Intracranial atherosclerosis: current understanding and perspectives

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.