Neutrophil extracellular trap biomarkers in aneurysmal subarachnoid hemorrhage: early decline of DNase 1 activity associated with delayed cerebral ischemia.

Introduction: High-mobility group box 1 (HMGB1) protein is a critical mediator of neutrophil extracellular trap (NET) formation (NETosis). Myeloperoxidase (MPO)-DNA complexes, a biomarker of NETs, and HMGB1 have been associated with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Additional mechanistic NET-related biomarkers and their role in the neuroinflammatory cascade surrounding DCI remain to be explored. Methods: A post-hoc analysis of a prospective, blinded, single-center biomarker observational study was performed. De novo measurements of serum citrullinated histone H3-DNA complexes (H3Cit-DNA), peptidylarginine deiminase 4 (PAD4), cell-free DNA (cf-DNA), and DNase 1 activity were conducted on admission (D0) and day 4 (D4). Delayed cerebral infarction (DCI) was defined as new cerebral infarction on CT head not present on the post-treatment scan. Results: H3Cit-DNA, PAD4, cf-DNA, and DNase 1 activity were within quantifiable ranges in all serum samples analyzed at D0 and D4. Admission biomarker levels were not associated with DCI development. From D0 to D4, in both the DCI and the non-DCI groups, H3Cit-DNA levels significantly decreased, cf-DNA levels significantly increased, and PAD4 levels remained stable. In contrast, DNase 1 activity significantly decreased from D0 to D4 in the DCI group (p < 0.001) but not in the non-DCI group. Conclusion: This exploratory analysis demonstrated NET-related biomarkers such as H3Cit-DNA, PAD4, cf-DNA, and DNase 1 activity in all aSAH patients. A decline of systemic DNase 1 activity in the early phase might increase the risk of delayed cerebral ischemia.

Polytomous Rasch Analyses of Surgeons' Decision-Making on Choice of Procedure in Endoscopic Lumbar Spinal Stenosis Decompression Surgeries.

BACKGROUND: With the growing prevalence of lumbar spinal stenosis, endoscopic surgery, which incorporates techniques such as transforaminal, interlaminar, and unilateral biportal (UBE) endoscopy, is increasingly considered. However, the patient selection criteria are debated among spine surgeons. OBJECTIVE: This study used a polytomous Rasch analysis to evaluate the factors influencing surgeon decision-making in selecting patients for endoscopic surgical treatment of lumbar spinal stenosis. METHODS: A comprehensive survey was distributed to a representative sample of 296 spine surgeons. Questions encompassed various patient-related and clinical factors, and responses were captured on a logit scale graphically displaying person-item maps and category probability curves for each test item. Using a Rasch analysis, the data were subsequently analyzed to determine the latent traits influencing decision-making. RESULTS: The Rasch analysis revealed that surgeons' preferences for transforaminal, interlaminar, and UBE techniques were easily influenced by comfort level and experience with the endoscopic procedure and patient-related factors. Harder-to-agree items included technological aspects, favorable clinical outcomes, and postoperative functional recovery and rehabilitation. Descriptive statistics suggested interlaminar as the best endoscopic spinal stenosis decompression technique. However, logit person-item analysis integral to the Rasch methodology showed highest intensity for transforaminal followed by interlaminar endoscopic lumbar stenosis decompression. The UBE technique was the hardest to agree on with a disordered person-item analysis and thresholds in category probability curve plots. CONCLUSION: Surgeon decision-making in selecting patients for endoscopic surgery for lumbar spinal stenosis is multifaceted. While the framework of clinical guidelines remains paramount, on-the-ground experience-based factors significantly influence surgeons' selection of patients for endoscopic lumbar spinal stenosis surgeries. The Rasch methodology allows for a more granular psychometric evaluation of surgeon decision-making and accounts better for years-long experience that may be lost in standardized clinical guideline development. This new approach to assessing spine surgeons' thought processes may improve the implementation of evidence-based protocol change dictated by technological advances was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the International Society for Minimal Intervention in Spinal Surgery (ISMISS), the Mexican Spine Society (AMCICO), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Society (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS).

Comparative Analysis of Learning Curve, Complexity, Psychological Stress, and Work Relative Value Units for CPT 62380 Endoscopic Lumbar Spinal Decompression vs Traditional Lumbar Spine Surgeries: A Paired Rasch Survey Study.

BACKGROUND: Effective 1 January 2017, single-level endoscopic lumbar discectomy received a Category I Current Procedural Terminology (CPT) code 62380. However, no work relative value units (RVUs) are currently assigned to the procedure. An international team of endoscopic spine surgeons conducted a study, endorsed by several spine societies, analyzing the learning curve, difficulty, psychological intensity, and estimated work RVUs of endoscopic lumbar spinal decompression compared with other common lumbar spine surgeries. METHODS: A survey comparing CPT 62380 to 10 other comparator CPT codes reflective of common spine surgeries was developed to assess the work RVUs in terms of learning curve, difficulty, psychological intensity, and work effort using a paired Rasch method. RESULTS: The survey was sent to 542 spine specialists. Of 322 respondents, 150 completed the survey for a 43.1% completion rate. Rasch analysis of the submitted responses statistically corroborated common knowledge that the learning curve with lumbar endoscopic spinal surgery is steeper and more complex than with traditional translaminar lumbar decompression surgeries. It also showed that the psychological stress and mental and work effort with the lumbar endoscopic decompression surgery were perceived to be higher by responding spine surgeons compared with posterior comparator decompression and fusion surgeries and even posterior interbody and posterolateral fusion surgeries. The regression analysis of work effort vs procedural difficulty showed the real-world evaluation of the lumbar endoscopic decompression surgery described in CPT code 62380 with a calculated work RVU of 18.2464. CONCLUSION: The Rasch analysis suggested the valuation for the endoscopic lumbar decompression surgery should be higher than for standard lumbar surgeries: 111.1% of the laminectomy with exploration and/or decompression of spinal cord and/or cauda equina (CPT 63005), 118.71% of the laminectomy code (CPT 63047), which includes foraminotomy and facetectomy, 152.1% of the hemilaminectomy code (CPT 63030), and 259.55% of the interlaminar or interspinous process stabilization/distraction without decompression code (CPT 22869). This research methodology was endorsed by the Interamerican Society for Minimally Invasive Spine Surgery (SICCMI), the Mexican Society of Spinal Surgeons (AMCICO), the International Society For Minimally Invasive Spine Surgery (ISMISS), the Brazilian Spine Society (SBC), the Society for Minimally Invasive Spine Surgery (SMISS), the Korean Minimally Invasive Spine Surgery (KOMISS), and the International Society for the Advancement of Spine Surgery (ISASS). CLINICAL RELEVANCE: This study provides an updated reimbursement recommendation for endoscopic spine surgery. LEVEL OF EVIDENCE: Level 3.

Acute back pain - Role of injection techniques and surgery: WFNS spine committee recommendations.

Objective: Lower back pain is a significant cause of morbidity, and despite a range of interventions available, there is a lack of consensus on the most efficacious treatments. The aim of this systematic review is to formulate a list of recommendations for the role of spinal injections and surgery in the treatment of acute back pain. Methods: A systematic literature search from 2012 to 2022 was conducted on Pubmed, Medline, and Cochrane Central Register of Controlled Trials for papers focusing on the role of injections and surgery for the management of acute lower back pain. Inclusion criteria included randomised controlled trials, as well as prospective and retrospective studies reporting primary outcomes (pain improvement (VAS score) and back-specific functional status) and secondary outcomes (post-procedure complications). These data were reviewed, presented, and voted on by an expert panel consisting of 14 attending spine surgeons from 14 countries at the consensus meeting of the World Federation of Neurosurgical Societies (WFNS) Spine Committee. A two-round consensus-based Delphi method was used to generate consensus, and topics with >66% agreement were categorized as having reached consensus. Results: 100 studies met inclusion criteria. Of these, 20 were selected by the committee for full text review and presented at the consensus meeting. The committee voted on 8 statements and achieved consensus on the following 7 statements: (1) Epidural steroid injections (ESIs) show significant benefit to discogenic back pain; (2) A lateral approach is superior to a midline approach for ESIs; (3) Short-term (<1 week) effect of ESIs is similar between steroids; (4) ESIs have a variety of potential complications; (5) CT or fluoroscopy guidance can be used for lumbar medial branch blocks; (6) Lumbar medial branch radiofrequency ablations can be performed on patients with recurrent pain after a successful ESI, and (7) Acute lower back pain is usually self-limiting, resolves in <6 weeks, and does not require surgical intervention. Conclusion: Given significant treatment heterogeneity, we provide the latest, evidence-based recommendations for management of acute lower back pain. ESIs are effective at short-term pain relief, and surgical intervention should be reserved for patients failing conservative measures.

Role of surgery in primary lumbar disk herniation: WFNS spine committee recommendations.

Objective: To provide the most up-to-date recommendations on the role of surgery in first-time lumbar disk herniations (LDH) in order to standardize surgical management. Methods: We performed a literature search in PubMed, Scopus, and Embase from 2012 to 2022 using the following keywords: "lumbar disk herniation AND surgery". Our initial search yielded 2610 results, which were narrowed down to 283 papers after standardized screening critera were applied. The data from these 283 papers were presented and discussed at two international meetings of the World Federation of Neurosurgical Societies (WFNS) Spine Committee, where the Delphi method was employed and ten spine experts voted on five final consensus statements. Results: and Conclusions: The WFNS Spine Committee's guidelines cover four main topics: (1) role and timing of surgery in first-time LDH; (2) role of minimally invasive techniques in LDH; (3) extent of disk resection in LDH surgery; (4) role of lumbar fusion in the context of LDH. Surgery for LDH is recommended for failure of conservative treatment, cauda equina syndrome, and progressive neurological impairment, including severe motor deficits. In the latter cases, early surgery is associated with faster recovery and may improve patient outcomes. Minimally invasive techniques have short-term advantages over open procedures, but there is insufficient evidence to make a recommendation for or against the choice of a specific surgical procedure. Sequestrectomy and standard microdiscectomy demonstrated similar clinical results in terms of pain control, recurrence rate, functional outcome, and complications at short and medium-term follow-up. Lumbar fusion is not recommended as a routine treatment for first-time LDH, although it may be considered in specific patients affected by chronic axial pain or instability.

Cauda equina, conus medullaris and syndromes mimicking sciatic pain: WFNS spine committee recommendations.

Introduction: Cauda equina syndrome (CES), conus medullaris syndrome (CMS), and sciatica-like syndromes or "sciatica mimics" (SM) may present as diagnostic and/or therapeutic dilemmas for the practicing spine surgeon. There is considerable controversy regarding the appropriate definition and diagnosis of these entities, as well as indications for and timing of surgery. Our goal is to formulate the most current, evidence-based recommendations for the definition, diagnosis, and management of CES, CMS, and SM syndromes. Methods: We performed a systematic literature search in PubMed from 2012 to 2022 using the keywords "cauda equina syndrome", "conus medullaris syndrome", "sciatica", and "sciatica mimics". Standardized screening criteria yielded a total of 43 manuscripts, whose data was summarized and presented at two international consensus meetings of the World Federation of Neurosurgical Societies (WFNS) Spine Committee. Utilizing the Delphi method, we generated seven final consensus statements. Results and conclusion: s: We provide standardized definitions of cauda equina, cauda equina syndrome, conus medullaris, and conus medullaris syndrome. We advocate for the use of the Lavy et al classification system to categorize different types of CES, and recommend urgent MRI in all patients with suspected CES (CESS), considering the low sensitivity of clinical examination in excluding CES. Surgical decompression for CES and CMS is recommended within 48 h, preferably within less than 24 h. There is no data regarding the role of steroids in acute CES or CMS. The treating physician should be cognizant of a variety of other pathologies that may mimic sciatica, including piriformis syndrome, and how to manage these.

Lumbar disc herniation: Epidemiology, clinical and radiologic diagnosis WFNS spine committee recommendations.

Objective: To formulate the most current, evidence-based recommendations regarding the epidemiology, clinical diagnosis, and radiographic diagnosis of lumbar herniated disk (LDH). Methods: A systematic literature search in PubMed, MEDLINE, and CENTRAL was performed from 2012 to 2022 using the search terms "herniated lumbar disc", "epidemiology", "prevention" "clinical diagnosis", and "radiological diagnosis". Screening criteria resulted in 17, 16, and 90 studies respectively that were analyzed regarding epidemiology, clinical diagnosis, and radiographic diagnosis of LDH. Using the Delphi method and two rounds of voting at two separate international meetings, ten members of the WFNS (World Federation of Neurosurgical Societies) Spine Committee generated eleven final consensus statements. Results: The lifetime risk for symptomatic LDH is 1-3%; of these, 60-90% resolve spontaneously. Risk factors for LDH include genetic and environmental factors, strenuous activity, and smoking. LDH is more common in males and in 30-50 year olds. A set of clinical tests, including manual muscle testing, sensory testing, Lasegue sign, and crossed Lasegue sign are recommended to diagnose LDH. Magnetic resonance imaging (MRI) is the gold standard for confirming suspected LDH. Conclusions: These eleven final consensus statements provide current, evidence-based guidelines on the epidemiology, clinical diagnosis, and radiographic diagnosis of LDH for practicing spine surgeons worldwide.

Disability-adjusted life years from bone and joint infections associated with antimicrobial resistance: an insight from the 2019 Global Burden of Disease Study.

PURPOSE: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. METHODS: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. RESULTS: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. CONCLUSIONS: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities.

Acute low back pain: Epidemiology, etiology, and prevention: WFNS spine committee recommendations.

Objective: Acute low back pain is a highly prevalent condition that poses significant challenges to healthcare systems worldwide. In this manuscript, we present the most current, evidence-based guidelines from the World Federation of Neurosurgical Societies (WFNS) Spine Committee on the epidemiology, etiology, and prevention of acute low back pain (LBP) lasting ≤ 4 weeks. Methods: We performed a literature review 2012-2022 using the PubMed, Medline, and CENTRAL databases with the keywords "acute low back pain", "acute back pain", "low back pain", "epidemiology", "etiology", "costs", "risk factor", "cultural", "developed", "developing" and "prevention". Systematic screening criteria were applied, resulting in 13 final articles on epidemiology and etiology of LBP, 2 manuscripts on costs, 5 articles on risk factors, and 23 articles on prevention strategies for acute LBP. These were presented at two separate international meetings, where members of the WFNS Spine Committee voted on five final consensus statements presented here. Results: and Conclusions: There is a high incidence and prevalence of acute LBP, particularly in high-income countries, which is felt to be at least partially due to demographic shifts with an aging population and lifestyle changes including higher rates of obesity and physical inactivity. Acute LBP has a significant impact on quality of life and ability to work, resulting in high direct and indirect costs worldwide. Early diagnosis and appropriate management of acute LBP is recommended to prevent this pain from turning into chronic LBP. The WFNS Spine Committee's recommendations respresent the latest guidelies to help improve patient care for acute LBP worldwide.

Lumbar disc herniation: Prevention and treatment of recurrence: WFNS spine committee recommendations.

Objective: This review aims to formulate the most current evidence-based recommendations on the epidemiology, prevention, and treatment of recurrent lumbar disc herniation (LDH). Methods: We performed a systematic literature search in PubMed, Medline, and Google Scholar databases from 2012 to 2022 using the keywords "lumbar disc recurrence." Screening criteria resulted in 57 papers, which were summarized and presented at two international consensus meetings of the World Federation of Neurosurgical Societies (WFNS) Spine Committee. The 57 papers covered the following topics: (1) Definition and incidence of recurrence after lumbar disc surgery; (2) Prediction of recurrence before primary surgery; (3) Prevention of recurrence by surgical measures; (4) Prevention of recurrence by postoperative measures; (5) Treatment options for recurrent disc herniation; (6) The outcomes of recurrent disc herniation surgery. We utilized the Delphi method and voted on eight final consensus statements. Results and conclusion: Recurrence after disc herniation surgery may be considered a surgical complication, its incidence is approximately 5% and is different from overall re-operation incidence. There are multiple risk factors predicting LDH recurrence, including smoking, younger age, male gender, obesity, diabetes, disc degeneration, and presence of lumbosacral transitional vertebrae. The level of lumbar discectomy surgery and the amount of disc material removed do not correlate with recurrence rate. Minimally invasive discectomies may have higher recurrence rates, especially during the surgeon's learning period. However, the experience of the surgeon is not related to recurrence. High-quality studies are needed to determine if activity restriction, weight loss, smoking cessation, and muscle-strengthening exercises after primary surgery can help prevent recurrence of LDH.The best treatment option for recurrent disc herniation is still being discussed. While complications of minimally invasive techniques may be lower than open discectomy, outcomes are similar. Fusion should only be considered when spinal instability and/or spinal deformity are present. Clinical outcomes and patient satisfaction after recurrent disc herniation surgery are inferior to those after initial discectomy.

The role of conservative treatment in lumbar disc herniations: WFNS spine committee recommendations.

Objective: To formulate the most current, evidence-based recommendations for the conservative management of lumbar disc herniations (LDH). Methods: A systematic literatüre search was performed 2012-2022 in PubMed/Medline and Cochrane using the keywords ''lumbar disc herniation'' and ''conservative treatment,'' yielding 342 total manuscripts. Screening criteria resulted in 12 final manuscripts which were summarized and presented at two international consensus meetings of the World Federation of Neurosurgical Societies (WFNS) Spine Committee. The Delphi method was utilized to arrive at three final consensus statements. Results and conclusion: s: In the absence of cauda equina syndrome, motor, or other serious neurologic deficits, conservative treatment should be the first line of treatment for LDH. NSAIDs may significantly improve acute low back and sciatic pain caused by LDH. A combination of activity modification, pharmacotherapy, and physical therapy provides good outcomes in most LDH patients.

Acute back pain: Clinical and radiologic diagnosis: WFNS spine committee recommendations.

Objective: To formulate the most current, evidence-based recommendations for the clinical and radiologic diagnosis of acute low back pain lasting <4 weeks. Methods: A systematic literature search in PubMed and Google Scholar databases was performed from 2012 to 2022 using the search terms "acute back pain AND clinical diagnosis" and "acute back pain AND radiologic diagnosis". Screening criteria resulted in a total of 97 papers analyzed. Using the Delphi method and two rounds of voting, the WFNS (World Federation of Neurosurgical Societies) Spine Committee generated ten final consensus statements. Results: Ten final consensus statements address the clinical diagnosis of acute LBP, including which clinical conditions cause acute LBP and how we can distinguish between the different causes of LBP, including discogenic, facet joint, sacroiliac joint, and myofascial pain. The most important step for the radiologic diagnosis of acute LBP is to evaluate the necessity of radiologic investigation, as well as its timing and the most appropriate type of imaging modality. Importantly, imaging should not be a routine diagnostic tool, unless red flag signs are present. In fact, routine imaging for acute LBP can actually have a negative effect as it may reveal incidental radiographic findings that exacerbate patient fear and anxiety. Conclusion: Overall, the quality of evidence is not high for most of our consensus statements, and further studies are needed to validate the WFNS Spine Committee recommendations on the clinical and radiographic diagnosis of acute LBP.

Confocal laser endomicroscopy in glial tumors-a histomorphological analysis.

OBJECTIVE: The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors. MATERIAL AND METHODS: One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature. RESULTS: All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas  (p < 0.002). CONCLUSION: Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

Endoscopic transaqueductal stent placement for tumor-related aqueductal compression in pediatric patients: surgical consideration, technique, and results.

PURPOSE: Endoscopic transaqueductal stenting has become a well-accepted treatment option for a selected small subset of aqueductal stenosis-related obstructive hydrocephalus. However, transaqueductal stenting poses unique challenges and risks which requires critical consideration. This report discusses the clinical experiences with transaqueductal stenting for periaqueductal tumor-related aqueductal stenosis focusing on pediatric patients. METHODS: A retrospective analysis of all patients undergoing endoscopic TAS from 01/1993 to 01/2022 in the author's departments was performed. Demographic, clinical, radiological, and intraoperative endoscopic data were evaluated. All patients with AS-related occlusive hydrocephalus that was treated with TAS were analyzed and prospectively followed. Special attention has been given to providing insights into indications, surgical technique, and limitations. RESULTS: Out of 28 endoscopic transaqueductal endoscopis stenting procedures, five procedures were performed on periaqueductal tumor-related obstructive hydrocephalus, two children and three adult patients. CSF pathway was obstructed by tumor located in the aqueduct in 2, by tumor in the thalamus/mesencephalon in 1, by a tumor within the third ventricle in 1, and by a tumor of the lamina tecti in 1. Simultaneously with transaqueductal stenting, 2 endoscopic third ventriculostomies (ETV), 3 tumor biopsies, and 1 tumor resection were performed. Postoperative complications included the following: CSF fistula (1 case), and asymptomatic fornix contusion (1 case). A working aqueductal stent was achieved in all cases based on clinical follow-up evaluation. Postoperatively, all patients showed improvement or resolution of their symptoms. The mean follow-up period was 25.2 months (range, 1-108 months). One patient died due to tumor progression during early follow-up. No stent migration was seen. CONCLUSION: Endoscopic third ventriculostomy remains the gold standard for treatment of CSF circulation obstructions with lesions in the posterior third ventricle and aqueduct. Transaqueductal stenting for periaqueductal tumor-related aqueductal compression is technically feasible. However, because of the potential high risks and subtle advantages compared with ETV transaqueductal stenting, it might be indicated in a small subset of well-selected patients if alternative treatment options are not at hand.

Prolonged course of brain edema and neurological recovery in a translational model of decompressive craniectomy after closed head injury in mice.

Background: The use of decompressive craniectomy in traumatic brain injury (TBI) remains a matter of debate. According to the DECRA trial, craniectomy may have a negative impact on functional outcome, while the RescueICP trial revealed a positive effect of surgical decompression, which is evolving over time. This ambivalence of craniectomy has not been studied extensively in controlled laboratory experiments. Objective: The goal of the current study was to investigate the prolonged effects of decompressive craniectomy (both positive and negative) in an animal model. Methods: Male mice were assigned to the following groups: sham, decompressive craniectomy, TBI and TBI followed by craniectomy. The analysis of functional outcome was performed at time points 3d, 7d, 14d and 28d post trauma according to the Neurological Severity Score and Beam Balance Score. At the same time points, magnetic resonance imaging was performed, and brain edema was analyzed. Results: Animals subjected to both trauma and craniectomy presented the exacerbation of the neurological impairment that was apparent mostly in the early course (up to 7d) after injury. Decompressive craniectomy also caused a significant increase in brain edema volume (initially cytotoxic with a secondary shift to vasogenic edema and gliosis). Notably, delayed edema plus gliosis appeared also after decompression even without preceding trauma. Conclusion: In prolonged outcomes, craniectomy applied after closed head injury in mice aggravates posttraumatic brain edema, leading to additional functional impairment. This effect is, however, transient. Treatment options that reduce brain swelling after decompression may accelerate neurological recovery and should be explored in future experiments.

Development and Evaluation of an MRI Artifact-Free Aneurysm Clip.

BACKGROUND AND OBJECTIVES: The digital subtraction angiography is still the gold standard in the follow-up after aneurysm surgery, although it remains a repeating invasive technique with accumulating X-ray exposure. An alternative magnetic resonance angiography has the disadvantage of metal-related artifacts. A metal-free aneurysm clip could overcome this problem. Recent advances in manufacturing technologies of fiber-reinforced plastics might allow developing a prototype of a metal-free clip. METHODS: The prototype was formed out of carbon fiber-reinforced polyetheretherketone (CF-PEEK) in accordance with the standard clip design. In vivo and in vitro studies were performed to analyze the central nervous system biocompatibility. The prototype was tested in a phantom in a 3 T MRI scanner and microtomography scanner. For in vivo assessment, the left renal artery of rats was either ligated with a suture, clipped with a regular titanium clip or with the CF-PEEK prototype clip. The animals underwent standard MRI sequences and magnetic resonance angiography and assessment by a blinded neuroradiologist. RESULTS: Phantom studies showed no signs of artifacts. The prototype showed a reliable clamping and reopening after clip application, although the clamping force was reduced. In vivo studies showed a successful occlusion of the renal artery in all cases in the magnetic resonance angiography. Clip artifacts were statistically significant reduced in the prototype group (P < .01). CF-PEEK showed no signs of impaired biocompatibility compared with the titanium samples in vitro and in vivo. CONCLUSION: Former attempts of metal-free aneurysm clips did not meet the criteria of the standard clip design. In this study, the practicability of this new CF-PEEK artifact-free aneurysm clip has been proven. The further fabrication developments should overcome the problem of a reduced clamping force in the future. After clinical approval, it will improve the magnetic resonance image quality and might help to reduce the amount of digital subtraction angiography in the follow-up.

Considerations on surgical strategies and associated risk profiles for endoscopic tumor biopsies within the third ventricle and periaqueductal region.

INTRODUCTION: Neuroendoscopic techniques have proven to be a successful and minimally-invasive technique for tumor biopsies within the third ventricle in pediatric patients. However, a comprehensive assessment of associated surgical strategies, techniques, and morbidity is essential to optimize patient outcomes. METHODS: This retrospective study analyzed full endoscopic tumor biopsies in pediatric patients with tumors in the third ventricle and periaqueductal region. Data from 1995 to 2022 were collected from medical records, imaging, and intraoperative video documentation. RESULTS: In this study, 16 shear endoscopic tumor biopsies were performed using the transventricular transforaminal approach. Tumors were located in the anterior or mid part of the third ventricle (50%) or in the periaqueductal and pineal recess region (50%). Preoperative hydrocephalus was seen in 81.25%. Tumor biopsies were harvested successfully in all cases. Simultaneous ETV was performed in 12 (75%) cases and additional septostomy in 3 (18.75%). Significant intraoperative bleeding occurred in 3 cases (18.75%). All bleeding situations could be successfully managed with continuous irrigation. Histopathology revealed astrocytoma as the predominant diagnosis (75%). No new neurologic deficits were observed, except for one case of transient oculomotor nerve paralysis after ETV. Hydrocephalus persisted in 18.6% of all cases with the need of urgent ventriculoperitoneal shunting in two patients. CONCLUSION: In conclusion, neuroendoscopy emerges as an effective technique for tumor biopsies within the third ventricle in pediatric patients, offering the added advantage of simultaneous treatment of obstructive hydrocephalus. However, it is essential to acknowledge the specific intra- and postoperative risks associated with various surgical strategies. The safe management and achievement of favorable clinical results demand extensive experience and expertise.

Development of an Enzyme-Linked Immunosorbent Assay (ELISA) for the Quantification of ARID1A in Tissue Lysates.

ARID1A is a subunit of the mammalian SWI/SNF complex, which is thought to regulate gene expression through restructuring chromatin structures. Its gene ARID1A is frequently mutated and ARID1A levels are lowered in several human cancers, especially gynecologic ones. A functional ARID1A loss may have prognostic or predictive value in terms of therapeutic strategies but has not been proposed based on a quantitative method. Hardly any literature is available on ARID1A levels in tumor samples. We developed an indirect enzyme-linked immunosorbent assay (ELISA) for ARID1A based on the current EMA and FDA criteria. We demonstrated that our ELISA provides the objective, accurate, and precise quantification of ARID1A concentrations in recombinant protein solutions, cell culture standards, and tissue lysates of tumors. A standard curve analysis yielded a 'goodness of fit' of R2 = 0.99. Standards measured on several plates and days achieved an inter-assay accuracy of 90.26% and an inter-assay precision with a coefficient of variation of 4.53%. When tumor lysates were prepared and measured multiple times, our method had an inter-assay precision with a coefficient of variation of 11.78%. We believe that our suggested method ensures a high reproducibility and can be used for a high sample throughput to determine the ARID1A concentration in different tumor entities. The application of our ELISA on various tumor and control tissues will allow us to explore whether quantitative ARID1A measurements in tumor samples are of predictive value.

Image Quality and Related Outcomes of the ShuntScope-Guided Catheter Implantation in Adult Hydrocephalus: Experience of 63 Procedures.

BACKGROUND: Ventricular catheter (VC) placement in the selected subset of adult hydrocephalus can be highly challenging due to abnormal anatomical configuration or the need for trans-aqueductal stent placement. Transluminal endoscopy with the ShuntScope has been invented to increase the success rate of catheter placement. This study evaluates the image qualities of ShuntScope and related surgical outcomes in adults. METHODS: A retrospective analysis of all adult patients undergoing VC placement using the ShuntScope from November 2011 to July 2022 in the authors' department was performed. Demographic, clinical, and radiologic data were evaluated. The visualization quality of the intraoperative endoscopy was stratified into excellent, medium, and poor, and compared to the postoperative catheter tip placement. Follow-up evaluation included the surgical revision rate due to proximal catheter misplacement. RESULTS: A total of 63 ShuntScope-assisted surgeries have been performed on 60 adults. The mean age of the patients was 48.43 years. The most common underlying pathology was a tumor- or cyst-related cerebrospinal fluid (CSF) impairment in 38.33%, followed by a pseudotumor cerebri in 21.66%. The achieved image quality was excellent in 39.68%, medium in 47.62%, and poor in 12.7%. Ideal catheter placement was achieved in 79.37%. There were no intraoperative complications associated with the use of the ShuntScope. The revision rate due to suboptimal proximal VC placement was 4.76% during a mean follow-up period of 27.75 months. A statistical correlation between the image quality and accuracy of the catheter position was observed (p < 0.001). CONCLUSION: The ShuntScope can be considered an important addition to standard surgical tools in treating a selected subset of adult hydrocephalus. Direct visualization might even help achieve correct placement of the catheter in the cases with blurred vision and limited visual overview.

The minimally invasive transventricular endoscopic approach to third ventricular lesions in pediatric patients-all-rounder with limitations?

INTRODUCTION: The surgical management of third ventricular lesions poses unique challenges, requiring careful consideration of various approaches and techniques. This study focuses on the transventricular transforaminal endoscopic approach and aims to provide insights into its indications, limitations, technical nuances, and potential complications in pediatric patients. METHODS: A retrospective analysis was conducted using data from a 13-year period on pediatric patients who were subjected to transforaminal endoscopic surgery for third ventricular lesions. The study utilized a prospectively maintained internal database, extracting demographic data, preoperative assessment, surgical details, and postoperative follow-up information. The surgical technique is presented in detail, and exemplary case reports highlight relevant surgical considerations. RESULTS: Out of 578 endoscopic transforaminal procedures, 24 surgeries were performed on pediatric patients with third ventricular lesions. Performed procedures consisted of cyst resection (13 cases), solid tumor resection (4 cases), and tumor biopsies with CSF pathway restoration (7 cases). The mean age at the time of surgery was 7.6 years. Postoperatively, 14 patients showed transient nausea and vomiting (58.3%); 10 patients showed pneumocephalus on postoperative MRI (41.7%). No emergency postoperative re-interventions nor perioperative mortality were observed. CONCLUSION: The endoscopic transventricular transforaminal approach is a safe approach for lesion resection, CSF pathway restoration, and tumor biopsy in pediatric patients with third ventricle lesions. The author's results support the use of this minimally invasive technique as an alternative to more extensive approaches, particularly to the interforniceal interhemispheric approach. However, surgical success is highly dependent to the individual surgeon's experience and moreover to a suitable indication setting. Careful preoperative planning and knowledge of the approaches' pro and cons is mandatory for successful application of this approach.