Natural History and Medical Management

Conducted between 1999 and 2003, the WASID trial aimed to better understand the natural history of ICAD and choice of medical therapy, enrolling 569 patients with recent transient ischemic attack (TIA) or minor stroke and angiographically proven 50 to 99% stenosis of a major intracranial artery, attributable to ICAD. In this prospective, randomized controlled trial, roughly 40% of the patients had vertebrobasilar ICAD. The WASID study was stopped early—within 1.8 years of follow-up—as warfarin showed significantly higher rates of adverse events and provided no benefit over aspirin. In the territory of the stenosis, the overall rate of ischemic stroke was 11% at 1 year and 14% at 2 years, despite the use of aspirin or warfarin.4 In subset analysis, the risk of subsequent stroke in the WASID population was found to be greatest in symptomatic patients with 70 to 99% stenosis (20% in the first year), which was significantly higher than those patients with moderate stenosis.5 Although an earlier retrospective report from the WASID study group in 1996 showed patients with vertebrobasilar ICAD to be at particularly high risk of stroke, the prospective WASID trial determined that the location of the stenosis (i.e., vertebrobasilar disease versus carotid middle cerebral artery disease) was not significantly associated with an increased risk of stroke in the territory of the stenotic vessel.6 Multiple other variables were examined, such as age, length of stenosis, and prior use of antithrombotic medications. No variables were found to be significantly associated with an increased risk of stroke in the territory of the stenotic artery.5 Additional subgroup analysis of the posterior circulation showed that warfarin provided no definite benefit over aspirin.7

However, in 2009, it was reported that, in a population of 538 unselected patients, the prevalence of ≥50% vertebrobasilar stenosis was significantly greater than the prevalence of ≥50% carotid stenosis when comparing posterior versus anterior circulation TIA or minor stroke.8 The same study also showed that ≥50% vertebrobasilar stenosis had a high 90-day risk of recurrent events, reaching 22% for stroke and 46% for stroke and TIA.8 Looking at outcomes from a stroke-free survival perspective, a 2003 study determined stroke-free survival in 102 patients with symptomatic 50% or greater vertebrobasilar stenosis. The study found that 14% of patients experienced recurrent stroke over a mean follow-up period of 15 months. At 5 years, only half of the patients who had presented with ischemic symptoms were estimated to have survived without a second stroke. Death was attributable to initial and recurrent stroke (14 of 21 deaths), which the authors felt highlighted the high mortality associated with ischemic injury of the brainstem and its associated complications.9

Stroke prevention strategies for ICAD follow standard stroke prevention guidelines in addition to antiplatelet agents, including pharmacological treatments for blood sugar control for diabetics, statins for lipid disorders, and antihypertensive medications. Lifestyle management, including weight loss for overweight patients, moderate physical activity, and smoking cessation, are also part of the secondary stroke prevention strategies directed at atherosclerosis in general.10 During WASID follow-up, poorly controlled blood pressure and low-density lipoprotein (LDL) levels were shown to be the most important risk factors for stroke, vascular death, or myocardial infarction.11,12 Based on large studies of the link between serum cholesterol and ischemic stroke,13,14 the lowering of cholesterol concentrations with atorvastatin has been shown in a randomized trial to reduce the risk of stroke in high-risk populations and in patients with noncardioembolic stroke or TIA.15 The use of statins with intensive lipid-lowering effects is recommended in the updated American Heart Association guidelines for patients with atherosclerotic ischemic stroke or TIA without known coronary heart disease ( Fig. 30.1 ).16

Endovascular Therapy

Due to the high rate of recurrent stroke and lack of successful medical therapy for intracranial stenosis secondary to ICAD, the investigation of endovascular intervention as an alternative treatment option has evolved since 1980, when Sundt and colleagues reported the first successful percutaneous intracranial transluminal angioplasty of the basilar artery,17 on the premise that angioplasty alone or in conjunction with stenting may have a potential benefit for reducing recurrent stroke in these patients. Over the past 20 years, the development of microcatheters, balloons, and stents intended for cerebrovascular use has contributed to increased technical success by virtue of the increased compliance and navigability in the complex neurovascular anatomy.

Primary Angioplasty

Angioplasty is aimed at increasing perfusion of an arterial territory at risk, preventing vessel occlusion, and decreasing the risk of future embolic events. As flow is proportional to the fourth power of radius, any small improvement in vessel stenosis following angioplasty can lead to significant improvement in perfusion ( Fig. 30.2 ). The risks of primary angioplasty of intracranial vessels include dissection, rebound stenosis, vessel rupture, thromboembolic events, and acute vessel closure. Thromboembolic complications in the posterior circulation can be significant and lead to death if brainstem perforators are involved. Early data regarding posterior circulation intracranial angioplasty without stent placement are retrospective and largely pertain to technical success and angiographic outcomes, with few reports of long-term follow-up.18–21 These studies report less than 40% residual stenosis following angioplasty in a majority of patients and had complication rates ranging from 14 to 30%, with the periprocedural risk of stroke or death being 7 to 16%. When reported, the angiographic outcomes up to 1 year following angioplasty ranged from improvement or stability of stenosis to complete vessel occlusion.

After performing balloon angioplasty on 42 patients, 13 of whom had posterior circulation stenosis, Mori and colleagues described an angiographic classification of intracranial atherosclerotic lesions that indicated suitability for the procedure. The three different lesions types described were as follows:

1. 
   

   Type A: short (<5 mm), concentric or moderately eccentric, without vessel occlusion

   
   
2. 
   

   Type B: 5 to 10 mm long, tubular configuration, eccentric, moderately angulated or totally occluded lesions but less than 3 months old

   
   
3. 
   

   Type C: >10 mm long, tortuous configuration, angulated more than 90 degrees or totally occluded lesions and 3 or more months old

In this retrospective study, immediate clinical success rates of angioplasty in 80 hemodynamically significant extracranial and intracranial lesions for types A, B, and C were 92%, 86%, and 33%, with a 1-year restenosis rate of 0%, 33%, and 100%, respectively.22

In 1999, Connors and colleagues reported on their technique as it evolved over their retrospective 9-year experience with balloon angioplasty, with 35% of the 70 patients having posterior circulation intracranial stenosis. Their technique evolved from approximating the size of the balloon to the vessel caliber with rapid inflation to undersizing the balloon compared with the treated vessel with extremely slow inflation. Their technique of a very slow balloon inflation rate (1 atm/min) with an undersized angioplasty balloon resulted in lower periprocedural complication rates. Additionally, undersizing the balloon may have resulted in a suboptimal angiographic image but provided safer clinical results with reduced intimal damage, vessel dissection, and platelet aggregation.23 In 2006, Marks and colleagues published long-term follow-up data on 120 patients (50% in the posterior circulation) with a mean posttreatment stenosis of 36%, a periprocedural stroke and death rate of 5.8%, and a 4.4% annual stroke rate for all strokes over a mean follow-up of 42 months.24 Of note, this study contained patients with combined moderate and severe stenosis. A similarly large retrospective study by Wojak and colleagues on 84 lesions, all of which had greater than 70% initial stenosis and included 45% intracranial posterior circulation lesions, showed a low periprocedural stroke and death rate of 4.8% and a remarkably low annualized stroke and death rate of 3%, with a mean follow-up of 45 months.25 Stents were used in 26% of the procedures, either primarily or secondarily, because of an inadequate response to angioplasty. Ten procedures had radiographic evidence of dissection that did not require treatment with a stent.

A 2008 retrospective comparison by Siddiq and colleagues confirms that angioplasty alone tends to have higher residual stenosis compared with stenting in 95 angioplasties and 98 stenting procedures.26 However, this particular study found no statistically significant difference in the rates of periprocedural stroke, angiographic restenosis, or stroke-free and/or death-free survival between the two groups. The 2006 Wojak study states that only five were symptomatic, although 23% of their lesions developed restenosis. The degree of angiographic reduction to achieve clinical benefit has thus been controversial (i.e., whether less than 30 or 50% residual stenosis constitutes a technical success). Although stenting achieves an immediate greater reduction in degree of stenosis, this reduction may not translate into clinical benefit and is offset by greater technical difficulties. Several studies have suggested that stenting is technically more challenging than angioplasty,27 though this challenge may become less of an issue with the widespread use of self-expanding stents, as discussed in the next section.