Kieran Murphy

A review of complications associated with vertebroplasty and kyphoplasty as reported to the food and drug administration medical device related web site

In 2002, approximately 38,000 vertebroplasties and 16,000 kyphoplasties were performed in the United States. As the use of both modalities for the treatment of vertebral compression fractures has increased, so have questions regarding safety and efficacy. The authors addressed this by reviewing both the current literature and complications data reported to the Food and Drug Administration (FDA) Center for Devices and Radiological Health through the on-line database (http://www.fda.gov/cdrh/maude.html) and through the Office of the Freedom of Information Act at the FDA. Although both procedures are largely safe, the FDA data highlight two main concerns: reactions to the use of acrylic (polymethylmethacrylate) bone cement, including hypotension and, in some cases, death, especially when multiple vertebral levels are treated in one setting; and a possible increased risk with kyphoplasty of pedicle fracture and cord compression.

Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm

Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B) was differentially expressed in aneurysmal samples (n=44) as compared to control samples (n=16) (false discovery rate adjusted p-value=0.023). We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.

Local Intraarterial Fibrinolysis Administered in Aliquots for the Treatment of Central Retinal Artery Occlusion. The Johns Hopkins Hospital Experience

Background and Purpose— Central retinal artery occlusion results in acute visual loss with poor spontaneous recovery. Current standard therapies do not alter the natural history of disease. Several open-label clinical studies using continuous infusion of thrombolytic agents have suggested that local intraarterial fibrinolysis (LIF) is efficacious in the treatment of central retinal artery occlusion. The aim is to compare the visual outcome in patients with acute central retinal artery occlusion of presumed thromboembolic etiology treated with LIF administered in aliquots with that of patients treated with standard therapy. Methods— We conducted a single-center, nonrandomized interventional study of consecutive patients with acute central retinal artery occlusion from July 1999 to July 2006. Results— Twenty-one patients received LIF and 21 received standard therapy. Seventy-six percent of subjects in the LIF group had a visual acuity improvement of one line or more compared with 33% in the standard therapy group (P=0.012, Fisher exact). Multivariate logistic regression controlling for gender, history of prior stroke/transient ischemic attack, and history of hypercholesterolemia showed that patients who received tissue plasminogen activator were 36 times more likely to have improvement in visual acuity (P=0.0001) after adjusting for these covariates. Post hoc analysis showed that patients who received tissue plasminogen activator were 13 times more likely to have improvement in visual acuity of 3 lines or more (P=0.03) and 4.9 times more likely to have a final visual acuity of 20/200 or better (P=0.04). Two groin hematomas were documented in the LIF group. No ischemic strokes, retinal or intracerebral hemorrhages were documented. Conclusions— LIF administered in aliquots is associated with an improvement in visual acuity compared with standard therapy and has few side effects.

The Chemistry of Acrylic Bone Cements and Implications for Clinical Use in Image-guided Therapy

Advances in image-guided therapy for vertebral fractures and other bone-related disorders have made acrylic bone cement an integral part of the interventional armamentarium. Unfortunately, information on the properties and chemistry of these compounds is mostly published in the biomaterial sciences literature, a source with which the interventional community is generally unfamiliar. This review focuses on the chemistry of bone cement polymerization and the properties of components in polymethylmethacrylate (PMMA)-based polymers, the most commonly used bone cements in interventional procedures such as percutaneous vertebroplasty. The effects of altering the concentration of components such as methylmethacrylate monomers, PMMA beads, benzoyl peroxide activator, N,N-dimethyl-p-toluidine (DMPT) initiator, and radiopacifiers on the setting time, polymerization temperature, and compressive strength of the cement are also considered. This information will allow interventional radiologists to manipulate bone cement characteristics for specific applications and maximize the clinical potential of image-guided interventions.

Intraoperative localization of thoracic spine level with preoperative percutaneous placement of intravertebral polymethylmethacrylate.

Objective To evaluate the safety and utility of preoperative vertebroplasty for intraoperative localization of thoracic spinal levels. Summary of Background Data Intraoperative fluoroscopy or plain radiographs are traditionally used to localize thoracic spine levels during thoracic spine operations. Unfortunately, such localization can occasionally be difficult in the midthoracic levels due to lack of landmarks, scapular shadows, and the body habitus of the morbidly obese. There are multiple techniques described in the literature that allow for preoperative localization of thoracic spinal levels during approaches to the posterior thoracic spine. For efficient and accurate intraoperative localization of thoracic spinal levels during anterior thoracic spine procedures, we describe a method that uses preoperative percutaneous placement of polymethylmethacrylate (PMMA) into the vertebral body using standard vertebroplasty technique. Methods Four patients with morbid obesity and symptomatic thoracic disc herniations underwent preoperative vertebroplasty procedures using standard percutaneous techniques. The PMMA cement was used to expeditiously identify thoracic spinal levels of interest using intraoperative fluoroscopy. Results All 4 patients underwent successful vertebroplasty procedures without complications. The PMMA cement was easily identified intraoperatively and led to the correct identification of the thoracic spinal levels of interest. Conclusions Preoperative placement of PMMA into thoracic vertebral bodies using standard vertebroplasty technique provides a safe, efficient, and reliable method of localizing thoracic spine levels intraoperatively. Such procedures can be performed in the outpatient setting and can be associated with extremely low morbidity when done by experienced practitioners. This procedure should be reserved for patients in whom a surgeon anticipates difficulty using standard radiographs or fluoroscopy to localize thoracic spinal levels intraoperatively.

Local delivery of ibuprofen via controlled-release polymers prevents angiographic vasospasm in a monkey model of subarachnoid hemorrhage

OBJECTIVE: Adhesion and migration of leukocytes into the periadventitial space play a role in the pathophysiology of vasospasm after subarachnoid hemorrhage (SAH). Intercellular adhesion molecule-1 is a determinant cell adhesion molecule involved in this process. Ibuprofen has been shown to inhibit intercellular adhesion molecule-1 upregulation and prevent vasospasm in animal models of SAH. In this study, we report the toxicity and efficacy of locally delivered ibuprofen incorporated into controlled-release polymers to prevent vasospasm in a monkey model of SAH. METHODS: Ibuprofen was incorporated into ethylene-vinyl acetate (EVAc) polymers at 45% loading (wt:wt). For the toxicity study, cynomolgus monkeys (n = 5) underwent surgical implantation of either blank/EVAc polymers (n = 3) or 45% ibuprofen/EVAc polymers (n = 2) in the subarachnoid space, were followed up for 13 weeks, and were killed for histopathological analysis. For the efficacy study, cynomolgus monkeys (n = 14) underwent cerebral angiography 7 days before and 7 days after surgery and SAH and were randomized to receive either a 45% ibuprofen/EVAc polymer (n = 7; mean dose of ibuprofen, 6 mg/kg) or blank EVAc polymers (n = 7) in the subarachnoid space. Angiographic vasospasm was determined by digital image analysis. Student’s t test was used for analysis. RESULTS: Animals implanted with ibuprofen polymers showed no signs of local or systemic toxicity. Animals treated with ibuprofen polymers had 91 ± 9% lumen patency of the middle cerebral artery, compared with 53 ± 11% of animals treated with blank/EVAc polymers (P < 0.001). CONCLUSION: Ibuprofen polymers are safe and prevent angiographic vasospasm after SAH in the monkey model. These findings support the role of cell adhesion molecules and inflammation in the pathophysiology of vasospasm.

Training and pretreatment planning of interventional neuroradiology procedures--initial clinical validation.

A PC based system for simulating image-guided interventional neuroradiological procedures for physician training and patient specific pretreatment planning is described. The system allows physicians to manipulate and interface interventional devices such as catheters, guidewires, stents and coils within 2-D and hybrid surface and volume rendered 3-D patient vascular images in real time. A finite element method is employed to model the interaction of the catheters and guidewires with the vascular system. Fluoroscopic, roadmapping and volume rendered 3-D presentations of the vasculature are provided. System software libraries allow for the use of commonly employed catheters, guidewires, stents and occluding coils of various shapes and sizes. The results of an initial clinical validation suggest that the experience gained from our simulator is comparable with that of using a vascular phantom. We are conducting further validation with the aim of providing patient specific pretreatment planning.

Embolization of bronchial arteries with N-butyl cyanoacrylate for management of massive hemoptysis: a technical review.

N-butyl cyanoacrylate (NBCA) is an adhesive material, which has been used as an embolic agent in various vascular beds. Its role in the management of patients with acute massive hemoptysis has not been reported. In this article we report our experience with 12 such patients who underwent bronchial artery embolization using NBCA and compare the results with 36 procedures using polyvinyl alcohol (PVA) particles. As compared with PVA, NBCA embolizations appear more durable, leading to fewer rebleeds. There were 12 episodes of recurrent hemoptysis after 36 procedures using PVA (33%) with 8 being due to bleeding from a previously embolized vessel. Conversely, there were only 2 of the 12 patients who were treated by NBCA who experienced rebleed (16.6%). In this article, we describe the technical nuances of NBCA embolization of bronchial arteries and review potential pitfalls.

Unilateral mydriasis without ophthalmoplegia-A sign of neurovascular compression?: Case report

OBJECTIVE: We aimed to demonstrate the use of neuroimaging studies in vascular compression of the oculomotor nerve. CLINICAL PRESENTATION: A 24-year-old woman was noted by her dentist to have anisocoria, with the left pupil being larger than the right. After detailed ophthalmologic and neurological examination, we proceeded to peform neuroimaging. T2-weighted images (2 mm) and constructive interference in steady-state (0.3 mm) images were utilized. INTERVENTION: Magnetic reasonance imaging showed that duplicated left superior cerebellar artery, a prominent posterior communicating artery, and a posterior cerebral artery combined to compress the superomedial portion of the left oculomotor nerve. CONCLUSION: With continued improvements in neuroimaging, we think that more cases of isolated cranial neuropathies previously labeled as “idiopathic” will be shown to result from vascular compression.

CT Fluoroscopically Guided Percutaneous Placement of Transiliosacral Rod for Sacral Insufficiency Fracture: Case Report and Technique

SUMMARY: Treatment of sacral insufficiency fractures (SIFs) has traditionally been conservative, but several patients have been treated with percutaneous sacroplasty. Unfortunately, in the setting of severe, bilateral SIFs, cement may not withstand shear forces present at the lumbosacral junction, and surgical hardware may not provide adequate fixation in osteoporotic, cancellous bone of the sacrum, leading to eventual pseudarthrosis. Thus, we propose a novel technique in which guidance with CT fluoroscopy allows placement of a transiliosacral bar in conjunction with sacroplasty.