Richard Jackson, MD
Despite the prevalence of symptomatic intracranial stenosis, there has been little progress into biomarkers that may identify patients at the highest risk of stroke recurrence. This article attempts to find an imaging biomarker for symptomatic intracranial atherosclerotic plaques.
From a prospectively enrolled MCA infarct population, a retrospective analysis was undertaken in a small cohort of 74 Asian patients with symptomatic intracranial stenosis of the middle cerebral artery (MCA). Whole brain high resolution pre and post-contrast magnetic resonance imaging (MRI) was used to evaluate MCA plaques. Patients were divided into A-to-A and non-A-to-A embolic infarction groups based on MR diffusion-weighted imaging infarct patterns. Patients with a previous history of stroke or transient ischemic attack on the symptomatic side, history of ipsilateral MCA or internal carotid artery occlusion, significant occlusion or plaque on the ipsilateral extra-cranial internal carotid artery, non-atherosclerotic vasculopathy and risk factors for cardiac embolism were excluded. Quantitative data were analyzed using t-test and chi squared testing. Hyperintense plaques (HIP) were more frequently observed in the A-to-A embolism group (75% versus 21.1%; p<0.001). In the A-to-A embolism patients, two thirds of HIPs were located adjacent to the lumen and one third of HIPs were located within the plaque (Figure 1).
Figure 1. Different types of hyperintense plaques (HIPs) and plaque surface. High-resolution magnetic resonance imaging (HRMRI) demonstrated HIPs with hyperintense areas (arrow) located adjacent to the lumen (A)/within the plaque (B) and irregular (C)/regular (D) plaque surface (arrowhead).
A higher prevalence of plaque surface irregularity was also observed in the A-to-A group (41.7% versus 18.4%; P=0.029). The proportions of plaque enhancement were not significantly different between the two groups nor were the mean remodeling indexes (Figure 2). The authors hypothesized that the plaque enhancement is consistent with higher rates of intra-plaque hemorrhage and plaque rupture with superimposed thrombus in the A-to-A embolic group. The authors concluded that A-to-A embolic infarction in intracranial atherosclerotic disease has distinct vulnerable plaque characteristics that may predict further infarction. The limitations of the study were the small number of patients, the generalizability to United States populations and the lack of long-term follow-up. Also, this imaging capability is not available in a majority of stroke centers.
Figure 2. Comparison between 2 groups in vessel wall characteristics. Number of hyperintense plaques (HIPs; A), plaques with surface irregularity (B), plaques with various degree of enhancement (C), and mean remodeling index (D) in artery-to-artery (A-to-A) embolism and non–A-to-A embolism group.
Explorations such as this are a first step to designing focused trials on treatment and prevention of intracranial stenosis to address the current dilemma created by the Stenting Versus Aggressive Medical Management for Intracranial Arterial Stenosis (SAMMPRIS) trial as to whether dual antiplatelet for 3 months or monotherapy antiplatelet is the optimal secondary stroke prevention strategy. In the SAMMPRIS trial, patients in the medical management arm treated with dual antiplatelet therapy for 3 months had better outcomes than the medical management plus stenting arm. There is, therefore, only indirect evidence that dual antiplatelet therapy for 3 months is the best medical management. All that can be said from the evidence is that in 2012 dual antiplatelet therapy was the more efficacious treatment in comparison to stenting methods and technology from 2011–2012. Further investigations could lead to the use of HIP and surface irregularity as a biomarker for use in randomized control trials of secondary prevention and treatment of symptomatic intracranial atherosclerosis.
