Taylor A. Wilson

Glioblastoma multiforme: State of the art and future therapeutics

Background: Glioblastoma multiforme (GBM) is the most common and lethal primary malignancy of the central nervous system (CNS). Despite the proven benefit of surgical resection and aggressive treatment with chemo- and radiotherapy, the prognosis remains very poor. Recent advances of our understanding of the biology and pathophysiology of GBM have allowed the development of a wide array of novel therapeutic approaches, which have been developed. These novel approaches include molecularly targeted therapies, immunotherapies, and gene therapy. Methods: We offer a brief review of the current standard of care, and a survey of novel therapeutic approaches for treatment of GBM. Results: Despite promising results in preclinical trials, many of these therapies have demonstrated limited therapeutic efficacy in human clinical trials. Thus, although survival of patients with GBM continues to slowly improve, treatment of GBM remains extremely challenging. Conclusion: Continued research and development of targeted therapies, based on a detailed understanding of molecular pathogenesis can reasonably be expected to yield improved outcomes for patients with GBM.

Glioblastoma - A tale of two tumors: Case comparison and literature review.

In the paper entitled “Glioblastoma – A tale of two tumors: Case comparison and literature review,” the authors discuss several molecular biomarkers for glioblastoma (GBM), and the role of these markers clinically for directing treatment and predicting prognosis. Currently, there are many molecular tests that can be performed and are routinely reported with the histopathological analysis of GBM. As demonstrated in the existing literature and further highlighted by this paper, there are both benefits and limitations to using molecular testing in GBM.[1,2] Thus, the authors raise the question of cost versus utility of more extensive routine molecular testing on patients with GBM. Furthermore, this raises the issue of how the results of these tests impact patient care and clinical management of patients with GBM, as well as whether the data acquired from these tests are worth the additional cost. Clinically, the role of molecular testing remains unclear; however, this is not to undermine the importance of understanding the molecular biology and genomics of GBM. Molecular biomarkers can be useful in identifying GBM subtypes, which can be used to better drive treatment on an individual basis.[2] For example, many of these molecular biomarkers also function as therapeutic targets. In these cases, testing for specific molecular alterations does play an important role in directing treatment. In other cases, the molecular biomarkers have a less meaningful impact on care and prognosis. Many of these tests are expensive and not covered under insurance. Thus, it is important to consider how the molecular test ordered will impact the clinical management of the patient when ordering these tests. As stated by the authors, there is currently little data regarding cost versus utility analysis of molecular testing for GBM. In a study done by Holdhoff et al. in the Journal of Neuro-Oncology assessing the use of molecular biomarkers in the clinical care of patients with GBM, they found that only small proportion of physicians ordering these tests found that the results impacted clinical management of their patients.[1] Understanding the genomics of GBM is critical for research in order to develop new therapeutic targets and approaches to treating GBM, but until particular biomarkers are used in a way where the result of the test directly alters patient management, such as a clinical trial for a small molecular inhibitor or monoclonal antibody, routine molecular testing may not be necessary for all patients. There is a lot of information available, but understanding how to use this information to guide patient care is critical to maximize treatment benefits for the patients as well as avoid unnecessary costs.

A Comparative Review of the Hemodynamics and Pathogenesis of Cerebral and Abdominal Aortic Aneurysms: Lessons to Learn From Each Other

Objective Cerebral aneurysms (CAs) and abdominal aortic aneurysms (AAAs) are degenerative vascular pathologies that manifest as abnormal dilations of the arterial wall. They arise with different morphologies in different types of blood vessels under different hemodynamic conditions. Although treated as different pathologies, we examine common pathways in their hemodynamic pathogenesis in order to elucidate mechanisms of formation. Materials and Methods A systematic review of the literature was performed. Current concepts on pathogenesis and hemodynamics were collected and compared. Results CAs arise as saccular dilations on the cerebral arteries of the circle of Willis under high blood flow, high wall shear stress (WSS), and high wall shear stress gradient (WSSG) conditions. AAAs arise as fusiform dilations on the infrarenal aorta under low blood flow, low, oscillating WSS, and high WSSG conditions. While at opposite ends of the WSS spectrum, they share high WSSG, a critical factor in arterial remodeling. This alone may not be enough to initiate aneurysm formation, but may ignite a cascade of downstream events that leads to aneurysm development. Despite differences in morphology and the structure, CAs and AAAs share many histopathological and biomechanical characteristics. Endothelial cell damage, loss of elastin, and smooth muscle cell loss are universal findings in CAs and AAAs. Increased matrix metalloproteinases and other proteinases, reactive oxygen species, and inflammation also contribute to the pathogenesis of both aneurysms. Conclusion Our review revealed similar pathways in seemingly different pathologies. We also highlight the need for cross-disciplinary studies to aid in finding similarities between pathologies.

Cortical screw trajectory for instrumentation and fusion in the setting of osteopathic compression fracture allows for percutaneous kyphoplasty for adjacent level compression fractures

Spinal fixation in the osteoporotic patient can be challenging due to the poor trabecular bone quality of the vertebral body. Patients with osteoporotic vertebral body compression fractures are at risk for future compression fractures at adjacent levels, especially after cement augmentation. The purpose of this technical report is to describe the utilization of a cortical screw trajectory along with kyphoplasty for a patient with an osteoporotic compression fracture as well as degenerative spinal disease. This trajectory allows for the possibility of percutaneous pedicle access in the event of future compression fractures. Our patient underwent a decompressive laminectomy and kyphoplasty at the level of an osteoporotic compression fracture. The fracture was stabilized with cortical screw instrumentation and fusion at a level above and a level below the fracture. Subsequently the patient developed an adjacent level fracture within the fusion construct. Due to the utilization of a cortical screw trajectory for the initial fusion, the traditional pedicle trajectory was still accessible. As a result, the new fracture was treated with a percutaneous kyphoplasty through a standard pedicle trajectory. In conclusion, the use of a cortical screw trajectory for stabilization of osteoporotic compression fractures provides for a stronger bone screw interface and avoids osteoporotic trabecular vertebral body bone. At the same time this trajectory allows for future percutaneous pedicular access in the event that the patient suffers future compression fractures.

National trends in utilization and outcomes of angioplasty and stenting for revascularization in intracranial stenosis.

INTRODUCTION Angioplasty and intracranial stenting (ICS) are both endovascular revascularization procedures that have emerged as treatment options for intracranial atherosclerotic disease (ICAD). Some believe angioplasty alone is better, while others believe stenting is better. This study examines recent trends in utilization and outcomes of angioplasty alone and ICS in the United States using a population-based cohort. METHODS The National Inpatient Sample (NIS) database was queried for patients with ICAD who underwent angioplasty or ICS from 2005 to 2010. RESULTS There were 1115 patients (angioplasty: n=495, ICS: n=620) with ICAD who underwent endovascular revascularization. Over time, the number of endovascular revascularization procedures increased. The percentage of symptomatic patients (p=0.015) as well as in the number of comorbidities of patients treated (p<0.001) also increased. Combined post-procedure stroke and death rates were 16% and 28.9% for angioplasty and ICS, respectively (p<0.001). A larger percentage of angioplasty patients presented symptomatically compared to those who underwent ICS (p<0.001). CONCLUSION Angioplasty appears to be associated with higher rates of peri-procedural complications; however, that may represent patient selection bias. Further studies are needed to identify patients who would benefit from revascularization and to clarify the roles of angioplasty and ICS.

Epidural Blood Patch Performed for Severe Intracranial Hypotension Following Lumbar Cerebrospinal Fluid Drainage for Intracranial Aneurysm Surgery. Retrospective Series and Literature Review.

Intracranial hypotension (IH) can occur following lumbar drainage for clipping of an intracranial aneurysm. We observed 3 cases of IH, which were all successfully treated by epidural blood patch (EBP). Herein, the authors report our cases.

Comparison of outcomes and utilization of extracranial-intracranial bypass versus intracranial stenting for intracranial stenosis.

Background: Extracranial–intracranial (EC-IC) bypass and intracranial stenting (ICS) are both revascularization procedures that have emerged as treatment options for intracranial atherosclerotic disease (ICAD). This study describes and compares recent trends in utilization and outcomes of intracranial revascularization procedures in the United States using a population-based cohort. It also investigates the association of ICS and EC-IC bypass with periprocedural morbidity and mortality, unfavorable discharge status, length of stay (LOS), and total hospital charges. Methods: The National Inpatient Sample (NIS) was queried for patients with ICAD who underwent EC-IC bypass or ICS during the years 2004–2010. Patient characteristics, demographics, perioperative complications, outcomes, and discharge data were collected. Results: There were 627 patients who underwent ICS and 249 patients who underwent EC-IC bypass. Patients who underwent ICS were significantly older (P < 0.001) with more comorbidities (P = 0.027) than those who underwent EC-IC bypass. Patients who underwent EC-IC bypass experienced higher rates of postprocedure stroke (P = 0.014), but those who underwent ICS experienced higher rates of death (P = 0.006). Among asymptomatic patients, the rates of postprocedure stroke (P = 0.341) and death (P = 0.887) were similar between patients who underwent ICS and those who underwent EC-IC bypass. Among symptomatic patients, however, there was a higher rate of postprocedure stroke in patients who underwent EC-IC bypass (P < 0.001) and a higher rate of death among patients who underwent ICS (P = 0.015). Conclusion: The ideal management of patients with ICAD cannot yet be defined. Although much data from randomized and prospective trials on revascularization have been collected, many questions remain unanswered. There still remain cohorts of patients, specifically patients who have failed aggressive medical management, where not enough evidence is available to dictate decision-making. In order to further elucidate the safety and efficacy of these intracranial revascularization procedures, further clinical trials are needed.

E-016 A Comparative Review of the Hemodynamics and Pathogenesis of Cerebral and Abdominal Aortic Aneurysms: Lessons to Learn From Each Other

Introduction/purpose Cerebral aneurysms (CAs) and abdominal aortic aneurysms (AAAs) are both degenerative vascular pathologies that manifest as an abnormal dilation of the arterial wall. They arise with different morphologies in different types of blood vessels under different haemodynamic conditions. Although these aneurysms are treated as very different and separate pathologies, we sought to examine common pathways in the haemodynamic pathogenesis to further elucidate mechanisms of formation. Materials and methods A systematic review of the literature was performed. Current concepts on the pathogenesis and hemodynamics of CAs and AAAs were collected and compared. Results CAs arise as saccular (berry-like) dilation on the cerebral arteries of the circle of Willis under high blood flow, high wall shear stress (WSS), and high wall shear stress gradient (WSSG) conditions. AAAs arise as fusiform (spindle-like) dilations on the infrarenal aorta under low blood flow, low, oscillating WSS, and high WSSG conditions. While the two pathologies exist at likely the opposite ends of the spectrum of WSS, they both share high WSSG. These changes in blood flow have been shown to be a critical factor of introducing arterial remodeling. It is possible that the unique haemodynamic environments in which CAs and AAAs arise cause mechanical damage to the arterial wall. This mechanical damage alone may not be enough to initiate the aneurysm formation, but may ignite a cascade of downstream events that lead to the development of aneurysms. Despite marked differences in their morphology and the structure of the arteries in which they form, CAs and AAAs share many histopathological and biomechanical characteristics. Endothelial cell damage, loss of elastin, and smooth muscle cell loss are universal findings in CAs and AAAs. Increased matrix metalloproteinases and other proteinases as well as reactive oxygen species likely play an important role in the pathogenesis of both CAs and AAAs. Inflammation, which plays an integral role in the initiation of AAAs, seems to play a stronger role in CAs downstream from initiation events. Conclusion A critical review of the literature revealed similar pathways in two seemingly different pathologies. Specifically, the roles of WSSG, inflammation and sequences of endothelial dysfunction play an important role in both AAA and CA formation. We also highlight the need for cross-disciplinary reviews that help aid in finding similar threads between pathologies. Abstract E-016 Figure 1 Disclosures O. Tanweer: None. T. Wilson: None. E. Metaxa: None. H. Riina: None. H. Meng: None.

Minimally invasive approach to resection of paraspinal schwannoma

In this video, the authors demonstrate a minimally invasive approach and resection of a paraspinal schwannoma. Using an expandable retractor, the authors were able to identify important adjacent bony landmarks and hence visualize and remove this peripheral nerve sheath tumor. While a tubular retractor is commonly used for interbody fusion procedures, the location of the tumor allowed this minimally invasive approach resulting in excellent access, minimal soft-tissue injury, and a short hospital stay. The authors present this approach as a less invasive and yet effective technique for resection of otherwise difficult-to-access nerve lesions. The video can be found here: https://youtu.be/89OY5wdMB_k .

E-017 Cerebrovascular Decision Making: Professional and Personal Preferences

Introduction It is known that physicians sometimes recommend treatment that, in a similar clinical scenario, they might not choose for themselves. We sought to understand this dynamic across cerebrovascular practice and examine how neurosurgeons value the procedures they offer. Methods We conducted an online survey sent to a large cohort of neurosurgeons in May 2013. Respondents were randomised to answer either as the surgeon or as the patient. The questions involved patients presenting with 1) an epidural hematoma (control), 2) un-ruptured anterior communicating artery aneurysm, 3) incidentally found right temporal AVM, 4) spontaneous intracranial and intraventricular haemorrhage in deep structure. Data on practice parameters and experience levels was also collected. Results We obtained 534 survey responses, 279 responding as the “neurosurgeon”, and 255 as the “patient,” with a response rate of 19.7%. Demographics amongst the two groups of survey takers was similar. There was no difference in the management of an epidural hematoma, as expected. For the unruptured aneurysm, the rates of opting for treatment was similar amongst respondees. However within the treatment group there was a trend for survey takers to more often chose coiling for themselves and clipping for patients (p = 0.056). Surgeons, however, with a greater than 30% open-cerebrovascular practice had less of a tendency to do so. For arteriovenous malformation management, there was no statistical difference between choosing treatment or conservative management. However, amongst the respondees who chose treatment, more respondees chose resection/embolization for their patient but radiosurgery for self (p = 0.001). In a case of a large spontaneous intracranial and intraventricular haemorrhage neurosurgeons were more likely to place a ventricular drain in a patient than himself or herself. Neurosurgeons in practice more than 10 years since residency were more likely to recommend against interventions for aneurysms, AVMs or intracranial haemorrhage. Conclusions In the majority of cases altering the role of the surgeon did not change the decision to pursue treatment or conservative treatment. In certain clinical scenarios, however, neurosurgeons choose treatment options for themselves that are different than what they would choose for their patients. For the management of an arteriovenous malformations, intracranial aneurysms, and hypertensive haemorrhage, responses favored less invasive interventions when the surgeon was the patient. These findings are likely a result of cognitive biases, previous training, experience, areas of expertise, and personal values. Disclosures O. Tanweer: None. T. Wilson: None. S. Kalhorn: None. J. Golfinos: None. P. Huang: None. D. Kondziolka: None.