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Ricardo A. Hanel, Alan S. Boulos, Eric G. Sauvageau, Elad I. Levy, Lee R. Guterman and L. Nelson Hopkins

Vertebrobasilar nonsaccular aneurysms represent a small subset of intracranial aneurysms and usually are among the most challenging to be treated. The aim of this article was to review the literature and summarize the experience in the treatment of these lesions with endovascular approaches. The method of stent implantation as it is performed at the authors' institution, including options available for vertebral artery access, is described. Practitioners involved in the treatment of these lesions should be aware of the potential application of intravascular stent placement as well as the associated postprocedure risks and potential complications.

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Elad I. Levy, Ricardo A. Hanel, Bernard R. Bendok, Alan S. Boulos, Mary L. Hartney, Lee R. Guterman, Adnan I. Qureshi and L. Nelson Hopkins

Object. Medically refractory symptomatic vertebrobasilar atherosclerotic disease has a poor prognosis. Studies have shown that longer (≥ 10 mm), eccentric, high-grade (> 70%) stenoses portend increased procedure-related morbidity. The authors reviewed their experience to determine whether a staged procedure consisting of angioplasty followed by delayed (≥ 1 month later) repeated angioplasty and stent placement reduces the morbidity associated with endovascular treatment of symptomatic basilar and/or intracranial vertebral artery (VA) stenoses.

Methods. The authors retrospectively reviewed the medical records in a consecutive series of eight patients who underwent planned stent-assisted angioplasty for medically refractory, symptomatic atherosclerotic disease of the intracranial posterior circulation between February 1999 and January 2002. Staged stent-assisted angioplasty was planned for these patients because the extent and degree of stenosis of the VA and/or basilar artery (BA) lesion portended an excessive procedure-related risk. The degree of stenosis, recent onset of symptoms (unstable plaque), vessel tortuosity, and lesion length and morphological features were contributing factors in determining procedure-related risk. Patient records were analyzed for location and degree of stenosis, preprocedural regimen of antiplatelet and/or anticoagulation agents, devices used, procedure-related complications, and clinical and radiographic outcomes.

Among the patients in whom staged stent-assisted angioplasty was planned, vessel dissection, which necessitated immediate stent placement, occurred during passage of the balloon in one of them. In a second patient, the stent could not be maneuvered through the tortuous VA. In a third patient, the VA and BAs remained widely patent after angioplasty alone, and therefore stent placement was not required. Significant complications among the eight patients included transient aphasia and hemiparesis in one and a groin hematoma that necessitated surgical intervention in another; there was no permanent neurological morbidity. The mean stenosis before treatment was 78%, which fell to 54% after angioplasty, and the mean residual stenosis after stent placement was 30%. At the last follow-up examination, none of the treated patients had further symptoms attributable to the treated stenosis.

Conclusions. The novel combination of initial angioplasty followed by delayed endoluminal stent placement may reduce the neurological morbidity associated with endovascular treatment of long, high-grade stenotic lesions. Attempting to cross high-grade stenoses with higher-profile devices such as stents may result in an embolic shower. Furthermore, neointimal proliferation and scar formation after angioplasty result in a thickened fibrous layer, which may be protective during delayed stent deployment. Larger-scale studies involving multiple centers are needed to elucidate further the lesion morphological characteristics and patient population most likely to benefit from staged procedures.

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Elad I. Levy, Alan S. Boulos, Ricardo A. Hanel, Fermin O. Tio, Ronald A. Alberico, Mary Duffy Fronckowiak, Balazs Nemes, Ann Marie Paciorek, Lee R. Guterman and L. Nelson Hopkins

Object. No animal model currently exists for the examination of time-dependent histological changes occurring in intracranial vessels after endoluminal stent placement. The authors' goal was to develop a reproducible in vivo model of stent implantation in intracranial vessels in dogs that was capable of demonstrating stent-related vascular changes after the implantation of coated and uncoated devices.

Methods. The authors implanted heparin-coated or uncoated stents in the basilar arteries (BAs) of 11 mongrel dogs. In a 12th animal, one coated stent was implanted in the BA and a second uncoated one was implanted in the distal anterior spinal artery. All the devices were oversized to induce intimal injury. Surviving animals were observed for 12 weeks, after which they underwent repeated angiography before planned death and removal of the brain. Histological studies and computer-assisted morphometric analyses were conducted on stent-treated and untreated sections of the BAs to assess the percentage of stenosis, neointimal proliferation, vessel injury, and inflammation. Perforating vessels partially covered by stent struts (“jailing”) were studied for evidence of stenosis or occlusion. The pathologist, interventionists, histopathologist, histopathology technicians, and radiologist were blinded to the stent type.

Seven stents (three uncoated and four coated) were removed from the six animals that were observed during the follow-up period. The mean neointimal proliferation was 0.42 mm2 in the group treated with uncoated stents and 0.18 mm2 in the group treated with heparin-coated devices (p = 0.04). Neointimal thickness was significantly increased in the group with uncoated stents (p = 0.04). The mean percentage of occlusion was less (12%) in the group with heparin-coated stents, compared with 22% in the group with uncoated devices (p = 0.07). When comparing results between the heparin-coated and uncoated devices implanted in the five animals that received a single stent only, greater differences (indicating a benefit from heparin-coated stents) were observed in neointimal area (p = 0.009), neointima/media ratio (p = 0.001), neointimal thickness (p = 0.002), and percentage of occlusion (p = 0.009). All brainstem perforating vessels covered by stent struts remained patent.

Conclusions. This in vivo intracranial stent model was developed to assess proliferative and inflammatory responses to endoluminal stent implantation in the cerebrovasculature. The results indicate that a lower percentage of occlusion occurs 12 weeks after implantation of heparin-coated compared with uncoated stents.

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Elad I. Levy, Ricardo A. Hanel, Jay U. Howington, Balazs Nemes, Alan S. Boulos, Fermin O. Tio, Ann Marie Paciorek, Shoaib Amlani, Kathleen S. Kagan-Hallett, Mary Duffy Fronckowiak, Lee R. Guterman and L. Nelson Hopkins

Object. Use of the sirolimus-eluting stent has led to a reduction of in-stent stenosis following treatment of coronary atherosclerosis, whereas treatment of intracranial atherosclerosis with bare-metal stents results in excessive restenosis rates of approximately 40%. Neurotoxicity effects and vessel injury are unknown in the cerebral vasculature. To assess the safety profile and vascular effects of sirolimus-coated stents, the authors conducted a prospective comparative study in which drug-eluting and bare-metal stents were implanted in the canine basilar artery (BA).

Methods. Sixteen mongrel dogs were randomized (eight animals per group) to receive either bare-metal 1.5 × 8—mm (six-cell) stents or sirolimus-eluting stents of the same dimensions. Interventionists, histopathologists, and histopathology technicians who participated in the study were blinded to the stent characteristics. Stents were implanted in the canine BA. Serial peripheral blood samples were obtained during the 1st week after implantation to determine the time-dependent serum concentration of sirolimus. Follow-up angiographic studies were performed 30 days after stent implantation to assess the effects of stent placement on the BA and brainstem perforating vessels. Explantation of the stent and BA was performed immediately after angiography by using a pressurized formalin fixation procedure. Histological and computer-assisted morphometric analyses of specimens obtained in each animal were performed.

Sirolimus could not be detected in peripheral blood samples obtained later than 24 hours posttreatment. On follow-up angiography, all perforating vessels observed on initial angiograms remained patent, and no evidence of parent vessel damage or pseudoaneurysm formation was observed. Explanted vessels and brainstem sections did not demonstrate evidence of histological neurotoxicity, such as gliosis or infarction. No significant differences were found in the time to endothelialization of bare-metal and sirolimus-coated stents. Smooth-muscle cell (SMC) proliferation, the putative agent for restenosis, was lower in animals receiving sirolimus-coated stents (p = 0.003). Additionally, intimal fibrin density was increased in the dogs treated with sirolimus-coated stents (p < 0.0001). Histological evidence of an inflammatory response demonstrated a trend toward a reduced response in the sirolimus group (mean 0.58) compared with the bare-metal group (mean 0.83, p = 0.33).

Conclusions. No neurotoxic effects were observed in the intracranial vessel walls or brainstem tissue in which sirolimus-coated stents were implanted. Compared with bare-metal stents, the sirolimus-coated devices did not impair endothelialization and, furthermore, tended to reduce the proliferation of SMCs. These findings indicate that sirolimus-coated devices may inhibit in-stent stenosis. Further studies with longer-term follow up are required to assess the restenosis rates of sirolimus-coated stents implanted in the intracranial vasculature.

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J Mocco, Ricardo A. Hanel, Jitendra Sharma, Erik F. Hauck, Kenneth V. Snyder, Sabareesh K. Natarajan, Italo Linfante, Adnan H. Siddiqui, L. Nelson Hopkins, Alan S. Boulos and Elad I. Levy


Acute revascularization has been associated with improved stroke outcomes. The Prolyse in Acute Cerebral Thromboembolism (PROACT II) trial achieved recanalization rates of 66%. The Multi Mechanical Embolus Removal in Cerebral Ischemia (Multi MERCI) trial achieved recanalization in 70% of patients. However, these interventional tools are not always successful. The Enterprise vascular reconstruction device was recently introduced for treatment of cerebral aneurysms previously untreatable with endovascular techniques. The authors evaluated a multicenter experience using this stent as a salvage revascularization tool for acute stroke treatment.


Four medical centers participated in a retrospective review of endovascularly treated patients with acute stroke for cases treated with the Enterprise stent after routine interventions had been unsuccessful. Data collected included preprocedure information, intraprocedure findings, and outcomes.


Twenty patients with acute stroke (mean age 61.6 ± 22 years) were treated with the Enterprise stent. Ten patients received intravenous recombinant tissue plasminogen activator before catheter intervention, without improvement. Intraarterial interventions attempted unsuccessfully before Enterprise deployment included the Merci retriever (12 patients), angioplasty (7 patients), glycoprotein IIb–IIIa inhibitor administration (12 patients), intraarterial nitroglycerin (1 patient), Wingspan stent deployment (3 patients), and Xpert stent deployment (1 patient). The mean preintervention National Institutes of Health Stroke Scale (NIHSS) score was 17 ± 6 (median 17). All patients presented with a Thrombolysis in Myocardial Infarction (TIMI) score of 0 or 1. Revascularization was achieved in all patients (75% with a TIMI score of 3, 25% with a TIMI score of 2). Improvement (≥ 4 points on the NIHSS) was documented in 75% of patients. Mean NIHSS improvement from intervention to discharge was 8 ± 7 points (median 9 points).


These preliminary data suggest a potential benefit to the use of the Enterprise stent when routine intervention methods fail.