C1-2 hypermobility and its impact on the spinal cord: a finite element analysis.

OBJECTIVE: The authors present a finite element analysis (FEA) evaluating the mechanical impact of C1-2 hypermobility on the spinal cord. METHODS: The Code_Aster program was used to perform an FEA to determine the mechanical impact of C1-2 hypermobility on the spinal cord. Normative values of Young's modulus were applied to the various components of the model, including bone, ligaments, and gray and white matter. Two models were created: 25° and 50° of C1-on-C2 rotation, and 2.5 and 5 mm of C1-on-C2 lateral translation. Maximum von Mises stress (VMS) throughout the cervicomedullary junction was calculated and analyzed. RESULTS: The FEA model of 2.5 mm lateral translation of C1 on C2 revealed maximum VMS for gray and white matter of 0.041 and 0.097 MPa, respectively. In the 5-mm translation model, the maximum VMS for gray and white matter was 0.069 and 0.162 MPa. The FEA model of 25° of C1-on-C2 rotation revealed maximum VMS for gray and white matter of 0.052 and 0.123 MPa. In the 50° rotation model, the maximum VMS for gray and white matter was 0.113 and 0.264 MPa. CONCLUSIONS: This FEA revealed significant spinal cord stress during pathological rotation (50°) and lateral translation (5 mm) consistent with values found during severe spinal cord compression and in patients with myelopathy. While this finite element model requires oversimplification of the atlantoaxial joint, the study provides biomechanical evidence that hypermobility within the C1-2 joint leads to pathological spinal cord stress.

The Reciprocal Relationship Between Lumbar Intervertebral Disc Degeneration and the MRI-Based Vertebral Bone Quality Score.

STUDY DESIGN: Retrospective longitudinal study. OBJECTIVE: To investigate the association between lumbar intervertebral disc degeneration (DD) and the vertebral bone quality (VBQ) score. SUMMARY OF BACKGROUND DATA: The VBQ score that is based on magnetic resonance imaging (MRI) has been proposed as a measure of lumbar spine bone quality and is a significant predictor of healthy versus osteoporotic bone. However, the role of segmental contributing factors on VBQ is unknown. METHODS: Non-surgical patients who underwent repeated lumbar MRI scans, at least three years apart primarily for low back pain were retrospectively included. VBQ was assessed as previously described. DD was assessed using the Pfirrmann grading (PFG) scale. PFG grades were summarized as PFGL1-4 for the upper three lumbar disc levels, as PFGL4-S1 for the lower two lumbar disc levels, and as PFGL1-S1 for all lumbar disc levels. Multivariable linear mixed models were used with adjustments for age, sex, race, body mass index (BMI), and the clustering of repeated measurements. RESULTS: 350 patients (54.6% female, 85.4% Caucasian) were included in the final analysis, with a median age at baseline of 60.1 years and a BMI of 25.8 kg/m2. VBQ significantly increased from 2.28 at baseline to 2.36 at follow-up (P = 0.001). In the unadjusted analysis, a significant positive correlation was found between PFGL1-4, PFGL1-S1, and VBQ at baseline (P < 0.05) that increased over time (P < 0.005). In the adjusted multivariable analysis, PFGL1-4 (ß = -0.0195; P = 0.021), PFGL4-S1 (ß = -0.0310; P = 0.007), and PFGL1-S1 (ß = -0.0160; P = 0.012) were independently and negatively associated with VBQ. CONCLUSION: More advanced and long-lasting DD is associated with lower VBQ indicating less bone marrow fat content and potentially stronger bone. VBQ score as a marker of bone quality seems affected by DD.

Aneurysm healing following treatment with biodegradable embolization materials: assessment in a rat sidewall aneurysm model.

BACKGROUND: Biodegradable materials that dissolve after aneurysm healing are promising techniques in the field of neurointerventional surgery. We investigated the effects of various bioabsorable materials in combination with degradable magnesium alloy stents and evaluated aneurysm healing in a rat aneurysm model. METHODS: Saccular aneurysms were created by end-to-side anastomosis in the abdominal aorta of Wistar rats. Untreated arterial grafts were immediately transplanted (vital aneurysms) whereas aneurysms with loss of mural cells were chemically decellularized before implantation. All aneurysms were treated with biodegradable magnesium stents. The animals were assigned to vital aneurysms treated with stent alone or decellularized aneurysms treated with stent alone, detachable coil, or long-term or short-term biodegradable thread. Aneurysm healing, rated microscopically and macroscopically at follow-up days 7 and 21, was defined by both neointima formation and absence of aneurysm volume increase over time. RESULTS: Of 56 animals included, significant increases in aneurysm volume 7 days after surgery were observed in aneurysms with vital and decellularized walls treated with a stent only (P=0.043 each group). Twenty-one days after surgery an increase in aneurysm volume was observed in decellularized aneurysms treated with long- and short-term biodegradable threads (P=0.027 and P=0.028, respectively). Histological changes associated with an increase in aneurysm volume were seen for aneurysm wall inflammation, periadventitial fibrosis, and luminal thrombus. CONCLUSIONS: An increase in aneurysm volume was associated with an absence of intrasaccular embolization material (early phase) and the breakdown of intrasaccular biodegradable material over time (late phase). Thrombus remnant and aneurysm wall inflammation promote aneurysm volume increase.

Establishing the Swiss Spinal Tumor Registry (Swiss-STR): a prospective observation of surgical treatment patterns and long-term outcomes in patients with primary and metastatic spinal tumors.

Background: Tumors of the vertebral column consist of primary spinal tumors and malignancies metastasizing to the spine. Although primary spine tumors are rare, metastases to the spine have gradually increased over past decades because of aging populations and improved survival for various cancer subtypes achieved by advances in cancer therapy. Metastases to the vertebral column occur in up to 70% of cancer patients, with 10% of patients demonstrating epidural spinal cord compression. Therefore, many cancer patients may face spinal surgical intervention during their chronic illness; such interventions range from simple cement augmentation over decompression of neural elements to extended instrumentation or spinal reconstruction. However, precise surgical treatment guidelines do not exist, likely due to the lack of robust, long-term clinical outcomes data and the overall heterogeneous nature of spinal tumors. Objectives of launching the Swiss Spinal Tumor Registry (Swiss-STR) are to collect and analyze high-quality, prospective, observational data on treatment patterns, clinical outcomes, and health-related quality of life (HRQoL) in adult patients undergoing spinal tumor surgery. This narrative review discusses our rationale and process of establishing this spinal cancer registry. Methods: A REDCap-based registry was created for the standardized collection of clinical, radiographic, surgical, histological, radio-oncologial and oncological variables, as well as patient-reported outcome measures (PROMs). Discussion: We propose that the Swiss-STR will inform on the effectiveness of current practices in spinal oncology and their impact on patient outcomes. Furthermore, the registry will enable better categorization of the various clinical presentations of spinal tumors, thereby facilitating treatment recommendations, defining the socio-economic burden on the healthcare system, and improving the quality of care. In cases of rare tumors, the multi-center data pooling will fill significant data gaps to yield better understanding of these entities. Finally, our two-step approach first implements a high-quality registry with efficient electronic data capture strategies across hospital sites in Switzerland, and second follows with potential to expand internationally, thus fostering future international scientific collaboration to further push the envelope in cancer research.

Reducing morbidity associated with subdural drain placement after burr-hole drainage of unilateral chronic subdural hematomas: a retrospective series comparing conventional and modified Nelaton catheter techniques.

PURPOSE: Placement of a subdural drain after burr-hole drainage of chronic subdural hematoma (cSDH) significantly reduces risk of its recurrence and lowers mortality at 6 months. Nonetheless, measures to reduce morbidity related to drain placement are rarely addressed in the literature. Toward reducing drain-related morbidity, we compare outcomes achieved by conventional insertion and our proposed modification. METHODS: In this retrospective series from two institutions, 362 patients underwent burr-hole drainage of unilateral cSDH with subsequent subdural drain insertion by conventional technique or modified Nelaton catheter (NC) technique. Primary endpoints were iatrogenic brain contusion or new neurological deficit. Secondary endpoints were drain misplacement, indication for computed tomography (CT) scan, re-operation for hematoma recurrence, and favorable Glasgow Outcome Scale (GOS) score (≥ 4) at final follow-up. RESULTS: The 362 patients (63.8% male) in our final analysis included drains inserted in 56 patients by NC and 306 patients by conventional technique. Brain contusions or new neurological deficits occurred significantly less often in the NC (1.8%) than conventional group (10.5%) (P = .041). Compared with the conventional group, the NC group had no drain misplacement (3.6% versus 0%; P = .23) and significantly fewer non-routine CT imaging related to symptoms (36.5% versus 5.4%; P < .001). Re-operation rates and favorable GOS scores were comparable between groups. CONCLUSION: We propose the NC technique as an easy-to-use measure for accurate drain positioning within the subdural space that may yield meaningful benefits for patients undergoing treatment for cSDH and vulnerable to complication risks.

Clinically relevant biomechanical properties of three different fixation techniques of the upper instrumented vertebra in deformity surgery.

OBJECTIVE: Adjacent segment disease, junctional kyphosis/failure and pseudarthrosis can negatively impact the mid to long-term outcome in spinal deformity surgery. These complications might be influenced by upper instrumented vertebra (UIV) fixation techniques. In this study we analyze key biomechanical properties of three different UIV fixation techniques and define their ideal clinical use based on patient-specific risk profiles using a finite element analysis (FEA) model. METHODS: A T9-pelvis posterior instrumented spinal fusion was assumed. Three different FEA models were created based on the UIV fixation technique: T9 pedicle screws (PS); T9 cortical bone screws (CBS); T9 transverse process hooks (TPH). The three FEA models consisted of T8-T10 bone and ligamentous anatomy derived from a CT scan of a healthy patient as well as spinal implants consisting of either pedicle screws, cortical bone screws or transverse process hooks as well as cobalt chromium rods. The FEA models were constrained at T10, axial load as assumed for a healthy 80 kg male during flexion, extension and lateral bending were applied. As surrogate markers for risk of proximal junctional kyphosis, proximal junctional failure, adjacent segment disease and pseudarthrosis the following biomechanical parameters were calculated: UIV range of motion (ROM); intradiscal stress at UIV/UIV + 1; UIV intravertebral stress and screw pull out forces. One-way ANOVA analyses have been performed to compare biomechanical outcome parameters between the three construct variants under investigation. RESULTS: UIV-ROM was restricted during flexion/extension/lateral bending by: PS: 73%/80%/86%, CBS: 71%/81%/85% and TPH: 62%/76%/85%. Average intradiscal stress at UIV/UIV + 1 during flexion/extension/lateral bending was (Mega Pascal, MPa): PS 0.42/0.44/0.38, CBS 0.49/0.4/0.44, TPH 0.66/0.51/0.58; average intravertebral stress of the UIV superior endplate during flexion/extension/lateral bending was (MPa): PS 2.23/2.12/2.21, CBS 1.87/1.98/1.8, TPH 1.67/0.98/1.53. Screw pull-out forces (N) at UIV during flexion/extension/lateral bending were: PS 476/320/375, CBS 444/245/308. Statistically significant differences were found for intradiscal stress as well as vertebral body average stress (p = 0.02 and p = 0.02). CONCLUSION: Different UIV fixation techniques carry different biomechanical properties. Pedicle screw fixation is the most rigid, leading to the highest UIV stress and UIV screw pull out forces. Cortical bones screw fixation is similarly rigid; however, UIV stress and UIV screw pull out is significantly lower. Transverse process hook fixation is the least rigid, with the lowest UIV stress, however highest intradiscal stress at UIV/UIV + 1. Thus, these biomechanical differences may help select optimal UIV fixation techniques according to patient specific risk factors.

Compensatory mechanisms in adult degenerative thoracolumbar spinal deformity - Radiographic patterns, their reversibility after corrective surgery, and the influence of pelvic morphology.

Objective: Loss of lumbar lordosis (LL) in degenerative deformity activates spinal compensatory mechanisms to maintain neutral C7 sagittal vertical axis (C7SVA), such as an increase in pelvic tilt (PT) and decreased thoracic kyphosis (TK). We study the extent to which PT increase and TK reduction contribute to the compensation of pelvic incidence (PI)-LL mismatch. Methods: A cohort of 43 adult patients with adult degenerative thoracolumbar deformity were included in this retrospective study. Radiographic spinopelvic measurements were obtained before and after corrective surgery. Pearson correlations were calculated. Results: Preoperative PI-LL mismatch significantly correlated with an increase in PT and a decrease in TK in the whole cohort r = +0.66 (95% confidence interval [CI] 0.44-0.8) and r = -0.67 (95% CI - 0.81--0.47), respectively, at a relative rate of 0.37 (standard deviation [SD]: 0.07) and - 0.57 (SD: 0.09), respectively. In patients with low PI, only TK showed a significant correlation with PI-LL mismatch, r = -0.56 (95% CI - 0.8 to - 0.16), at a rate of - 0.57 (SD: 0.19). The high PI subgroup showed a significant correlation with PT, TK, and C7SVA, r = 0.62 (95% CI 0.26-0.82), r = -0.8 (95% CI - 0.9--0.58), and r = 0.71 (95% CI 0.41-0.87) at rates of 0.48 (SD: 0.11), -0.72 (SD: 0.12), and 0.62 (SD: 1.27). Conclusions: Decreased TK represented a more consistent compensatory mechanism in patients with high and low PI when compared to an increase in PT. PI-LL mismatch induced more pronounced changes in TK than did PT in both subgroups. Patients with high PI relied more on increases in PT and a relative decrease in TK to compensate for PI-LL mismatch than patients with low PI.

Spondylectomy in the treatment of neoplastic spinal lesions - A retrospective outcome analysis of 582 patients using a patient-level meta-analysis.

This study aims at identifying predictors of postoperative complications, lesion recurrence, and overall survival in patients undergoing en bloc spondylectomy (EBS) for spinal tumors. For this purpose a systematic review of the literature was conducted and patient-level data extracted. Linear-regression models were calculated to predict postoperative complications, lesion recurrence and overall survival based on age, tumor etiology, surgical approach, mode of resection (extra- vs. intralesional), tumor extension, and number of levels treated. A total of 582 patients were identified from the literature: 45% of females, median age 46 years (5-78); most common etiologies were: sarcoma (46%), metastases (31%), chordoma (11%); surgical approach was anterior (2.5%), combined (45%), and posterior (52.4%); 68.5% underwent EBS; average levels resected were 1.6 (1-6); average survival was 2.6 years; Complication rate was 17.7%. The following significant correlations were found: postoperative complications and resection mode (Odds ratio [OR] 1.35) as well as number of levels treated (OR 1.35); tumor recurrence and resection mode (OR 0.78); 5-year survival and age (OR 0.79), tumor grade (OR 0.65), tumor stage at diagnosis (OR 0.79), and resection mode (OR 1.68). EBS was shown to improve survival, decreases recurrence rates but also has a higher complication rate. Interestingly, the complication rate was not influenced by tumor extension or tumor etiology.

Clinical Studies and Pre-clinical Animal Models on Facial Nerve Preservation, Reconstruction, and Regeneration Following Cerebellopontine Angle Tumor Surgery-A Systematic Review and Future Perspectives.

Background and purpose: Tumorous lesions developing in the cerebellopontine angle (CPA) get into close contact with the 1st (cisternal) and 2nd (meatal) intra-arachnoidal portion of the facial nerve (FN). When surgical damage occurs, commonly known reconstruction strategies are often associated with poor functional recovery. This article aims to provide a systematic overview for translational research by establishing the current evidence on available clinical studies and experimental models reporting on intracranial FN injury. Methods: A systematic literature search of several databases (PubMed, EMBASE, Medline) was performed prior to July 2020. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Included clinical studies were reviewed and categorized according to the pathology and surgical resection strategy, and experimental studies according to the animal. For anatomical study purposes, perfusion-fixed adult New Zealand white rabbits were used for radiological high-resolution imaging and anatomical dissection of the CPA and periotic skull base. Results: One hundred forty four out of 166 included publications were clinical studies reporting on FN outcomes after CPA-tumor surgery in 19,136 patients. During CPA-tumor surgery, the specific vulnerability of the intracranial FN to stretching and compression more likely leads to neurapraxia or axonotmesis than neurotmesis. Severe FN palsy was reported in 7 to 15 % after vestibular schwannoma surgery, and 6% following the resection of CPA-meningioma. Twenty-two papers reported on experimental studies, out of which only 6 specifically used intracranial FN injury in a rodent (n = 4) or non-rodent model (n = 2). Rats and rabbits offer a feasible model for manipulation of the FN in the CPA, the latter was further confirmed in our study covering the radiological and anatomical analysis of perfusion fixed periotic bones. Conclusion: The particular anatomical and physiological features of the intracranial FN warrant a distinguishment of experimental models for intracranial FN injuries. New Zealand White rabbits might be a very cost-effective and valuable option to test new experimental approaches for intracranial FN regeneration. Flexible and bioactive biomaterials, commonly used in skull base surgery, endowed with trophic and topographical functions, should address the specific needs of intracranial FN injuries.

Kyphoplasty versus percutaneous posterior instrumentation for osteoporotic vertebral fractures with posterior wall injury: a propensity score matched cohort study.

BACKGROUND: Osteoporotic vertebral fractures (OVFs) that present with posterior wall cortical injury pose a higher risk for instability. Surgical management includes standard cement augmentation techniques like balloon kyphoplasty (BKP) or percutaneous posterior instrumentation with pedicle screws (PS) or both. Neither treatment has yet demonstrated superiority, and posterior cement leakage is of special concern in these fractures. METHODS: At a single tertiary care center, 25 patients with 32 OVFs with posterior wall injury treated with percutaneous instrumentation and cement augmentation (PS group) were retrospectively included and matched (1:1) using propensity scores to 25 patients with 29 OVFs with posterior wall injury treated with standalone BKP (BKP group) from 2010 to 2018. Our primary study aim identified 30-day morbidity rates using a 4-point grading system by comparing BKP with and without percutaneous instrumentation with PS for the treatment of OVFs with posterior wall injury. Our secondary aims evaluated cement leakage, radiographic results, surgical time, length of stay (LOS), pain relief, and subsequent fractures. RESULTS: Overall 30-day morbidity was 34% and did not differ between groups (24% BKP vs. 44% PS groups, P=0.136). Most complications were mild (82.4%), requiring no interventions beyond drug treatment. In the PS group, a trend towards more mild complications was observed (16% vs. 40%, P=0.059). Moderate and severe complications affected 17.6% of all morbidity cases and were comparable between groups. Asymptomatic cement leakage into the spinal canal was noted in 2 (8%) BKP patients and symptomatic pulmonary cement embolism in 1 (4.8%) PS patient. Compared with baseline, all radiographic parameters significantly improved in both groups. In the BKP group, mean surgical times (52±32.9 vs. 164.9±48.4 minutes, P<0.001) and LOS (4.3±2.5 vs. 7±2.9 days, P<0.001) were significantly shorter, and use of opioids at discharge was significantly lower (52% vs. 84%, P=0.015). At 3-month follow-up, no differences between groups were seen in back pain, use of opioids, and occurrence of subsequent OVFs. Follow-up averaged 8.4 months. CONCLUSIONS: Standalone BKP may be a viable option for the treatment of OVFs even in the presence of posterior wall cortical injury.

Patterns of Neointima Formation After Coil or Stent Treatment in a Rat Saccular Sidewall Aneurysm Model.

BACKGROUND AND PURPOSE: Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model. METHODS: Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology. RESULTS: In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; P=0.008). CONCLUSIONS: Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery's lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.

Primary extradural tumors of the spinal column: A comprehensive treatment guide for the spine surgeon based on the 5th Edition of the World Health Organization bone and soft-tissue tumor classification.

BACKGROUND: In 2020, the World Health Organization (WHO) published the 5th version of the soft tissue and bone tumor classification. Based on this novel classification system, we reviewed the current knowledge on all tumor entities with spinal manifestations, their biologic behavior, and most importantly the appropriate treatment options as well as surgical approaches. METHODS: All tumor entities were extracted from the WHO Soft-Tissue and Bone Tumor Classification (5th Edition). PubMed and Google Scholar were searched for the published cases of spinal tumor manifestations for each entity, and the following characteristics were extracted: Growth pattern, ability to metastasize, peak age, incidence, treatment, type of surgical resection indicated, recurrence rate, risk factors, 5-year survival rate, key molecular or genetic alterations, and possible associated tumor syndromes. Surgical treatment strategies as well as nonsurgical treatment recommendations are presented based on the biologic behavior of each lesion. RESULTS: Out of 163 primary tumor entities of bone and soft tissue, 92 lesions have been reported along the spinal axis. Of these 92 entities, 54 have the potential to metastasize. The peak age ranges from conatal lesions to 72 years. For each tumor entity, we present recommended surgical treatment strategies based on the ability to locally destruct tissue, to grow, recur after resection, undergo malignant transformation as well as survival rates. In addition, potential systemic treatment recommendations for each tumor entity are outlined. CONCLUSION: Based on the 5th Edition of the WHO bone and soft tumor classification, we identified 92 out of 163 tumor entities, which potentially can have spinal manifestations. Exact preoperative tissue diagnosis and interdisciplinary case discussions are crucial. Surgical resection is indicated in a significant subset of patients and has to be tailored to the specific biologic behavior of the targeted tumor entity based on the considerations outlined in detail in this article.

Incidence and Outcome of Aneurysmal Subarachnoid Hemorrhage: The Swiss Study on Subarachnoid Hemorrhage (Swiss SOS).

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

Changes in the cerebrospinal fluid lipid profile following subarachnoid hemorrhage in a closed cranium model: Correlations to cerebral vasospasm, neuronal cell death and Interleukin-6 synthesis. A pilot study.

BACKGROUND: Phospholipids and sphingolipids are cell membrane components, that participate in signaling events and regulate a wide variety of vital cellular processes. Sphingolipids are involved in ischemic stroke pathophysiology. Throughout cleavage of membrane sphingomyelin by sphingomyelinase in stroke patients, it results in increased Ceramide (Cer) levels in brain tissue. Different studies showed the evidence that sphingomyelinase with Cer production induces expression of interleukin (IL)-6 and have vasoconstrictive proprieties. With this study, we intend to evaluate cerebrospinal fluid (CSF) lipid profile changes in a rabbit closed cranium subarachnoid hemorrhage (SAH) model. METHODS: A total of 14 New Zealand white rabbits were randomly allocated either to SAH or sham group. In the first group SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cisterna magna. Intracranial pressure (ICP) and arterial blood pressure were continuously monitored. Digital subtraction angiography of the basilar artery, CSF and blood samples were performed at day 0 pre SAH and on day 3 post SAH. The amount of IL-6 and various lipids in CSF were quantified using ELISA and Liquid Chromatography-Mass Spectrometry respectively. Cell death was detected in bilateral basal cortex, hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: SAH Induction led to acute increase of ICP and increased delayed cerebral vasospasm (DCVS). At follow up CSF IL-6 levels showed a significant increase compared to baseline. Between baseline and follow up there were no significant differences in any of the measured CSF Lipids irrespective of subgroups. No relevant correlation was found between IL-6 and any of the sphingolipids. We found a correlation between baseline and follow up for the phospholipids phosphatidylethanolamine and phosphatidylcholine. CONCLUSIONS: Neuronal apoptosis, DCVS and IL-6 seems not to be related to changes in CSF lipid profiles except for PEA and PC in a rabbit closed cranium SAH model.

Development of a Technical Skills Test to Improve Assessment and Evaluation in Neuroendoscopic Education.

BACKGROUND: Endoscopy requires a unique set of skills that are difficult to acquire in most training programs. A method to test technical skills, in a validated manner, has rarely been attempted. The purpose of this study was to develop a technical skills examination for objective assessment in neuroendoscopic education. METHODS: Twenty-nine participants were included for analysis and divided by seniority level into 2 groups defined as before or upon postgraduation year (PGY) 5 (n = 18, junior surgeons) or after PGY5 (n = 11, senior surgeons). Study participants were assessed for baseline performance and then again following a 4-hour neuroendoscopy course. Wilcoxon test was used to evaluate for performance differences between cohorts. Correlation analyses were performed using the Pearson or Spearman coefficient. RESULTS: Increasing PGY level was correlated with a decreased average time to complete all 3 tasks (r = -0.44, P = 0.03) at baseline. Overall performance improved in both cohorts following the course (P < 0.001). When comparing junior surgeons after endoscopy training (posttest) to senior surgeons at their baseline (pretest), the junior surgeons were faster after endoscopic training than the senior surgeons were before training (P < 0.001). CONCLUSIONS: A neuroendoscopic skills test can distinguish between more or less experienced surgeons. Significant overall performance improvement, regardless of seniority level, following neuroendoscopic training demonstrates the accuracy of the test at detecting operating improvement in all stages of learning.

Reliability of fluorescein-assisted stereotactic brain biopsies in predicting conclusive tissue diagnosis.

BACKGROUND: The purpose of this study was to assess the reliability of fluorescein sodium in predicting conclusive tissue diagnosis in stereotactic brain biopsies and to characterize features of contrast-enhancing and non-enhancing MRI lesions associated with fluorescence. METHODS: A total of 19 patients were studied, 14 of which had contrast-enhancing and 5 of which had non-enhancing lesions on preoperative T1 post-gadolinium MRI scan. All patients received 3 mg/kg fluorescein sodium during anesthesia induction. Biopsy specimens were photographed under the operating microscope, using the Yellow560 module, prior to histopathological analysis. Two observers blinded to the MRI scans and histopathological results categorized the photographs retrospectively as "fluorescent" or "not fluorescent." Inter-rater agreement was assessed using Cohen's kappa coefficient. Sensitivity, specificity, and positive predictive value of fluorescence reliability were calculated for MRI contrast-enhancing lesions and confirmed location-concordance of tumor pathology based on rater's fluorescence status assessment. Results were correlated finally with final results on permanent sections. RESULTS: Strength of inter-rater fluorescence status agreement was found to be "substantial" (kappa = 0.771). Sensitivity, specificity, and positive predictive value for "fluorescent" and "not fluorescent" specimen in comparison with MRI contrast-enhancing lesions were 97%, 40%, and 82%, respectively. Sensitivity, specificity, and positive predictive value for confirmed tumor pathology were 100%, 63%, and 91%, respectively. Permanent pathology revealed high-grade glioma n = 5, low-grade glioma n = 3, lymphoma n = 5, pineal tumor n = 2, hamartoma n = 1, and nonspecific hypercellularity n = 3. CONCLUSIONS: Fluorescein-assisted stereotactic brain biopsies demonstrated a high likelihood to manifest fluorescence in contrast-enhancing MRI lesions, while adequately predicting conclusive tumor pathology.

Systematic Review and Meta-analysis of Methodological Quality in In Vivo Animal Studies of Subarachnoid Hemorrhage.

As a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists and guidelines were developed over the past decades. This systematic review assesses the overall methodological quality of preclinical SAH research. An electronic search for preclinical studies on SAH revealed 3415 potential articles. Of these, 765 original research papers conducted in vivo in mice, rats, rabbits, cats, dogs, pigs, goats, and non-human primates with a focus on brain damage related to delayed cerebral vasospasm and early brain injury met the inclusion criteria. We found methodological shortcomings still to prevail in preclinical SAH research. In addition, basic animal characteristics were typically well described but important technical parameters of SAH induction were often underreported. None of the species, models, or techniques used in preclinical SAH research was methodologically superior to the others. Methodological quality of preclinical SAH research was independent of the number of citations or impact factor of a publication. Consequently, we suggest the SAH research community should consider strategies to improve preclinical research quality in their field, such as public platforms to (pre)register preclinical experiments, consequent support of open science policies, stricter editorial (and reviewer) control of (pre)existing guidelines, and increased efforts in education and training of good laboratory practice for the next generation of researchers.

Surgical management considerations in cystic prolactinomas-a single center case series.

PURPOSE: The optimal treatment of prolactinomas with a predominantly cystic component remains poorly defined. The cystic tumor component is considered to respond less favorably to medical treatment, thereby advocating surgical management. The purpose of this study was to assess remission rates in surgically treated cystic prolactinomas, and to compare outcomes to similarly treated solid micro- and macroprolactinomas. METHODS: Clinical and imaging data were retrospectively compiled from 56 patients who underwent transsphenoidal resection, for symptomatic prolactinomas, from 2004 to 2018, at a single academic institution. Pituitary adenomas were subdivided according to tumor size and tumor consistency: cystic prolactinomas (>50% cystic tumor component) n = 17; solid microprolactinomas (<10 mm) n = 10; and solid macroprolactinomas (≥10 mm) n = 29. Remission was defined as a prolactin level of <10 ng/dl either immediately postoperative or at a later time point. RESULTS: Median tumor size was 15 mm for cystic prolactinomas, 7 mm for solid microprolactinomas, and 25.5 mm for solid macroprolactinomas. Remission was achieved in 76% (n = 13/17) of surgically treated cystic prolactinomas, 100% (n = 10/10) of solid microprolactinomas, and 24% (n = 7/29) of solid macroprolactinomas. More than 44% of solid macroprolactinomas had a Knosp grade > 3, while most cystic prolactinomas (93.8%) and all solid microprolactinomas (100%) had a Knosp grade ≤ 2. CONCLUSIONS: Despite their large tumor size (≥10 mm), high remission rates can be expected with surgically treated cystic prolactinomas. This case series of cystic prolactinomas demonstrates the successful use of transsphenoidal surgery as a favorable, and a potentially curative alternative to dopaminergic therapy in this patient population.

Aneurysm wall cellularity affects healing after coil embolization: assessment in a rat saccular aneurysm model.

BACKGROUND AND PURPOSE: Despite significant technical advances, recanalization rates after endovascular therapy of ruptured intracranial aneurysms (IAs) remain a clinical challenge. A histopathological hallmark of ruptured human IA walls is mural cell loss. Mural smooth muscle cells (SMCs) are known to promote intraluminal healing in thrombosed experimental aneurysms. In this rat model we assess the natural history and healing process after coil embolization in SMC-rich and decellularized aneurysms. METHODS: Saccular aneurysms were created by end-to-side anastomosis of an arterial graft from the descending thoracic aorta of a syngeneic donor rat to the infrarenal abdominal aorta of recipient male Wistar rats. Untreated arterial grafts were immediately transplanted, whereas aneurysms with loss of mural cells were chemically decellularized before implantation. Aneurysms underwent coil implantation during aneurysm anastomosis. Animals were randomly assigned either to the non-decellularized or decellularized group and underwent macroscopic and histological analyses on days 3, 7, 21, or 90 post-coil implantation. RESULTS: A total of 55 rats underwent macroscopic and histologic analysis. After coil embolization, aneurysms with SMC-rich walls showed a linear course of thrombosis and neointima formation whereas decellularized aneurysms showed marked inflammatory wall degeneration with increased recanalization rates 21 days (p=0.002) and 90 days (p=0.037) later. The SMCs showed the ability to actively migrate into the intra-aneurysmal thrombus and participate in thrombus organization. CONCLUSIONS: Coil embolization of aneurysms with highly degenerated walls is prone to further wall degeneration, increased inflammation, and recanalization compared with aneurysms with vital SMC-rich walls.

Fluorescence Video Angiography for Evaluation of Dynamic Perfusion Status in an Aneurysm Preclinical Experimental Setting.

BACKGROUND: Experimental studies to assess aneurysm occlusion or perfusion typically rely on macroscopic examination or histological analysis but cannot assess dynamic perfusion. OBJECTIVE: To describe an easy-to-implement and inexpensive fluorescence angiographic technique for the in vivo assessment and imaging of the dynamic perfusion status of aneurysms and their underlying blood vessels in a rat model. METHODS: In a rat sidewall aneurysm model, the angiographic setup included 2 bandpass filters, a video camera, and a bicycle spotlight. After 48 rats underwent fluorescein angiography, dissections were performed to confirm the perfusion status by macroscopic and histologic examination of the aneurysm. RESULTS: Direct injection of 0.2 mL fluorescein 10% Faure achieved strong, clear visibility in all 48 aneurysms. Macro-/microscopic examination identified residual perfusion in 25 and complete healing in 23 aneurysms. Fluorescein imaging identified 21 of these 25 aneurysms (84%) with residual perfusion and 22 of 23 aneurysms (96%) with no residual perfusion. CONCLUSION: Our fluorescein imaging technique proved efficient for the evaluation of aneurysm patency and parent artery integrity in this experimental setting. Fluorescein is nontoxic, can be re-administered if needed, and, in this technique, can expand the armamentarium for the preclinical evaluation of dynamic perfusion status.