Endovascular Treatment of Intracranial Occlusive Disease

Introduction

Atherosclerosis and moyamoya disease (MMD) are the two most common forms of intracranial occlusive disease. In this chapter, we discuss endovascular options for the treatment of intracranial atherosclerotic disease (ICAD) and MMD.

Approximately 8% to 10% of ischemic strokes in the United States are attributed to ICAD. ^, This accounts for 70,000 to 90,000 new strokes each year. Nearly 25% of strokes occurring in ethnic populations, including Asians and African Americans, are ascribed to intracranial occlusive disease. With the use of advanced imaging options, ICAD is recognized more frequently. Given the high prevalence of intracranial subocclusive and occlusive disease, the management of asymptomatic disease and an understanding of the indications for treatment of symptomatic disease have become more important.

Natural History

The annual ipsilateral stroke risk based on the natural history of ICAD is 3.1% to 8.1% for the internal carotid artery (ICA) and 0% to 7.8% for the middle cerebral artery (MCA). The most common locations for intracranial stenosis in decreasing order are MCA, 33.9%; ICA, 20.3%; basilar artery (BA), 20.3%; vertebral artery (VA), 19.6%; and a combination of these arteries, 5.9%. Although anterior circulation strokes do not have a mortality rate as high as posterior circulation strokes, due to the area they supply, they account for a large number of strokes and significant morbidity.

The most definitive evaluation of symptomatic intracranial stenosis to date has been the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial in which the investigators found an 11% to 12% first-year risk of stroke in the same area of stenosis. Not surprisingly, three-quarters of strokes were found to be in the distribution of stenotic vessels, and patients who had 50% to 69% stenosis were noted to have a 1-year stroke risk of 6% and those with more than 70% stenosis had a 1-year stroke risk of 19%. In a study of serial angiography for ICAD, 40% of untreated patients demonstrated a progression in stenosis severity, 20% showed regression of stenotic lesions, and 40% of lesions remained unchanged. Identification of patients at risk of ICAD progression is a matter of debate.

Pathophysiology

ICAD is characterized by the presence of atheromatous plaques deposited in the vessel wall by mechanisms similar to the atherosclerosis of extracranial larger arteries. ICAD may be asymptomatic or present with transient ischemic attacks (TIAs) or cause a large vessel occlusion (LVO), subcortical or lacunar infarct, and cognitive deficits. Underlying mechanisms for symptomatic ICAD are artery-to-artery emboli, in-situ thromboembolism, reduction of blood flow due to stenosis, and occlusion of local branches.

Understanding cardiac and cerebrovascular reserve is important to understanding the pathophysiology of occlusive disease. Hypoperfusion across a stenotic segment increases velocities within proximal vasculature and leads to decreased flow, which can cause patients to become symptomatic. Similarly, thrombosis at the site of stenosis secondary to plaque rupture, plaque hemorrhage, or progressive occlusive plaque growth may cause an acute LVO stroke. ICAD is the leading cause of LVO in Asia and the second most common cause of LVO in North America after cardioembolic phenomenon. Endovascular treatment of LVO becomes more challenging in the presence of an underlying ICAD and is discussed below. Other mechanisms for symptomatic ICAD include thromboembolism distal to the stenotic segment as well as occlusion of small perforating arteries and branch vessels at the site of the plaque. ^, These mechanisms tend to cause acute hemodynamic changes that can be evaluated by computed tomography (CT) perfusion and magnetic resonance (MR) imaging.

In addition to acute changes, chronic hemodynamic insufficiency plays a large role in ICAD and subocclusive disease. Chronic hemodynamic insufficiency has been classified into three stages: stage 0, normal hemodynamics; stage 1, reflex vasodilation in response to poor collateral flow and falling perfusion pressures with increased time-to-peak, preserved cerebral blood flow (CBF), and elevated cerebral blood volume (CBV); and stage 2, poor perfusion in response to cerebral perfusion pressure being outside the autoregulatory range. Stage 2 can best be noted with acetazolamide (Diamox, Teva Pharmaceuticals, North Wales, Pennsylvania) perfusion studies (referred to as acetazolamide challenge testing).

Classification

Mori et al. described the classification of intracranial stenosis according to lesion type and length as follows: type A, ≤5 mm and concentric; type B, 5 to 10 mm with eccentric plaque or completely occlusion for less than 3 months of follow-up evaluation; and type C, greater than 10 mm and angulated with substantial tortuosity. This classification system plays a role in stroke risk and restenosis rates on follow up.

Medical Management

For asymptomatic patients, aggressive lifestyle modifications and medical management of risk factors including diabetes, hypercholesterolemia, and hypertension remain the crucial pillars of medical management. The use of dual antiplatelet therapy has not been well validated in ICAD but has been significant in reducing atherosclerotic burden and has become the mainstay of therapy for cardiac disease.

Currently, the most definitive study of the medical management of symptomatic intracranial stenosis has been the prospective WASID trial. The 2-year risk for stroke was 19.7% in the aspirin group and 17.2% in the warfarin group. At the conclusion of the study, it was noted that there were significant morbidities associated with warfarin therapy for medical management and that such therapy did not address the pathophysiology of the disease process. A randomized controlled trial involving 100 patients with acute symptomatic cerebral or carotid artery stenosis found combination therapy with clopidogrel and aspirin to be more effective than aspirin alone and that is the current treatment regimen. Although dual antiplatelet therapy did reduce the 1-year stroke risk for that patient population, patients who have continued signs of chronic hypoperfusion or stroke may do better with surgical or endovascular management.

Evolution and Results of Endovascular Therapy

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial investigators showed that 1 in 8 symptomatic patients had a recurrent stroke within 1 year of observation after stent placement. There was an elevated rate of stroke in stented patients with a higher perioperative morbidity related to revascularization procedures. The study used only Wingspan stents (Stryker, Kalamazoo, Michigan). Patients who had undergone submaximal angioplasty were excluded, and angioplasty alone was not performed in this study. The 1-month stroke and death rate in SAMMPRIS was 14.7% in the stenting group. In subsequent studies, the 1-month stroke and death rates were 6.6%, 4.5%, and 6.5% for the Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA) study, Wingspan study, and Apollo Stent for Symptomatic Atherosclerotic Intracranial Stenosis study, respectively. The reason for high morbidity and mortality in SAMMPRIS was thought to be improper selection of patients. A multicenter trial by Gao et al. applied SAMMPRIS criteria with some modifications; for example, they did not select patients who had a stroke within 3 weeks of a prior episode of stroke. Patients with perforator-only strokes were also excluded. One hundred patients with target artery stenosis of 70% to 99% were treated with angioplasty and stenting 3 weeks after an episode of acute ischemic stroke. The overall mortality in the study was 2% (95% confidence interval, 0.2% to 7.0%). Angioplasty and stenting have become much safer and therefore can be performed in carefully selected patients.