Extracranial vascular disease
The term stroke encapsulates the potentially devastating consequences when blood supply to the brain is disrupted. There are two main types of stroke:
- Ischaemic stroke due to inadequate blood supply, usually by embolisation from or occlusion of an artery that supplies the brain.
- Haemorrhagic stroke due to bleeding from a ruptured cerebral blood vessel in the brain.
More than 40,000 Australians each year experience a stroke, nearly a third of which are fatal. Another third of patients who suffer a stroke will be left with significant neurological deficit, making up almost one in four of Australia's chronic disabled population. The already considerable economic impact of stroke is likely to rise with Australia's ageing population.
Unlike cellular recovery after liver injury, dead neurons in the brain cannot regenerate. There is therefore an increasing emphasis on the emergency nature of impending stroke so that intervention can be undertaken before irreversible cerebral damage occurs. Like ‘heart attack’ the concept of ‘brain attack’ has arisen.
The four major arteries that supply the brain are the vertebral arteries originating from the subclavian arteries forming the basilar artery and supplying the posterior cerebral circulation and the internal carotid arteries. These arise from the carotid bifurcation in the neck and lead onto the middle cerebral arteries, the most important branches in the anterior cerebral circulation. The Circle of Willis provides potential communication between the anterior and posterior cerebral circulations but may be inadequate to fully compensate for an occluded internal carotid artery in about 20% of individuals.
Although the death rate from stroke has more than halved since 1980 in common with other forms of cardiovascular disease, cerebrovascular disease remains the third commonest cause of death after heart disease and cancer, accounting for 10% of all mortality in the Australian community. Predominantly middleaged males are affected but the incidence of stroke increases exponentially with age, with 50% of all strokes occurring in patients over 75 years of age.
Risk factors for stroke
Stroke arising from extra-cranial arterial disease is most likely to occur when there is a high grade (>70%) stenosis of the internal carotid artery, particularly if there have been recent transient ischaemic attacks (TIAs).
Risk factors for stroke include high blood pressure, tobacco smoking, heavy alcohol consumption, high cholesterol, obesity, diabetes and insufficient physical activity. Hypertension is associated with both ischaemic and haemorrhagic stroke. Improved medical management of high blood pressure has contributed to the decreasing incidence of stroke (Management algorithm presentation). Carotid stenosis occurs more frequently in patients who have co-existent coronary artery disease or lower extremity peripheral arterial disease.
Embolic stroke is most likely in patients with atrial fibrillation or after an acute myocardial infarction.
Overall, 70% of strokes are ischaemic and 15% haemorrhagic, either from primary intracranial hemorrhage (11%) or subarachnoid hemorrhage (4%). Haemorrhagic stroke can be readily differentiated from ischaemic stroke by computed tomography (CT) or magnetic resonance imaging (MRI) and will not be considered further.
Ischaemic stroke results in cerebral infarction, due to atherosclerosis affecting the large arteries in 75%, from cardiac embolism in 15% or from small vessel occlusion, usually related to hypertension, causing lacunar infarction in 10%.
Atherosclerosis affecting the extracranial circulation most commonly occurs at the carotid bifurcation, particularly at the origin of the internal carotid artery, where there is a region of turbulent flow as the common carotid artery divides into the high-resistance external carotid artery and low-resistance internal carotid artery.
There are two main theories of how disease at the carotid bifurcation may cause transient ischaemic attacks and stroke.
Embolic theory: Embolisation of atherosclerotic material or thrombus can arise from the carotid bifurcation. This is more likely to occur, with complicated atherosclerotic plaques forming a tight (>70%) stenosis.
Haemodynamic theory: Blood flow to the brain may be reduced by a tight stenosis or occlusion of the carotid arteries. The effect of such lesions will depend on the extent of intracranial collateral circulation. This is the mechanism of stroke after profound hypotension from any cause.
The theories are not mutually exclusive, as the likelihood of embolisation from carotid plaque and occlusion of the internal carotid artery increases with the degree of stenosis.
Extracranial arterial pathology
Atherosclerosis is the pathological basis of extracranial arterial disease in about 90% of cases, with less common conditions occurring in 10%, including fibromuscular disease, dissection, aneurysm, arteritis such as Takayasu's disease and carotid body tumours. Recurrent stenosis of the carotid artery due to neointimal hyperplasia can occur after surgery or carotid stenting.
Fibromuscular dysplasia occurs mainly in young females and causes irregular webs and dilatations, causing a ‘string of beads’ sign on angiography in the internal carotid artery or even dissection or aneurysm formation. Takayasu's disease is a non-specific arteritis that can occlude the major branches of the thoracic or abdominal aorta (hence the term pulseless disease). Carotid body tumours are rare, arise from the chemoreceptors, and are therefore highly vascular and occasionally malignant. They present as a pulsatile mass in the neck that can be moved from side to side and should not be biopsied.
Another mechanism of haemodynamic cerebral hypoperfusion occurs on basis of ‘subclavian steal’. If the left subclavian artery or more rarely the innominate artery is stenosed or occluded, then the vertebral artery becomes an important collateral pathway to sustain blood flow to the arm. When the arm is exercised, vertebral arterial flow reverses resulting in cerebral hypoperfusion. This is usually asymptomatic unless there is co-existent internal carotid stenosis.
Extracranial cerebrovascular disease may be either symptomatic or clinically silent. This will depend on whether the carotid plaque is affecting blood flow or embolising and on the sensitivity of the affected part of the brain. Symptoms will depend on whether the anterior (carotid) or posterior (vertebrobasilar) circulations are involved. The left hemisphere, largely supplied by the anterior circulation, is usually dominant in a right-handed person, so emboli to the left cerebral hemisphere are more likely to result in disabling symptoms.
A bruit in the neck may indicate asymptomatic extracranial arterial disease. It is important to distinguish between bruits arising from the heart or great vessels and bruits due to turbulence at the carotid bifurcation, which are loudest in the neck. A carotid bruit is a poor marker of internal carotid stenosis and is probably a better guide to the presence of general atherosclerosis, particularly coronary artery disease. Only about a third of patients with a carotid bruit will have a significant stenosis of their internal carotid artery and a bruit is rarely present with the most severe stenosis (>90%) because of reduced blood flow.
An asymptomatic internal carotid stenosis is an occasional incidental finding on duplex ultrasound scanning.
All the major clinical trials have confirmed that the likelihood of symptoms and stroke is directly related to the severity of internal carotid stenosis. Microemboli from carotid plaque induce a transient cerebral ischaemia in either the carotid (anterior) or vertebrobasilar (posterior) circulation. Symptoms may occur as an isolated event or may recur or progress to a major stroke.
Transient ischaemic attacks
A TIA is a reversible neurological deficit that resolves in 24 hours, but is usually briefer, lasting for less than 15 minutes and resolving without a persistent neurological deficit. Classical carotid (anterior circulation) TIAs involve ipsilateral retinal ischaemia manifest as amaurosis fugax (fleeting blindness) described as a curtain coming down over the eye. Cholesterol emboli (Hollenhorst plaques) and fibrin-platelet emboli (Fisher plugs) can be seen on fundoscopy in the retinal arteries, and both are strongly indicative of ulcerative atheromatous disease of the carotid arteries, particularly at the carotid bifurcation in the neck.
Motor and sensory symptoms involve the contralateral limbs because of the crossover of the major motor and sensory neural pathways. The symptoms and signs are focal and may be motor, with weakness, paralysis, poor function, or clumsiness in one or both extremities. There may be sensory symptoms, with numbness or paraesthesiae affecting one or both extremities on the same side. Dysphasia with speech disturbance is common, particularly when the dominant hemisphere is affected (usually the left in a right-handed individual).
When the vertebrobasilar system is involved, the symptoms are less specific but may affect both sides of the body, with bilateral visual disturbance. Symptoms such as ataxia, imbalance, unsteadiness and vertigo can also be caused by middle ear disorders or bradycardia causing the patient to collapse (Stokes Adams attacks).
Headache more commonly occurs with intracranial hemorrhage, migraine or a space-occupying neoplasm.
Clinical examination will often fail to reveal any neurological deficit but there may be a bruit in the neck. This condition is one diagnosed on history and should prompt further investigation to define the state of the extracranial blood vessels.
Stroke in evolution/complete stroke
If the neurological deficit fluctuates and a progressive motor or sensory deficit is evident, then a stroke-inevolution, potentially leading to a complete stroke, should be suspected. This is a medical emergency, requiring prompt neurological evaluation.
In a patient who presents with focal neurological symptoms investigations are needed to determine the cause, particularly whether cerebral infarction or haemorrhage has occurred and if there is correctible extra-cranial arterial disease responsible.
With the advent of CT and carotid duplex scanning it has become easier to define those patients who are likely to have hemispheric neurological symptoms on a potentially correctible basis of thromboembolic phenomenon arising from the carotid bifurcation.
General medical evaluation includes cardiovascular evaluation with blood pressure measurement to detect hypertension and electrocardiography to assess any cardiac rhythm disturbance like atrial fibrillation or evidence of co-existent coronary artery disease. Haematological disorders such as polycythaemia, leukaemia or coagulopathies can cause stroke and should be sought. Similarly, renal function, lipid and glucose levels are measured to exclude renal failure, hyperlipidaemia and diabetes respectively.
CT scanning or MRI will identify intracranial blood if a haemorrhagic stroke has occurred and will demonstrate cerebral infarction or space-occupying lesions such as a brain tumour. Although sophisticated 3-D reconstruction of the extracranial vasculature can be done with both MRI and CT, these are usually not the first-line investigations to assess the carotid arteries.
Duplex ultrasound is used in most centres as the initial diagnostic test to evaluate the carotid arteries and used as the definitive investigation by many vascular surgeons in planning carotid endarterectomy. Duplex ultrasound is operator-dependent but in good hands can show the morphology of the carotid bifurcation and accurately identify the degree of stenosis present (Carotid duplex scan showing turbulent flow at the origin of the internal carotid artery with a peak systolic velocity of 571.5 cm/s and an endiastoic velocity of 198.5 cm/s indicating more than 80% stenosis of the artery.).
Carotid angiography, considered the diagnostic gold standard, is now used more selectively, particularly if the ultrasound findings are uncertain, or if the major aortic arch branches need to be imaged in planning carotid stenting (Carotid angiogram showing more than 80% stenosis at the origin of the internal carotid artery.).
Optimal medical control of risk factors, in particular hypertension and smoking, have significantly reduced the risk of stroke and remains the most important part of overall management. Anti-platelet aggregate therapy, usually with aspirin, will help prevent recurrent TIAs but does not reduce the risk of stroke.
There are defined sub-groups of patients who will benefit from surgery or endovascular intervention to remove an identified embolic source or improve cerebral blood flow. Age should not preclude treatment that would otherwise be indicated.
Fortuitously, the carotid bifurcation is the commonest site for extra-cranial stenotic disease, as it is surgically accessible unlike the aortic arch branches or vertebral arteries that pose more complex treatment problems.
Symptomatic carotid disease
Two major clinical trials have confirmed the clear advantage of surgery over best medical management for patients with recent TIAs associated with a high-grade (>70% angiographic diameter reducing) stenosis of the relevant internal carotid artery.
Asymptomatic carotid disease
Although the benefit of carotid endarterectomy is not as great for asymptomatic patients as it is for symptomatic patients with an equivalent stenosis, guidelines prepared by the American Heart Association recommend prophylactic carotid endarterectomy for asymptomatic patients with higher than 60% stenosis of the internal carotid artery, if the surgical risk is estimated at less than 3% and life expectancy is at least 5 years. Surgery is generally not recommended if the surgical risk is higher or with limited life expectancy. There is a tendency in the Australian setting to consider surgery only for more severe (>80%) asymptomatic stenoses.
The carotid bifurcation is exposed in the neck and, after heparinisation, the carotid arteries are clamped so that artery can be opened to core out the atherosclerotic plaque (After the carotid arteries are clamped, the plaque (A) is removed (B) and the arteriotomy closed either primarily or with a patch (C).). There is a plane between the diseased portion of the carotid artery and the outer media so that a smooth surface can be restored to the artery. A patch is often used to close the artery to ensure a widely patent lumen and to decrease the risk of re-stenosis. A shunt is occasionally used during carotid surgery to maintain cerebral blood flow if the cerebral collateral circulation is judged inadequate. Occasionally a bypass procedure is needed to restore cerebral perfusion; for example an occluded common carotid artery can be treated by a bypass from the subclavian artery to the internal carotid artery.
Carotid stenting is a more recent technical advance and remains a controversial aspect of carotid therapy. Carotid angioplasty has for some time been the therapy of choice for symptomatic fibromuscular dysplasia, a relatively rare condition occurring in less than 3% of patients with symptomatic carotid arterial disease. There has been continuing improvement in the reported results of balloon dilatation and stenting for atherosclerotic carotid arterial disease. The proposed benefit of carotid artery stenting is that an anaesthetic can be avoided as can the neck incision and risk of cranial nerve injury. However, there have been concerns about a higher risk of peri-procedural cerebral embolisation and stroke and late recurrent stenosis. The risk of peri-procedural stroke has been reduced with cerebral protection devices, designed to catch embolic material before it can pass into the brain.
Controlled clinical trials should resolve the relative merits of carotid stenting and endarterectomy. Until that time, carotid endarterectomy is the established intervention for high-risk patients with high-grade symptomatic internal carotid stenosis.
Angioplasty and stenting is usually indicated to treat subclavian artery stenosis or occlusion causing subclavian steal.
Close monitoring is essential after any form of cerebrovascular intervention to observe for neurological deficit, to guide blood pressure control and to decrease the risk of adverse cardiovascular events. Patients are usually started on Aspirin therapy soon after surgery to decrease the risk of thrombosis at the endarterectomy site.
The incidence of carotid re-stenosis due to neointimal hyperplasia after surgery can be reduced by use of a patch to close the artery. Re-stenosis is more common after stenting. Post-operative surveillance using ultrasound is commonly done to monitor the operated or stented carotid artery.
There is a 2–3% risk of ipsilateral stroke after carotid endarterectomy or stenting related to embolisation from the carotid during the manipulation of intervention or to the interruption of cerebral blood flow. Labile blood pressure is common and hypertension is related to the risk of post-operative intracerebral hemorrhage. Co-existent coronary artery disease is an important cause of post-operative myocardial infarction and death. Important local complications after surgery are neck haematomas and cranial nerve injuries, which can include the hypoglossal and recurrent laryngeal nerves. Sensory loss in the distribution of the greater auricular nerve is commonly observed. Neck haematomas are an occasional problem and, if severe, can obstruct respiration, requiring prompt return to the operating theatre.
Prognosis and results of surgery
The North American Symptomatic Carotid Endarterectomy Trial (NASCET) showed that the risk of stroke in symptomatic patients with greater than 70% stenosis of the relevant internal carotid could be reduced at two years from 26% to 9% with carotid endarterectomy, provided that the surgery is done with an acceptably low morbidity and mortality. A recent audit of carotid surgery in New South Wales confirmed that in an Australian setting, carotid endarterectomy is being performed with less than 2–3% combined stroke/death rate, in keeping with NASCET recommendations.
The overall benefit is not as great for asymptomatic carotid stenosis. However, the Asymptomatic Carotid Atherosclerosis Study did confirm an advantage for surgery for asymptomatic patients with more than60% internal carotid stenosis. The surgical group in this study incurred a 2.3% peri-operative risk of stroke or death, and had a 5.1% cumulative 5-year risk of ipsilateral stroke, peri-operative stroke or death. The medical group had an 11% cumulative risk of the same late endpoints. Surgery reduced the absolute risk by 5.9% and relative risk by 53% at 5 years. Although there was therapeutic benefit at 1 year, the benefit was greater at 5 years. The benefit appeared greater for men than women.
Carotid endarterectomy is the most frequently performed peripheral vascular surgical operation, with its efficacy confirmed by Level 1 evidence. Carotid stenting is evolving as a less invasive alternative and is being subjected to rigourous evaluation through controlled trials.There is an increased focus on preventing stroke by risk factor modification and by identification of subgroups at high risk of stroke who will benefit from prophylactic intervention.