1-hexyl n-cyanoacrylate compound (Neucrylate™ AN), a new berry aneurysm treatment. II. Rabbit implant studies: technique and histology.

INTRODUCTION: Following satisfactory benchtop testing of a new liquid embolic agent, animal implant studies were performed. MATERIALS AND METHOD: Elastase aneurysms were created in the right common carotid artery of New Zealand rabbits under approved institutional guidelines. Using direct fluoroscopic control and commercially available microcatheters, the device was introduced into the aneurysms. At 2 months, 12 months and 24 months, follow-up angiography was performed and analyzed. The animals were sacrificed, the brachiocephalic arteries were explanted and fixed, and the histologic appearance of the treated aneurysms was evaluated. RESULTS: The Neucrylate polymerized into an open pore elastic sponge. The open pores permitted fibrous tissue ingrowth. By 2 months, all of the aneurysm necks had been covered by fibrous tissue and a neointima. Two of the aneurysms originally inadequately filled allowed opportunity for retreatment. The reactive change within the aneurysms demonstrated fibroblastic proliferation, collagen and some giant cells but no vascular necrosis. Results at 2 months, 12 months and 24 months were for all practical purposes similar. CONCLUSION: The lack of necrosis, the mild inflammatory response and the permanence of the implant are interesting in a cyanoacrylate based embolic agent, especially in light of the experience with lower chain homologs and other liquid embolic agents.

1-Hexyl n-cyanoacrylate compound (Neucrylate™ AN), a new berry aneurysm treatment. I. Theoretical basis and laboratory evaluation.

PURPOSE: To develop and optimize a system for treating cerebral berry aneurysm using a new polymer based liquid embolic agent. MATERIALS AND METHODS: Using a variety of human corrosion casting aneurysm replicas placed in a circuit of pulsatile flowing blood, techniques were developed to optimize aneurysm filling and recreate good blood flow dynamics. As part of this effort, both experienced physicians and lay personnel were asked to treat these replicas to discover common failure modes. Additional surgically created aneurysms in dog carotid arteries were treated by experienced physicians. RESULTS: Physicians experienced in the use of microcatheters and endovascular techniques learned to use the device effectively after, on average, five aneurysm treatments. In the dog aneurysms, all were treated to complete filling.

Over-the-catheter retrieval of a retained microcatheter following Onyx embolization: a technical report.

BACKGROUND: Brain arteriovenous malformations are vascular lesions that are increasingly being treated with endovascular embolization. A potential complication with endovascular embolization is microcatheter entrapment within the embolic material. In the present report, a novel technique for the retrieval of microcatheters retained during Onyx embolization of intracranial lesions is described. CLINICAL PRESENTATION: Two patients (one boy and one girl, aged 13 and 15 years, respectively) with arteriovenous malformations (one unruptured, one ruptured; Spetzler-Martin grades 4 and 3) presented for embolization. INTERVENTION: During Onyx 18 embolization of the arteriovenous malformations, Echelon-10 microcatheters became entrapped into the arterial feeders by casts of the Onyx. Initial attempts to remove the microcatheters by traction were unsuccessful. The hubs of the microcatheters were transected and Concentric Medical Outreach distal access catheters were then advanced over the microcatheters and positioned at the proximal aspects of the microcatheter-Onyx plugs. Using the Outreach catheters for countertraction, the Echelon-10 microcatheters were then successfully released from the Onyx plugs under fluoroscopic visualization without significant distortion of the arteries. There were no complications related to the microcatheter extractions. CONCLUSIONS: A novel technique, which may be useful in the removal of retained microcatheters during Onyx embolization of Brain arteriovenous malformations, is presented.

1-hexyl-2-cyanoacrylate compound (Neucrylate) bactericidal properties.

INTRODUCTION: The need for medical grade tissue adhesives both in surgery and to treat trauma has become well established. Such a device has been developed and preliminary toxicity testing completed on a compounded cyanoacrylate (Neucrylate), and its properties have been modified so it may be used as an intravascular embolic agent. Given the high incidence of iatrogenic infections in hospital, it would be desirable to have such an implantable device that inhibits dangerous bacteria. MATERIALS AND METHOD: Seven separate cultures of common bacteria were grown and exposed to Neucrylate. The impact on the exposed microorganisms was analyzed visually as well as by means of fluorescence and optical microscopy. RESULTS: The device produced high degrees of antibacterial effect when exposed to gram positive bacteria whereas it had modest impact on gram negative bacteria.

Can a self-expanding aneurysm stent be clipped? Emergency proximal control options for the vascular neurosurgeon.

BACKGROUND: If a self-expanding stent has been placed during endovascular treatment of an aneurysm and subsequently an open aneurysm surgery becomes necessary in the same or an adjacent area, is it possible and safe to obtain proximal control by placing a temporary clip on the artery at a point where it contains the stent? OBJECTIVE: To evaluate the effect of temporary clip application to 3 separate stent systems in an in vitro flow model with the stated hypothesis that clip application to these stents will result in permanent stent deformation. METHODS: This is an in vitro flow model study using an accepted synthetic blood vessel substitute. The Neuroform(3) (Boston Scientific), Enterprise (Cordis/Codman), and Pipeline (ev3) stents were deployed within the flow model; temporary clips were applied; and angiographic measurements subsequently made. RESULTS: Two 4 × 30-mm Neuroform(3) stents, two 4.5 × 28-mm Enterprise stents, and two 3.75 × 20-mm Pipeline stents were successfully deployed and clipped repeatedly (4 iterations). Two- and 3-dimensional angiograms were obtained. After repeated clip occlusion, the Neuroform(3) and Enterprise stents returned to their original configuration and diameter. Clip application to both also resulted in immediate flow arrest. In contrast, initial clip application to the Pipeline stents did not result in flow arrest, but the second single clip application did. The Pipeline stents were also irreversibly deformed after the experimental protocol, with an average luminal diameter reduction of 26.85% (P < .05). CONCLUSION: The Neuroform(3) and Enterprise stents responded favorably to temporary clip application, returning to their original diameter after clip removal and showing no sign of permanent structural modification. The Pipeline flow-diverting stent, however, was irreversibly deformed by clip application. These data indicate that temporary clip application to certain stents is possible. Further in vivo study is required.

Endovascular treatment of extensive cerebral sinus thrombosis.

Cerebral venous and sinus thrombosis is an uncommon but potentially lethal event. Although thrombosis accounts for only 1% of all strokes, if it is left untreated patients suffer from continuing headaches, vague neurological complaints, and may even progress to coma and death. New endovascular techniques and technology allow the possibility of more aggressive thrombolysis and thrombectomy in the setting of acute thrombosis. The authors present a case of recanalization of an extensive cerebral thrombosis using a new endovascular retrieval device.

A parametric model for studies of flow in arterial bifurcations.

Regional differences in hemodynamic loads on arterial walls have been associated with localized vascular disease such as atherosclerosis and cerebral aneurysms. Due to their intrinsic geometric relevance, three-dimensional (3D) reconstructions of arterial segments are frequently used in hemodynamic studies of these diseases. However, it is not possible to use them to systematically vary geometric features for parametric studies. Idealized vascular models are inherently suited for parametric studies, but are limited by their tendency to oversimplify the vessel geometry. In this work, a hierarchy of three parametric bifurcation models is introduced. The models are relatively simple, yet capture all geometric features identified as common to cerebral bifurcations in the complex transition from parent to daughter branches. While these models were initially designed for parametric studies, we also evaluate the possibility of using them for 3D reconstruction of cerebral arteries, with the future goal of improving reconstruction of poor quality clinical data. The lumen surface and vessel hemodynamics are compared between two reconstructed cerebral bifurcations and matched parametric models. Good agreement is found. The average and maximum geometric differences are less than 3.1 and 10%, respectively for all three parametric models. The maximum difference in wall shear stress is less than 8% for the most complex parametric model.

Stenting of vertebral artery origin atherosclerosis in high-risk patients: bare or coated? A single-center consecutive case series.

UNLABELLED: Atherosclerotic disease of the vertebrobasilar vessels is an important cause of posterior circulation infarction. Commonly, the primary atheroma forms at the origin of the vertebral arteries. We have recently treated 12 high-risk patients with dilatation and stenting of symptomatic vertebral-origin disease and report our technique and results. METHODS: Twelve patients with proximal vertebral stents placed between 1999-2005 were identified from a computerized registry of 3,046 records. All patients had high-grade origin stenoses, symptoms of cerebral ischemia and the following additional risk factors: 6 had contralateral vertebral occlusions; 1 had bilateral carotid occlusion; 2 had combined subclavian/vertebral-origin disease. After treatment, all patients were monitored with ultrasound and angiography and were aggressively managed for vascular disease risk factors. RESULTS: Patients had: hyperlipidemia, 90%; hypertension, 80%; tobacco use, 70%; homocysteine > 10, 50%; coronary disease, 40%; diabetes mellitus, 20%. No deaths or procedural complications occurred during the neurointerventional procedures. Drug-eluting stents (tacrolimus) were used in the last 5 cases. Three of the 7 patients treated with uncoated stents developed restenosis. Angioplasty for restenosis was durable in 2. One patient developed asymptomatic occlusion of her bare-metal stent. None of the patients treated with tacrolimus stents had recurrence of stenosis (p = 0.08). One patient died from pharyngeal cancer at 8 months, and 1 from lung cancer at 17 months. CONCLUSIONS: In high-risk patients with vertebralorigin disease, stenting demonstrated a low procedural complication rate, a moderate restenosis rate, good long-term patency and good longterm stroke-free survival. Placement of drug-eluting stents appears to reduce in-stent restenosis.

Rapid clot removal for acute stroke therapy: technical case report.

OBJECTIVE: Endovascular therapy for acute ischemic stroke offers hope to those patients who do not meet the strict inclusion criteria for intravenous tissue plasminogen activator. Because no approach or device can be optimal for every patient, it is desirable to have options. This case is the first report on a novel retrieval device which proved to be very effective in our patient. CLINICAL PRESENTATION: A 69-year-old woman with an acute ischemic stroke was excluded from treatment with intravenous tissue plasminogen activator because of an elevated international normalized ratio. INTERVENTION: We successfully treated this patient endovascularly using a device newly approved by the Food and Drug Administration. We achieved rapid recanalization and an excellent clinical outcome. CONCLUSION: Using a new retrieval device, we were able to rapidly and successfully treat an acute ischemic stroke in a patient not eligible for intravenous thrombolysis. This may offer another alternative in endovascular acute stroke therapy.

Development of spontaneous intracranial hypotension concurrent with grade IV mobilization of the cervical and thoracic spine: a case report.

Spontaneous intracranial hypotension (SIH) has been clinically defined as the development of severe orthostatic headaches caused by an acute cerebrospinal fluid (CSF) leak. Typically, intracranial hypotension occurs as a complication of lumbar puncture, but recent reports have identified cases caused by minor trauma. We report a case of SIH secondary to a dural tear caused by a cervical and thoracic spine mobilization. A 32-year-old woman with SIH presented with severe positional headaches with associated hearing loss and C6-8 nerve root distribution weakness. CSF opening pressure was less than 5cmH(2)O and showed no abnormalities in white blood cell count. Cranial, cervical, and thoracic magnetic resonance imaging revealed epidural and subdural collections of CSF with associated meningeal enhancement. Repeated computed tomography myelograms localized the leak to multiple levels of the lower cervical and upper thoracic spine. A conservative management approach of bedrest and increased caffeine intake had no effect on the dural tear. The headache, hearing loss, and arm symptoms resolved completely after 2 epidural blood patches were performed. Practitioners performing manual therapy should be aware of this rare, yet potential complication of spinal mobilizations and manipulations.

Stereolithographic vascular replicas from CT scans: choosing treatment strategies, teaching, and research from live patient scan data.

Our goal was to develop a system that would allow us to recreate live patient arterial pathology by using an industrial technique known as stereolithography (or rapid prototyping). In industry, drawings rendered into dicom files can be exported to a computer programmed to drive various industrial tools. Those tools then make a 3D structure shown by the original drawings. We manipulated CT scan dicom files to drive a stereolithography machine and were able to make replicas of the vascular diseases of three patients.

Aneurysmal pressure changes with nondetachable balloon placement and fluid infusion: rationale for liquid embolization.

BACKGROUND AND PURPOSE: To improve the safety and efficacy of liquid embolization, we evaluated changes in pressures in experimental aneurysms. METHODS: We created three replicas of a lateral sidewall aneurysm and placed them in a physiologic flow circuit. A 3 x 10-mm nondetachable balloon was positioned in the parent vessel across the aneurysmal neck. Intra-aneurysmal pressures were measured at baseline and after balloon inflation. Fluid was infused into the sac via a 1.45F microcatheter during inflation, and maximal pressures were noted. Measurements were repeated eight times in each aneurysm. RESULTS: After balloon inflation, average intra-aneurysmal pressures increased: 12 mm Hg (13%, sigma(n - 1) = 0.46) for aneurysm 1 (baseline mean arterial pressure [MAP], 94 mm Hg), 15 mm Hg (58%, sigma(n - 1) = 0.88) for aneurysm 2 (baseline MAP, 26 mm Hg), and 15 mm Hg (58%, sigma(n - 1) = 0.92) for aneurysm 3 (baseline MAP, 26 mm Hg). During inflation and infusion, pressures increased slightly: 1.1 (0.94%, sigma(n - 1) = 0.64), 1.6 (3.9%, sigma(n - 1) = 1.1), and 1.9 (4.6%, sigma(n - 1) = 1.2) mm Hg for aneurysms 1, 2, and 3, respectively. Despite complete balloon occlusion of the distal aneurysmal neck, a channel between the proximal aneurysmal neck and the parent-vessel lumen persisted along the microcatheter. Fluid exited the sac via this channel, preventing a concomitant, significant increase in pressure during infusion. CONCLUSION: Intra-aneurysmal pressure modestly increased with inflation of a parent-vessel balloon across the neck. When liquid was infused into the sac during inflation, further increases were minimal.

Rapid prototyping to create vascular replicas from CT scan data: making tools to teach, rehearse, and choose treatment strategies.

Our goal was to develop and prove the accuracy of a system that would allow us to re-create live patient arterial pathology. Anatomically accurate replicas of blood vessels could allow physicians to teach and practice dangerous interventional techniques and might also be used to gather basic physiologic information. The preparation of replicas has, until now, depended on acquisition of fresh cadaver material. Using rapid prototyping, it should be able to replicate vascular pathology in a live patient. We obtained CT angiographic scan data from two patients with known arterial abnormalities. We took such data and, using proprietary software, created a 3D replica using a commercially available rapid prototyping machine. From the prototypes, using a lost wax technique, we created vessel replicas, placed those replicas in the CT scanner, then compared those images with the original scans. Comparison of the images made directly from the patient and from the replica showed that with each step, the relationships were maintained, remaining within 3% of the original, but some smoothing occurred in the final computer manipulation. From routinely obtainable CT angiographic data, it is possible to create accurate replicas of human vascular pathology with the aid of commercially available stereolithography equipment. Visual analysis of the images appeared to be as important as the measurements. With 64 and 128 slice detector scanners becoming available, acquisition times fall enough that we should be able to model rapidly moving structures such as the aortic root.

Aneurysm flow dynamics: alterations of slipstream flow for neuroendovascular treatment with liquid embolic agents.

BACKGROUND AND PURPOSE: The main issue with use of a liquid embolic agent is one of safety. To determine and improve the efficacy of potential neuroendovascular treatment regimens, particularly the use of liquid embolic agents, we evaluated the changes in aneurysm flow dynamics resulting from alterations of parent vessel flow. METHODS: We created silicone replicas of a laboratory-created aneurysm model and a basilar artery aneurysm cast from a human cadaver. Replicas were placed in a circuit of pulsatile non-Newtonian fluid, and flows were adjusted to simulate human physiologic flow velocity, profile, and volume. Individual fluid slipstreams were opacified with isobaric dyes. Images were obtained of the unaltered vascular replica; after placement of a nondetachable balloon in the parent vessel at multiple locations proximal to, across, and distal to the aneurysm neck; and after placement of a stent across the aneurysm neck. Aneurysms were then occluded with a cyanoacrylate liquid embolic agent in association with each device. RESULTS: In the unaltered replica, flow entered the distal aneurysm neck and impacted against the distal lateral aneurysm wall. Disturbed, but nonturbulent, flow then continued along the aneurysm wall in a vortex pattern and exited at the proximal aspect of the aneurysm neck. With the balloon partially inflated in the parent vessel, the slipstream velocity increased. This resulted in more rapid flow in the aneurysm sac, a less favorable condition for deposition of liquid embolic material. The effect was more pronounced with greater degrees of balloon inflation (resulting in greater parent vessel narrowing) and when the balloon was proximal to the aneurysm neck compared with more distal parent vessel positioning. Only with complete occlusion of the parent vessel lumen, either proximal to, across, or distal to the aneurysm sac, was there intraaneurysmal flow reduction (ie, stasis), a more favorable condition for liquid embolic material deposition. Also, with the balloon positioned across the aneurysm neck, not only did the liquid agent remain in the aneurysm sac, but also the surface could be molded to re-create a normal parent vessel lumen. A stent placed across the aneurysm neck caused the slipstreams to lose their coherence as they passed through the stent mesh. This prevented slipstream impact against the aneurysm sidewall and decreased the intraaneurysmal fluid velocity. During deposition of liquid embolic agent through the stent sidewall into the aneurysm sac, the stent mesh appeared to provide a barrier to passage of the embolic agent into the adjacent parent vessel, also a more favorable condition for liquid embolic material deposition. CONCLUSION: Knowledge of aneurysm flow dynamics and the changes incurred after endovascular parent vessel flow alteration provides a basis for safer aneurysm obliteration by using a liquid embolic agent with a neurointerventional technique.

Snare retrieval of intracranial thrombus in patients with acute stroke.

Intravenous or intraarterial thrombolysis of intracranial emboli is becoming an accepted clinical treatment modality for acute ischemic stroke, but not all emboli respond to the lytic drug regimens available today. If drug therapy fails, mechanical retrieval seems warranted. Four patients whose condition was resistant to intravenous and intraarterial thrombolytic drug treatment underwent at least partial clot removal with use of a snare, and almost immediate clinical improvement was noted. A fifth patient's clot was removed before lytic drugs were administered. All five patients, who presented with a sudden onset of stroke, were evaluated by arterial angiography; then, after a failed trial of intraarterial fibrinolytic drugs, they were treated by passing a 2- or 4-mm snare through a microcatheter. The snare wire was guided around the thrombus, gently brought back toward the microcatheter-but not into it-and the entire microcatheter and snare assembly was then removed. In four of the five cases, follow-up angiography performed immediately after the retrieval showed wider distal branches than normal. Follow-up computed tomography results were abnormal in all cases, showing hyperdense material in the territory that was previously ischemic. This hyperdensity subsided within 48 hours in all but one patient who developed small parenchymal hemorrhages; however, he remained asymptomatic. The snare device offers an additional or alternative therapy until completely effective thrombolytic agents become available. Although use of a snare is not ideal, device improvements should make the retrieval less technically challenging and more effective. There is a need for improved mechanical extraction devices, especially in light of the patient improvement that occurred. This experience also suggests that immediate removal of a mature clot could reduce the total time of brain ischemia more quickly than administration of thrombolytic drugs.

Reproducibility analysis of a new objective method for measuring arteriovenous malformation nidus size at angiography.

BACKGROUND AND PURPOSE: Currently, no specific method exists to measure arteriovenous malformation (AVM) nidus size, a requirement in assessing the success of treatment. Additionally, the commonly used evaluation provides only a linear one-dimensional measurement of this three-dimensional entity. The purpose of this study was to devise an improved method for measuring AVM nidus size, an irregularly shaped radiologic entity, that provides objective and reproducible results. METHODS: The procedure involved digitizing angiograms obtained before and after treatment, making the gray scale uniform, printing images on standard bond paper, delineating the nidus area, measuring the nidus area with a polar planimeter, and finally, correcting for geometric magnification. Three observers made the measurements. The corrected nidus areas were tabulated, and the mean, standard deviation, interobserver variability, and confidence intervals (CIs) were calculated. RESULTS: On both anteroposterior and lateral views, the Kendall coefficient of concordance (a measure of interobserver variability) was equal to 0.97, signifying excellent agreement. Additionally, these values were within the 95% CIs; this result showed that they were unlikely the result of chance. CONCLUSION: Precise measurements of an AVM nidus are required to properly analyze changes in the lesion after endovascular embolization (ie, to evaluate treatment success). Because of the irregular contours of an AVM nidus, measuring an area with planimetry, rather than with the usual linear dimensions, should yield more exact results.