Review articleCulprit intracranial plaque without substantial stenosis in acute ischemic stroke on vessel wall MRI: A systematic review
Graphical abstract
Introduction
Accurate identification of stroke etiology is crucial in guiding clinical treatment and improving outcomes [1]. Intracranial atherosclerotic stenosis is a major cause of ischemic stroke, accounting for 40% of stroke in Asian, 29% in African-American, and 15% in Caucasian populations [2,3]. Luminal stenosis, often assessed by noninvasive methods such as computed tomographic angiographic (CTA) and magnetic resonance angiography (MRA), has been independently associated with increased risk of acute ischemic strokes, and current practice guidelines rely mainly on the degree of stenosis (often ≥ 50%) within major intracranial arteries to decide treatment strategies [[4], [5], [6], [7]]. However, many authors have argued that such vascular assessment is limited in evaluating only the vessel lumen, while atherosclerotic plaque originates in the vessel wall, and may cause ischemic stroke in the absence of luminal stenosis [[8], [9], [10]].
During the past two decades, intracranial atherosclerotic disease (ICAD) imaging has shifted from an indirect assessment of atherosclerosis by measuring luminal stenosis toward a more direct assessment of atherosclerotic plaque itself, with increasing acknowledgment of the role of vascular remodeling patterns and the clinical significance of atherosclerotic plaque features [[11], [12], [13]]. Positive remodeling results in compensatory enlargement of the arterial outer wall with plaque growth, increasing the luminal diameter, thereby resulting in underestimation of the atherosclerotic plaque burden by traditional luminal angiographic techniques (CTA, MRA and Digital Subtraction Angiography (DSA)) [[14], [15], [16]]. Previous studies have shown positive remodeling to precede detectable stenosis, and its association with high risk of acute ischemic stroke [[17], [18], [19]]. Conventional luminal imaging techniques cannot characterize or differentiate features of atherosclerotic plaques pathologies, including thrombotic occlusion, occlusion of perforating arteries and plaque rupture, leading to distal embolization [7,20]. There has been increasing use of high-resolution vessel wall magnetic resonance imaging (vwMRI) to study intracranial plaques, and a recent meta-analysis identified characteristics of intracranial plaques on vwMRI that were significantly associated with plaque vulnerability and increased risk of stroke, with odds ratios between 1.22 and 10.09[12]. It is even argued that some, if not all, treatment failure may arise from limited awareness of high-risk intracranial arterial lesion properties [9]. However, most studies have focused only on intracranial arteries with high-grade stenosis (at least >50% stenosis). While up to 27% of fatal ischemic strokes could be attributed to an intracranial plaque with mild to moderate (30–75%) stenosis in autopsy studies [[20], [21], [22]], such atheromatous plaques are most often neglected in clinical setting. The clinical prevalence, characteristics and significance of atherosclerotic plaques of intracranial arteries with mild or no stenosis have been historically under-reported. For those individual studies that had included non-stenotic intracranial arteries, results were often based on small samples, aggregated with severely stenotic plaque, and varied widely between studies, limiting the appreciation of their significance.
Therefore, this study aimed to systematically review existing literature evidence to report (1) the relative prevalence, characteristics and clinical significance of non-stenotic atherosclerotic plaque by vwMRI and (2) the prevalence of culprit plaques with <50% stenosis in acute/subacute stroke patients. This information would define the clinical benefit and appropriate application of intracranial vwMRI in non-stenotic intracranial arteries both for clinical use and future prospective studies.
Section snippets
Materials and methods
This systematic review was performed with a standardized written protocol with reference to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
Search results
The detailed study selection process is shown in Fig. 1. A total of 634 articles were identified after the removal of duplicates. After screening of titles and abstract, 583 were excluded, as not investigating intracranial plaques by high resolution vwMRI. Thirty studies were excluded after full-text examination due to reporting of patients with stenosis degree of >50% only, or lack of sufficient data to allow specific analysis on arteries with <50% stenosis. Finally, 21 studies were identified
Discussion
Despite comprehensive workup of acute ischemic stroke, as many as 23–40% of strokes have no identifiable cause, and these so-called “cryptogenic strokes” are even more frequent in younger patients [42]. ICAD is increasingly recognized as an important etiology when other potential stroke causes such as cardiac etiologies and extracranial atherosclerotic stenosis were excluded [43]. However, ICAD has been likely under-appreciated due to the current reliance on conventional luminal stenosis-based
Conflicts of interest
The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.
Financial support
This study is supported by United States National Institutes of Health (NIH) grant K99HL136883.
Author contributions
Chengcheng Zhu designed the main ideas and methodology of the review. Yuting Wang and Xinke Liu did data collection, extraction, calculation, summary and wrote the manuscript. Xiao Wu helped with data analysis and preparation of figures. Andrew J Degnan and Ajay Malhotra gave critical suggestions on the design of this review. All authors revised the manuscript and approved the final submission.
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These authors contribute equally to this work.