Management Of Intracranial Atherosclerotic Disease Research Articles

311 A Feasibility Study for a Multicenter Phase-III Randomized Clinical Trial of Encephaloduroarteriosynagiosis Revascularization for Symptomatic Intracranial Atherosclerosis

INTRODUCTION: Stroke due to intracranial-atherosclerotic-disease (ICAD) remains a major public health concern, accounting for more than one-tenth of all ischemic-strokes in the US. METHODS: New data from advanced cerebral imaging and angiographic studies showed that revascularization after indirect-bypass occurs earlier than appreciated before. A pilot study of EDAS in ICAD patients demonstrated angiographic neovascularization as early as 1 month. An NINDS-funded phase-II objective-performance-criterion trial demonstrated reduction in the rate of stroke and death from 21.1% in the medical group to 9.6% in the surgical group at 2 years, passing the threshold for advancement to phase III. In collaboration with the NIH-StrokeNet, a national feasibility survey was sent to sites across the country to evaluate the feasibility of a phase-III clinical trial of EDAS in ICAD. RESULTS: Among 72 surveys completed by prospective sites, 90% (n = 65) indicated interest in participating and 96% of these (n = 63) had neurosurgeons and anesthesiologists with sufficient experience in EDAS and cerebrovascular disorders. The mean number of direct/indirect cerebral bypass surgeries per year completed at the prospective 40 sites was 19 (Range = 10-37). StrokeNet sites cared for a median of 42.5 patients/site/year (IQR = 25-100 patients/site/year) who met enrollment criteria. With 40 participating sites, the rate of enrollment needed for successful recruitment of 516 patients in a phase-III trial is 0.28 patients/site/month (3-4 patients/year), which is an order of magnitude less than the number of relevant cases receiving care at the sites (3.54 patients/month). CONCLUSIONS: EDAS is a promising technique in the management of ICAD and its performance is feasible within 40 high volume institutions. Engagement of the neurosurgical community on revitalizing a surgical form of revascularization can expand the role of neurosurgery in stroke management.

Abstract Number ‐ 247: Multimodal imaging approach for the diagnosis of (ICAD): basic principles, current and future perspectives

Introduction Symptomatic intracranial atherosclerotic disease is among the most common causes of acute ischemic stroke. The imaging tools utilized for the diagnostic of ICAD have significantly evolved over the past few decades. This paper is a review the different imaging modalities utilized in the diagnosis of Intracranial Atherosclerotic Disease (ICAD) including their latest development and relevance in management of ICAD. Methods A review of the literature was conducted through a search in google scholar, PubMed/Medline, EMBASE, Scopus, clinical trials.gov and the Cochrane Library. Search terms included “imaging modalities in ICAD” “ICAD diagnostic” “Neuroimaging of ICAD” “Evaluation of ICAD”. A summary and comparison of each modality’s basic principles, advantages and disadvantages were included. Results A total of 144 articles were identified and reviewed. The most common imaging used in ICAD diagnoses were DSA, CTA, MRA and TCD. They all had proven accuracy, their own benefits, and limitations. Newer modalities such as VWI, IVUS, OCT, PWI and CFD provide more detailed information regarding the vessel walls, plaque characteristics, and flow dynamics, which play a tremendous role in treatment guidance. In certain clinical scenarios, using more than one modality has been shown to be helpful in ICAD identification. The rapidly evolving software related to imaging studies, such as virtual histology, are very promising for the diagnostic and management of ICAD. Conclusions ICAD is a common cause of recurrent ischemic stroke. Its management can be both medical and/or procedural. Many different imaging modalities are used in its diagnosis. In certain clinical scenario a combination of two more modalities can be critical in the management of ICAD. We expect that continuous development of imaging technique will lead to individualized and less invasive management with adequate outcome.

Multimodal imaging approach for the diagnosis of intracranial atherosclerotic disease (ICAD): Basic principles, current and future perspectives.

To review the different imaging modalities utilized in the diagnosis of Intracranial Atherosclerotic Disease (ICAD) including their latest development and relevance in management of ICAD. A review of the literature was conducted through a search in google scholar, PubMed/Medline, EMBASE, Scopus, clinical trials.gov and the Cochrane Library. Search terms included, "imaging modalities in ICAD," "ICAD diagnostic," "Neuroimaging of ICAD," "Evaluation of ICAD". A summary and comparison of each modality's basic principles, advantages and disadvantages were included. A total of 144 articles were identified and reviewed. The most common imaging used in ICAD diagnoses were DSA, CTA, MRA and TCD. They all had proven accuracy, their own benefits, and limitations. Newer modalities such as VWI, IVUS, OCT, PWI and CFD provide more detailed information regarding the vessel walls, plaque characteristics, and flow dynamics, which play a tremendous role in treatment guidance. In certain clinical scenarios, using more than one modality has been shown to be helpful in ICAD identification. The rapidly evolving software related to imaging studies, such as virtual histology, are very promising for the diagnostic and management of ICAD. ICAD is a common cause of recurrent ischemic stroke. Its management can be both medical and/or procedural. Many different imaging modalities are used in its diagnosis. In certain clinical scenario, a combination of two more modalities can be critical in the management of ICAD. We expect that continuous development of imaging technique will lead to individualized and less invasive management with adequate outcome.

Management strategies of unanticipated intracranial stenosis during mechanical thrombectomy for acute stroke: A survey of academic neurointerventionalists.

The optimal approach to the management of intracranial atherosclerotic disease (ICAD) at the time of mechanical thrombectomy (MT) for large vessel occlusion (LVO) remains controversial. The goal of this study is to characterize current practices concerning this challenging clinical situation in a survey of practicing neurointerventionalists. An electronic questionnaire was sent to a cross-section of North American academic neurointerventionalists using publicly available contact information and departmental websites. Prior to analysis, responses were anonymized and categorized by region. A total of 136/360 responses were recorded from the U.S. and Canada. The mean number of years of practicing as a neurointerventionalist among the respondents was 10.5 (± 6.2 years). ICAD was perceived as a causative factor during MT for LVO in 5-10% of thrombectomy cases. The most common first-line treatment approach for significant ICAD, assuming a TICI 2b or better reperfusion, was medical therapy (77.9% of respondents), followed by angioplasty + stent placement (8.8% of respondents). There were no significant differences in the first line treatment of ICAD in LVO between geographical regions (p = 0.815). The approach to underlying ICAD in LVO varies widely; however, the majority of neurointerventionalists prefer medical therapy with DAPT as a first-line treatment approach. The current survey highlights the need for studies that better define the optimal timing and modality of treatment, along with an evidence-based framework for balancing the risks associated with these treatment approaches.

European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease.

The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of patients with intracranial atherosclerotic disease (ICAD). The guidelines were prepared following the Standard Operational Procedure of the European Stroke Organisation guidelines and according to GRADE methodology. ICAD represents a major cause of ischemic stroke worldwide, and patients affected by this condition are exposed to a high risk for future strokes and other major cardiovascular events, despite best medical therapy available. We identified 11 relevant clinical problems affecting ICAD patients and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions. The first two questions refer to the asymptomatic stage of the disease, which is being increasingly detected thanks to the routine use of noninvasive vascular imaging. We were not able to provide evidence-based recommendations regarding the optimal detection strategy and management of asymptomatic ICAD, and further research in the field is encouraged as subclinical ICAD may represent a big opportunity to improve primary stroke prevention. The second block of PICOs (3-5) is dedicated to the management of acute large vessel occlusion (LVO) ischemic stroke caused by ICAD, a clinical presentation of this disease that is becoming increasingly relevant and problematic, since it is associated with more refractory endovascular reperfusion procedures. An operational definition of probable ICAD-related LVO is proposed in the guideline. Despite the challenging context, no dedicated randomized clinical trials (RCTs) were identified, and therefore the guideline can only provide with suggestions derived from observational studies and our expert consensus, such as the escalated use of glycoprotein IIb-IIIa inhibitors and angioplasty/stenting in cases of refractory thrombectomies due to underlying ICAD. The last block of PICOs is devoted to the secondary prevention of patients with symptomatic ICAD. Moderate-level evidence was found to recommend against the use of oral anticoagulation as preferred antithrombotic drug, in favor of antiplatelets. Low-level evidence based our recommendation in favor of double antiplatelet as the antithrombotic treatment of choice in symptomatic ICAD patients, which we suggest to maintain during 90 days as per our expert consensus. Endovascular therapy with intracranial angioplasty and or stenting is not recommended as a treatment of first choice in high-grade symptomatic ICAD (moderate-level evidence). Regarding neurosurgical interventions, the available evidence does not support their use as front line therapies in patients with high-grade ICAD. There is not enough evidence as to provide any specific recommendation regarding the use of remote ischemic conditioning in ICAD patients, and further RCTs are needed to shed light on the utility of this promising therapy. Finally, we dedicate the last PICO to the importance of aggressive vascular risk factor management in ICAD, although the evidence derived from RCTs specifically addressing this question is still scarce.

Management of intracranial atherosclerotic disease

Management of intracranial atherosclerotic disease

Evidence-based optimization of the management of intracranial atherosclerotic disease

Dear Editor,The recently published article in Neurological Sciences byMattioni et al. [1] titled ‘Prevalence of intracranial largeartery stenosis and occlusion in patients with acuteischaemic stroke or TIA’ was very interesting. The authorsretrospectively evaluated all consecutive patients whopresented with an ischemic stroke or transient ischemicattack (TIA) and also underwent computed tomographyangiography (CTA) in the emergency room of a singleinstitution in The Netherlands over a 2-year span. Of the220 patients included for analysis, 39 % were found tohave intracranial atherosclerotic disease (ICAD) including35 % with intracranial arterial occlusion, 6 % with steno-sis, and 2 % with both. Multivariate analysis identifiedonly extracranial carotid disease and partial or total anteriorcirculation syndromes as predictors of symptomatic ICAD.Given the contribution of ICAD to ischemic cerebro-vascular disease, optimizing its management has been thesource of significant debate within the neurological andneurointerventional communities for over a decade. In2005, the warfarin–aspirin symptomatic intracranial dis-ease (WASID) trial showed that warfarin and aspirin eachafforded the same protection from recurrent ischemicstroke or TIA, but warfarin was associated with a higherrate of adverse events [2]. For symptomatic patients whofailed medical therapy, endovascular intervention withangioplasty and stenting began to emerge as a potentialtreatment option [3]. In 2005, the United States Food andDrug Administration approved the Wingspan stent (BostonScientific, Natick, MA, USA) under a humanitarian deviceexemption for the treatment of symptomatic ICAD patientswith at least 50 % stenosis of a major intracranial arterywho were refractory to antithrombotic therapy. InitialICAD stenting outcomes with the Wingspan system werepromising, with excellent rates of technical success andacceptably low complication rates [4]. For the time being,it appeared that the neurointerventional community hadprovided an effective solution for symptomatic ICAD.The initial enthusiasm which accompanied the advent ofstenting for ICAD treatment was quelled in 2011 by thesobering results of the stenting and aggressive medicalmanagement for preventing recurrent stroke in intracranialstenosis (SAMMPRIS) trial, which reported higher rates ofcerebral ischemic events in the intervention cohort com-pared to the medical cohort [5]. The medical therapy inSAMMPRIS was composed of dual antiplatelet therapywith aspirin and clopidogrel combined with aggressivemedical treatment of modifiable risk factors such ashypertension and hyperlipidemia. In the modern era ofICAD management, the options for symptomatic patientswho have failed maximal medical management which istypically the same as the therapy utilized in SAMMPRIS, isat best experimental. Although the enthusiasm for ICADtreatment with stenting has waned following SAMMPRIS,neurointerventionalists have continued to offer this thera-peutic option to carefully selected patients. The currentendovascular strategies for symptomatic ICAD are predi-cated on diminishing the incidence of in-stent restenosis(ISR), which has been shown to be relatively high inpatients treated with the Wingspan stent. The use of closedcell, low radial force devices, such as the Enterprise stent(Cordis Corporation, Miami Lakes, FL, USA), balloon-expandable stents, and drug-eluting stents have all beenreported to reduce the rate of ISR in retrospective case

Impact of SAMMPRIS on the future of intracranial atherosclerotic disease management: polling results from the ICAD symposium at the International Stroke Conference

ObjectiveThere are few data regarding the effect of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial results on the management of intracranial atherosclerotic...

The Evolving Paradigm in the Management of Intracranial Atherosclerotic Disease

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke worldwide and represents a significant health problem. The pathogenesis and natural history of ICAD are poorly understood, and rigorous treatment paradigms do not exist as they do for extracranial atherosclerosis. Currently, the best treatment for ICAD remains aspirin therapy, but many patients who are placed on aspirin continue to experience recurrent strokes. As microsurgical and endovascular techniques continue to evolve, the role of extracranial to intracranial bypass operations and stenting are increasingly being reconsidered. We performed a PubMed review of the English literature with a particular focus on treatment options for ICAD and present evidence-based data for the role of surgery and stenting in ICAD against medical therapy alone.

Intracranial Stenting With Wingspan

See related articles, pages 1971–1975 and 1976–1981. Intracranial atherosclerotic disease (ICAD) is a major cause of stroke and yet there are no proven effective treatments for it. Medical therapy has been associated with a high rate of recurrence, particularly in those with the most severe stenoses who have a 22.5% risk of stroke or death in the first year after a stroke.1 Clearly better alternatives are needed. Surgical bypass has been shown in at least 1 trial to be worse than medical therapy in the era before thienopyridines, statins, and angiotensin-converting enzyme inhibitors. In this issue of Stroke , Fiorella and colleagues describe their longer-term experience with intracranial stenting with the Wingspan (Stryker Inc, Fremont, CA) stent system and last year in this Journal, Jiang and colleagues published their long-term experience with 100 consecutive patients also treated with the Wingspan stent system.2,3 The question is do these publications broaden our knowledge enough to alter management of patients with ICAD? Do they prove that endovascular therapy is superior to medical treatment and that it is safe enough to be performed routinely? The article by Fiorella et al represents the largest (N=158) published series of Wingspan in the United States to treat ≥50% symptomatic stenoses.2 The immediate perioperative stroke and death rates were 5.7% (N=9) and 2.5% (N=4), respectively. Over a mean follow-up period of 14.2 months (only 110 patients [69.6%] had 12 months of follow-up), the primary end point (any perioperative stroke or death and any ipsilateral stroke thereafter) was noted in 15.7% of patients or approximately 13.2%/year. Seventy-six percent of the ipsilateral strokes occurred within the first 6 months with no events beyond 12 months. These event rates did not include transient ischemic attacks (TIAs) and did not include target lesion revascularization (TLR) for …

Epidemiology, diagnosis and management of intracranial atherosclerotic disease

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke, with higher occurrence rates in Asian, black and Hispanic individuals than in white individuals. Important risk factors for ICAD include age, hypertension, diabetes mellitus and metabolic syndrome. ICAD patients have a 10–20% annual risk of stroke, with greater risk in patients with high-grade stenosis (70–99%). Given the high risk of stroke recurrence in symptomatic ICAD patients, effective secondary prevention strategies are needed. Currently, there is no strong evidence supporting the use of anticoagulants in ICAD patients; antiplatelet drugs are still the preferred medication. Recently, angioplasty and stenting for ICAD has emerged as an alternative approach to medical treatment, owing to high technical success rates and low risk of periprocedural complications. However, the rate of in-stent restenosis is moderate, and the long-term benefit of endovascular treatment is not well established. High-quality randomized trials comparing angioplasty/stenting with the best medical therapy in ICAD patients are anticipated.

The Evolution and Role of Endovascular Therapy for the Treatment of Intracranial Atherosclerotic Disease

Intracranial atherosclerotic disease (ICAD) is being seen as an increasingly important cause of transient ischemic attack and stroke. Attention on this disease entity has been focused as a result of two recent events: the publication of the WASID trial and the recent Food and Drug Administration approval of the Wingspan-Gateway stent system. This manuscript will review the evolution of the role of endovascular therapy in the management of ICAD. In addition, the available devices currently available for endovascular therapy will be reviewed with an eye toward peri-procedural and follow-up complication rates.

Current Concepts in the Management of Intracranial Atherosclerotic Disease

Medically refractory, symptomatic intracranial atherosclerotic disease has a poor prognosis. Based on the results of the Warfarin-Aspirin Symptomatic Intracranial Disease study, the risk of ipsilateral stroke at 1.8 years is between 13 and 14% in patients with symptomatic intracranial atherosclerosis. Synergistic advances in intracranial angioplasty and stenting, modern neuroimaging techniques, and periprocedural and postprocedural antithrombotic regimens are creating new models for the diagnosis and successful endovascular treatment of intracranial stenosis. In this article, the most recent clinical developments and concepts for the diagnosis and endovascular treatment of intracranial atherosclerotic disease are discussed.