Direct, Indirect, and Combined Extracranial-to-Intracranial Bypass for Adult Moyamoya Disease: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Moyamoya disease is a chronic, progressive cerebrovascular disease involving occlusion or stenosis of the terminal portion of the internal carotid artery. We conducted an updated systematic review and meta-analysis to investigate clinical and angiographic outcomes comparing direct, combined, and indirect bypass for the treatment of moyamoya disease in adults. METHODS: Two independent authors performed Preferred Reporting Items for Systematic reviews and Meta-Analyses guided literature searches in December 2021 to identify articles reporting clinical/angiographic outcomes in adult moyamoya disease patients undergoing bypass. Primary end points used were ischemic and hemorrhagic strokes, clinical outcomes, and angiographic revascularization. Study quality was evaluated with Newcastle-Ottawa and the Oxford Center for Evidence-Based Medicine scales. RESULTS: Four thousand four hundred fifty seven articles were identified in the initial search; 143 articles were analyzed. There were 3827 direct, 3826 indirect, and 3801 combined bypasses. Average length of follow-up was 3.59±2.93 years. Pooled analysis significantly favored direct (odds ratio [OR], 0.62 [0.48-0.79]; P<0.0001; OR, 0.44 [0.32-0.59]; P<0.0001; OR, 0.56 [0.42-0.74]; P<0.0001; OR, 3.1 [2.5-3.8]; P=0.0001) and combined (OR, 0.53 [0.41-0.69]; P<0.0001; OR, 0.28 [0.2-0.41]; P<0.0001; OR, 0.41 [0.3-0.56]; P<0.0001; OR, 3.1 [2.8-4.3]; P=0.0001) over indirect bypass for early stroke, late stroke, late intracerebral hemorrhage, and favorable outcomes, respectively. Indirect bypass was favored over combined (OR, 3.1 [1.7-5.6]; P<0.0001) and direct (OR, 4.12 [2.34-7.25]; P<0.0001) for early intracerebral hemorrhage. The meta-analysis significantly favored direct (OR, 0.37 [0.23-0.60]; P<0.001; OR, 0.49 [0.31-0.77]; P=0.002) and combined (OR, 0.23 [0.12-0.43]; P<0.00001; OR, 0.30 [0.18-0.49]; P<0.00001) bypass over indirect bypass for late stroke and late hemorrhage, respectively. Combined bypass was favored over indirect bypass for favorable outcomes (OR, 2.06 [1.18-3.58]; P=0.01). CONCLUSIONS: Based on combined meta-analysis (43 articles) and pooled analysis (143 articles), the existing literature indicates that combined and direct bypasses have significant benefits for patients suffering from late stroke and hemorrhage versus indirect bypass. Combined bypass was favored over indirect bypass for favorable outcomes. This is a strong recommendation based on low-quality evidence when utilizing the Grades of Recommendation, Assessment, Development, and Evaluation system. These findings have important implications for bypass strategy selection.

Head and neck arteriovenous malformations: University of Tennessee experience, 2012-2022.

OBJECTIVE: Head and neck arteriovenous malformations (AVMs) are complex lesions that represent a subset of vascular anomalies (VAs). The authors present an analysis of their institutional experience managing these lesions as a multidisciplinary team. METHODS: A retrospective chart review was performed of head and neck AVM patients treated at the authors' institution from 2012 to 2022. Recorded data included patient demographic characteristics, details of clinical presentation, Schöbinger clinical scale and Yakes AVM classification results, and details of all endovascular and surgical treatments. The primary outcome of the study was clinical response to treatment. Angiographic occlusion and complication rates were reported. Chi-square tests were used for comparative statistics. RESULTS: Sixteen patients (9 female, 56%) with AVMs of the head and neck presented from age 3 to 77 years. The Schöbinger stage was stage II in 56% of patients (n = 9) and stage III in 44% of patients (n = 7). The Yakes AVM classification was nidus type (2a, 2b, or 4) in 7 patients (43%) and fistula type (1, 3a, or 3b) in 9 patients (57%). The majority of patients (n = 11, 69.0%) were managed with embolization as the only treatment modality, with an average of 1.5 embolizations/patient (range 1-3). Surgical resection was employed in 5 patients (4 in combination with embolization). Symptom resolution and symptom control were achieved in 69% and 31% of patients, respectively, in the entire cohort. A radiographic cure was demonstrated in 50% of patients. There were no statistical differences in clinical outcomes or radiographic cure rates between patients treated with different modalities. CONCLUSIONS: Head and neck AVMs can be treated successfully with a primarily endovascular management strategy by a multidisciplinary team with the goal of symptomatic control.

Big Data Research in Pediatric Neurosurgery: Content, Statistical Output, and Bibliometric Analysis.

BACKGROUND/AIMS: We sought to describe pediatric "big data" publications since 2000, their statistical output, and clinical implications. METHODS: We searched 4 major North American neurosurgical journals for articles utilizing non-neurosurgery-specific databases for clinical pediatric neurosurgery research. Articles were analyzed for descriptive and statistical information. We analyzed effect sizes (ESs), confidence intervals (CIs), and p values for clinical relevance. A bibliometric analysis was performed using several key citation metrics. RESULTS: We identified 74 articles, which constituted 1.7% of all pediatric articles (n = 4,436) published, with an exponential increase after 2013 (53/74, 72%). The Healthcare Cost and Utilization Project (HCUP) databases were most frequently utilized (n = 33); hydrocephalus (n = 19) was the most common study topic. The statistical output (n = 49 studies with 464 ESs, 456 CIs, and 389 p values) demonstrated that the majority of the ESs (253/464, 55%) were categorized as small; half or more of the CI spread (CIS) values and p values were high (274/456, 60%) and very strong (195/389, 50%), respectively. Associations with a combination of medium-to-large ESs (i.e., magnitude of difference), medium-to-high CISs (i.e., precision), and strong-to-very strong p values comprised only 20% (75/381) of the reported ESs. The total number of citations for the 74 articles was 1,115 (range per article, 0-129), with the median number of citations per article being 8.5. Four studies had > 50 citations, and 2 of them had > 100 citations. The calculated h-index was 16, h-core citations were 718, the e-index was 21.5, and the Google i10-index was 34. CONCLUSIONS: There has been a dramatic increase in the use of "big data" in the pediatric neurosurgical literature. Reported associations that may, as a group, be of greatest interest to practitioners represented only 20% of the total output from these publications. Citations were weighted towards a few highly cited publications.

Emergent and Urgent Craniotomies in Pediatric Patients: Resource Utilization and Cost Analysis.

BACKGROUND: Pediatric neurosurgeons are occasionally tasked with performing surgery expeditiously to preserve a child's neurologic faculties and life. OBJECTIVE: This study examines the etiologies, outcomes, and costs for urgent or emergent craniotomies at a Level I Pediatric Trauma center over a 7-year time period. METHODS: A retrospective review was conducted for each patient who underwent an emergent or urgent craniotomy within 24 hours of presentation between January 2010 and April 2017. Demographic, clinical, and surgical details were recorded for a total of 48 variables. Any readmission within 90 days was analyzed. Hospital charges for each admission and readmission were collected and adjusted for inflation to October 2018 values. RESULTS: Among the 223 children who underwent urgent or emergent craniotomies, the majority were admitted for traumatic injuries (n = 163, 73.1%). The most common traumatic mechanism was fall (n = 51, 22.9%), and the most common non-traumatic cause was tumor (n = 21, 9.4%). Overall, craniotomies were typically performed for hematoma evacuation of one type or combination (n = 115, 51.6%) during off-peak times (n = 178, 79.8%). Seventy-seven (34.5%) subjects experienced 1 or more postoperative events, 22 of whom returned to the operating room. There were 13 (5.8%) and 33 (14.8%) readmissions within 30 days and 90 days of discharge, respectively. Non-trauma patients (compared with trauma patients) and polytrauma (compared with isolated head injury) had greater healthcare needs, resulting in higher charges. CONCLUSION: Most urgent or emergent pediatric craniotomies were performed for the treatment of traumatic injuries involving hematoma evacuation, but non-traumatic patients were more complex requiring greater resources.

Effectiveness of Cerebrospinal Fluid Lumbar Drainage Among Patients with Aneurysmal Subarachnoid Hemorrhage: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH) continues to be a major source of morbidity despite significant clinical and basic science research. The removal of blood and its degradation products from the subarachnoid space through prophylactic lumbar drainage (LD) is a favorable option. However, several studies have delivered conflicting conclusions on its efficacy after aSAH. METHODS: Systematic searches of Medline, Embase, and Cochrane Central Register of Controlled Trials were performed. The primary outcome was a good functional outcome (modified Rankin scale score, 0-2). Secondary outcomes included symptomatic vasospasm, secondary cerebral infarction, and mortality. RESULTS: A total of 14 studies reporting on 2473 patients with aSAH were included in the meta-analysis. Compared with the non-LD group, no significant differences were found in the rates of good functional outcomes in the LD group at discharge to 1 month (risk ratio [RR], 1.28; 95% confidence interval [CI], 0.64-2.58) or at 6 months (RR, 1.12; 95% CI, 0.97-1.41). These findings were consistent in the subgroup analyses of only randomized controlled trials or observational studies. LD was associated with lower rates of symptomatic vasospasm (RR, 0.61; 95% CI, 0.48-0.77), secondary cerebral infarction (RR, 0.59; 95% CI, 0.45-0.79), and mortality at discharge to 1 month (RR, 0.58; 95% CI, 0.41-0.82). The effect on mortality diminished at 6 months (RR, 0.70; 95% CI, 0.34-1.45). However, when analyzing only randomized controlled trials, the benefit of LD on lower rates of mortality continued even at 6 months (RR, 0.75; 95% CI, 0.58-0.99). CONCLUSIONS: For aSAH patients, the use of LD is associated with benefits in the rates of vasospasm, secondary cerebral infarctions, and mortality, without an increased risk of adverse events.

Microsurgical Resection of Trigeminal Schwannoma Through Transorbital Approach: 2-Dimensional Operative Video.

We present the case of an asymptomatic 34-year-old woman who was found to have an incidental left trigeminal schwannoma.1,2 Owing to the rapid increase in size on imaging, an atypical finding for this type of lesion,3 as well as the risk of cranial nerve involvement and need for tissue diagnosis, the patient underwent a microsurgical left transorbital approach with lateral orbitotomy to resect the lesion.4,5 Piecemeal resection was performed, and the internal contents of the cavernous sinus were preserved. Ultimately, gross total resection was achieved with no residual disease identified on postoperative imaging. No new neurologic deficits were noted after surgery. The technical considerations for the transorbital approach and the literature review on the outcomes for middle fossa lesions accessed by a lateral orbitotomy are reviewed.6-10 The patient consented to the procedure and to the publication of her images. Institutional Review Board approval was deemed unnecessary due to the retrospective, case-report nature of this work.

A Scoping Review of Professionalism in Neurosurgery.

BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education's Milestones provides a foundation for professionalism in residency training. Specific professionalism concepts from neurosurgery could augment and expand milestones for the specialty. We reviewed the current literature and identified professionalism concepts within the context of neurosurgical practice and training. METHODS: We used a scoping review methodology to search PubMed/MEDLINE and Scopus and identify English-language articles with the search terms "professionalism" and "neurosurgery." We excluded articles that were not in English, not relevant to professionalism within neurosurgery, or could not be accessed. Non-peer-reviewed and qualitative publications, such as commentaries, were included in the review. RESULTS: A total of 193 articles were included in the review. We identified 6 professionalism themes among these results: professional identity (n = 53), burnout and wellness (n = 51), professional development (n = 34), ethics and conflicts of interest (n = 27), diversity and gender (n = 19), and misconduct (n = 9). CONCLUSION: These 6 concepts illustrate concerns that neurosurgeons have concerning professionalism. Diversity and gender, professional identity, and misconduct are not specifically addressed in the Accreditation Council for Graduate Medical Education's Milestones. This review could be used to aid the development of organizational policy statements on professionalism.

Expanded endoscopic endonasal approach for resection of residual parasellar growth hormone-secreting pituitary adenoma in a patient with kissing internal carotid arteries: Technical nuances.

Background: Growth hormone (GH)--secreting pituitary adenomas can be aggressive and difficult to manage. Surgical resection for GH-secreting tumors remains the gold standard with increasing use of expanded endoscopic endonasal (EEA) techniques. Certain anatomical considerations make postsurgical biochemical remission challenging. Case Description: We describe the case of a 43-year-old male presenting with acromegaly after a lack of biochemical remission from a previous surgery. Resection of the residual tumor invading the retrogenu compartment of the cavernous sinus was challenging for several reasons: (a) its location adjacent to the right parasellar horizontal internal carotid artery (ICA) with involvement of the medial wall, (b) the large kissing bilateral ICAs reducing the intercarotid distance, and (c) potential scar tissue. EEA was undertaken with key surgical steps, including wide bilateral sphenoidotomies, right middle clinoidectomy to access the clinoidal ICA and the retrogenu compartment, identification of the top of the paraclival ICA by drilling across the sella floor, division of the sellar floor dura to increase the intercarotid distance and transcavernous mobilization of medial wall, and the tumor capsule away from the horizontal parasellar ICA and across to the diaphragm and pituitary gland. Postoperatively, biochemical remission was achieved with no new endocrine deficits. Conclusion: These surgical nuances permit biochemical remission in complex revisional cases with acromegaly.

Microsurgical Resection of Calcified C2 Cavernous Malformation: 2-Dimensional Operative Video.

We present the case of a 58-year-old woman presenting with left upper limb paresthesia and bilateral lower limb spasm who was found to have a likely radiation-induced calcified intramedullary cavernous malformation at the level of C2.1-4 Owing to the symptomatic nature of the lesion with progressive increase in size and associated cord edema on serial imaging, through a lateral approach, the patient underwent a microsurgical left C2-3 hemilaminectomy and medial facetectomy to access the ventral exophytic calcified component.5-7 Debulking and piecemeal resection were performed with the aid of an ultrasonic bone aspirator with "claw" attachment while minimizing any manipulation of neural parenchyma.8-13 Ultimately, near total resection was achieved as a rim of capsule was left densely adherent to the spinal cord. Postoperatively, no new neurologic deficits were noted, and imaging as early as 1 week postoperatively showed significant reduction of cord signal abnormality. The technical considerations for the ultrasonic bone claw and the literature on treatment outcomes for calcified intramedullary spinal cavernous malformations are reviewed. The patient consented to the procedure and to the publication of her images. Institutional review board approval was deemed not necessary because of the retrospective, case report nature of this work.

Increasing Neurosurgical Resident Research Productivity Through Cultural Shift: Choosing Carrots Over Sticks.

Introduction As part of the Milestones Initiative of the Accreditation Council for Graduate Medical Education (ACGME), residents in neurosurgery are expected to participate in either clinical research or basic science research. Therefore, each neurosurgical training program must offer the support and opportunity to achieve this goal. In 2012, a structured effort to promote a resident culture of research was introduced into the authors' neurosurgery residency training curriculum. This study reviews this experience over the last decade. Methods Data were collected from the authors' departmental neurosurgery website and Scopus to create a database of neurosurgical residents who graduated 10 years before and after 2012 and their publication output. Bibliometric measures were collected for all articles published by residents. Results were compared between residents who graduated before and after the introduction of the research initiative. Results A total of 127 publications were analyzed from 37 residents, constituting 174 authorships. There was a statistically significant increase in the number of publications per resident (P < 0.001), citation number per author (P = 0.002), and author h-index (P < 0.001) after implementing the initiative. There were no significant differences in the pre-residency and baseline demographic variables between the two groups. Conclusion This study relates the experience of initiating a research culture at the authors' neurosurgery training program, which did not emphasize scholarly productivity historically. The effort focused on creating a culture of curiosity as opposed to formal requirements. The results provided evidence that this strategy yielded a significant increase in academic output and impact. These findings have important implications for neurosurgical training programs.

Prevalence of unruptured intracranial aneurysms (UIAs) examined in the trauma population.

BACKGROUND: Previous data on the prevalence of unruptured intracranial aneurysms (UIAs) vary widely, and studies based on these data are plagued with unintentional bias. Accurate prevalence data are paramount for any physician who counsels patients with intracranial aneurysms on rupture risk and treatment. We therefore sought to determine a more accurate number for the true prevalence of UIAs. METHODS: A retrospective chart review was conducted at a level 1 trauma center and tertiary care hospital in an urban setting between 2019 and 2020. Inclusion criteria included patients admitted with blunt trauma. Exclusion criteria included not having a head and neck CTA performed and read by an attending radiologist. All head and neck CTA radiology reads were reviewed for incidentally discovered UIAs. Subgroup analysis was performed by age group, race, and gender. RESULTS: A total of 5978 out of 8999 patients met the inclusion criteria, and 54 patients with 58 total aneurysms were identified giving an overall prevalence of 0.9%. Subgroup analysis was performed for all age groups, genders, and racial groups. CONCLUSION: The overall aneurysm prevalence was found to be 0.9% in this sample. This rate is lower than rates previously cited in the literature and those quoted in local practice. This finding has significant implications when attempting to understand average rupture risk. Further studies are needed to power more subgroup analyses to use a more personalized approach to understanding an individual's risk of rupture.

Acute and Long-Term Management of Blunt Cerebrovascular Injury at a Quaternary Referral Level 1 Trauma Center: The Memphis Experience and Comparison of a New Scoring System.

BACKGROUND AND OBJECTIVES: The management of blunt cerebrovascular injuries (BCVIs) remains an important topic within trauma and neurosurgery today. There remains a lack of consensus within the literature and significant variation across institutions. The purpose of this study was to evaluate management of BCVI at a large, tertiary referral trauma center. METHODS: Institutional Review Board approval was obtained to conduct a retrospective review of patients with BCVI at our Level 1 Trauma Center. Computed tomography angiography was used to identify BCVI for each patient. Patient information was collected, and statistical analysis was performed. With the included risk factors for ischemic complications, a novel scoring system based on ischemic risk, the "Memphis Score," was developed and evaluated to grade BCVI. RESULTS: Two hundred seventeen patients with BCVI from July 2020 to August 2022 were identified. The most common mechanism of injury was motor vehicle collision (141, 65.0%). Vertebral arteries were the most common vessel injured (136, 51.1%) with most injuries occurring at a high cervical location (101, 38.0%). Denver Grade 1 injuries (89, 33.5%) and a Memphis Score of 1 were most frequent (172, 64.6%), and initial anticoagulation with heparin drip was initiated 56.7% of the time (123). Endovascular treatment was required in 24 patients (11.1%) and was usually performed in the first 48 hours (15, 62.5%). While Denver Grade (P = .019) and Memphis Score (P < .00001) were significantly higher in those patients undergoing endovascular treatment, only the Memphis Score demonstrated a significant difference between those patients who had stroke or worsening on follow-up imaging and those who did not (P = .0009). CONCLUSION: Although BCVI management has improved since early investigative efforts, institutions must evaluate and share their data to help clarify outcomes. The novel "Memphis Score" presents a standardized framework to communicate ischemic risk and guide management of BCVI.

Extracranial-Intracranial Cerebral Revascularization for Atherosclerotic Vessel Occlusion: An Updated Systematic Review of the Literature.

BACKGROUND: Atherosclerotic steno-occlusive cerebrovascular disease includes extracranial carotid occlusive and intracranial atherosclerotic disease. Despite the negative findings in Carotid Occlusion Surgery Study (COSS), many large centers continue to report favorable results for revascularization surgery in select groups of patients. The aim of our study was to perform an updated systematic review to investigate the role of revascularization surgery for atherosclerotic steno-occlusive patients in the modern era. METHODS: Five independent reviewers performed Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided literature searches in October 2022 to identify articles reporting clinical outcomes in adult patients undergoing bypass for atherosclerotic steno-occlusive disease. Primary endpoints used were perioperative and long-term ischemic strokes, intracerebral hemorrhage, bypass patency, and favorable clinical outcomes. Study quality was evaluated with Newcastle-Ottawa, JADAD, and the Oxford Center for Evidence-Based Medicine scales. RESULTS: A total of 6709 articles were identified in the initial search. Of these articles, 50 met the inclusion criteria and were included in the systematic review. A notable increase in the proportion of articles published over the past 10 years was observed. There were 6046 total patients with 4447 bypasses performed over the period from 1978 to 2022. The average length of follow-up was 2.75 ± 2.71 years. The average Newcastle-Ottawa was 6.23 out of 9 stars. There was a significant difference in perioperative stroke (odds ratio [OR], 0.65 [0.48-0.87]; P = 0.004), long-term ischemia (OR, 0.32 [0.23-0.44]; P < 0.0001), overall ischemia (OR, 0.36 [0.28-0.44]; P < 0.0001), and favorable outcomes (OR, 3.63 [2.84-4.64]; P < 0.0001) when comparing pre-COSS to post-COSS time frames in favor of post-COSS. CONCLUSIONS: Based on a systematic review of 50 articles, the existing literature indicates that long-term stroke rates and favorable outcomes for surgical revascularization for steno-occlusive disease have improved over time and are lower than previously reported. Improved patient selection, perioperative care, and surgical techniques may contribute to improved outcomes.

Surgical techniques and indications for treatment of adult moyamoya disease.

Moyamoya disease (MMD) is a chronic, progressive cerebrovascular disease involving the occlusion or stenosis of the terminal portion of the internal carotid artery (ICA) and the proximal anterior and middle cerebral arteries. Adults with MMD have been shown to progressively accumulate neurological and cognitive deficits without treatment, with a mortality rate double that of pediatric patients with MMD. Surgical intervention is the mainstay of treatment to prevent disease progression and improve clinical outcomes. Several different types of bypasses can be utilized for revascularization in MMD, including indirect, direct, and combined forms of extracranial-to-intracranial (EC-IC) bypass. Overall, the choice of appropriate technique requires consideration of the age of the patient, preoperative hemodynamics, neurologic status, and territories most at risk and in need of revascularization. Here, we will review the indications and surgical techniques for the treatment of adult MMD. Step-by-step instructions for performing several bypass variants with technical pearls are discussed.

Erratum: Skull Base Registries: A Roadmap.

[This corrects the article DOI: 10.1055/a-1934-9191.].

Double-Barrel (2-Donor-2-Recipient) Bypass as Rescue Treatment for Patient with Occluded Middle Cerebral Artery Intracranial Stent and Recurrent Ischemia.

Stent occlusion is a challenging complication following endovascular interventions that require intracranial stenting.1-4 Although there are small series describing revascularization for stenoocclusive disease failing best medical management,5-14 there are few reports in the literature regarding surgical bypass as a treatment for stent occlusion.5 We present the case of a 37-year-old man who presented with right-sided weakness, numbness, and difficulty with speech and ambulation. His history is notable for a left M1 (segment of middle cerebral artery) occlusion 6 months prior that was treated with mechanical thrombectomy requiring repeat thrombectomy and rescue acute middle cerebral artery (MCA) stent placement given vessel reocclusion. Diagnostic cerebral angiography demonstrated stent occlusion. Given his continued ischemic symptoms despite best medical management, the patient underwent a double-barrel superficial temporal artery-MCA direct bypass to revascularize the MCA territory. To our knowledge, there is no literature to date describing a 2-donor-2-recipient direct bypass for the rescue treatment of symptomatic intracranial stent occlusion with recurrent ischemia. We review the case presentation, angiographic findings, surgical nuances, and postoperative course with imaging. The patient provided informed consent for the procedure and verbal support for publishing his image and inclusion in this submission.

Skull Base Registries: A Roadmap.

Hospitals, payors, and patients increasingly expect us to report our outcomes in more detail and to justify our treatment decisions and costs. Although there are many stakeholders in surgical outcomes, physicians must take the lead role in defining how outcomes are assessed. Skull base lesions interact with surrounding anatomy to produce a complex spectrum of presentations and surgical challenges, requiring a wide variety of surgical approaches. Moreover, many skull base lesions are relatively rare. These factors and others often preclude the use of prospective randomized clinical trials, thus necessitating alternate methods of scientific inquiry. In this paper, we propose a roadmap for implementing a skull base registry, along with expected benefits and challenges.

Angiotensin II-induced process of angiogenesis is mediated by spleen tyrosine kinase via VEGF receptor-1 phosphorylation.

Spleen tyrosine kinase (Syk), expressed in endothelial cells, has been implicated in migration and proliferation and in vasculogenesis. This study was conducted to determine the contribution of Syk and the underlying mechanism to the angiogenic effect of ANG II and VEGF. Angiogenesis was determined by tube formation from the endothelial cell line EA.hy926 (EA) and human umbilical vein endothelial cells (HUVECs) and microvessel sprouting in rat aortic rings. ANG II (10 nM), EGF (30 ng/ml), and VEGF (50 ng/ml) stimulated EA cells and HUVECs to form tubular networks and increased aortic sprouting; these effects were blocked by VEGF receptor-1 and Flt-1 antibody (Flt-1/Fc) but not by the VEGF receptor-2 (Flk-1) antagonist SU-1498. ANG II increased the phosphorylation of Flt-1 but not Flk-1, whereas VEGF increased the phosphorylation of both receptors in EA cells and HUVECs. VEGF expression elicited by ANG II was not altered by Flt-1/Fc or SU-1498. EGF stimulated tube formation from EA cells and HUVECs and Flt-1 phosphorylation and aortic sprouting, which were blocked by the EGF receptor antagonist AG-1478 and Flt-1/Fc but not by SU-1498. ANG II-, EGF-, and VEGF-induced tube formation and aortic sprouting were attenuated by the Syk inhibitor piceatannol and by Syk short hairpin interfering (sh)RNA and small interfering RNA, respectively. ANG II, EGF, and VEGF increased Syk phosphorylation, which was inhibited by piceatannol and Syk shRNA in EA cells and HUVECs. Neither piceatannol nor Syk shRNA altered ANG II-, EGF-, or VEGF-induced phosphorylation of Flt-1. These data suggest that ANG II stimulates angiogenesis via transactivation of the EGF receptor, which promotes the phosphorylation of Flt-1 and activation of Syk independent of VEGF expression.

C4-T3 Replacement Laminoplasty and Microsurgical Resection of Ependymoma: 2-Dimensional Operative Video.

Spinal ependymomas are the most common intramedullary spinal cord tumors in adults.1-4 They are benign histologically, and maximum safe surgical resection should be pursued with the goal of maintaining neurological integrity.4 Spinal ependymoma resections have been described in the operative video literature, including those using techniques of laminoplasty to prevent postlaminectomy kyphosis.1-3,5 Defining the planes between tumor and normal spinal cord is critical to achieving safe maximum resection.3 This video will illustrate the microsurgical techniques used in the resection of a large spinal cord ependymoma in a patient who presented with progressive lower extremity paraparesis and incontinence and was found to have a large intradural, intramedullary C4-T3 lesion with a rostral glial tumor cyst. The patient consented to surgical intervention. The patient was placed prone in MAYFIELD 3-point pin fixation (Integra LifeSciences, Plainsboro Township, New Jersey). Intraoperative neurophysiological electrodes were placed for somatosensory evoked potentials, motor evoked potentials, and D-wave monitoring of corticospinal tracts.6,7 C3-T4 replacement laminoplasties were performed. A midline dural incision spanning C4-T4 was made. A midline myelotomy preserving the pial venous plexus was performed with a 69 Beaver blade.2 The attachments of the tumor to the normal white matter of the spinal cord were microsurgically defined, coagulated, and divided. Tumor debulking was performed with an ultrasonic aspirator. Once gross total resection was achieved, the pial edges of the spinal cord were reapproximated. The dura was closed in a watertight fashion. The patient recovered from surgery well with preservation of her motor function with a continued T7 sensory level.

2-Methoxyestradiol Ameliorates Angiotensin II-Induced Hypertension by Inhibiting Cytosolic Phospholipase A2α Activity in Female Mice.

[Figure: see text].