Intracranial atherosclerosis: current understanding and perspectives

Abstract

The importance of intracranial atherosclerotic disease (ICAD) as a cause of stroke is underscored as compared to that of extracranial carotid stenosis and nonvalvular atrial fibrillation. Recent large clinical trials of ICAD, which evaluated the effectiveness of anticoagulation and stenting to prevent thromboembolism and restore hemodynamic compromise, failed to reduce major vascular events in patients with ICAD. These trials showed the importance of optimal control of risk factors to reduce major vascular events in these patients. Recent advances in risk factors for ICAD are summarized, together with possible reasons for race-ethnic differences in the prevalence of ICAD. In addition, the failure of the major clinical trials of ICAD may be caused by limitations in the understanding of ICAD. Unlike in patients with extracranial carotid stenosis or atrial fibrillation, stroke associated with ICAD occurs in association with various stroke mechanisms such as in situ thrombotic occlusion, artery-to-artery embolism, hemodynamic insufficiency, and branch occlusion. In clinical trials of ICAD, patients with all these types of ICAD were included. However, treatment effects may differ among the different types of ICAD. Treatment strategies might be selected based on clinical features (including the time after onset) and serologic and neuroimaging biomarkers (including diffusion-weighted image pattern and plaque images). Additional clinical trials considering these features are needed.

Keywords: Atherosclerosis; Intracranial; Plaque; Stroke.

Figure 1

Mechanisms of stroke in patients with ICAD. (A) Thrombotic occlusion is a rare phenotype of ICAD. Magnetic resonance angiography (MRA) shows in situ thrombotic occlusion at the site of stenotic plaque. DWI shows territorial infarcts by severe hemodynamic compromise and embolic infarcts on the cortex. High-resolution MRI can show vulnerable plaque on intracranial vessels. (B) Artery-to-artery embolism is one of common phenotypes of ICAD. Artery-to-artery embolism is usually associated with a severe degree of intracranial stenosis, and transcranial Doppler ultrasonography can detect symptomatic or asymptomatic embolism during microembolic signal monitoring. DWI shows small, scattered, cortical embolic infarcts. (C) Hemodynamic impairment is another phenotype of ICAD. This phenotype is usually associated with a severe stenosis and a marked hemodynamic compromise, as seen on a perfusion-weighted image (PWI). DWI typically shows borderzone-type infarcts, and infarct growth is common with clinical deterioration. (D) Branch occlusive disease is a common phenotype of ICAD. This phenotype is often misclassified as small arterial disease due to a mild degree of stenosis on MRA, small deep infarcts on DWI, and relatively small perfusion defects. High-resolution MRI can reveal plaque without stenosis near the orifices of penetrating arteries.