Showing papers by "Jeffrey Bennett published in 2015"

International consensus diagnostic criteria for neuromyelitis optica spectrum disorders

Abstract: Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS.

Neuromyelitis optica and multiple sclerosis: Seeing differences through optical coherence tomography

Abstract: Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel aquaporin-4 present in up to 80% of NMO patients enables distinction from MS. Optic neuritis may occur in either condition resulting in neuro-anatomical retinal changes. Optical coherence tomography (OCT) has become a useful tool for analyzing retinal damage both in MS and NMO. Numerous studies showed that optic neuritis in NMO typically results in more severe retinal nerve fiber layer (RNFL) and ganglion cell layer thinning and more frequent development of microcystic macular edema than in MS. Furthermore, while patients' RNFL thinning also occurs in the absence of optic neuritis in MS, subclinical damage seems to be rare in NMO. Thus, OCT might be useful in differentiating NMO from MS and serve as an outcome parameter in clinical studies.

Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis

Abstract: Objective: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA). Methods: Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen–positive slides were analyzed by PCR for VZV DNA. Results: VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs ( p Conclusions: Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

B lymphocytes in neuromyelitis optica

Abstract: Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the CNS that predominantly affects the spinal cord and optic nerves. A majority (approximately 75%) of patients with NMO are seropositive for autoantibodies against the astrocyte water channel aquaporin-4 (AQP4). These autoantibodies are predominantly IgG1, and considerable evidence supports their pathogenicity, presumably by binding to AQP4 on CNS astrocytes, resulting in astrocyte injury and inflammation. Convergent clinical and laboratory-based investigations have indicated that B cells play a fundamental role in NMO immunopathology. Multiple mechanisms have been hypothesized: AQP4 autoantibody production, enhanced proinflammatory B cell and plasmablast activity, aberrant B cell tolerance checkpoints, diminished B cell regulatory function, and loss of B cell anergy. Accordingly, many current off-label therapies for NMO deplete B cells or modulate their activity. Understanding the role and mechanisms whereby B cells contribute to initiation, maintenance, and propagation of disease activity is important to advancing our understanding of NMO pathogenesis and developing effective disease-specific therapies.

Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis

Abstract: Importance Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV). Objective To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals. Design, Setting, and Participants A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years. Main Outcomes and Measures Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. Results Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR] = 2.86; 95% CI, 1.75-5.31; P P P P Conclusions and Relevance In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Update on biomarkers in neuromyelitis optica.

Abstract: Neuromyelitis optica (NMO) (and NMO spectrum disorder) is an autoimmune inflammatory disease of the CNS primarily affecting spinal cord and optic nerves. Reliable and sensitive biomarkers for onset, relapse, and progression in NMO are urgently needed because of the heterogeneous clinical presentation, severity of neurologic disability following relapses, and variability of therapeutic response. Detecting aquaporin-4 (AQP4) antibodies (AQP4-IgG or NMO-IgG) in serum supports the diagnosis of seropositive NMO. However, whether AQP4-IgG levels correlate with disease activity, severity, response to therapy, or long-term outcomes is unclear. Moreover, biomarkers for patients with seronegative NMO have yet to be defined and validated. Collaborative international studies hold great promise for establishing and validating biomarkers that are useful in therapeutic trials and clinical management. In this review, we discuss known and potential biomarkers for NMO.

Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid cause demyelination of spinal cord explants

Abstract: B cells are implicated in the etiology of multiple sclerosis (MS). Intrathecal IgG synthesis, cerebrospinal fluid (CSF) oligoclonal bands and lesional IgG deposition suggest a role for antibody-mediated pathology. We examined the binding of IgG1 monoclonal recombinant antibodies (rAbs) derived from MS patient CSF expanded B cell clones to central nervous system (CNS) tissue. MS rAbs displaying CNS binding to mouse and human CNS tissue were further tested for their ability to induce complement-mediated tissue injury in ex vivo spinal cord explant cultures. The staining of CNS tissue, primary human astrocytes and human neurons revealed a measurable bias in MS rAb binding to antigens preferentially expressed on astrocytes and neurons. MS rAbs that recognize myelin-enriched antigens were rarely detected. Both myelin-specific and some astrocyte/neuronal-specific MS rAbs caused significant myelin loss and astrocyte activation when applied to spinal cord explant cultures in the presence of complement. Overall, the intrathecal B cell response in multiple sclerosis binds to both glial and neuronal targets and produces demyelination in spinal cord explant cultures implicating intrathecal IgG in MS pathogenesis.

Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder.

Abstract: Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than gray matter degradation. These findings could be confirmed by ultrahigh-field MRI. The use of nonconventional MRI techniques may further our understanding of the pathogenic processes in NMO spectrum disorders and may help us identify the distinct radiographic features corresponding to specific phenotypic manifestations of this disease.

The cerebrospinal fluid immunoglobulin transcriptome and proteome in neuromyelitis optica reveals central nervous system-specific B cell populations

Abstract: Background Neuromyelitis optica (NMO) is a severe demyelinating disorder of the central nervous system (CNS) associated with the presence of an autoimmune antibody response (AQP4-IgG) against the water channel aquaporin-4 (AQP4). It remains unclear whether pathologic AQP4-IgG in the CNS is produced entirely by peripheral plasma cells or is generated in part by infiltrating B cells. To determine the overlap of AQP4-IgG idiotypes between the CNS and periphery, we compared the immunoglobulin G (IgG) transcriptome of cerebrospinal fluid (CSF) plasmablasts with the CSF and serum IgG proteomes in 7 AQP4-seropositive NMO patients following exacerbation.

The Ins and Outs of B Cells in Multiple Sclerosis.

Abstract: B cells play a central role in multiple sclerosis (MS) pathology. B and plasma cells may contribute to disease activity through multiple mechanisms: antigen presentation, cytokine secretion, or antibody production. Molecular analyses of B cell populations in MS patients have revealed significant overlaps between peripheral lymphoid and clonally expanded central nervous system (CNS) B cell populations, indicating that B cell trafficking may play a critical role in driving MS exacerbations. In this review, we will assess our current knowledge of the mechanisms and pathways governing B cell migration into the CNS and examine evidence for and against a compartmentalized B cell response driving progressive MS pathology.

Spatiotemporal dynamics of the postnatal developing primate brain transcriptome

Abstract: Developmental changes in the temporal and spatial regulation of gene expression drive the emergence of normal mature brain function, while disruptions in these processes underlie many neurodevelopmental abnormalities. To solidify our foundational knowledge of such changes in a primate brain with an extended period of postnatal maturation like in human, we investigated the whole-genome transcriptional profiles of rhesus monkey brains from birth to adulthood. We found that gene expression dynamics are largest from birth through infancy, after which gene expression profiles transition to a relatively stable state by young adulthood. Biological pathway enrichment analysis revealed that genes more highly expressed at birth are associated with cell adhesion and neuron differentiation, while genes more highly expressed in juveniles and adults are associated with cell death. Neocortex showed significantly greater differential expression over time than subcortical structures, and this trend likely reflects the protracted postnatal development of the cortex. Using network analysis, we identified 27 co-expression modules containing genes with highly correlated expression patterns that are associated with specific brain regions, ages or both. In particular, one module with high expression in neonatal cortex and striatum that decreases during infancy and juvenile development was significantly enriched for autism spectrum disorder (ASD)-related genes. This network was enriched for genes associated with axon guidance and interneuron differentiation, consistent with a disruption in the formation of functional cortical circuitry in ASD.

Re-evaluating the treatment of acute optic neuritis

Abstract: Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury.In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration.In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function.

Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. neurology

Abstract: Objective: Intracranial aneurysms, especially those of the cavernous segment of the internal carotid artery (ICA), can present with cranial nerve (CN) palsies. The Pipeline Embolization Device (PED) has demonstrated safety and efficacy in the treatment of cerebral aneurysms by flow diversion, but little data exist reporting the outcomes of cranial neuropathies after treatment with the device. Methods: The prospectively maintained Barrow Neurological Institute’s endovascular database was reviewed for all patients treated with the PED after presenting with 1 or more CN palsies secondary to a cerebral aneurysm since May 2011. Patient charts and digital subtraction angiograms were reviewed to report clinical and angiographic outcomes. Only patients with clinical follow-up were included in the analysis. Results: A total of 127 patients were treated with the PED at the authors’ institution after Food and Drug Administration approval. Twenty-two patients presented with cranial neuropathies, for initial inclusion in this study. Of these patients, 20 had sufficient follow-up for analysis. Cranial neuropathies included those of CN II, III, V, and VI, with presenting symptoms of diplopia, decreased visual acuity, and facial numbness and/or pain. Thirteen lesions were cavernous segment ICA aneurysms, whereas the remainder included supraclinoid and petrous segment ICA, posterior communicating artery, and basilar trunk aneurysms. At an average clinical follow-up of 9.55 months, 15 patients (75%) had resolution or significant improvement of their cranial neuropathies, and the remaining 5 had stable symptoms. Of the 18 patients with angiographic follow-up, 12 (66.7%) demonstrated complete obliteration or small neck residual, whereas 6 (33.3%) had residual lesion. Patients with complete or near-complete obliteration of their lesion were significantly more likely to demonstrate symptomatic improvement at follow-up (P = 0.009). Two patients with persistent symptoms were eventually treated with microsurgical bypass. Transient complications in this series included 6 extracranial hemorrhagic complications (30%) related to dual-antiplatelet therapy, all of which were managed medically. There was 1 delayed right ICA occlusion after retreatment that led to microsurgical bypass. Conclusions: Intracranial aneurysms presenting with 1 or more CN palsies show a high rate of clinical improvement after treatment with the PED. Clinical outcomes must be weighed against the risks and challenges faced with flow diverters. Further research is warranted for patients whose symptoms do not respond optimally to device placement.

Benefit Transfer: Insights from Choice Experiments

Abstract: In this chapter we explore six key reasons for the close alignment of choice modeling (CM) experiments with benefit transfer applications. Of these six, some relate to the richness of value estimate output that is generated in CM applications, whereas others involve the insights into choice behavior and the nature of preferences that are gained through the use of the technique. These outcomes improve the accuracy of the benefit transfer process and also provide more verification and confidence in the results. An additional focus of the chapter is to explore the tension between improving the accuracy and insights from CM on the one hand against, on the other, the need to make benefit transfer practical and operational. Although there is an extensive literature on the development and operation of the CM technique, it is not practical to cover this in a single chapter; instead the focus here is on the aspects of CMs that offer the most insight into benefit transfer processes.

Applied Benefit Transfer: An Australian and New Zealand Policy Perspective

Abstract: This chapter provides an introduction to and review of the use of benefit transfer approaches and data within Australasian policy making. The focus is on applications within the last two decades and the role of transfer methods within legal, policy and institutional structures. While there has been substantial interest in benefit transfer, the number of practical applications remains limited in both Australia and New Zealand . The limited pool of primary valuation studies and challenges in value transfer has meant that to date, understanding about the validity and reliability of benefit transfer and the development of protocols to guide its use are still limited. Nonetheless, recent major policy issues and controversies such as conservation of the Great Barrier Reef and management of water in the Murray-Darling Basin have led to an increase in applications of benefit transfer, and also to the potential for misuse. Included in this chapter is a discussion of the acceptance of benefit transfer approaches for various applications, the prevalence of benefit transfer, and the legal role of benefit transfers within Australasian policy analysis. The chapter will also highlight the potential for benefit transfer to make benefit- cost analysis more useful to policy makers and more easily evaluated within Australasian policy contexts. The need for more work to provide confidence around processes and results is assessed.

Arrested Pneumatization of the Sphenoid Sinus on Large Field-of-View Cone Beam Computed Tomography Studies

Abstract: Arrested pneumatization of the sphenoid sinus is a normal anatomical variant The aim of this report is to define cone beam computed tomography (CBCT) characteristics of arrested pneumatization of sphenoid sinus in an effort to help differentiate it from invasive or lytic skull base lesions Two cases are presented with incidental findings Both studies, acquired for other diagnostic purposes, demonstrated unique osseous patterns that were eventually deemed to be anatomic variations in the absence of clinical signs and symptoms although the pattern of bone loss and remodeling was diagnosed as pneumatization of the sphenoid sinus by a panel of medical and maxillofacial radiologists following contrasted advanced imaging It is important to differentiate arrested pneumatization of the sphenoid sinus from lesions, such as arachnoid granulations, acoustic neuroma, glioma, metastatic lesions, meningioma, or chordoma, to prevent unnecessary biopsies or exploratory surgeries that would consequently reduce treatment costs and alleviate anxiety in patients

Valuing access to biological collections with contingent valuation and cost-benefit analysis

Abstract: Biological collections may be underutilised because of transaction costs incurred in their use. One way to reduce transaction costs and foster greater utilisation of biological collections that could benefit society is through the creation of a virtual central database of biological collections, available online. The objective of this paper is to estimate the benefits of this policy change using a dichotomous choice contingent valuation survey of the primary users of biological collections. Marginal willingness to pay (WTP) for access to a new central database linking collections around Australia was investigated through an annual user fee payment vehicle. The mean WTP of direct users of the proposed program was Australian dollar (A$) 149 per annum (95% confidence interval of $102–$348). We conducted a cost–benefit analysis of the proposal, showing that the aggregate benefits are likely to outweigh the total costs of setting up and maintaining the database in the longer term. These findings are useful for...

Challenges in Including BCA in Planning Approval Processes: Coal Mine Projects in New South Wales, Australia

Abstract: A requirement for project proponents to include a benefit-cost analysis (BCA) as a component of their environmental impact assessments is implied in planning approval legislation in New South Wales, Australia. Fulfilling that requirement in the context of three large-scale expansions of coal mines has led to the application of choice modeling to estimate values for the main environmental, social, and heritage impacts. A number of particular issues have emerged in those applications: the framing of choice sets so that incentive-compatible willingness-to-pay questions are asked; the inclusion of “existence values” associated with employment opportunities provided by mines; and the incorporation of environmental offsets as part of the choice task given to respondents. The benefit-cost analyses of the coal mining projects have proven controversial. While the government agency responsible for administering the project approval process has used them as an input to decision-making, in some cases its recommendations have been “over-ridden” by the imposition of subjectively determined administrative rules. In one case, an appeal through legal channels against an approval was successful in part because the judge who heard the appeal dismissed the BCA findings because it was contrary to his own viewpoint of the merits of the case. In response, the state government has introduced legislation that requires greater “weight” to be given to the development benefits of coal mining. These responses have left the role of BCA and nonmarket valuation in the decision-making process in “limbo,” with practitioners and policy makers unsure as to the future of the methods in politically charged contexts.

Protecting the Environment, Privately

Abstract: Most volumes in the environmental economics literature consider the environment to be a public good and hence write out a role for the private sector in a source of supply. Yet there is ample evidence of the private sector being involved, driven both by profit and altruism. This book provides the necessary conceptual base for the inclusion of the private sector in the environmental protection supply equation and deliver an extensive set of examples in a wide range of contexts. In an economic climate where governments are attempting to reduce expenditures, the increased role for the private sector will be readily embraced by policy makers. The aim of the book is to establish the principles of markets in the provision of environmental protection and to provide an extensive experience-based set of contexts in which the private sector has acted to enhance the supply of environmental goods and services. These contexts include both pure-private sector initiatives in terrestrial, aquatic and marine ecosystems and public-private sector ‘joint initiatives’ such as payment for environmental services (PES) schemes.

Post-cyclone emergency services: a cost–benefit analysis for Cairns, Australia

Abstract: If scarce community resources for emergency services are to be allocated efficiently from a social perspective, decision-makers should be informed by social cost–benefit analysis (CBA). However, this is rarely, if ever, the case in Australia. One reason may be the challenge of estimating benefits that are not provided fully by private markets. In a case study of post-cyclone emergency services in Cairns, Australia, we employ Choice Modelling to estimate the willingness to pay of households for a set of publicly supplied emergency services. Accelerated reconnection of utilities like sewerage and electricity is the most highly valued, about three times as much as faster resupply of fresh food, while additional police patrols are far less valued and accommodation for pets negatively so. These results are reflected in a standard, deterministic CBA that suggests that all but pet accommodation should be publicly provided. However, Monte Carlo analysis incorporating variability in estimates of costs and benefits resulted in lower mean expected levels of Net Present Values, a salutary reminder that deterministic estimates may not be appropriate in circumstances of uncertainty about costs and benefits.

Safety, Tolerability, and Efficacy of Rituximab in the Treatment of Multiple Sclerosis: 285 Patients Treated in a Single Center. (P3.262)

Abstract: OBJECTIVE: To assess the safety, tolerability and efficacy of rituximab treatment in multiple sclerosis (MS) in a clinical setting. BACKGROUND: Phase II studies suggest a therapeutic effect of drugs targeting CD20+ B-cells such as rituximab in MS. The safety and efficacy of these medications beyond one year has not been described in MS. METHODS: Retrospective chart review of MS patients at the University of Colorado Denver MS Center who have received treatment with rituximab. Clinical information was collected including demographic information, laboratory data, clinical relapses, MRI lesions, and infusion reactions. RESULTS: 285 patients were treated with rituximab, including 200 patients treated with 蠅2 courses with a median duration of 18 months (range from 6-72 months). The median age was 45.8 years (15-79 years); 67.5[percnt] were women; 83.2[percnt] were Caucasian. Patients had a mean duration of disease of 11 years and had been previously treated with a median of 2 disease modifying treatments. 66.2[percnt], 20.3[percnt], and 13.5[percnt], were diagnosed with relapsing remitting, secondary progressive, and primary progressive MS, respectively. The majority of patients were treated with 1gram initially with subsequent courses of 500mg every 6 months. 18 of 185(9.7[percnt]) patients reconstituted their CD20+ cells (>1[percnt]) prior to their next infusion. 19[percnt] of patients reported minor first dose infusion-related reactions (7[percnt] with follow up courses). 81.6[percnt] had positive JC serology prior to infusion with no cases of progressive multifocal leukoencephalopathy. Two patients experienced 3 clinical relapses. Seven of 140 patients(5[percnt]) with subsequent MRIs demonstrated new T2 lesions with no enhancing lesions seen. Three patients had neutropenic fevers attributable to rituximab. CONCLUSIONS: Rituximab was well tolerated and safe for the treatment of MS in our single center clinical setting. Although this is a retrospective study, rituximab was extremely effective at reducing relapses in MS with minimal clinical relapses or new MRI activity. Disclosure: Dr. Seibert has nothing to disclose. Dr. Blackburn has nothing to disclose. Dr. Vollmer has nothing to disclose. Dr. Bennett has received personal compensation for activities with Teva Neuroscience, EMD Serono, and Biogen Idec as a speaker and/or consultant. Dr. Corboy has received personal compensation for activities with ProCE, Celgene, Teva, Novartis, and Biogen Idec. Dr. Miravalle has nothing to disclose. Dr. Schreiner stands to receive personal compensation for activities with Teva Neuroscience. Dr. Vollmer has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Genentech, Inc., Novartis, Ono Pharmaceutical, Teva Neuroscience, and XenoPort as a consultant. Dr. Alvarez has received personal compensation for activities with Teva Neuroscience.

Projectile embolization to the left femoral artery with stroke following gunshot wound to the chest.

Abstract: Missile embolization is a rare phenomenon with most cases reported in the literature as a consequence of direct or indirect vascular trauma. Despite their characterization as toys, traumatic injuries from pellet guns are associated with significant rates of morbidity related to their vascular and neurological complications. We present a 9-year-old boy who was shot in the chest with a pellet gun and suffered a femoral arterial occlusion and a delayed stroke in the middle cerebral arterial distribution.