Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment

Abstract

Intracranial atherosclerosis is one of the most common causes of stroke worldwide and is associated with a high risk of recurrent stroke. New therapeutic approaches to treat this high-risk disease include dual antiplatelet treatment, intensive management of risk factors, and endovascular therapy. Early data from randomised trials indicate that aggressive medical therapy is better than stenting for prevention of recurrent stroke in high-risk patients with atherosclerotic stenosis of a major intracranial artery. Nevertheless, there are subgroups of patients who remain at high risk of stroke despite aggressive medical therapy. Further research is needed to identify these high-risk subgroups and to develop more effective treatments. Non-invasive vascular imaging methods that could be used to identify high-risk patients include fractional flow on magnetic resonance angiography (MRA), quantitative MRA, and high-resolution MRI of the atherosclerotic plaque. Alternative therapies to consider for future clinical trials include angioplasty alone, indirect surgical bypass procedures, ischaemic preconditioning, and new anticoagulants (direct thrombin or Xa inhibitors).

Conflict of interest statement

Conflicts of interest

CAH has consulted for Covidien LP, Boehringer Ingelheim, and CE Outcomes LLP, and has served as an expert witness in non-corporate medical malpractice cases involving stroke. MIC was the principal investigator of the SAMMPRIS trial, funded by NIH; Stryker Neurovascular provided stents for the SAMMPRIS trial and paid for some of the third party monitoring of sites in that trial; AstraZeneca Corporation provided rosuvastatin for patients in the SAMMPRIS trial. MIC was the principal investigator of the WASID trial and NIH Wingspan registry, both of which were also funded by NIH; Bayer provided aspirin and Bristol-Myers Squibb provided warfarin for the WASID trial. MIC has received personal fees from GORE Associates, Merck/Ponexel, and Medtronic for participating as a stroke adjudicator or data safety board monitoring member on clinical trials unrelated to the submitted work. MIC has also been an expert witness in non-corporate medical malpractice cases involving stroke. TNT was an investigator on the SAMMPRIS trial, funded by NIH. She was an investigator on the CHIASM (Characterization of Intracranial Atherosclerotic Stenosis using HR MRI) study, funded by NIH. She was on the clinical event adjudication committee for the VERITAS study, funded by NIH.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Figures

Figure 1. Magnetic resonance angiography showing a flow gap in the right middle cerebral artery in a patient with a recent right hemisphere infarct

This gap suggests a flow-limiting stenosis, but the degree of stenosis cannot be accurately measured.

Figure 2. Catheter angiogram showing 90% stenosis of the right middle cerebral artery in the patient whose magnetic resonance angiography is shown in figure 1

If the patient’s stroke occurred within 30 days, this degree of stenosis is associated with a particularly high risk of recurrent stroke (as high as 23% at 1 year, based on data from the WASID trial).

Figure 3. Treatment recommendations for patients with symptomatic 50–99% intracranial arterial stenosis, based on the results of the WASID and SAMMPRIS trials,

*75% of patients with symptomatic intracranial arterial stenosis in the WASID trial were in this category. †25% of patients in the WASID trial and 100% of patients in the SAMMPRIS trial were in this category.

Figure 4. High-resolution MRI of vertebral artery stenoses with plaque components

Panels A–D show T2-weighted and T1 post-contrast images (panels C and D have plaque components marked) of a cross-section of a vertebral artery plaque with a thick, intact, fibrous cap (grey) and lipid core (white with black asterisk). Panels E–H show T2-weighted and T1 post-contrast images (panels G and H have plaque components marked) of a cross-section of a vertebral artery plaque with a ruptured fibrous cap (grey) and lipid core (white with black asterisk), which enhances with contrast (white asterisk) and is also indicative of plaque rupture. The solid white line shows the outside vessel wall and the dashed white line the lumen.