We based our Seminar on personal knowledge of the subject supplemented by data derived from multicentre randomised trials and selected non-randomised or observational clinical studies that included ten or more patients. The information was identified by searches on Medline from January, 2004, to April, 2013, by cross-referencing keywords of “cerebral atherosclerosis”, “ischaemic stroke”, “intracranial stenosis”, “intracranial atherosclerosis”, “neuroimaging”, “clinical studies”, “randomised
SeminarIntracranial atherosclerosis
Introduction
Atherosclerotic lesions ranging from slight wall thickening and non-stenosing plaques to severe luminal narrowing often involve intracranial arteries encased by cranial bones and dura, or those located in the subarachnoid space. The most common sites, in order, are the basilar artery, the internal carotid arteries, the middle cerebral arteries, the intracranial vertebral arteries, the posterior cerebral arteries, and the anterior cerebral arteries.1 Intracranial atherosclerosis can occur in isolation or as part of systemic atherosclerotic disease involving the coronary, extracranial, and other peripheral arteries.2, 3 A disproportionately high rate of stroke mortality occurs in Asian countries such as China, Japan, and South Korea where intracranial atherosclerosis is highly prevalent.4 Therefore, intracranial atherosclerosis could be a major cause of regional variation in stroke mortality.
Section snippets
Epidemiology
Data for atherosclerotic disease prevalence are based on either studies of pathological changes in autopsy specimens or detection of arterial calcification or lumen narrowing by neuroimaging in population-based screening.5 In a study,6 atherosclerosis was evident in 10–30% of Europeans aged 20–29 years, and by the age of 65 years, 80–97% of the population had pathological evidence of intracranial atherosclerosis. In the population-based Rotterdam Study,6 intracranial internal carotid artery
Pathological appearance
Fatty streaks and fibrous plaques in intracranial arteries are evident by age 24 years,27 followed by intimal necrosis and thickenings in older individuals.28 Proliferative fibrosis of the intima or adventitia is more prevalent than is lipid infiltration in intracranial atherosclerosis, and changes appear later than those seen in coronary arteries.2, 29 Well defined plaques (figure 1) are most frequent in elderly people.14, 30 Vasa vasorum extending into the vascular media (neovascularisation)
Risk factors
Age, hypertension, and type 2 diabetes mellitus are consistently identified as independent risk factors for TCD-documented intracranial stenosis in studies that include asymptomatic8, 38, 39 or symptomatic patients.40 Metabolic syndrome—a disorder of metabolic risk factors, insulin resistance, and vascular inflammation—is identified in almost half of patients.41, 42, 43 In the Barcelona Asymptomatic Intracranial Atherosclerosis (AsIA) study,44 diabetes mellitus and metabolic syndrome increased
Clinical manifestations
Intracranial stenosis presents with one or many recurrent ischaemic strokes and transient ischaemic attacks (TIA).54 Intracranial plaques and stenoses on autopsy are identified in 45–62% of patients who have had an ischaemic stroke,33, 50 and are causal in about 10% of ischaemic strokes.50 Other ischaemic strokes are probably related to concomitant proximal extracranial stenosis or atrial fibrillation identified in 10–20% of patients with intracranial atherosclerosis.55, 56, 57 In the Northern
Diagnosis, quantification, and characterisation
Raised mean blood flow velocities on TCD or luminal narrowing and absence of flow, or both, on MRI, CT, and catheter angiography are used to identify and quantify the severity of intracranial atherosclerosis (table 1).87, 88, 89, 90, 91 Because of high negative predictive values, non-invasive methods are good screening tests, but might be inadequate to measure the severity of disease in some circumstances. Other appropriate features, such as the presence of multiple cardiovascular risk factors
Stroke, cardiovascular events, and mortality
After an initial TIA or ischaemic stroke, brain ischaemia can recur in the distribution of the stenotic artery and infrequently in another distribution in patients with intracranial stenosis. The high rate of vascular events emphasises the importance of timely diagnosis and treatment in these patients. Several studies have investigated patients given antithrombotic treatment but without intensive medical management. Early progression in deficits and mortality is underestimated in studies that
Antithrombotic treatment
The present treatment of patients with ischaemic events attributable to intracranial stenosis is based on a combination of antiplatelet drugs and optimisation of blood pressure and LDL cholesterol values through lifestyle modification and drug treatment (figure 4).
Early initiation of antiplatelet drugs is preferred over parenteral anticoagulation in patients who present with brain ischaemic events related to intracranial atherosclerosis because of easy administration, similar efficacy, and
Prevention of progression of stenosis
An increase in severity of stenosis due to continued inflammatory changes, lipid deposition, fibrosis, in-situ thrombus formation, and intraplaque haemorrhage is identified in 33% of patients during 2 years, and might result in occurrence of new ipsilateral ischaemic events.166, 167 In one study,123 457 patients with intracranial stenosis in the middle cerebral arteries or basilar artery and on aspirin were randomly assigned to either cilostazol or clopidogrel. The progression of intracranial
Conclusions
Intracranial atherosclerosis is a highly prevalent disorder that has gained recent attention because of the high risk of recurrent subclinical and clinical ischaemic events, and its association with cognitive deficits and dementia. Concurrent existence of extracranial and coronary artery atherosclerosis necessitates a targeted and global approach to reduce the risk of new or recurrent cerebral and coronary ischaemic events in patients with intracranial atherosclerosis.
Search strategy and selection criteria
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