patients managed conservatively is almost as low as in patients treated surgically and much lower than in frequently cited reports, most probably due to the good selection nowadays in regard to surgery.

HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy.

BACKGROUND: The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level. METHODS: Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing. RESULTS: The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 90,428 HLA-I- and 142,625 HLA-II ligands. The HLA allotypes are representative for the world population. We observe that immunopeptidomes differ considerably between tissues and individuals on source protein and HLA-ligand level. Moreover, we discover 1407 HLA-I ligands from non-canonical genomic regions. Such peptides were previously described in tumors, peripheral blood mononuclear cells (PBMCs), healthy lung tissues and cell lines. In a case study in glioblastoma, we show that potential on-target off-tumor adverse events in immunotherapy can be avoided by comparing tumor immunopeptidomes to the provided multi-tissue reference. CONCLUSION: Given that T-cell-based immunotherapies, such as CAR-T cells, affinity-enhanced T cell transfer, cancer vaccines and immune checkpoint inhibition, have significant side effects, the HLA Ligand Atlas is the first step toward defining tumor-associated targets with an improved safety profile. The resource provides insights into basic and applied immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy and autoimmunity. It is publicly available and can be browsed in an easy-to-use web interface at https://hla-ligand-atlas.org .

Traumatic Distal Anterior Cerebral Artery Aneurysms - Pathomechanism and Revascularisation Strategies.

Traumatic intracranial aneurysms (TICA) of the distal anterior cerebral artery (dACA) are exceptionally rare and display therapeutic challenges due to their angioanatomical characteristics. The objective of this work was to discuss the mechanisms of TICA formation of the dACA and to elucidate the best treatment and revascularization strategies in these patients based on two illustrative cases. Case 1: 20-year-old patient with a traumatic, partially thrombosed 14 × 10 mm aneurysm of the right pericallosal artery (rPericA), distal to the origin of the right callosomarginal artery (rCMA). Complete trapping of the right dissection A3 aneurysm and flow replacement extra-to-intracranial (EC-IC) bypass (STA - radial artery - A4) was performed. Case 2: 16-year-old patient with a traumatic polylobulated, partially thrombosed 16 × 10 mm aneurysm of the rPericA. Microsurgical excision of the A3- segment harboring the aneurysm and flow replacement intra-to-intracranial (IC-IC) bypass via reimplantation of the right remaining PericA on the contralateral PericA (end-to-side anastomosis) was performed (in situ bypass). TICA of the dACA are exceptionally rare. Mechanical vessel wall injury and aneurysm formation of the dACA in blunt head trauma is very likely due to the proximity of the dACA with the rigid free edge of the falx. Given their nature as dissecting (complex) aneurysm, trapping and revascularization is a very important strategy. The interhemispheric cistern offers multiple revascularization options with its numerous donor vessels. The IC-IC bypass is often the simplest revascularization construct.

The association of patient age with postoperative morbidity and mortality following resection of intracranial tumors.

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 â€‹± â€‹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.

Limited Impact of Serial Follow-Up Imaging in Clinically Stable Patients With Brainstem Cavernous Malformations.

Background: Clinical management of patients with brainstem cavernous malformations (BSCM) is often challenging due to the unpredictable clinical course and lack of high-quality evidence. Nevertheless, radiologic follow-up is often performed routinely. The objective of this work was to investigate whether active follow-up by serial imaging is justified and how planned imaging will impact clinical decision making in absence of clinical progression. Methods: We included all consecutive patients with BSCM treated and followed at our Department between 2006 and 2018. Results: Of 429 patients with CCM, 118 were diagnosed with BSCM (27.5%). Patients were followed for a mean of 8.1 (± 7.4 SD) years. Conservative treatment was recommended in 54 patients over the complete follow-up period, whereas 64 patients underwent surgical extirpation of BSCM. In total, 75 surgical procedures were performed. Over a period of 961 follow-up years in total, routinely performed follow-up MRI in clinically stable patients did not lead to a single indication for surgery. Conclusion: Due to the difficult-to-predict clinical course of patients with BSCM and the relatively high risk associated with surgery, routine imaging is unlikely to have any influence on surgical decision making in clinically stable patients with BSCM.

Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery.

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.

Topographic brain tumor anatomy drives seizure risk and enables machine learning based prediction.

OBJECTIVE: The aim of this study was to identify relevant risk factors for epileptic seizures upon initial diagnosis of a brain tumor and to develop and validate a machine learning based prediction to allow for a tailored risk-based antiepileptic therapy. METHODS: Clinical, electrophysiological and high-resolution imaging data was obtained from a consecutive cohort of 1051 patients with newly diagnosed brain tumors. Factor-associated seizure risk difference allowed to determine the relevance of specific topographic, demographic and histopathologic variables available at the time of diagnosis for seizure risk. The data was divided in a 70/30 ratio into a training and test set. Different machine learning based predictive models were evaluated before a generalized additive model (GAM) was selected considering its traceability while maintaining high performance. Based on a clinical stratification of the risk factors, three different GAM were trained and internally validated. RESULTS: A total of 923 patients had full data and were included. Specific topographic anatomical patterns that drive seizure risk could be identified. The involvement of allopallial, mesopallial or primary motor/somatosensory neopallial structures by brain tumors results in a significant and clinically relevant increase in seizure risk. While topographic input was most relevant for the GAM, the best prediction was achieved by a combination of topographic, demographic and histopathologic information (Validation: AUC: 0.79, Accuracy: 0.72, Sensitivity: 0.81, Specificity: 0.66). CONCLUSIONS: This study identifies specific phylogenetic anatomical patterns as epileptic drivers. A GAM allowed the prediction of seizure risk using topographic, demographic and histopathologic data achieving fair performance while maintaining transparency.

COveRs to impRove AesthetiC ouTcome after Surgery for Chronic subdural haemAtoma by buRr hole trepanation (CORRECT-SCAR): protocol of a Swiss single-blinded, randomised controlled trial.

INTRODUCTION: Outcomes rated on impairment scales are satisfactory after burr hole trepanation for chronic subdural haematoma (cSDH). However, the surgery leads to bony defects in the skull with skin depressions above that are frequently considered aesthetically unsatisfactory by the patients. Those defects could be covered by the approved medical devices (burr hole covers), but this is rarely done today. We wish to assess, whether the application of burr hole covers after trepanation for the evacuation of cSDH leads to higher patient satisfaction with the aesthetical result at 90 days postoperative, without worsening disability outcomes or increasing the complication rate. METHODS AND ANALYSIS: This is a prospective, single-blinded, randomised, controlled, investigator-initiated clinical trial enrolling 80 adult patients with first-time unilateral or bilateral cSDH in Switzerland. The primary outcome is the difference in satisfaction with the aesthetic result of the scar, comparing patients allocated to the intervention (burr hole cover) and control (no burr hole cover) group, measured on the Aesthetic Numeric Analogue scale at 90 days postoperative. Secondary outcomes include differences in the rates of skin depression, complications, as well as neurological, disability and health-related quality of life outcomes until 12 months postoperative. ETHICS AND DISSEMINATION: The institutional review board (Kantonale Ethikkommission Zürich) approved this study on 29 January 2019 under case number BASEC 2018-01180. This study determines, whether a relatively minor modification of a standard surgical procedure can improve patient satisfaction, without worsening functional outcomes or increasing the complication rate. The outcome corresponds to the value-based medicine approach of modern patient-centred medicine. Results will be published in peer-reviewed journals and electronic patient data will be safely stored for 15 years. TRIAL REGISTRATION NUMBER: NCT03755349.

Patterns of care: burr-hole cover application for chronic subdural hematoma trepanation.

OBJECTIVE: Skin depressions may appear as undesired effects after burr-hole trepanation for the evacuation of chronic subdural hematomas (cSDH). Placement of burr-hole covers to reconstruct skull defects can prevent skin depressions, with the potential to improve the aesthetic result and patient satisfaction. The perception of the relevance of this practice, however, appears to vary substantially among neurosurgeons. The authors aimed to identify current practice variations with regard to the application of burr-hole covers after trepanation for cSDH. METHODS: An electronic survey containing 12 questions was sent to resident and faculty neurosurgeons practicing in different parts of the world, as identified by an Internet search. All responses completed between September 2018 and December 2018 were considered. Descriptive statistics and logistic regression were used to analyze the data. RESULTS: A total of 604 responses were obtained, of which 576 (95.4%) provided complete data. The respondents' mean age was 42.4 years (SD 10.5), and 86.5% were male. The sample consisted of residents, fellows, junior/senior consultants, and department chairs from 79 countries (77.4% Europe, 11.8% Asia, 5.4% America, 3.5% Africa, and 1.9% Australasia). Skin depressions were considered a relevant issue by 31.6%, and 76.0% indicated that patients complain about skin depressions more or less frequently. Burr-hole covers are placed by 28.1% in the context of cSDH evacuation more or less frequently. The most frequent reasons for not placing a burr-hole cover were the lack of proven benefit (34.8%), followed by additional costs (21.9%), technical difficulty (19.9%), and fear of increased complications (4.9%). Most respondents (77.5%) stated that they would consider placing burr-hole covers in the future if there was evidence for superiority of the practice. The use of burr-hole covers varied substantially across countries, but a country's gross domestic product per capita was not associated with their placement. CONCLUSIONS: Only a minority of neurosurgeons place burr-hole covers after trepanation for cSDH on a regular basis, even though the majority of participants reported complaints from patients regarding postoperative skin depressions. There are significant differences in the patterns of care among countries. Class I evidence with regard to patient satisfaction and safety of burr-hole cover placement is likely to have an impact on future cSDH management.