Cause and Mechanisms of Intracranial Atherosclerosis

Intracranial atherosclerosis, one of the leading causes of ischemic stroke, is associated with an increased risk for recurrent stroke and dementia.1,2 Individuals of Asian, Hispanic, and African American ancestry are especially affected. Recent European studies revealed a much higher prevalence of intracranial lesions than commonly presumed, suggesting that intracranial atherosclerotic disease is potentially the most common cause of ischemic stroke worldwide.1,3 Ischemic strokes are clinically categorized into 5 subtypes based on their underlying cause: large-artery atherosclerotic stenosis, small-artery disease (lacunes), cryptogenic, major-risk-source cardiogenic embolism, and unusual (eg, dissections, arteritis). Most nonlacunar ischemic strokes are thought to be thromboembolic, which presumably also accounts for most cryptogenic strokes. Embolic sources include minor-risk or covert cardiac sources, veins via paradoxical embolism, and nonocclusive atherosclerotic plaques in the aortic arch or cervical or cerebral arteries.4 Besides embolic strokes, 2 other mechanisms have been associated with intracranial atherosclerosis-related strokes, namely hypoperfusion through a stenotic artery causing watershed or border-zone stroke and plaque overgrowth of perforator artery ostia, which is associated with penetrating artery disease and lacunar infarcts and has been related to cryptogenic strokes.5–7 Even mild stenosis of intracranial atherosclerotic arteries (<50%) may therefore be clinically relevant, and high-resolution magnetic resonance imaging studies are needed to identify and determine the degree and location of stenosis in this patient group.5,8 The possibly causal role of nonstenotic plaques in ischemic stroke highlights the need for more insight into the mechanisms and occurrence of intracranial atherosclerosis. In the 1960s and 1970s, large, descriptive autopsy studies were conducted, providing classic morphological features of intracranial arteries. Despite the importance of intracranial atherosclerosis to stroke and dementia, there is a lack of more recent mechanistic studies. Therefore, we intend to draw attention to this neglected research field by …