A 60-year-old woman with transient speech arrest and a small acute left frontal stroke. A. Magnetic resonance angiography of the circle of Willis demonstrates a flow gap (arrow) in the M1 segment of the middle cerebral artery indicating severe stenosis. B. Magnetic resonance imaging brain scan with diffusion- weighted sequence demonstrates an acute infarct in the paraventricular left frontal lobe (arrow) likely due to arterial-to-arterial embolization. C. Catheter angiography of the left internal carotid artery in the frontal projection during the arterial phase reveals severe (80%-90%) stenosis of the M1 segment of the left middle cerebral artery (arrow). D. Endovascular revascularization with stent-supported angioplasty using a 2.4 mm × 9.0 mm Wingspan stent resulted in restoration of the vessel lumen and cessation of further embolization (arrow). The patient has been monitored periodically using transcranial Doppler ultrasonography for evidence of restenosis but has maintained normal Doppler velocities and no further strokes or transient ishemic attacks.
Intracranial atherosclerotic disease (ICAD) carries a significant risk and has been recognized as the cause of 8% to 10% of ischemic strokes by population-based and hospital patient–based studies.93-95 When transient ischemic attacks are considered in addition to ischemic stroke, approximately 100,000 people in the United States experience ischemic events due to ICAD each year. ICAD is associated with diabetes mellitus, smoking, hypertension, and hypercholesterolemia, and can lead to hemodynamic compromise by producing local thrombosis, occluding perforator arteries, or otherwise causing perfusion failure.96 It is this hemodynamic compromise, which may be divided into three categories, that ultimately increases the risk of ipsilateral stroke (Table 20-397).
Table 20-3.Hemodynamic Effects of Intracranial Atherosclerotic Disease ||Download (.pdf) Table 20-3. Hemodynamic Effects of Intracranial Atherosclerotic Disease
|Stage 0 ||Normal cerebral hemodynamics |
|Stage 1 ||Reflex vasodilation with increased cerebral blood volume and prolonged mean transit time; preserved cerebral blood flow and normal oxygen extraction coefficient |
|Stage 2 ||Misery perfusion with falling cerebral blood flow and increased oxygen extraction coefficient |
Numerous studies have associated symptomatic intracranial atherosclerosis with a high risk of stroke or death. Patients with symptomatic ICAD, followed in the Warfarin Versus Aspirin Symptomatic Intracranial Disease Study for Stroke (WASID), experienced a 9% to 12% annual risk of ischemic stroke, with 77% of strokes occurring within the first year of follow-up despite optimal medical management and either systemic anticoagulation or antiplatelet therapy. Stenosis of at least 70% increased this risk; such lesions carried a 19% annual risk of stroke in the symptomatic territory.98 Similarly, the EC/IC (extracranial/intracranial) Bypass Trial demonstrated that patients treated medically, with management of stroke risk factors and 1300 mg per day of aspirin, for symptomatic ICAD experienced an annual mortality and stroke rate of 8% to 10%.99 Annual rates of stroke or death attributable to vascular causes are even higher in those failing antithrombotic therapy, and have been shown to approach 56%.100
Given the risk associated with symptomatic intracranial atherosclerosis, the failure of medical management to sufficiently mitigate that risk, and lack of a demonstrable decreased risk of recurrent ischemic events following extracranial/intracranial bypass procedures, interventions including angioplasty and stenting have been pursued. Initial procedures were largely corollaries of established techniques in interventional cardiology, utilizing percutaneous coronary intervention balloons to dilate intracranial vessels. However, cerebral arteries differ from their coronary counterparts on several grounds, generally exhibiting smaller diameters, a well-developed tunica media, and a relatively scarce tunica adventitia.96 Accordingly, they are more prone to vasospasm and also more likely to rupture at lower forces than are coronary arteries. Furthermore, intracranial vessels may be exceedingly tortuous. Endovascular catheter technology has since progressed, making it an increasingly viable and accepted intervention for patients with ICAD. Currently, patients most likely to undergo endovascular treatment for ICAD remain symptomatic despite optimal medical management with stenosis greater than 50%.96 However, decisions regarding individual patients must be made on an individual basis.
Balloon angioplasty has been performed with successful results reported in several case studies. A recent large study followed 120 patients with 124 symptomatic intracranial stenoses treated with angioplasty. Pretreatment stenoses averaged 82.2%, and ranged from 50% to 95%; angioplastic intervention reduced the average to 36%, with a range from 0% to 90%. The investigators observed a combined periprocedural stroke and death rate of 5.8%; after an average of 42.3 months of follow-up, the overall rate of stroke or death was 4.4% annually.101 As expected with any procedure, certain atherosclerotic lesions are more amenable to angioplastic manipulation. Mori and colleagues correlated angiographic features of hemodynamically significant intracranial stenoses with clinical success of intracranial percutaneous transluminal cerebral balloon angioplasty (PTCBA).96,102
Clinical success rates for types A, B, and C (as described in Table 20-4) were 92%, 86%, and 33%, respectively. Type C lesions were most likely to undergo restenosis, with 100% demonstrating restenosis after 1 year; conversely, no type A lesions restenosed. Risk of fatal or nonfatal ischemic stroke or ipsilateral bypass surgery similarly related to type, with cumulative risks of 8%, 26%, and 87% observed in types A, B, and C, respectively. 102 Thus, the success of angioplasty depends strongly on the characteristics of the lesion.
Table 20-4.Angiographic Features of Hemodynamically Significant Intracranial Stenoses ||Download (.pdf) Table 20-4. Angiographic Features of Hemodynamically Significant Intracranial Stenoses
|Type A ||Short (< 5 mm in length); concentric or moderately eccentric; nonocclusive |
|Type B ||Tubular (5-10 mm in length); extremely eccentric or fully occluded, moderately angulated, < 3 months old |
|Type C ||Diffuse (more than 10 mm in length); extremely angulated (> 90°); very tortuous proximal segment or total occlusion; ≥ 3 months |
Despite the general success of balloon angioplasty, certain complications associated with the procedure, such as elastic recoil and intimal dissection, are averted through stent-supported angioplasty. The Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA) trial introduced the Neurolink stent (Guidant Corporation; Menlo Park, CA), a balloon expandable intracranial stent composed of interconnected bare stainless steel rings and specifically designed to be flexible enough to navigate the tortuous intracranial vessels without causing injury. The multicenter, prospective feasibility study involved patients with symptoms attributable to a single lesion with greater than 50% stenosis. The majority of patients, 43 of 61 (70.5%) had intracranial stenosis, while all others had extracranial vertebral artery stenosis. In 95% of cases the stent was successfully placed, such that less than 30% residual stenosis remained. Within the first 30 days, 6.6% of patients had nonfatal strokes; 7.3% of patients suffered strokes between 30 days and 1 year following stent placement. Restenosis greater than 50% occurred in 32.4% of patients with intracranial lesions; however, 61% of all patients demonstrating restenosis remained asymptomatic, with no strokes or transient ischemic attacks (TIAs).103 Although the manufacturers of Neurolink received a humanitarian device exemption (HDE) from the FDA to treat patients with significant atherosclerotic disease, the device is not currently available for commercial use.
The Wingspan stent (Boston Scientific SMART; San Leandro, CA) has also received an HDE and is available to treat patients refractory to medical therapy with symptomatic intracranial stenosis greater than 50%.96 It combines balloon dilatation with the subsequent placement of a self-expanding microstent. The study underlying the HDE involved 45 patients with symptomatic intracranial stenosis greater than 50% in a vessel 2.5 to 4.5 mm in diameter, who had been proven to be refractory to medical therapy.104 Angioplasty and stent deployment was successful in 98% of patients. The 30-day postintervention combined ipsilateral stroke and death rate was 4.5%, whereas the 6-month ipsilateral stroke and death rate was 7.1%. The 6-month rate of all strokes was 9.7%, and all-cause mortality at the same time point was 2.3%. Patients averaged a 74.9% degree stenosis at baseline, which decreased to 31.9% after stenting. At the 6-month follow-up, the average degree of stenosis was 28%. Three patients, however, lost lumen diameter and restenosed to greater than 50% by 6 months of follow-up but were not symptomatic.104
Since intimal hyperplasia and vascular remodeling theoretically lead to restenosis, stents secreting antiproliferative drugs have been studied as a means of preventing restenosis. Recently, 18 patients were treated with either sirolimus- or paclitaxel-eluting stents.105 All patients had symptomatic intracranial stenosis greater than 50% despite medical treatment. Within the first month, one major stroke and no deaths occurred; there were no additional such events at the 6-month time point. One of seven patients undergoing follow-up angiography at 6 months had developed restenosis greater than 50%.105 A larger study also investigating drug-eluting stents detected 1 restenosis from 26 treated intracranial lesions (5%).106
There exists debate concerning whether angioplasty alone or angioplasty followed by stent placement provides better results. A recent multicenter study compared 95 primary angioplasty procedures against 98 intracranial stent placements.107 There were no significant differences between the groups in terms of age, gender, or medical history, including hypertension, diabetes, and previous stroke or TIA. Preprocedure stenosis averaged 89.2% and 90.1% in patients undergoing primary angioplasty and those undergoing stent placement, respectively. However, residual stenosis greater than 50% was significantly more common in the angioplasty-treated group, at 15% of patients compared with 4%. The angioplasty-treated group had one periprocedural death and seven periprocedural strokes, whereas the stent-treated group had two periprocedural deaths and seven strokes. These differences as well as differences in terms of stroke- and death-free survival at 2 years were not significant. Similarly, where follow-up data were available, there was no significant difference in the occurrence of restentosis at follow-up: 25 of 66 (38.9%) in the angioplasty-treated group versus 23 of 68 (34%) in the stent-treated group. The investigators concluded that stent placement conferred no significant benefit over angioplasty alone except in the reduction of residual stenosis.
A meta-analysis conducted by Siddiq et al again compared angioplasty and stent placement in patients with symptomatic ICAD.108 In pooling selected publications, the investigators established a significantly lower rate of death or stroke at 1 year in patients treated with stent placement (14.2%) as opposed to those undergoing primary angioplasty (19.7%). However, periprocedural death and stroke did not differ significantly between the groups. Stent placement was also associated with a lower percentage of restenosis at 11.1% compared with angioplasty alone at 14.2%.108 These findings indicate that angioplasty followed by stenting may provide benefits over angioplasty alone; however, treatment decisions must be made by experienced interventionalists on a case-by-case basis.