Elsevier

The Lancet Neurology

Volume 12, Issue 11, November 2013, Pages 1106-1114
The Lancet Neurology

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

https://doi.org/10.1016/S1474-4422(13)70195-9Get rights and content

Summary

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).

Introduction

Intracranial atherosclerotic stenosis (ICAS) of a major intracranial artery is one of the most common causes of stroke worldwide and is associated with a high risk of recurrent stroke compared with other stroke subtypes. ICAS is particularly prevalent in black, Asian, Hispanic, and Indian populations, and in some Arabic countries, which suggests that the global burden of stroke from ICAS is likely to grow as populations continue to expand in regions most affected by the disease.1

Recent clinical trials have improved understanding of risk factors associated with stroke recurrence, imaging characteristics that are associated with prognosis, and treatments that significantly reduce stroke recurrence in patients with ICAS. Although the results of these trials are changing the standard of care for patients with ICAS, they also emphasise the need for further research into identification of patients at highest risk of stroke from ICAS and development of new therapies to lower the risk of stroke in these patients. In this Review, we discuss the findings from these studies, focusing on randomised therapeutic trials. We also discuss novel imaging techniques that are being developed to identify the patients at highest risk of stroke and new therapeutic strategies that might improve the prognosis of these high-risk patients.

Section snippets

Epidemiology and risk factors for recurrent stroke

ICAS causes about 5–10% of strokes in white people, 15–29% of transient ischaemic attacks or strokes in black people, and up to 30–50% of strokes in Asian people.1, 2, 3, 4, 5, 6 The frequency of ICAS as a cause of stroke also seems to be higher in northern India and Egypt than in white populations.7, 8 Potential explanations for racial and ethnic differences in the prevalence of ICAS include genetic susceptibility of some racial and ethnic groups, and differences in lifestyle and risk factor

Mechanisms of stroke associated with ICAS

There are three main hypothesised mechanisms of stroke related to ICAS: hypoperfusion, artery-to-artery embolism, and plaque extension over small penetrating artery ostia (also known as branch atheromatous disease).27, 29 Combinations of these ischaemic mechanisms can also occur—eg, when hypoperfusion prevents clearing of a distal embolus.30, 31, 32, 33

The underlying mechanism of stroke is typically inferred by characteristics on neuroimaging. For example, ischaemic infarcts in a watershed

Diagnostic imaging

Diagnostic methods used to identify ICAS include transcranial Doppler (TCD) ultrasound, MRA, CT angiography (CTA), conventional cerebral angiography, and high-resolution MRI. TCD, MRA, CTA, and high-resolution MRI are non-invasive methods that provide safer and less expensive ways to assess the intracranial arteries than conventional cerebral angiography; however, the accuracy of these methods is less clearly established. The Stroke Outcomes and Neuroimaging of Intracranial Atheroclerosis

Antithrombotic therapy

Anticoagulation was first reported as a treatment for symptomatic ICAS in 1955.39 Subsequently, data from a retrospective study suggested that warfarin was more effective than aspirin for stroke prevention in patients with symptomatic ICAS.40 However, data from WASID (a double-blinded, randomised trial comparing aspirin [1300 mg per day] with warfarin [target international normalised ratio (INR) 2–3]) showed no benefit of warfarin over aspirin for prevention of stroke and vascular death in

Directions for future research

Future research should focus on identification of this particularly high-risk subgroup and testing of alternative therapies in these patients. Novel non-invasive imaging techniques that could have a role in identification of high-risk patients include quantitative MRA,81 fractional flow reserve on MRA,82 high-resolution MRI,83, 84, 85, 86, 87 and vasomotor reactivity and emboli detection on TCD.43 Quantitative MRA is a technique that combines time-of-flight (TOF) and phase-contrast MRA

Conclusions

In summary, substantial progress has been made in the treatment of patients with ICAS over the past decade, which has resulted in a better prognosis for patients with this high-risk disease. Multifaceted medical management that incorporates short-term dual antiplatelet treatment (for 90 days) followed by aspirin monotherapy, coupled with intensive management of vascular risk factors is the treatment of choice for stroke prevention in these patients. Despite this aggressive medical management, a

Search strategy and selection criteria

We searched PubMed between 2000 and 2013 with the search terms “intercranial atherosclerosis”, “stroke”, “angioplasty”, “stenting”, “antiplatelet therapy”, “vascular imaging”, and “epidemiology”. Additionally, we searched references from relevant articles and those from a personal library. We included only references relevant to the topics covered in the Review. There were no language restrictions.

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