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.
ReviewAtherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment
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
References (91)
- et al.
Magnetic resonance angiography findings in patients with ischemic stroke from north India
J Stroke Cerebrovasc Dis
(2010) - et al.
Lipoprotein-associated phospholipase A2 testing usefulness among patients with symptomatic intracranial atherosclerotic disease
Atherosclerosis
(2011) - et al.
Clopidogrel plus aspirin versus aspirin alone for reducing embolisation in patients with acute symptomatic cerebral or carotid artery stenosis (CLAIR study): a randomised, open-label, blinded-endpoint trial
Lancet Neurol
(2010) - et al.
The association of cigarette smoking with enhanced platelet inhibition by clopidogrel
J Am Coll Cardiol
(2008) - et al.
Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial
Lancet
(2004) - et al.
In vivo high-resolution MR imaging of symptomatic and asymptomatic middle cerebral artery atherosclerotic stenosis
Atherosclerosis
(2010) - et al.
Large artery intracranial occlusive disease: a large worldwide burden but a relatively neglected frontier
Stroke
(2008) - et al.
Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction
Stroke
(1995) - et al.
Stroke in young black patients. Risk factors, subtypes, and prognosis
Stroke
(1995) Cl inical characteristics of transient ischemic attacks in black patients
Neurology
(1991)
Race and sex differences in the distribution of cerebral atherosclerosis
Stroke
Global burden of intracranial atherosclerosis
Int J Stroke
Intracranial steno-occlusive arterial disease and its associations in Egyptian ischemic stroke patients
Stroke
Chinese-white differences in the distribution of occlusive cerebrovascular disease
Neurology
Clinical and angiographic comparison of asymptomatic occlusive cerebrovascular disease
Neurology
Cerebral atherosclerosis—a comparative autopsy study between Nigerian Negroes and American Negroes and Caucasians
Neurology
High lipoprotein (a), diabetes, and the extent of symptomatic intracranial atherosclerosis
Neurology
Etiologic mechanisms in cerebral atherosclerosis. Preliminary study of 3,839 cases
Arch Neurol
Race-ethnic differences in stroke risk factors among hospitalized patients with cerebral infarction: the Northern Manhattan Stroke Study
Neurology
Predictors of intracranial carotid artery atherosclerosis. Duration of cigarette smoking and hypertension are more powerful than serum lipid levels
Arch Neurol
Incidence and risk factors of intracranial atherosclerotic stroke: the Northern Manhattan Stroke Study
Cerebrovasc Dis
Risk factor status and vascular events in patients with symptomatic intracranial stenosis
Neurology
Relationship between blood pressure and stroke recurrence in patients with intracranial arterial stenosis
Circulation
Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis
N Engl J Med
Association between changes in lipid profiles and progression of symptomatic intracranial atherosclerotic stenosis: a prospective multicenter study
Stroke
Impact of metabolic syndrome on prognosis of symptomatic intracranial atherostenosis
Neurology
Association of the metabolic syndrome with intracranial atherosclerotic stroke
Neurology
Adiponectin levels in patients with intracranial atherosclerosis
Neurology
Progression of symptomatic intracranial large artery atherosclerosis is associated with a proinflammatory state and impaired fibrinolysis
Stroke
Predictors of ischemic stroke in the territory of a symptomatic intracranial arterial stenosis
Circulation
Collaterals dramatically alter stroke risk in intracranial atherosclerosis
Ann Neurol
Significance of good collateral compensation in symptomatic intracranial atherosclerosis
Cerebrovasc Dis
Intracranial branch atheromatous disease: a neglected, understudied, and underused concept
Neurology
Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke
Arch Neurol
Lesion patterns and stroke mechanism in atherosclerotic middle cerebral artery disease: early diffusion-weighted imaging study
Stroke
Simultaneous occurrence and interaction of hypoperfusion and embolism in a patient with severe middle cerebral artery stenosis
Stroke
Is hypoperfusion an important cause of strokes? If so, how?
Cerebrovasc Dis
Risk factors and outcome of patients with symptomatic intracranial stenosis presenting with lacunar stroke
Stroke
The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial
Neurology
Intracranial vascular stenosis and occlusive disease: evaluation with CT angiography, MR angiography, and digital subtraction angiography
AJNR Am J Neuroradiol
How accurate is CT angiography in evaluating intracranial atherosclerotic disease?
Stroke
A standardized method for measuring intracranial arterial stenosis
AJNR Am J Neuroradiol
Studies in cerebrovascular disease. III. The use of anticoagulant drugs in the treatment of insufficiency or thrombosis within the basilar arterial system
Proc Staff Meet Mayo Clin
The Warfarin-Aspirin Symptomatic Intracranial Disease Study
Neurology
Failure of antithrombotic therapy and risk of stroke in patients with symptomatic intracranial stenosis
Stroke
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