Subarachnoid Hemorrhage

Current Treatment Options in Cardiovascular Medicine. Oct, 2001  |  Pubmed ID: 11527524

Patients presenting with subarachnoid hemorrhage from aneurysmal rupture benefit from early repair of the aneurysm. Recent advances in endovascular technology now allow informed discussion of the merits of surgical versus endovascular repair of the aneurysm. Patients need close observation in an intensive-care unit following subarachnoid hemorrhage to diagnose and treat the multiple complications that result. These complications include hydrocephalus, fever, neurogenic pulmonary and cardiac dysfunction, and the development of delayed cerebral ischemia from vasospasm. There exist effective medical and endovascular treatments for cerebral vasospasm.

Antitumor Activity of Cytotoxic T Lymphocytes Engineered to Target Vascular Endothelial Growth Factor Receptors

Proceedings of the National Academy of Sciences of the United States of America. May, 2002  |  Pubmed ID: 11997459

The demonstration that angiogenesis is required for the growth of solid tumors has fueled an intense interest in the development of new therapeutic strategies that target the tumor vasculature. Here we report the development of an immune-based antiangiogenic strategy that is based on the generation of T lymphocytes that possess a killing specificity for cells expressing vascular endothelial growth factor receptors (VEGFRs). To target VEGFR-expressing cells, recombinant retroviral vectors were generated that encoded a chimeric T cell receptor comprised of VEGF sequences linked to intracellular signaling sequences derived from the zeta chain of the T cell receptor. After transduction of primary murine CD8 lymphocytes by such vectors, the transduced cells were shown to possess an efficient killing specificity for cells expressing the VEGF receptor, Flk-1, as measured by in vitro cytotoxicity assays. After adoptive transfer into tumor-bearing mice, the genetically modified cytotoxic T lymphocytes strongly inhibited the growth of a variety of syngeneic murine tumors and human tumor xenografts. An increased effect on in vivo tumor growth inhibition was seen when this therapy was combined with the systemic administration of TNP-470, a conventional angiogenesis inhibitor. The utilization of the immune system to target angiogenic markers expressed on tumor vasculature may prove to be a powerful means for controlling tumor growth.

Risk of Hemorrhage from Unsecured, Unruptured Aneurysms During and After Hypertensive Hypervolemic Therapy

Neurosurgery. Jun, 2002  |  Pubmed ID: 12015837

Hypertensive hypervolemic therapy for vasospasm is widely practiced. It is not clear, however, whether the use of hypertension and hypervolemia as a treatment for vasospasm risks hemorrhage from an unsecured, unruptured aneurysm.

Proposed Use of Prophylactic Decompressive Craniectomy in Poor-grade Aneurysmal Subarachnoid Hemorrhage Patients Presenting with Associated Large Sylvian Hematomas

Neurosurgery. Jul, 2002  |  Pubmed ID: 12182408

As a group, patients who present in poor neurological grade after aneurysmal subarachnoid hemorrhage (SAH) often have poor outcomes. There may be subgroups of these patients, however, in which one pathological process predominates and for which the initiation of specific therapeutic interventions that target the predominant pathological process may result in improved outcome. We report the use of prophylactic decompressive craniectomy in patients presenting in poor neurological condition after SAH from middle cerebral artery aneurysms with associated large sylvian fissure hematomas. Craniectomy allowed significant parenchymal swelling in the posthemorrhagic period without increased intracranial pressure (ICP) or herniation syndrome.

Results of Multimodality Treatment for 141 Patients with Brain Arteriovenous Malformations and Seizures: Factors Associated with Seizure Incidence and Seizure Outcomes

Neurosurgery. Aug, 2002  |  Pubmed ID: 12182768

Previous reports of seizure outcomes after arteriovenous malformation (AVM) treatment have involved single-treatment modality (surgery, radiosurgery, or embolization) series. Such series reflect only selected lesions, of certain sizes, locations, and other clinical and anatomic characteristics, that are amenable to the single therapy, limiting the analysis of those factors. We report the results of AVM treatment using a multimodality approach that we think encompasses a broader spectrum of treatable brain AVMs. We tested for factors associated with seizure presentation and seizure outcomes.

Medical Management of Increased Intracranial Pressure After Spontaneous Intracerebral Hemorrhage

Neurosurgery Clinics of North America. Jul, 2002  |  Pubmed ID: 12486922

There are several medical therapies available to lower unacceptable ICP. We advocate the stepwise institution of these therapies to maintain adequate CPP. At every step in the process, consideration of definitive surgical intervention (e.g., hemicraniectomy, clot evacuation) should be entertained. At this time, we cannot recommend hypothermia as a routine last step of therapy given the complications and lack of clinical effect described previously. Research into this therapy continues, however. The next several years may show us when, how, and in what situations this strategy can be applied.

Stratification of Outcome for Surgically Treated Unruptured Intracranial Aneurysms

Neurosurgery. Jan, 2003  |  Pubmed ID: 12493104

The combination of low anticipated rupture rates for many unruptured aneurysms, better delineation of treatment risks, and the availability of alternative modalities of treatment have led to heightened scrutiny of the surgical management of unruptured intracranial aneurysms. Most reports to date have provided aggregate data concerning surgical treatment risks. This study was performed to better delineate risk estimates for the surgical treatment of patients with unruptured intracranial aneurysms according to a patient's risk profile with regard to age, aneurysm location, and aneurysm size.

Important Factors for a Combined Neurovascular Team to Consider in Selecting a Treatment Modality for Patients with Previously Clipped Residual and Recurrent Intracranial Aneurysms

Neurosurgery. Apr, 2003  |  Pubmed ID: 12657168

Intracranial residual and recurrent aneurysms can occur after surgical clipping, with risks of growth and rupture. In the past, surgical reoperation, which can be associated with higher risk than the initial operation, was the only available treatment. A combined neurovascular team that uses both surgical and endovascular therapies could maximize efficacy and outcomes while minimizing risks in these difficult cases. The indications for which surgical or endovascular treatment should be used to treat patients with residual or recurrent aneurysms, however, have not been elucidated well. We have reviewed the 10-year experience of our combined neurovascular team to determine in a retrospective manner which factors were important to treatment modality selection for patients with these residual and recurrent lesions.

In-hospital Mortality and Morbidity After Surgical Treatment of Unruptured Intracranial Aneurysms in the United States, 1996-2000: the Effect of Hospital and Surgeon Volume

Neurosurgery. May, 2003  |  Pubmed ID: 12699540

We sought to determine the risk of adverse outcome after contemporary surgical treatment of patients with unruptured intracranial aneurysms in the United States. Patient, surgeon, and hospital characteristics were tested as potential outcome predictors, with particular attention to the surgeon's and hospital's volume of care.

Microvascular Decompression Surgery in the United States, 1996 to 2000: Mortality Rates, Morbidity Rates, and the Effects of Hospital and Surgeon Volumes

Neurosurgery. Jun, 2003  |  Pubmed ID: 12762870

Microvascular decompression (MVD) is associated with low mortality and morbidity rates at specialized centers, but many MVD procedures are performed outside such centers. We studied short-term end points after MVD in a national hospital discharge database sample.

Subarachnoid Hemorrhage Without Evident Cause on Initial Angiography Studies: Diagnostic Yield of Subsequent Angiography and Other Neuroimaging Tests

Journal of Neurosurgery. Jun, 2003  |  Pubmed ID: 12816270

The aim of this study was to assess the diagnostic yield of imaging tests performed in patients in whom the cause of subarachnoid hemorrhage (SAH) had not been demonstrated on initial angiography.

Surgical Excision of Acoustic Neuroma: Patient Outcome and Provider Caseload

The Laryngoscope. Aug, 2003  |  Pubmed ID: 12897555

For many complex surgical procedures, larger hospital or surgeon caseload is associated with better patient outcome. We examined the volume-outcome relationship for surgical excision of acoustic neuromas.

In-hospital Morbidity and Mortality After Endovascular Treatment of Unruptured Intracranial Aneurysms in the United States, 1996-2000: Effect of Hospital and Physician Volume

AJNR. American Journal of Neuroradiology. Aug, 2003  |  Pubmed ID: 12917139

Endovascular therapy is increasingly being used for the treatment of unruptured intracranial aneurysms. Our purpose was to determine the risk of adverse outcomes after contemporary endovascular treatment of unruptured intracranial aneurysms in the United States. Patient, treating physician, and hospital characteristics were tested as potential outcome predictors, with particular attention paid to volume of care.

Age-dependent Differences in Short-term Outcome After Surgical or Endovascular Treatment of Unruptured Intracranial Aneurysms in the United States, 1996-2000

Neurosurgery. Jan, 2004  |  Pubmed ID: 14683537

Unruptured intracranial aneurysm patients are frequently eligible for both open surgery ("clipping") and endovascular repair ("coiling"). We compared short-term end points (mortality, discharge disposition, complications, length of stay, and charges) for clipping and coiling in a nationally representative discharge database.

Case Records of the Massachusetts General Hospital. Weekly Clinicopathological Exercises. Case 5-2004 - a 57-year-old Man with Slurred Speech and Left Hemiparesis

The New England Journal of Medicine. Feb, 2004  |  Pubmed ID: 14960747

Hemicraniectomy for Massive Cerebral Infarction

Topics in Stroke Rehabilitation. 2004  |  Pubmed ID: 15118962

The most important acute phase complication of massive cerebral infarction is cerebral herniation secondary to brain edema. In the past decade, there has been heightened interest in surgical treatment of this problem with the use of the techniques of hemicraniectomy and dural augmentation. In this article, we review the theoretical and clinical data supporting the use of hemicraniectomy in malignant cerebral infarction and the range of outcomes expected in patients who undergo this procedure.

Preliminary Experience with Intra-arterial Nicardipine As a Treatment for Cerebral Vasospasm

AJNR. American Journal of Neuroradiology. May, 2004  |  Pubmed ID: 15140728

Papaverine is the primary intra-arterial (IA) treatment for vasospasm after aneurysmal subarachnoid hemorrhage (SAH); however, is it limited in effect and by adverse effects. We prospectively studied the use of IA nicardipine as a treatment for vasospasm.

Results of a Prospective Protocol of Computed Tomographic Angiography in Place of Catheter Angiography As the Only Diagnostic and Pretreatment Planning Study for Cerebral Aneurysms by a Combined Neurovascular Team

Neurosurgery. Jun, 2004  |  Pubmed ID: 15157289

At many centers, patients undergo both computed tomographic angiography (CTA) and digital subtraction angiography (DSA). This practice negates most of the advantages of CTA, and it renders the risks and disadvantages of the two techniques additive. Previous reports in the literature have assessed the sensitivity and specificity of CTA compared with DSA; however, these investigations have not analyzed the clinical implications of a protocol that replaces DSA with CTA as the only diagnostic and pretreatment planning study for patients with cerebral aneurysms.

Genetic and Cellular Therapies for Cerebral Infarction

Neurosurgery. Aug, 2004  |  Pubmed ID: 15271234

Neurosurgeons, working as surgical scientists, can have a prominent role in developing and implementing genetic and cellular therapies for cerebral ischemia. The rapid emergence of both genetic and cellular therapies for neural regeneration warrants a careful analysis before implementation of human studies to understand the pitfalls and promises of this strategy. In this article, we review the topic of genetic and cellular therapy for stroke to provide a foundation for practicing neurosurgeons and clinical scientists who may become involved in this type of work. In Part 1, we review preclinical approaches with gene transfer, such as 1) improved energy delivery, 2) reduction of intracellular calcium availability, 3) abrogation of effects of reactive oxygen species, 4) reduction of proinflammatory cytokine signaling, 5) inhibition of apoptosis mediators, and 6) restorative gene therapy, that are paving the way to develop new strategies to treat cerebral infarction. In Part 2, we discuss the results of studies that address the possibility of using cellular therapies for stroke in animal models and in human trials by reviewing 1) the basics of stem cell biology, 2) exogenous and 3) and endogenous cell sources for therapy, and 4) clinical considerations in cell therapy applications. These emerging technologies based on the advancements made in recent years in the fields of genetics, therapeutic cloning, neuroscience, stem cell biology, and gene therapy provide significant potential for new therapies for stroke.

Effect of Clipping, Craniotomy, or Intravascular Coiling on Cerebral Vasospasm and Patient Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery. Oct, 2004  |  Pubmed ID: 15458586

Although several recent studies have suggested that the incidence of vasospasm after aneurysmal subarachnoid hemorrhage is lower in patients undergoing aneurysmal coiling as compared with clipping, other studies have had conflicting results. We reviewed our experience over 8 years and assessed whether clipping, craniotomy, or coiling affects patient outcomes or the risk for vasospasm.

Achieving Normothermia in Patients with Febrile Subarachnoid Hemorrhage: Feasibility and Safety of a Novel Intravascular Cooling Catheter

Neurocritical Care. 2004  |  Pubmed ID: 16174910

Fever is common and difficult to control in patients with subarachnoid hemorrhage (SAH). We have previously shown an inverse relationship between fever and outcome in patients with SAH.

Synthesizing Medical Evidence: Systematic Reviews and Metaanalyses

Neurosurgical Focus. Oct, 2005  |  Pubmed ID: 16241107

Systematic reviews and metaanalyses have become increasingly popular ways of summarizing, and sometimes extending, existing medical knowledge. In this review the authors summarize current methods of performing metaanalyses, including the following: formulating a research question; performing a structured literature search and a search for trials not published in the formal medical literature; summarizing and, where appropriate, combining results from several trials; and reporting and presenting results. Topics such as cumulative and Bayesian metaanalysis and metaregression are also addressed. References to textbooks, articles, and Internet resources are also provided. The goal is to assist readers who wish to perform their own metaanalysis or to interpret critically a published example.

Adult-born and Preexisting Olfactory Granule Neurons Undergo Distinct Experience-dependent Modifications of Their Olfactory Responses in Vivo

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. Nov, 2005  |  Pubmed ID: 16291946

Neurogenesis continues throughout adulthood in the mammalian olfactory bulb and hippocampal dentate gyrus, suggesting the hypothesis that recently generated, adult-born neurons contribute to neural plasticity and learning. To explore this hypothesis, we examined whether olfactory experience modifies the responses of adult-born neurons to odorants, using immediate early genes (IEGs) to assay the response of olfactory granule neurons. We find that, shortly after they differentiate and synaptically integrate, the population of adult-born olfactory granule neurons has a greater population IEG response to novel odors than mature, preexisting neurons. Familiarizing mice with test odors increases the response of the recently incorporated adult-born neuron population to the test odors, and this increased responsiveness is long lasting, demonstrating that the response of the adult-born neuron population is altered by experience. In contrast, familiarizing mice with test odors decreases the IEG response of developmentally generated neurons, suggesting that recently generated adult-born neurons play a distinct role in olfactory processing. The increased IEG response is stimulus specific; familiarizing mice with a set of different, "distractor" odors does not increase the adult-born neuron population response to the test odors. Odor familiarization does not influence the survival of adult-born neurons, indicating that the changes in the population response of adult-born neurons are not attributable to increased survival of odor-stimulated neurons. These results demonstrate that recently generated adult-born olfactory granule neurons and older, preexisting granule neurons undergo contrasting experience-dependent modifications in vivo and support the hypothesis that adult-born neurons are involved in olfactory learning.

Extracranial-intracranial Bypass in the Treatment of Occlusive Cerebrovascular Disease and Intracranial Aneurysms in the United States Between 1992 and 2001: a Population-based Study

Journal of Neurosurgery. Nov, 2005  |  Pubmed ID: 16304982

The authors assessed the results of extracranial-intracranial (EC-IC) bypass surgery in the treatment of occlusive cerebrovascular disease and intracranial aneurysms in the US between 1992 and 2001 by using population-based methods.

Surgery for Primary Supratentorial Brain Tumors in the United States, 1988 to 2000: the Effect of Provider Caseload and Centralization of Care

Neuro-oncology. Jan, 2005  |  Pubmed ID: 15701282

Contemporary reports of patient outcomes after biopsy or resection of primary brain tumors typically reflect results at specialized centers. Such reports may not be representative of practices in nonspecialized settings. This analysis uses a nationwide hospital discharge database to examine trends in mortality and outcome at hospital discharge in 38,028 admissions for biopsy or resection of supratentorial primary brain tumors in adults between 1988 and 2000, particularly in relation to provider caseload. Multivariate analyses showed that large-volume centers had lower in-hospital postoperative mortality rates than centers with lighter caseloads, both for craniotomies (odds ratio [OR] 0.75 for a tenfold larger caseload) and for needle (closed) biopsies (OR 0.54). Adverse discharge disposition was also less likely at high-volume hospitals, both for craniotomies (OR 0.77) and for needle biopsies (OR 0.67). The annual number of surgical admissions increased by 53% during the 12-year study period, and in-hospital mortality rates decreased during this period, from 4.8% to 1.8%. Mortality rates decreased over time, both for craniotomies and for needle biopsies. Subgroup analyses showed larger relative mortality rate reductions at large-volume centers than at small-volume centers (73% vs. 43%, respectively). The number of US hospitals performing one or more craniotomies annually for primary brain tumors decreased slightly, and the number performing needle biopsies increased. There was little change in median hospital annual craniotomy caseloads, but the largest centers had disproportionate growth in volume. The 100 highest-caseload US hospitals accounted for an estimated 30% of the total US surgical primary brain tumor caseload in 1988 and 41% in 2000. Our findings do not establish minimum volume thresholds for acceptable surgical care of primary brain tumors. However, they do suggest a trend toward progressive centralization of craniotomies for primary brain tumor toward large-volume US centers during this interval.

Factors Associated with Outcome After Hemicraniectomy for Large Middle Cerebral Artery Territory Infarction

Neurosurgery. Apr, 2005  |  Pubmed ID: 15792506

Large or malignant middle cerebral artery infarction is associated with a high mortality rate. Hemicraniectomy reduces intracranial pressure and has been demonstrated to increase survival. Questions remain regarding selection of patients for surgery and functional outcomes.

Relationship Between Hyperglycemia and Symptomatic Vasospasm After Subarachnoid Hemorrhage

Critical Care Medicine. Jul, 2005  |  Pubmed ID: 16003069

To determine the relationship between blood glucose levels (mg/dL) and occurrence of symptomatic vasospasm (VSP) and clinical outcomes after aneurysmal subarachnoid hemorrhage.

Craniotomy for Meningioma in the United States Between 1988 and 2000: Decreasing Rate of Mortality and the Effect of Provider Caseload

Journal of Neurosurgery. Jun, 2005  |  Pubmed ID: 16028755

The goal of this study was to determine the risk of adverse outcomes after contemporary surgical treatment of meningiomas in the US and trends in patient outcomes and patterns of care.

Epidemiology of the Size Distribution of Intracranial Bifurcation Aneurysms: Smaller Size of Distal Aneurysms and Increasing Size of Unruptured Aneurysms with Age

Neurosurgery. Feb, 2006  |  Pubmed ID: 16462474

To explore the epidemiology of the size distribution of intracranial bifurcation aneurysms at different locations and to specifically test the hypothesis that distal vessels develop, on average, smaller aneurysms.

Noninvasive Bioluminescence Imaging of Luciferase Expressing Intracranial U87 Xenografts: Correlation with Magnetic Resonance Imaging Determined Tumor Volume and Longitudinal Use in Assessing Tumor Growth and Antiangiogenic Treatment Effect

Neurosurgery. Feb, 2006  |  Pubmed ID: 16462491

Outcome studies in rodent tumor models rely on both histological and noninvasive study end points. Intracranial models require special tools to observe tumor growth over time noninvasively, such as magnetic resonance imaging (MRI), computed tomographic scanning, or cranial window techniques. These techniques share disadvantages in terms of cost, technical expertise required, and overall animal throughput for analysis. In this report, we sought to validate the use of the relatively newer technique of bioluminescence imaging (BLI) of intracranial glioblastoma xenograft growth by comparing it with gadolinium-enhanced MRI.

Complications of Cerebral Arteriovenous Malformation Embolization: Multivariate Analysis of Predictive Factors

Neurosurgery. Apr, 2006  |  Pubmed ID: 16575323

Embolization is an important therapeutic modality in the multidisciplinary management of arteriovenous malformations (AVM); however, prior series have reported a wide variability in overall complication rates caused by embolization (10-50% neurological deficit, 1-4% mortality). In this study, we reviewed our experience with AVM embolization and analyzed factors that might predict complications and clinical outcomes after AVM embolization.

Outcomes for Surgical and Endovascular Management of Intracranial Aneurysms Using a Comprehensive Grading System

Neurosurgery. Nov, 2006  |  Pubmed ID: 17143238

A systematic approach to the consideration of various factors on outcome demands a comprehensive grading system for patients with intracranial aneurysms. We have previously identified potential patient- and lesion-specific factors that correlate strongly with outcome after treatment for intracranial aneurysms, and we have developed a comprehensive grading system based on these factors. In this study, we evaluate this grading system in a large series of aneurysm patients treated by surgery and endovascular therapy.

Outcomes Studies in Cerebrovascular Neurosurgery

Neurosurgical Focus. 2007  |  Pubmed ID: 17608354

Successfully measuring cerebrovascular neurosurgery outcomes requires an appreciation of the current state-of-the-art epidemiological instruments, their specific relevance to surgical treatments and the underlying pathological entity, and ultimately the right set of questions for the next generation of studies. In this paper the authors address these questions with specific attention to measurement targets, individual modeling scales, and types of studies, all within a conceptual framework for specific disease models in their current state of outcomes modeling in cerebrovascular neurosurgery.

High-dose Bosentan in the Prevention and Treatment of Subarachnoid Hemorrhage-induced Cerebral Vasospasm: an Open-label Feasibility Study

Neurocritical Care. 2007  |  Pubmed ID: 17901934

To evaluate the safety of high-dosages of the endothelin ET(A/B )receptor antagonist bosentan in SAH patients at high-vasospasm risk.

Increased Prevalence of Obesity and Obesity-related Postoperative Complications in Male Patients with Meningiomas

Neurosurgery. Oct, 2007  |  Pubmed ID: 17986936

The female preponderance of meningiomas may reflect hormonal influences on meningioma growth. We hypothesized that because obesity affects male steroid hormone synthesis, male patients with meningiomas might exhibit a high obesity rate, which, in turn, might increase their frequency of postoperative complications.

Increased Prevalence of Obesity and Obesity-related Postoperative Complications in Male Meningioma Patients

Clinical Neurosurgery. 2007  |  Pubmed ID: 18504925

Genetic and Cellular Therapies for Cerebral Infarction

Neurosurgery. Jun, 2008  |  Pubmed ID: 18695566

Neurosurgeons, working as surgical scientists, can have a prominent role in developing and implementing genetic and cellular therapies for cerebral ischemia. The rapid emergence of both genetic and cellular therapies for neural regeneration warrants a careful analysis before implementation of human studies to understand the pitfalls and promises of this strategy. In this article, we review the topic of genetic and cellular therapy for stroke to provide a foundation for practicing neurosurgeons and clinical scientists who may become involved in this type of work. In Part 1, we review preclinical approaches with gene transfer, such as 1) improved energy delivery, 2) reduction of intracellular calcium availability, 3) abrogation of effects of reactive oxygen species, 4) reduction of proinflammatory cytokine signaling, 5) inhibition of apoptosis mediators, and 6) restorative gene therapy, that are paving the way to develop new strategies to treat cerebral infarction. In Part 2, we discuss the results of studies that address the possibility of using cellular therapies for stroke in animal models and in human trials by reviewing 1) the basics of stem cell biology, 2) exogenous and 3) and endogenous cell sources for therapy, and 4) clinical considerations in cell therapy applications. These emerging technologies based on the advancements made in recent years in the fields of genetics, therapeutic cloning, neuroscience, stem cell biology, and gene therapy provide significant potential for new therapies for stroke.

Surrogate Measures of Outcome in Clinical Trials: Clues Worth Examining?

Neurosurgery. Aug, 2008  |  Pubmed ID: 18797341

Shunting for Alzheimer's Disease: Stymied by a Different Sort of Placebo Effect?

Neurosurgery. Oct, 2008  |  Pubmed ID: 18981866

Glioblastoma Microvesicles Transport RNA and Proteins That Promote Tumour Growth and Provide Diagnostic Biomarkers

Nature Cell Biology. Dec, 2008  |  Pubmed ID: 19011622

Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.

ISAT Subgroups: is Aneurysm Clipping Better for Some Patients?

Neurosurgery. Dec, 2008  |  Pubmed ID: 19057309

Successful Inhibition of Intracranial Human Glioblastoma Multiforme Xenograft Growth Via Systemic Adenoviral Delivery of Soluble Endostatin and Soluble Vascular Endothelial Growth Factor Receptor-2: Laboratory Investigation

Journal of Neurosurgery. May, 2008  |  Pubmed ID: 18447716

Glioblastoma multiforme (GBM) is characterized by neovascularization, raising the question of whether angiogenic blockade may be a useful therapeutic strategy for this disease. It has been suggested, however, that, to be useful, angiogenic blockade must be persistent and at levels sufficient to overcome proangiogenic signals from tumor cells. In this report, the authors tested the hypothesis that sustained high concentrations of 2 different antiangiogenic proteins, delivered using a systemic gene therapy strategy, could inhibit the growth of established intracranial U87 human GBM xenografts in nude mice.

Long-term Recurrence Rates of Atypical Meningiomas After Gross Total Resection with or Without Postoperative Adjuvant Radiation

Neurosurgery. Jan, 2009  |  Pubmed ID: 19145156

Atypical meningioma (AM) patients often undergo gross total resection (GTR) at the time of presentation, but subsequent prognosis and optimal management remain unclear. We sought to define the long-term recurrence rate of AMs after GTR, along with factors predicting recurrence, including postoperative radiation.

Effective Glycemic Control with Aggressive Hyperglycemia Management is Associated with Improved Outcome in Aneurysmal Subarachnoid Hemorrhage

Stroke; a Journal of Cerebral Circulation. May, 2009  |  Pubmed ID: 19286596

Hyperglycemia strongly predicts poor outcome in patients with aneurysmal subarachnoid hemorrhage, but the effect of hyperglycemia management on outcome is unclear. We studied the impact of glycemic control on outcome of patients with aneurysmal subarachnoid hemorrhage.

Genetically Engineered T Cells to Target EGFRvIII Expressing Glioblastoma

Journal of Neuro-oncology. Sep, 2009  |  Pubmed ID: 19387557

Glioblastoma remains a significant therapeutic challenge, warranting further investigation of novel therapies. We describe an immunotherapeutic strategy to treat glioblastoma based on adoptive transfer of genetically modified T-lymphocytes (T cells) redirected to kill EGFRvIII expressing gliomas. We constructed a chimeric immune receptor (CIR) specific to EGFRvIII, (MR1-zeta). After in vitro selection and expansion, MR1-zeta genetically modified primary human T-cells specifically recognized EGFRvIII-positive tumor cells as demonstrated by IFN-gamma secretion and efficient tumor lysis compared to control CIRs defective in EGFRvIII binding (MRB-zeta) or signaling (MR1-delzeta). MR1-zeta expressing T cells also inhibited EGFRvIII-positive tumor growth in vivo in a xenografted mouse model. Successful targeting of EGFRvIII-positive tumors via adoptive transfer of genetically modified T cells may represent a new immunotherapy strategy with great potential for clinical applications.

A New Era of Outcomes Research

Neurosurgery. May, 2009  |  Pubmed ID: 19404137

Racial, Ethnic, and Socioeconomic Disparities in Patient Outcomes After Craniotomy for Tumor in Adult Patients in the United States, 1988-2004

Neurosurgery. Mar, 2010  |  Pubmed ID: 20124933

Racial disparities in American health care outcomes are well documented. We investigated racial disparities in hospital mortality and adverse discharge disposition after brain tumor craniotomies performed in the United States from 1988 to 2004. We explored potential explanations for the disparities.

Microfluidic Isolation and Transcriptome Analysis of Serum Microvesicles

Lab on a Chip. Feb, 2010  |  Pubmed ID: 20126692

Microvesicles (exosomes) shed from both normal and cancerous cells may serve as means of intercellular communication. These microvesicles carry proteins, lipids and nucleic acids derived from the host cell. Their isolation and analysis from blood samples have the potential to provide information about state and progression of malignancy and should prove of great clinical importance as biomarkers for a variety of disease states. However, current protocols for isolation of microvesicles from blood require high-speed centrifugation and filtration, which are cumbersome and time consuming. In order to take full advantage of the potential of microvesicles as biomarkers for clinical applications, faster and simpler methods of isolation will be needed. In this paper, we present an easy and rapid microfluidic immunoaffinity method to isolate microvesicles from small volumes of both serum from blood samples and conditioned medium from cells in culture. RNA of high quality can be extracted from these microvesicles providing a source of information about the genetic status of tumors to serve as biomarkers for diagnosis and prognosis of cancer.

Recombinant Adeno-associated Virus Type 2 Pseudotypes: Comparing Safety, Specificity, and Transduction Efficiency in the Primate Striatum. Laboratory Investigation

Journal of Neurosurgery. Mar, 2011  |  Pubmed ID: 20950087

Although several clinical trials utilizing the adeno-associated virus (AAV) type 2 serotype 2 (2/2) are now underway, it is unclear whether this particular serotype offers any advantage over others in terms of safety or efficiency when delivered directly to the CNS.

A Review of Lumbar Spinal Instrumentation: Evidence and Controversy

Journal of Neurology, Neurosurgery, and Psychiatry. Sep, 2011  |  Pubmed ID: 21602520

Disability secondary to disorders of the spine is a significant problem worldwide. In the USA, there has been a recent surge in the costs associated with caring for spinal pathology; from 1997 to 2005, there was a growth of 65% in healthcare expenditures on spinal disease, totalling $86 billion in 2005. Increasingly, there has been media and public scrutiny over the rapid rise in the volume of procedures with spinal instrumentation; some have suggested that this rise has been fuelled by non-medical drivers such as the financial incentives involved with the use of instrumentation; others suggest that innovation in spine technology and devices has led to improved options for the treatment of spine pathology.In this context, we conducted a review of the literature to assess the use of instrumentation in lumbar procedures and its relationship to successful fusion and patient outcome. Our review suggests that there is data supporting the thesis that lumbar instrumentation improves rates of fusion. However, there is no consistent correlation between increased rates of fusion and improved patient outcomes.

Role of Magnesium Sulfate in Aneurysmal Subarachnoid Hemorrhage Management: A Meta-analysis of Controlled Clinical Trials

Asian Journal of Neurosurgery. Jan, 2011  |  Pubmed ID: 22059101

There has been longstanding controversy over the use of magnesium sulfate infusion in the medical management of aneurysmal subarachnoid hemorrhage (SAH). Several clinical trials evaluating the beneficial effects of magnesium on cerebral vasospasm and their poor outcome have been published. However, results from the majority of these studies have been inconclusive. This meta-analysis was performed to evaluate the effectiveness of magnesium on patient outcomes after aneurysmal SAH.

RNA Expression Patterns in Serum Microvesicles from Patients with Glioblastoma Multiforme and Controls

BMC Cancer. Jan, 2012  |  Pubmed ID: 22251860

ABSTRACT: BACKGROUND: RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients. METHODS: Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N=9) and normal controls (N=7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N=10 in both groups). RESULTS: Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes >2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size <500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production. CONCLUSIONS: Serum microvesicle RNA from patients with glioblastoma multiforme has significantly downregulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size <500 nt.