Clinical Application and Further Development of Augmented Reality Guidance for the Surgical Localization of Pediatric Chest Wall Tumors.

BACKGROUND: Surgical treatment of pediatric chest wall tumors requires accurate surgical planning and tumor localization to achieve radical resections while sparing as much healthy tissue as possible. Augmented Reality (AR) could facilitate surgical decision making by improving anatomical understanding and intraoperative tumor localization. We present our clinical experience with the use of an AR system for intraoperative tumor localization during chest wall resections. Furthermore, we present the pre-clinical results of a new registration method to improve our conventional AR system. METHODS: From January 2021, we used the HoloLens 2 for pre-incisional tumor localization during all chest wall resections inside our center. A patient-specific 3D model was projected onto the patient by use of a five-point registration method based on anatomical landmarks. Furthermore, we developed and pre-clinically tested a surface matching method to allow post-incisional AR guidance by performing registration on the exposed surface of the ribs. RESULTS: Successful registration and holographic overlay were achieved in eight patients. The projection seemed most accurate when landmarks were positioned in a non-symmetric configuration in proximity to the tumor. Disagreements between the overlay and expected tumor location were mainly due to user-dependent registration errors. The pre-clinical tests of the surface matching method proved the feasibility of registration on the exposed ribs. CONCLUSIONS: Our results prove the applicability of AR guidance for the pre- and post-incisional localization of pediatric chest wall tumors during surgery. The system has the potential to enable intraoperative 3D visualization, hereby facilitating surgical planning and management of chest wall resections. LEVEL OF EVIDENCE: IV TYPE OF STUDY: Treatment Study.

NnU-Net versus mesh growing algorithm as a tool for the robust and timely segmentation of neurosurgical 3D images in contrast-enhanced T1 MRI scans.

PURPOSE: This study evaluates the nnU-Net for segmenting brain, skin, tumors, and ventricles in contrast-enhanced T1 (T1CE) images, benchmarking it against an established mesh growing algorithm (MGA). METHODS: We used 67 retrospectively collected annotated single-center T1CE brain scans for training models for brain, skin, tumor, and ventricle segmentation. An additional 32 scans from two centers were used test performance compared to that of the MGA. The performance was measured using the Dice-Sørensen coefficient (DSC), intersection over union (IoU), 95th percentile Hausdorff distance (HD95), and average symmetric surface distance (ASSD) metrics, with time to segment also compared. RESULTS: The nnU-Net models significantly outperformed the MGA (p < 0.0125) with a median brain segmentation DSC of 0.971 [95CI: 0.945-0.979], skin: 0.997 [95CI: 0.984-0.999], tumor: 0.926 [95CI: 0.508-0.968], and ventricles: 0.910 [95CI: 0.812-0.968]. Compared to the MGA's median DSC for brain: 0.936 [95CI: 0.890, 0.958], skin: 0.991 [95CI: 0.964, 0.996], tumor: 0.723 [95CI: 0.000-0.926], and ventricles: 0.856 [95CI: 0.216-0.916]. NnU-Net performance between centers did not significantly differ except for the skin segmentations Additionally, the nnU-Net models were faster (mean: 1139 s [95CI: 685.0-1616]) than the MGA (mean: 2851 s [95CI: 1482-6246]). CONCLUSIONS: The nnU-Net is a fast, reliable tool for creating automatic deep learning-based segmentation pipelines, reducing the need for extensive manual tuning and iteration. The models are able to achieve this performance despite a modestly sized training set. The ability to create high-quality segmentations in a short timespan can prove invaluable in neurosurgical settings.

Mixed Reality for Cranial Neurosurgical Planning: A Single-Center Applicability Study With the First 107 Subsequent Holograms.

BACKGROUND AND OBJECTIVES: Mixed reality (MxR) benefits neurosurgery by improving anatomic visualization, surgical planning and training. We aim to validate the usability of a dedicated certified system for this purpose. METHODS: All cases prepared with MxR in our center in 2022 were prospectively collected. Holographic rendering was achieved using an incorporated fully automatic algorithm in the MxR application, combined with contrast-based semiautomatic rendering and/or manual segmentation where necessary. Hologram segmentation times were documented. Visualization during surgical preparation (defined as the interval between finalized anesthesiological induction and sterile draping) was performed using MxR glasses and direct streaming to a side screen. Surgical preparation times were compared with a matched historical cohort of 2021. Modifications of the surgical approach after 3-dimensional (3D) visualization were noted. Usability was assessed by evaluating 7 neurosurgeons with more than 3 months of experience with the system using a Usefulness, Satisfaction and Ease of use (USE) questionnaire. RESULTS: One hundred-seven neurosurgical cases prepared with a 3D hologram were collected. Surgical indications were oncologic (63/107, 59%), cerebrovascular (27/107, 25%), and carotid endarterectomy (17/107, 16%). Mean hologram segmentation time was 39.4 ± 20.4 minutes. Average surgical preparation time was 48.0 ± 17.3 minutes for MxR cases vs 52 ± 17 minutes in the matched 2021 cohort without MxR (mean difference 4, 95% CI 1.7527-9.7527). Based on the 3D hologram, the surgical approach was modified in 3 cases. Good usability was found by 57% of the users. CONCLUSION: The perioperative use of 3D holograms improved direct anatomic visualization while not significantly increasing intraoperative surgical preparation time. Usability of the system was adequate. Further technological development is necessary to improve the automatic algorithms and reduce the preparation time by circumventing manual and semiautomatic segmentation. Future studies should focus on quantifying the potential benefits in teaching, training, and the impact on surgical and functional outcomes.

Evaluation Metrics for Augmented Reality in Neurosurgical Preoperative Planning, Surgical Navigation, and Surgical Treatment Guidance: A Systematic Review.

BACKGROUND AND OBJECTIVE: Recent years have shown an advancement in the development of augmented reality (AR) technologies for preoperative visualization, surgical navigation, and intraoperative guidance for neurosurgery. However, proving added value for AR in clinical practice is challenging, partly because of a lack of standardized evaluation metrics. We performed a systematic review to provide an overview of the reported evaluation metrics for AR technologies in neurosurgical practice and to establish a foundation for assessment and comparison of such technologies. METHODS: PubMed, Embase, and Cochrane were searched systematically for publications on assessment of AR for cranial neurosurgery on September 22, 2022. The findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: The systematic search yielded 830 publications; 114 were screened full text, and 80 were included for analysis. Among the included studies, 5% dealt with preoperative visualization using AR, with user perception as the most frequently reported metric. The majority (75%) researched AR technology for surgical navigation, with registration accuracy, clinical outcome, and time measurements as the most frequently reported metrics. In addition, 20% studied the use of AR for intraoperative guidance, with registration accuracy, task outcome, and user perception as the most frequently reported metrics. CONCLUSION: For quality benchmarking of AR technologies in neurosurgery, evaluation metrics should be specific to the risk profile and clinical objectives of the technology. A key focus should be on using validated questionnaires to assess user perception; ensuring clear and unambiguous reporting of registration accuracy, precision, robustness, and system stability; and accurately measuring task performance in clinical studies. We provided an overview suggesting which evaluation metrics to use per AR application and innovation phase, aiming to improve the assessment of added value of AR for neurosurgical practice and to facilitate the integration in the clinical workflow.

Application of virtual and mixed reality for 3D visualization in intracranial aneurysm surgery planning: a systematic review.

Background: Precise preoperative anatomical visualization and understanding of an intracranial aneurysm (IA) are fundamental for surgical planning and increased intraoperative confidence. Application of virtual reality (VR) and mixed reality (MR), thus three-dimensional (3D) visualization of IAs could be significant in surgical planning. Authors provide an up-to-date overview of VR and MR applied to IA surgery, with specific focus on tailoring of the surgical treatment. Methods: A systematic analysis of the literature was performed in accordance with the PRISMA guidelines. Pubmed, and Embase were searched to identify studies reporting use of MR and VR 3D visualization in IA surgery during the last 25 years. Type and number of IAs, category of input scan, visualization techniques (screen, glasses or head set), inclusion of haptic feedback, tested population (residents, fellows, attending neurosurgeons), and aim of the study (surgical planning/rehearsal, neurosurgical training, methodological validation) were noted. Results: Twenty-eight studies were included. Eighteen studies (64.3%) applied VR, and 10 (35.7%) used MR. A positive impact on surgical planning was documented by 19 studies (67.9%): 17 studies (60.7%) chose the tailoring of the surgical approach as primary outcome of the analysis. A more precise anatomical visualization and understanding with VR and MR was endorsed by all included studies (100%). Conclusion: Application of VR and MR to perioperative 3D visualization of IAs allowed an improved understanding of the patient-specific anatomy and surgical preparation. This review describes a tendency to utilize mostly VR-platforms, with the primary goals of a more accurate anatomical understanding, surgical planning and rehearsal.

Case report: Impact of mixed reality on anatomical understanding and surgical planning in a complex fourth ventricular tumor extending to the lamina quadrigemina.

Background and importance: Tumors of the fourth ventricle account for 1%-5% of all intracranial neoplastic lesions and present with different configurations and anatomical challenges. Microsurgery represents the primary therapeutic strategy for the majority of fourth ventricular tumors, and adequate anatomical understanding and visualization are paramount to surgical planning and success. The authors present the case of a young patient with a complex fourth ventricular tumor, whose surgery was successfully planned using a novel mixed reality (MxR) system. Case description: We present a case of a 31-year-old woman with a lesion extending from the fourth ventricle to the lamina quadrigemina and causing symptomatic hydrocephalus occlusus. Through the combined use of routine 2D images and an interactive 3D anatomical model, an interhemispheric transtentorial approach was used to remove 98% of the lesion with successful functional outcomes. Conclusions: The application of advanced 3D visualization with a novel MxR system to the surgical planning of a complex fourth ventricular lesion proved relevant in designing the best surgical approach and trajectory to better identify potential intraoperative challenges and rehearse the patient-specific anatomy. The present case report endorses the implementation of advanced 3D visualization in routine perioperative practice.

Clinical potential of automated convolutional neural network-based hematoma volumetry after aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Cerebrospinal fluid hemoglobin has been positioned as a potential biomarker and drug target for aneurysmal subarachnoid hemorrhage-related secondary brain injury (SAH-SBI). The maximum amount of hemoglobin, which may be released into the cerebrospinal fluid, is defined by the initial subarachnoid hematoma volume (ISHV). In patients without external ventricular or lumbar drain, there remains an unmet clinical need to predict the risk for SAH-SBI. The aim of this study was to explore automated segmentation of ISHV as a potential surrogate for cerebrospinal fluid hemoglobin to predict SAH-SBI. METHODS: This study is based on a retrospective analysis of imaging and clinical data from 220 consecutive patients with aneurysmal subarachnoid hemorrhage collected over a five-year period. 127 annotated initial non-contrast CT scans were used to train and test a convolutional neural network to automatically segment the ISHV in the remaining cohort. Performance was reported in terms of Dice score and intraclass correlation. We characterized the associations between ISHV and baseline cohort characteristics, SAH-SBI, ventriculoperitoneal shunt dependence, functional outcome, and survival. Established clinical (World Federation of Neurosurgical Societies, Hunt & Hess) and radiological (modified Fisher, Barrow Neurological Institute) scores served as references. RESULTS: A strong volume agreement (0.73 Dice, range 0.43 - 0.93) and intraclass correlation (0.89, 95% CI, 0.81-0.94) were shown. While ISHV was not associated with the use of antithrombotics or cardiovascular risk factors, there was strong evidence for an association with a lower Glasgow Coma Scale at hospital admission. Aneurysm size and location were not associated with ISHV, but the presence of intracerebral or intraventricular hemorrhage were independently associated with higher ISHV. Despite strong evidence for a positive association between ISHV and SAH-SBI, the discriminatory ability of ISHV for SAH-SBI was insufficient. The discriminatory ability of ISHV was, however, higher regarding ventriculoperitoneal shunt dependence and functional outcome at three-months follow-up. Multivariate survival analysis provided strong evidence for an independent negative association between survival probability and both ISHV and intraventricular hemorrhage. CONCLUSIONS: The proposed algorithm demonstrates strong performance in volumetric segmentation of the ISHV on the admission CT. While the discriminatory ability of ISHV for SAH-SBI was similar to established clinical and radiological scores, it showed a high discriminatory ability for ventriculoperitoneal shunt dependence and functional outcome at three-months follow-up.

Incisional CSF leakage after intradural cranial surgery in children: incidence, risk factors, and complications.

OBJECTIVE: The risk of cerebrospinal fluid (CSF) leakage after cranial surgery and its associated complications in children are unclear because of variable definitions and the lack of multicenter studies. In this study, the authors aimed to establish the incidence of CSF leakage after intradural cranial surgery in the pediatric population. In addition, they evaluated potential risk factors and complications related to CSF leakage in the pediatric population. METHODS: The authors performed an international multicenter retrospective cohort study in three tertiary neurosurgical referral centers. Included were all patients aged 18 years or younger who had undergone cranial surgery to reach the subdural space during the period between 2015 and 2021. Patients who died or were lost to follow-up within 6 weeks after surgery were excluded. The primary outcome measure was the incidence of CSF leakage, defined as leakage through the skin, within 6 weeks after surgery. Univariable and multivariable logistic regression analyses were performed to identify risk factors for and complications related to CSF leakage. RESULTS: In total, 759 procedures were identified, performed in 687 individual patients. The incidence of CSF leakage was 7.5% (95% CI 5.7%-9.6%). In the multivariate model, independent risk factors for CSF leakage were hydrocephalus (OR 4.5, 95% CI 2.2-8.9) and craniectomy (OR 7.6, 95% CI 3.0-19.5). Patients with CSF leakage had higher odds of pseudomeningocele (5.7, 95% CI 3.0-10.8), meningitis (21.1, 95% CI 9.5-46.8), and surgical site infection (7.4, 95% CI 2.6-20.8) than patients without leakage. CONCLUSIONS: CSF leakage risk in children after cranial surgery, which is comparable to the risk reported in adults, is an event of major concern and has a serious clinical impact.

Cerebrospinal fluid leakage after intradural spinal surgery in children.

PURPOSE: This study aimed to establish the incidence of CSF leakage in children and associated complications after intradural spinal surgery in three tertiary neurosurgical referral centers and to describe the treatment strategies applied. METHODS: Patients of 18 years or younger who underwent intradural spinal surgery between 2015 and 2021 in three tertiary neurosurgical referral centers were included. Patients who died or were lost to follow-up within six weeks after surgery were excluded. The primary outcome measure was CSF leakage within six weeks after surgery, defined as leakage of CSF through the skin. Secondary outcome measures included the presence of pseudomeningocele (PMC), meningitis, and surgical site infection (SSI). RESULTS: We included a total of 75 procedures, representing 66 individual patients. The median age in this cohort was 5 (IQR = 0-13 years. CSF leakage occurred in 2.7% (2/75) of procedures. It occurred on days 3 and 21 after the index procedure, respectively. One patient was treated with a pressure bandage and an external lumbar drain on day 4 after diagnosis of the leak, and the other was treated with wound revision surgery on day 1 after the leak occurred. In total, 1 patient developed a PMC without a CSF leak which was treated with wound revision surgery. SSI occurred in 10.7%, which included both cases of CSF leak. CONCLUSIONS: CSF leakage after intradural spinal surgery in the pediatric population is relatively rare (2.7%). Nevertheless, the clinical consequences with respect to secondary complications such as infection and the necessity for invasive treatment are serious.

Ex vivo and in vivo evaluation of transsphenoidal Liqoseal application to prevent cerebrospinal fluid leakage.

BACKGROUND: Despite improvements in closure techniques by using a vital nasoseptal flap, the use of sealing materials, and improved neurosurgical techniques, cerebrospinal fluid (CSF) leak after transsphenoidal surgery still is a clinically relevant problem. Liqoseal® (Polyganics bv, Groningen, The Netherlands) is a CE-approved bioresorbable sealant patch for use as an adjunct to standard methods of cranial dural closure to prevent CSF leakage. This study aims to evaluate the application of Liqoseal in transsphenoidal surgery ex vivo and in vivo. METHODS: 1. We created an ex vivo setup simulating the sphenoidal anatomy, using a fluid pump and porcine dura positioned on a conus with the anatomical dimensions of the sella to evaluate whether the burst pressure of Liqoseal applied to a bulging surface was above physiological intracranial pressure. Burst pressure was measured with a probe connected to dedicated computer software. Because of the challenging transsphenoidal environment, we tested in 4 groups with varying compression weight and time for the application of Liqoseal. 2. We subsequently describe the application of Liqoseal® in 3 patients during transsphenoidal procedures with intraoperative CSF leakage to prevent postoperative CSF leakage. RESULTS: 1. Ex vivo: The overall mean burst pressure in the transsphenoidal setup was 231 (± 103) mmHg. There was no significant difference in mean burst pressure between groups based on application weight and time (p = 0.227). 2. In Vivo: None of the patients had a postoperative CSF leak. No nose passage problems were observed. One patient had a postoperative meningitis and ventriculitis, most likely related to preoperative extensive CSF leakage. Postoperative imaging did not show any local infection, swelling, or other device-related adverse effects. CONCLUSIONS: We assess the use of Liqoseal® to seal a dural defect during an endoscopic transsphenoidal procedure as to be likely safe and potentially effective.

Mixed Reality in Modern Surgical and Interventional Practice: Narrative Review of the Literature.

BACKGROUND: Mixed reality (MR) and its potential applications have gained increasing interest within the medical community over the recent years. The ability to integrate virtual objects into a real-world environment within a single video-see-through display is a topic that sparks imagination. Given these characteristics, MR could facilitate preoperative and preinterventional planning, provide intraoperative and intrainterventional guidance, and aid in education and training, thereby improving the skills and merits of surgeons and residents alike. OBJECTIVE: In this narrative review, we provide a broad overview of the different applications of MR within the entire spectrum of surgical and interventional practice and elucidate on potential future directions. METHODS: A targeted literature search within the PubMed, Embase, and Cochrane databases was performed regarding the application of MR within surgical and interventional practice. Studies were included if they met the criteria for technological readiness level 5, and as such, had to be validated in a relevant environment. RESULTS: A total of 57 studies were included and divided into studies regarding preoperative and interventional planning, intraoperative and interventional guidance, as well as training and education. CONCLUSIONS: The overall experience with MR is positive. The main benefits of MR seem to be related to improved efficiency. Limitations primarily seem to be related to constraints associated with head-mounted display. Future directions should be aimed at improving head-mounted display technology as well as incorporation of MR within surgical microscopes, robots, and design of trials to prove superiority.

Risk Factors and Management of Incisional Cerebrospinal Fluid Leakage After Craniotomy: A Retrospective International Multicenter Study.

BACKGROUND: Incisional cerebrospinal fluid (iCSF) leakage is a serious complication after intradural cranial surgery. OBJECTIVE: To determine the incidence and risk factors of iCSF leakage after craniotomy. Secondarily, the complications after iCSF leakage and the success rate of iCSF leakage treatment was studied. METHODS: All patients who underwent an intradural cranial surgery from 2017 to 2018 at 5 neurosurgical centers were retrospectively included. Data were retrieved from medical records with 2 months of follow-up. First, univariate regression analyses were performed. Subsequently, identified risk factors were evaluated in a multivariate regression analysis. RESULTS: In total 2310 consecutive patients were included. Total iCSF leakage rate was 7.1% (n = 165). Younger age, male, higher body mass index, smoking, infratentorial surgery, and use of a dural substitute were associated with increased iCSF leakage risk, and use of a sealant reduced that risk. The odds for developing a wound infection and/or meningitis were 15 times higher in patients with iCSF leakage compared with patients without leakage. Initial conservative iCSF leakage treatment failed in 48% of patients. In 80% of cases, external cerebrospinal fluid drainage ceased the iCSF leakage. A total of 32% of patients with iCSF leakage required wound revision surgery. CONCLUSION: iCSF leakage risk increases by younger age, higher body mass index, smoking, infratentorial craniotomy, and dural substitute use, whereas sealant use reduced the risk for iCSF leakage. The leak increases the risk of postoperative infections. When iCSF leakage occurs, immediate external cerebrospinal fluid drainage or wound revision should be considered.

Histological and magnetic resonance imaging assessment of Liqoseal in a spinal in vivo pig model.

BACKGROUND: Liqoseal (Polyganics, B.V.) is a dural sealant patch for preventing postoperative cerebrospinal fluid (CSF) leakage. It has been extensively tested preclinically and CE (Conformité Européenne) approved for human use after a first cranial in-human study. However, the safety of Liqoseal for spinal application is still unknown. The aim of this study was to assess the safety of spinal Liqoseal application compared with cranial application using histology and magnetic resonance imaging characteristics. METHODS: Eight female Dutch Landrace pigs underwent laminectomy, durotomy with standard suturing and Liqoseal application. Three control animals underwent the same procedure without sealant application. The histological characteristics and imaging characteristics of animals with similar survival times were compared to data from a previous cranial porcine model. RESULTS: Similar foreign body reactions were observed in spinal and cranial dura. The foreign body reaction consisted of neutrophils and reactive fibroblasts in the first 3 days, changing to a chronic granulomatous inflammatory reaction with an increasing number of macrophages and lymphocytes and the formation of a fibroblast layer on the dura by day 7. Mean Liqoseal plus dura thickness reached a maximum of 1.2 mm (range 0.7-2.0 mm) at day 7. CONCLUSION: The spinal dural histological reaction to Liqoseal during the first 7 days was similar to the cranial dural reaction. Liqoseal did not swell significantly in both application areas over time. Given the current lack of a safe and effective dural sealant for spinal application, we propose that an in-human safety study of Liqoseal is the logical next step.

Segmentation techniques of brain arteriovenous malformations for 3D visualization: a systematic review.

BACKGROUND: Visualization, analysis and characterization of the angioarchitecture of a brain arteriovenous malformation (bAVM) present crucial steps for understanding and management of these complex lesions. Three-dimensional (3D) segmentation and 3D visualization of bAVMs play hereby a significant role. We performed a systematic review regarding currently available 3D segmentation and visualization techniques for bAVMs. METHODS: PubMed, Embase and Google Scholar were searched to identify studies reporting 3D segmentation techniques applied to bAVM characterization. Category of input scan, segmentation (automatic, semiautomatic, manual), time needed for segmentation and 3D visualization techniques were noted. RESULTS: Thirty-three studies were included. Thirteen (39%) used MRI as baseline imaging modality, 9 used DSA (27%), and 7 used CT (21%). Segmentation through automatic algorithms was used in 20 (61%), semiautomatic segmentation in 6 (18%), and manual segmentation in 7 (21%) studies. Median automatic segmentation time was 10 min (IQR 33), semiautomatic 25 min (IQR 73). Manual segmentation time was reported in only one study, with the mean of 5-10 min. Thirty-two (97%) studies used screens to visualize the 3D segmentations outcomes and 1 (3%) study utilized a heads-up display (HUD). Integration with mixed reality was used in 4 studies (12%). CONCLUSIONS: A golden standard for 3D visualization of bAVMs does not exist. This review describes a tendency over time to base segmentation on algorithms trained with machine learning. Unsupervised fuzzy-based algorithms thereby stand out as potential preferred strategy. Continued efforts will be necessary to improve algorithms, integrate complete hemodynamic assessment and find innovative tools for tridimensional visualization.

Development of the SAFETEA Scores for Predicting Risks of Complications of Preventive Endovascular or Microneurosurgical Intracranial Aneurysm Occlusion.

OBJECTIVE: Preventive unruptured intracranial aneurysm occlusion can reduce the risk of subarachnoid hemorrhage, but both endovascular and microneurosurgical treatment carry a risk of serious complications. To improve individualized management decisions, we developed risk scores for complications of endovascular and microneurosurgical treatment based on easily retrievable patient, aneurysm, and treatment characteristics. METHODS: For this multicenter cohort study, we combined individual patient data from unruptured intracranial aneurysm patients ≥18 years undergoing preventive endovascular treatment (standard, balloon-assisted or stent-assisted coiling, Woven EndoBridge-device, or flow-diverting stent) or microneurosurgical clipping at one of 10 participating centers from three continents between 2000-2018. The primary outcome was death from any cause or clinical deterioration from neurological complications ≤30 days. We selected predictors based on previous knowledge about relevant risk factors and predictor performance and studied the association between predictors and complications with logistic regression. We assessed model performance with calibration plots and concordance (c) statistics. RESULTS: Of 1282 included patients, 94 (7.3%) had neurological symptoms that resolved <30 days, 140 (10.9%) had persisting neurological symptoms, and 6 died (0.5%)). At 30 days, 52 patients (4.1%) were dead or dependent. Predictors of procedural complications were: size of aneurysm, aneurysm location, familial subarachnoid hemorrhage, earlier atherosclerotic disease, treatment volume, endovascular modality (for endovascular treatment) or extra aneurysm configuration factors (for microneurosurgical treatment; branching artery from aneurysm neck or unfavorable dome-to-neck ratio), and age (acronym: SAFETEA). For endovascular treatment (n=752), the c-statistic was 0.72 (95%CI:0.67-0.77) and the absolute complication risk ranged from 3.2% (95%CI:1.6%-14.9%;≤1 point) to 33.1% (95%CI:25.4%-41.5%;≥6 points). For microneurosurgical treatment (n=530), the c-statistic was 0.72 (95%CI:0.67-0.77) and the complication risk ranged from 4.9% (95%CI:1.5%-14.9%;≤1 point) to 49.9% (95%CI:39.4%-60.6%;≥6 points). CONCLUSIONS: The SAFETEA risk scores for endovascular and microneurosurgical treatment are based on seven easily retrievable risk factors to predict the absolute risk of procedural complications in patients with unruptured intracranial aneurysms. The scores need external validation before the predicted risks can be properly used to support decision making in clinical practice.

Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

The HeMoVal study protocol: a prospective international multicenter cohort study to validate cerebrospinal fluid hemoglobin as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury.

INTRODUCTION: Preclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI. METHODS: HeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses. DISCUSSION: We hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH. STUDY REGISTRATION: ClinicalTrials.gov Identifier NCT04998370 . Date of registration: August 10, 2021.

Cerebrospinal Fluid Leak after Transsphenoidal Surgery: A Systematic Review and Meta-analysis.

Background Cerebrospinal fluid (CSF) leak is widely recognized as a challenging and commonly occurring postoperative complication of transsphenoidal surgery (TSS). The primary objective of this study is to benchmark the current prevalence of CSF leak after TSS in the adult population. Methods The authors followed the PRISMA guidelines. The PubMed, Embase, and Cochrane Library databases were searched for articles reporting CSF leak after TSS in the adult population. Meta-analysis was performed using the Untransformed Proportion metric in OpenMetaAnalyst. For two between-group comparisons a generalized linear mixed model was applied. Results We identified 2,408 articles through the database search, of which 70, published since 2015, were included in this systematic review. These studies yielded 24,979 patients who underwent a total of 25,034 transsphenoidal surgeries. The overall prevalence of postoperative CSF leak was 3.4% (95% confidence interval or CI 2.8-4.0%). The prevalence of CSF leak found in patients undergoing pituitary adenoma resection was 3.2% (95% CI 2.5-4.2%), whereas patients who underwent TSS for another indication had a CSF leak prevalence rate of 7.1% (95% CI 3.0-15.7%) (odds ratio [OR] 2.3, 95% CI 0.9-5.7). Patients with cavernous sinus invasion (OR 3.0, 95% CI 1.1-8.7) and intraoperative CSF leak (OR 5.9, 95% CI 3.8-9.0) have increased risk of postoperative CSF leak. Previous TSS and microscopic surgery are not significantly associated with postoperative CSF leak. Conclusion The overall recent prevalence of CSF leak after TSS in adults is 3.4%. Intraoperative CSF leak and cavernous sinus invasion appear to be significant risk factors for postoperative CSF leak.

Spinal fixation after laminectomy in pigs prevents postoperative spinal cord injury.

BACKGROUND: A safe, effective, and ethically sound animal model is essential for preclinical research to investigate spinal medical devices. We report the initial failure of a porcine spinal survival model and a potential solution by fixating the spine. METHODS: Eleven female Dutch Landrace pigs underwent a spinal lumbar interlaminar decompression with durotomy and were randomized for implantation of a medical device or control group. Magnetic resonance imaging (MRI) was performed before termination. RESULTS: Neurological deficits were observed in 6 out of the first 8 animals. Three of these animals were terminated prematurely because they reached the predefined humane endpoint. Spinal cord compression and myelopathy was observed on postoperative MRI imaging. We hypothesized postoperative spinal instability with epidural hematoma, inherent to the biology of the model, and subsequent spinal cord injury as a potential cause. In the subsequent 3 animals, we fixated the spine with Lubra plates. All these animals recovered without neurological deficits. The extent of spinal cord compression on MRI was variable across animals and did not seem to correspond well with neurological outcome. CONCLUSION: This study shows that in a porcine in vivo model of interlaminar decompression and durotomy, fixation of the spine after lumbar interlaminar decompression is feasible and may improve neurological outcomes. Additional research is necessary to evaluate this hypothesis.

Cerebrospinal fluid leakage costs after craniotomy and health economic assessment of incidence reduction from a hospital perspective in the Netherlands.

OBJECTIVES: We aim to quantify the cost difference between patients with incisional cerebrospinal fluid (iCSF) leakage and those without after intradural cranial surgery. Second, the potential cost savings per patient when a decrease in iCSF leakage rate would be achieved with and without added costs for preventative measures of various price and efficacy are modelled. DESIGN: Health economic assessment from a hospital perspective based on a retrospective cohort study. SETTING: Dutch tertiary referral centre. PARTICIPANTS: We included 616 consecutive patients who underwent intradural cranial surgery between 1 September 2017 and 1 September 2018. Patients undergoing burr hole surgery or transsphenoidal surgery, or who died within 1 month after surgery or were lost to follow-up were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes of the cost analysis include a detailed breakdown of mean costs per patient for patients with postoperative iCSF leakage and patients without, and the mean cost difference. For the scenario analyses the outcomes are the potential cost savings per 1000 patients when a decrease in iCSF leakage would be achieved. RESULTS: Mean cost difference between patients with and without iCSF leakage was €9665 (95%CI, €5125 to €14 205). The main cost driver was hospital stay with a difference of 8.5 days. A 25% incidence reduction would result in a mean cost saving of -€94 039 (95% CI, -€218 258 to -€7077) per 1000 patients. A maximum cost reduction of -€653 025 (95% CI, -€1 204 243 to -€169 120) per 1000 patients could be achieved if iCSF leakage would be reduced with 75% in all patients, with 72 cases of iCSF leakage avoided. CONCLUSIONS: Postoperative iCSF leakage after intradural cranial surgery increases healthcare costs significantly and substantially. From a health economic perspective preventative measures to avoid iCSF leakage should be pursued.