Endovascular Clot Retrieval Research Articles

Unwanted detachment of the Solitaire device during mechanical thrombectomy in acute ischemic stroke

BackgroundThe use of retrievable stents for endovascular clot retrieval has dramatically improved successful revascularization and clinical outcome in selected patients with acute stroke.ObjectiveTo describe the rate and clinical consequences of...

Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles.

Computed tomography (CT) is the current standard for time-critical decision-making in stroke patients, informing decisions on thrombolytic therapy with tissue plasminogen activator (tPA), which has a narrow therapeutic index. We aimed to develop a CT-based method to directly visualize cerebrovascular thrombi and guide thrombolytic therapy. Glycol-chitosan-coated gold nanoparticles (GC-AuNPs) were synthesized and conjugated to fibrin-targeting peptides, forming fib-GC-AuNP. This targeted imaging agent and non-targeted control agent were characterized in vitro and in vivo in C57Bl/6 mice (n = 107) with FeCl3-induced carotid thrombosis and/or embolic ischemic stroke. Fibrin-binding capacity was superior with fib-GC-AuNPs compared to GC-AuNPs, with thrombi visualized as high density on microCT (mCT). mCT imaging using fib-GC-AuNP allowed the prompt detection and quantification of cerebral thrombi, and monitoring of tPA-mediated thrombolytic effect, which reflected histological stroke outcome. Furthermore, recurrent thrombosis could be diagnosed by mCT without further nanoparticle administration for up to 3 weeks. fib-GC-AuNP-based direct cerebral thrombus imaging greatly enhance the value and information obtainable by regular CT, has multiple uses in basic / translational vascular research, and will likely allow personalized thrombolytic therapy in clinic by a) optimizing tPA-dosing to match thrombus burden, b) enabling the rational triage of patients to more radical therapies such as endovascular clot-retrieval, and c) potentially serving as a theranostic platform for targeted delivery of concurrent thrombolysis.

Impact of Anesthesia on Mortality During Endovascular Clot Removal for Acute Ischemic Stroke

Endovascular clot retrieval is a technique available for removing intracranial arterial occlusions in acute ischemic stroke (AIS). This rescue therapy can be performed with moderate conscious sedation (CS) or general anesthesia (GA). The effect of GA on clinical outcome in AIS remains controversial. Therefore, we retrospectively investigated whether the use of CS or GA during endovascular intervention for AIS influenced outcomes. Patients who underwent emergent endovascular intervention for intracranial arterial occlusion during the years 2006 to 2012 were included in this study. Statistical analysis using the Spearman ρ was performed to examine demographic data and clinical outcomes between patients in the GA and CS groups. Binary logistic regression was used to determine the predictors of mortality. A total of 109 patients fit the inclusion criteria. Among them, 35 patients had GA and 74 patients had CS. Patients needing intubation upon admission for airway protection were more likely to receive GA (P<0.001). The duration of the procedure and the time-to-revascularization from symptom onset were significantly longer in the GA group. Mortality was higher in the GA group compared with the CS group (40% vs. 22%, P=0.045). Multivariate analysis, controlled for confounding variables, identified GA and elevated postprocedure glucose level to be significant predictors of mortality. Larger prospectively randomized multicenter trials evaluating the effects of GA and CS on clinical and radiographic outcomes seems warranted.

P18.05 * TREATMENT OF ACUTE ISCHEMIC STROKE IN CANCER PATIENTS

BACKGROUND: Intravenous thrombolysis using tissue plasminogen activator (iv-tPA) and endovascular clot retrieval have revolutionized treatment of acute ischemic stroke. Cancer patients are at increased risk of ischemic stroke because of inherent hypercoagulability. However, the benefit of active thrombolysis in this clinical setting is unknown and treatment with iv-tPA is often avoided because of possible hemorrhagic complications. METHODS: Retrospective screening of the institutional medical records for cancer patients presenting with acute ischemic stroke during the year 2011. Description of 4 representative clinical cases. RESULTS: During the one-year period, 33 cancer patients (16 men and 17 women) presented with and were evaluated for acute ischemic stroke at a mean age of 69 (45-92) years. Of these, 17 (52%) had lacunar strokes, 14 (42%) had large artery strokes and 2 (6%) presented with multiple cardioembolic strokes. At the time of presentation, 14/33 (42%) patients had evidence of systemic metastatic disease and 12/33 (36%) had active locally advanced disease. Most common malignancies included breast cancer, prostatic carcinoma, colorectal and urinary bladder tumors. According to the commonly accepted criteria for intravenous thrombolysis, 3/33 (9%) patients were treated with iv- tPA, and 1/33 (3%) underwent endovascular clot retrieval. No hemorrhagic complications were observed in these 4 patients and all had marked improvement of the neurological disability following treatment. CONCLUSION: Selected cancer patients with acute ischemic stroke may benefit from intravenous thrombolysis and endovascular clot retrieval. Application of the currently accepted clinical criteria for iv-tPA reduces the risk of hemorrhagic complications in this group of patients. Awareness to the available early therapeutic options in this clinical setup may improve outcome of cancer patients with acute ischemic stroke.

Experience of mechanical thrombectomy for paediatric arterial ischaemic stroke

BackgroundPaediatric arterial ischaemic stroke (AIS) is an important cause of acute neurological symptoms in children, it causes significant morbidity and is one of the top ten causes of childhood deaths. Consensus papers have suggested guidelines for the management of AIS in childhood, although none recommend thrombectomy. Despite this, children within our institution have undergone mechanical thrombectomy for large vessel occlusion. This is the first series of mechanical thrombectomy and outcomes performed in children in the UK. MethodsWe describe the endovascular management of paediatric arterial ischaemic stroke (AIS) in four children (5–15 years) with PedNIHSS > 17. ResultsThree had basilar artery (BA) occlusion and one left middle cerebral artery (MCA) occlusion. All underwent uncomplicated thrombectomy followed by intravenous heparin. One had a successful second attempt. The BA cases underwent thrombectomy 17–36 h after symptom onset; the left MCA case <6 h after symptom onset. Modified Rankin Scale (MRS) was 0–3, 50% had MRS 0. DiscussionAdult AIS guidelines recommend IV recombinant tissue plasminogen activator (r-tPA) within 4.5 h of onset and intra-arterial r-tPA within 6 h; thrombectomy being reserved for carefully selected patients. Paediatric AIS recognition is problematic, often with delayed imaging. There is little evidence regarding efficacy of thrombectomy for paediatric AIS. Our experience suggests there may be a role for endovascular clot retrieval in selected patients managed by an experienced multidisciplinary team. Careful data collection is mandatory.

Introduction: Management of ischemic cerebrovascular disease

The management of ischemic cerebrovascular disease has undergone significant changes in the past 25 years. However, despite enormous advances, there are still many unresolved and controversial issues. This issue of Neurosurgical Focus is dedicated to the current management of ischemic cerebrovascular disease and contains 12 articles evaluating different facets of this disease. Imaging techniques play a major role in allowing better characterization of plaque composition and “instability.” Further refinements will be critical in guiding individualized therapeutic decisions in patients with carotid artery stenosis. In the first article, DeMarco and Huston provide an update on this topic and summarize potential future directions. Despite the landmark trials completed in the past 20 years, the management of asymptomatic carotid artery stenosis continues to be a controversial topic. Progress in medical therapy with the widespread use of lipid-lowering agents and better antihypertensive drugs combined with lifestyle modifications has improved the outlook of patients with asymptomatic carotid artery stenosis. In view of these developments, it may be time to “rethink our therapeutic options” as suggested by the second article in this issue. Current ongoing and planned multicenter studies regarding the optimal management of asymptomatic carotid artery stenosis will not only compare endarterectomy with angioplasty and stenting, but will also include a “best current medical therapy” arm to reflect the ongoing controversy outlined in this article. The management of acute ischemic stroke has undergone dramatic changes. As recently as the early 1990s, a “nihilistic approach” was common among treating physicians faced with a patient with an acute ischemic stroke given the recognition that “little could be done once the stroke has occurred.” Intravenous thrombolysis for patients evaluated within the first few hours after an ischemic stroke has markedly affected this mindset. In patients with large-vessel occlusion who have a contraindication for intravenous thrombolysis or who fail to improve after intravenous thrombolytics, endovascular mechanical clot retrieval has become a rapidly evolving option with high rates of recanalization. The ability to identify “tissue at risk” based on imaging in these patients is very important for proper patient selection. The topic of imaging of acute ischemic stroke is reviewed by Tong and coworkers. Advances in wireless communication and mobile devices continue to dramatically alter the patient-doctor interaction. These recent technological developments have already begun to play a key role in broadening our ability to provide the highest level of expertise to stroke patients who may live some distance from a stroke center, as discussed by Rubin and coworkers in an update on these exciting initiatives. Despite the theoretical appeal of endovascular techniques and the ability to achieve very high rates of recanalization with modern endovascular mechanical devices, the role and efficacy of this therapy has recently been questioned by authors of several multicenter studies. Mokin and coworkers address, in a thoughtful review, the current role of endovascular revascularization for acute ischemic stroke in view of the results of the most recent trials. This article is also featured and discussed in a special podcast accompanying this issue. The 3 subsequent articles are also related to endovascular treatment and include a retrospective analysis of a large cohort of young patients with acute ischemic stroke treated using endovascular recanalization by Chalouhi et al., a review of the current status of endovascular treatment for acute retinal occlusion by Agarwal and coworkers, and a stand-alone editorial by Cloft on issues related to workforce demand in view of recent developments in the treatment of acute ischemic stroke. After the landmark Extracranial-Intracranial (EC-IC) Bypass Study was published in 1985, which showed no Introduction

How baseline severity affects efficacy and safety outcomes in acute ischemic stroke intervention trials

Baseline severity of stroke may be an important predictor of efficacy and safety outcomes in acute stroke intervention trials. This summary explores definitions of baseline variables and outcomes used to measure stroke severity, efficacy, and safety. In addition, the discussion here reviews select acute ischemic stroke intravenous thrombolytic studies, such as the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study and European Cooperative Acute Stroke Studies, select neuroprotectant and endovascular clot retrieval device studies, and large cooperative databases, such as the Virtual International Stroke Trials Archive and Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry, to explore relationships between baseline stroke severity and other possible factors associated with efficacy and safety outcomes. The NIH Stroke Scale and modified Rankin scale will be featured as major stroke outcome measures, based on frequency of use and reliability, familiarity, adaptability, and comparability.

Assessment of stent retrievers in acute ischaemic stroke

There has been healthy scepticism about the use of mechanical clot retrieval devices in the treatment of acute ischaemic stroke. Such devices give higher rates of recanalisation than does counterpart treatment with intravenous recombinant tissue plasminogen activator (rt-PA), but might not be associated with improvements in outcome for patients.1 Analysis of the National Inpatient Sample of almost 4000 patients who received endovascular clot retrieval therapy for acute ischaemic stroke showed that about 75% had either died in hospital or were discharged to long-term care facilities.

Pharmacological Revascularization of Acute Ischaemic Stroke

The only currently approved treatment for acute ischaemic stroke (AIS) is alteplase, a thrombolytic agent given intravenously (IV) within 4.5 hours of symptom onset, in an attempt to reopen occluded intracerebral arteries. However, no more than 5% of all AIS patients receive IV alteplase, mainly because of too long symptom-onset-to-hospital intervals. Moreover, this strategy is effective for less than half of the patients treated within the therapeutic window. Early recanalization is the most powerful prognostic factor, and novel drugs or therapeutic strategies are primarily aimed at improving alteplase efficacy to rapidly and safely reopen the occluded arteries. Because IV alteplase-resistant thrombi are those with the largest clot burden, responsible for the most devastating brain-tissue infarctions, development of novel approved AIS therapies is an urgent priority. At present, in the absence of controlled trials, no valid recommendations can be made. However, the most promising emerging strategy is a combination of standard or low-dose IV alteplase with an intra-arterial (IA) procedure, including additional endovascular thrombolytic and/or mechanical clot retrieval. Notably, results of open trials using the IA route had relatively disappointing clinical outcomes, despite remarkable arterial recanalization rates. Controlled trials are urgently needed to evaluate strategies including an IA route. In addition, logistic and cost constraints will likely limit their routine use, even in industrialized countries. Combining of another IV drug and IV alteplase is a far less studied option, although much easier to implement. Add-on IV drugs could be an antiplatelet glycoprotein (GP) IIb/IIIa receptor antagonist, a direct thrombin inhibitor or a second thrombolytic agent, e.g. tenecteplase. However, neuroimaging to measure the clot burden and infarction size will probably be necessary to predict IV alteplase failure and the subsequent use of these eventual additional therapies.

Patient Outcomes With Endovascular Embolectomy Therapy for Acute Ischemic Stroke

Maturing techniques have spurred widespread implementation of endovascular embolectomy therapy for ischemic stroke. We evaluated a large administrative database to determine outcomes in patients treated with endovascular embolectomy in the general population. Using the National Inpatient Sample, we evaluated outcomes of patients treated for acute ischemic stroke in the United States from 2006 to 2008. Patients who had an ischemic stroke and underwent endovascular clot retrieval were identified. Morbidity, defined as "discharge to long-term facility," and mortality were evaluated as a function of patient age and of concomitant thrombolytic agent administration. For 2006 to 2008, a total of 3864 patients received endovascular clot retrieval with 266 (6.9%) patients in 2006, 800 (20.7) patients in 2007, and 2798 (72.4%) patients in 2008. The discharge to a long-term facility rate was 51.3% (1983 of 3864). The in-hospital mortality rate was 24.3% (940 of 3864). For patients <65 years old, the rate of in-hospital death was 17.1% (283 of 1658) as compared with a rate of 29.7% (656 of 2206) for patients ≥65 years old (P<0.0001). The rate of discharge to a long-term facility was 47.6% (789 of 1658) for patients <65 years old and 54.1% (1193 of 2206) for patients ≥65 years old (P<0.0001). The rate of intracranial hemorrhage was 15.5% without concomitant thrombolysis and 20.0% with concomitant thrombolysis (P=0.0009). Rates of morbidity and mortality remain high for patients with acute stroke, even in the setting of endovascular embolectomy. Advanced age portends a worse outcome and patients treated with concomitant use of thrombolytic agent had higher rates of intracranial hemorrhage than those without such therapy.

Failure of a Clot Retrieval Device in an Adolescent Stroke Patient

A previously healthy 14-year-old boy collapsed after a football game, with aphasia and right hemiparesis. Cranial magnetic resonance imaging and magnetic resonance angiography revealed left middle cerebral artery distribution ischemic infarct with thrombus and possible dissection at the horizontal segment of the middle cerebral artery. The patient was treated 9 hours after collapse with intra-arterial tissue plasminogen activator, but without success. The Merci clot retrieval device was then used, but the device broke in the middle cerebral artery and led to complete occlusion. At follow-up 3 months later, the boy had persistent aphasia, but notable improvement in his right hemiparesis. This is a novel report of a complication of mechanical clot retrieval treatment in a child. Further research is needed to determine the safety and effectiveness of intracranial endovascular clot retrieval devices in children.

Evaluating therapeutic targets for reperfusion‐related brain hemorrhage

Early reperfusion after an ischemic stroke can cause blood-brain barrier injury with subsequent cerebral edema and devastating brain hemorrhage. These complications of early reperfusion, which result from excess production of reactive oxygen species, significantly limit the benefits of stroke therapies. In this article, we use a novel animal model that facilitates identification of specific components of the reperfusion injury process, including vascular injury and secondary brain damage, and allows assessment of therapeutic interventions. Knock-out (KO) mice containing 50% manganese-superoxide dismutase activity (SOD2-KO) and transgenic mice overexpressing SOD2 undergo transient focal ischemia and reperfusion followed by assessment of infarct, edema, hemorrhage rates, metalloproteinase activation, and microvascular injury. SOD2-KO mice demonstrate delayed (>24h) blood-brain barrier breakdown associated with activation of matrix metalloproteinases, inflammation, and high brain hemorrhage rates. These adverse consequences are absent in wild-type littermates and minocycline-treated SOD2-KO animals. Increased hemorrhage rates also are absent in SOD2 overexpressors, which have reduced vascular endothelial cell death. Finally, we show that the tight junction membrane protein, occludin, is an early and specific target in oxidative stress-induced microvascular injury. This model is ideal for studying ischemia/reperfusion-induced vascular injury and secondary brain hemorrhage and offers a unique opportunity to evaluate antioxidant-based neurovascular protective strategies as potential adjunct treatments to currently approved stroke therapies such as thrombolysis and endovascular clot retrieval.