CURRENT CONCEPTS IN THE MANAGEMENT OF INTRACRANIAL ATHEROSCLEROTIC DISEASE Robert D. Ecker, M.D. ~Neurosurgery 59:S3-210-S3-218, 2006 Feb. 06, 07 VJ

Intracranial atherosclerosis accounts for 8 to 10% of all ischemic strokes. Patients with symptomatic intracranial atherosclerotic disease >> oral antithrombotic medications as the first and only line of treatment till now

The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) investigators compared outcomes among patients with symptomatic intracranial stenosis receiving warfarin (INR: 2.0–3.0) and those receiving high-dose aspirin (1300 mg daily) in a randomized, double-blinded trial. -- In 569 patients at a mean follow-up period of 1.8 years, 1. warfarin was associated with a higher rate of death, major hemorrhage, myocardial infarction or sudden death, and death from nonvascular or 2. At 1 year, the stroke risk for patients with 50 to 69% stenosis was 6%, compared with 19% for those with 70 to 99% stenosis. 3. the ipsilateral stroke risk for patients with symptomatic intracranial stenosis is 13 ~ 14%

Experience from CATH of the treatment of intracranial atherosclerosis: 1) coronary stents were, until recently, the only available devices able to be navigated and deployed in the intracranial circulation; 2) lower restenosis rates with angioplasty and stenting than stand alone angioplasty; 3) well-defined antithrombotic regimens and evidence of the benefits of periprocedural bolus-dose administration and postprocedural therapy with aspirin and clopidogrel : decreases recurrent stenosis and postprocedural neurological events; and 4) implantation of new coated and drug-eluting stents is proving to yield significantly lower restenosis rates

strategy a technique of submaximal angioplasty followed by delayed repeat angioplasty and, if necessary, stenting was developed for intracranial symptomatic atherosclerotic disease. Repeated angiography approximately 4 to 6 weeks after angioplasty. If in-lesion binary stenosis (50% luminal- diameter stenosis) -- stenting neointimal proliferation and scar formation result in a thickened fibrous lesion -- incur a lower risk for plaque embolization and vessel dissection during a subsequent stenting procedure. mortality and permanent neurological morbidity for the procedure dropped to less than 5%, and between 20 and 30% of patients did not require further intervention at follow-up

CT perfusion imaging with and without acetazolamide challenge testing is used most often for evaluation of lesions located in the supratentorial vasculature, single-photon emission computed tomographic scanning -- posterior circulation or for those patients who cannot tolerate a significant load of contrast material. PATIENT SELECTION

72-year-old woman with a history of a 5-minute episode of unresponsiveness at home - increased time to peak in the right posterior cerebral territory. B, DWI MR scan - only a small area of infarction in the right posterior cerebral territory. C, DSA: a fetal posterior cerebral artery with more than 90% stenosis.

CLINICAL SERIES Humanitarian Device Exemption (HDE) program for use in patients with symptomatic intracranial stenosis of 50% or more in severity. Use of this system involves submaximal inflation of an angioplasty balloon, followed by removal of the balloon and subsequent deployment of the stent. The Wingspan is a self-expanding intracranial stent composed of nitinol with similar trackability but at least twice the radial outward strength of the Neuroform III stent (Boston Scientific).

SSYLVIA was a safety and feasibility study designed to evaluate the Neurolink stent (Guidant Corporation, Indianapolis, IN), a flexible, stainless steel stent specifically designed for intracranial placement, in 61 symptomatic patients with intracranial stenosis Jiang et al. -- In a single-center series consisting of 40 patients with 42 symptomatic M1 stenotic lesions treated with angioplasty and balloon-mounted coronary stenting

Between 1993 and 2000, technical and clinical success with stand-alone angioplasty was documented in 11 case series consisting of 193 patients Good revascularization-- 67 to 100% of the patients, with overall complication rates -- 5 to 40%. Technical success rates to 100%, major complication rates -- 0 to 36%.

In a single-center series consisting of 40 patients with 42 symptomatic M1 stenotic lesions treated with angioplasty and balloon-mounted coronary stenting, Jiang et al. reported a technical success rate (20% residual stenosis) of 97.6%, with a 10% major complication rate -- one died of a subarachnoid hemorrhage and three experienced no major neurological injury. The results of both the SSYLVIA study and the series reported by Jiang et al. clearly demonstrate more than 95% accuracy for deployment of a stent in the correct intracranial location. Despite improved technical success, it remains uncertain whether or not the cardiac literature, which demonstrates that stenting in small coronary arteries leads to less restenosis than stand-alone balloon angioplasty, is applicable to the intracranial circulation

A comparison of the findings of the Wingspan study with those from the SSYLVIA trial and the series reported by Jiang et al. demonstrates lower complication and restenosis rates for the self-expanding Wingspan stent

ANTITHROMBOTIC AGENTS IIb-IIIa inhibitors By binding the platelet GP IIb-IIIa receptor, these agents (abciximab, eptifibatide, tirofiban) are the most potent inhibitors of platelet aggregation. GP IIb-IIIa inhibitors to date -- a rescue drug when embolic phenomena have occurred during an endovascular procedure For patients with TIA or stroke medical treatment -- no benefit for the combination of aspirin and clopidogrel and an associated increase the risk of bleeding The Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events trial demonstrated a slight benefit for clopidogrel compared with aspirin

FROM THE PAST TO THE FUTURE Technique progressed from directly sizing the balloon to the artery caliber with rapid balloon inflation to undersizing the balloon with slow inflation. The occurrence of acute vessel occlusion and dissection dropped from 75 to 14% with this technique The classification scheme developed by Mori et al., ; based on length of stenosis, degree of stenosis,and eccentricity of plaque, is highly predictive of outcome, with 92, 86, and 33% clinical success rates in patients with Types A, B, and C lesions, respectively:

Type A, 5 mm or less in length concentric or moderately eccentric lesions less than totally occlusive; Type B, tubular 5 to 10 mm in length, extremely eccentric or totally occluded lesions, less than 3 months old; and Type C, diffuse, more than 10 mm in length, extremely angulated (90 degrees) lesions with excessive tortuosity of the proximal segment, or totally occluded lesions, and 3 or more months old. At the 1-year follow-up evaluation, restenosis rates associated with these lesion types were 0, 33, and 100%, respectively; the risk of major stroke or death was 8% in Type A, 26% in Type B, and 87% in Type C

In 2002, Levy et al. staged stent placement after angioplasty-- delayed stent placement gives the artery time to heal in the acute phase after angioplasty balloon angioplasty injures the intima, upregulating inflammatory mediators and leukocytes at the injury site >>> neointimal proliferation and fibrosis

Drug-eluting stents Sirolimus (rapamycin) -- antifungal agent induces cell-cycle arrest and reduce neointimal proliferation in animals. Paclitaxel, a microtubule inhibitor, also has been shown to prevent neointimal proliferation. An ideal stent would need to be visualized easily, to be navigable through the intracranial circulation, to be porous, to deploy reliably at low atmospheres of pressure, and to be coated with an agent to prevent restenosis and thrombosis.

CONCLUSION Intracranial stenosis is common and dangerous. Symptomatic stenosis carries a 10 to 20% 2-year risk of stroke and should be treated. Patients experiencing a single TIA and with less than 50% stenosis, no perfusion abnormality, or poor life expectancy -- treated medically with antiplatelet agents.

High-dose aspirin, clopidogrel, or dipyridamole : used as single agents. Warfarin : increase the risk of death and hemorrhage and no longer should be used Asymptomatic patients – medically Symptomatic patients: considered for treatment with interventional techniques. The risk of percutaneous angioplasty and stenting has been lowered by the staged technique. With new self-expanding stents, the restenosis rate has dropped, without compromising safety

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