Prevalence, diagnosis and management of intracranial atherosclerosis in White populations: a narrative review

Abstract

Background: Intracranial atherosclerotic disease (ICAD) represents a leading cause of ischemic stroke worldwide, conferring increased risk of recurrent stroke and poor clinical outcomes among stroke survivors. Emerging evidence indicates a paradigm shift, pointing towards increasing detection rates of ICAD among White populations and an evolving epidemiological profile across racial and ethnic groups. The present review aims to provide a comprehensive overview of ICAD, focusing on its pathophysiology, diagnostic approach, and evolving epidemiological trends, including underlying mechanisms, advanced neuroimaging techniques for diagnostic evaluation, racial disparities in prevalence, and current and emerging management strategies.

Main body: Atherosclerotic plaque accumulation and progressive arterial stenosis of major intracranial arteries comprise the pathophysiological hallmark of ICAD. In clinical practice, the diagnosis of intracranial artery stenosis (ICAS) or high-grade ICAS is reached when luminal narrowing exceeds 50% and 70%, respectively. Advanced neuroimaging, including high-resolution vessel wall MRI (HRVW-MRI), has recently enabled ICAD detection before luminal stenosis occurs. While earlier studies disclosed significant racial disparities in ICAS prevalence, with higher rates among Asians, Hispanics, and Blacks, recent evidence reveals rising detection rates of ICAD among White populations. Genetic, environmental and epigenetic factors have been suggested to confer an increased susceptibility of certain ethnicities and races to ICAD. Nevertheless, with improved accessibility to advanced neuroimaging, ICAD is increasingly recognized as an underlying stroke etiology among White patients presenting with acute ischemic stroke and stroke of undetermined etiology. While conventional management of ICAS entails risk factor modification, pharmacotherapy, and endovascular treatment in selected high-risk patients, substantial progress remains to be made in the management of ICAD at its early, pre-stenotic stages.

Conclusion: ICAD remains a critical yet underappreciated risk factor for ischemic stroke across all populations, highlighting the need for increased awareness and improved diagnostic strategies. The emerging epidemiological profile of ICAD across racial groups necessitates a reassessment of risk factors, screening protocols and preventive strategies. Future research should focus on refining the diagnostic criteria and expanding the therapeutic options to cover the full spectrum of ICAD, with the aim of improving patient outcomes and reducing the global burden of intracranial atherosclerosis and stroke.

Keywords: Endovascular; Intracranial artery stenosis; Intracranial atherosclerosis; Stenting; Stroke.

Fig. 1

Pathophysiology of Intracranial Atherosclerosis. Intracranial atherosclerotic disease (ICAD) is a chronic inflammatory disorder affecting arterial segments with high endothelial shear stress, such as bifurcations and curvatures. Early in atherogenesis, oxidized low-density lipoproteins (LDL) accumulate in the arterial intima, activating endothelial and smooth muscle cells (SMCs). This prompts monocytes to become macrophages and dendritic cells, which then differentiate into foam cells. As atherosclerosis progresses, immune cell infiltrates contribute to the thinning of the fibrous cap. Lipid accumulation and foam cell necrosis eventually form a necrotic core. At advanced stages of atherosclerosis, neovascularization from the adventitial vasa vasorum may lead to intraplaque hemorrhage and plaque instability. Image created with Biorender

Fig. 2

Mechanisms of ischemic stroke in Intracranial Atherosclerosis. Intracranial atherosclerotic disease (ICAD) can lead to ischemic events through various pathophysiological mechanisms, either individually or in combination. These comprise: (i) in-situ thrombosis and occlusion of the parent artery; (ii) artery-to-artery embolism, both resulting from atherosclerotic plaque rupture; (iii) progressive luminal stenosis causing hemodynamic compromise and cerebral hypoperfusion; and (iv) branch occlusive disease due to plaque expansion over small perforator artery openings, that leads to subcortical and/or lacunar strokes in the presence of ICAD. Adapted by Chen et al. [18] Image created with Biorender

Fig. 3

Diagnostic modalities for Intracranial Atherosclerosis. A: DSA reveals atherosclerotic stenosis of the M2 segment of the right MCA; B: Axial CTA shows high-grade stenosis of the M1 segment of the left MCA; C: Transcranial color-coded duplex ultrasonography (TCCS) reveals significant stenosis of the M1 segment of the right MCA with aliasing phenomenon; D: Axial MRA shows a high-grade stenosis of the M1 segment of the left MCA Abbreviations: DSA: Digital Subtraction Angiography; MCA: middle cerebral artery; CTA: Computed Tomography Angiography; MRA: Magnetic Resonance Angiography