- Email: [email protected]
Stroke: causes and clinical features
STROKE
Stroke: causes and clinical features
Key points C
Stroke is a syndrome, not a specific disease
Hugh Markus
C
It is caused by many different pathologies, some of which require specific treatment
Abstract
C
All result in usually sudden-onset focal loss of neurological function
C
About 80% of strokes are caused by primary cerebral ischaemia, and 20% by cerebral haemorrhage
C
A large number of risk factors, many modifiable, increase stroke risk
Stroke is a clinical syndrome rather than a specific disease. This article reviews risk factors for stroke, and the different pathologies that can cause stroke. Approximately 20% of strokes are due to cerebral haemorrhage, most of which is intracerebral, with a significant minority caused by subarachnoid haemorrhage. The remaining 80% are ischaemic, including large artery disease, cardioembolic and small vessel disease. Differentiation of cerebral ischaemia from haemorrhage is impossible without brain imaging. Assessment of a patient with ischaemic stroke requires knowledge of the cerebral arterial supply and cerebral anatomy to differentiate anterior and posterior territory involvement.
The National Audit Office report in 2005 found that stroke costs the UK National Health Service (NHS) and economy about £7 billion a year: £2.8 billion in direct costs to the NHS, £2.4 billion in informal care costs (e.g. costs of home nursing borne by patients’ families) and £1.8 billion in income lost to productivity and disability.2 Therefore preventive treatments with relative modest benefits in individual patients can have a major effect on public health and healthcare costs. Stroke and cerebrovascular disease is the second leading cause of dementia, and there is increasing evidence that coexisting cerebrovascular increases the risk that someone with Alzheimer’s disease pathology will develop clinical dementia. Stroke is also the most common cause of epilepsy in the elderly.
Keywords Brain imaging; cerebral haemorrhage; cerebral infarction; cerebrovascular disease; pathogenesis; risk factors; stroke; transient ischaemic attack
Introduction Each year over 17 million people worldwide suffer a stroke, with 5 million left significantly disabled; an estimated 34 million people worldwide are living with the effects of stroke.1 In the UK and USA, stroke is the third most common cause of death (>60,000 and 160,000 deaths per annum, respectively) and the leading cause of adult disability. Its incidence rises exponentially with age, and about 25% of men and 20% of women who live to 85 years of age can expect to suffer a stroke. The incidence of stroke is falling in some developed countries (e.g. by 19% from 1990 to 2010 in the UK), but rising in less developed countries, and it is more common in the elderly, who comprise a higher portion of the population in developed countries. This means that the impact of stroke is increasing. A recent study on global burden of stroke between 1990 and 2010 reported a 25% increase in stroke in individuals aged 20e64 years, 113% rise in prevalence of stroke survivors, 70% increase in all strokes and 36% increase in number of deaths caused by stroke. Over 60% of global stroke occurs in people aged <75 years.
Definitions Stroke Stroke is a clinical syndrome characterized by the rapid onset of focal neurological signs, lasting >24 hours or leading to death, with a presumed vascular cause (infarction and/or haemorrhage). Stroke results from a number of different diseases and processes that all cause a sudden-onset disruption of blood supply to a particular part of the brain. About 80% are caused by primary cerebral ischaemia resulting in infarction, while 20% are due to cerebral haemorrhage with intracerebral haemorrhage being much more common than stroke due to subarachnoid haemorrhage (SAH). The subtypes of ischaemic stroke and intracerebral haemorrhage contain multiple pathologies, which may have different risk factor profiles and different treatments.
Hugh Markus MA BM BCh DM FRCP is Professor of Stroke Medicine Neurology at the University of Cambridge, and Honorary Consultant Neurologist at Addenbrooke’s Hospital, Cambridge, UK. He trained in general medicine at Oxford and Nottingham and then in neurology in London. He was Foundation Professor of Neurology at St George’s University of London before moving to his current post in 2013. His research interests include investigating the pathophysiology of, and developing novel treatment approaches for, stroke using both imaging and molecular genetic approaches. He has a particular interest in cerebral small vessel disease and vascular cognitive impairment. Competing interests: none declared.
MEDICINE --:-
Transient ischaemic attack (TIA) TIA has the same definition as stroke except that symptoms last <24 hours. Imaging studies show that patients with TIA frequently suffer cerebral infarction despite complete clinical recovery, particularly when symptoms last hours rather than minutes. This suggests a pathophysiological continuum with stroke, and there are calls for a change in the definition e either to exclude these patients and call this a stroke, or to reduce the duration of symptoms in the definition of a TIA.
1
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
Cerebrovascular disease Cerebrovascular disease includes stroke and other diseases of the blood vessels of the brain, such as vascular dementia. It can be asymptomatic or subclinical (e.g. asymptomatic carotid stenosis or periventricular small vessel disease).
Alcohol Heavy alcohol consumption is a risk factor for stroke, particularly intracerebral haemorrhage, possibly by increasing blood pressure and predisposing to atrial fibrillation. Moderate alcohol consumption may protect against both ischaemic heart disease and stroke although the evidence is not all consistent.
Risk factors Ethnicity There is an increased incidence of stroke in African-Caribbean individuals in the UK and African-Americans compared with white individuals. Intracerebral haemorrhage and small vessel ischaemic stroke are particularly increased, which may relate partly to the increased prevalence and severity of hypertension. In the UK, South-Asian populations have a higher stroke mortality than white individuals, perhaps partly due to increased central obesity, insulin resistance and diabetes mellitus. There are differences in the distribution of stroke subtypes between ethnic groups: for example, intracranial disease is more common in Chinese than white European stroke patients.
Most epidemiological studies, including prospective ones, which provide the most robust data, have been unable to differentiate risk factors for stroke caused by haemorrhage or infarction, let alone different ischaemic stroke subtypes. Most risk factor data therefore apply to the stroke syndrome as a whole. Age Age is the strongest risk factor for both cerebral infarction and primary intracerebral haemorrhage. The risk of stroke in people aged 75e84 years is 25 times the risk for age 45e54 years. Sex Male sex is a risk factor for stroke but, because of their greater life expectancy, more women suffer a stroke.
Homocysteine Very high concentrations of serum homocysteine, associated with the autosomal recessive condition homocysteinuria, are associated with an increased risk of stroke and other arterial thrombosis at a young age. Increasing evidence has recently suggested that a moderately elevated serum homocysteine concentration is associated with stroke on a population basis. Raised serum homocysteine has been associated with endothelial dysfunction. However, randomized trials using B vitamins and folic acid to reduce serum homocysteine have had negative results, although a secondary analysis of the VITATOPS (VITAmins TO Prevent Stroke) study suggested a possible effect in lacunar stroke. A recent large Chinese primary prevention study found vitamins taken to lower homocysteine reduced stroke risk in hypertensive patients.
Blood pressure Increasing blood pressure is a major risk factor for stroke and is strongly and independently associated with both ischaemic and haemorrhagic strokes. The relationship between diastolic blood pressure and subsequent stroke is log-linear throughout the normal range. There is no apparent threshold below which the risk of stroke becomes stable, at least not over the normal range of blood pressure. The increase in stroke risk almost doubles with each 7.5 mmHg increase in diastolic blood pressure. Systolic blood pressure is also a risk factor for stroke. The causal nature of the relationship is strongly supported by randomized controlled trials, demonstrating that stroke can be prevented by treating blood pressure, even at ‘normal’ blood pressure levels.
Vascular disease elsewhere Many cases of stroke result directly or indirectly from atheromatous disease, which also causes ischaemic heart and peripheral vascular disease. It is not surprising that other evidence of cardiovascular disease is a risk factor for stroke. Furthermore, some risk factors, such as hypertension, are risk factors for both stroke and systemic atheroma. An increased risk of stroke has been associated with the presence of ischaemic heart disease, peripheral vascular disease, cardiac failure and atrial fibrillation. The latter is an important, and potentially preventable, cause of stroke. Elderly individuals with atrial fibrillation have an annual stroke risk of 5%.
Smoking Cigarette smoking doubles the risk of stroke. Diabetes mellitus Diabetes also doubles the risk of stroke. It is a risk factor for both carotid atherosclerosis and large vessel disease. Cholesterol Increased total cholesterol and low-density lipoprotein cholesterol are strong risk factors for ischaemic heart disease, but the relationship to stroke appears weaker. However, recent data have shown a relationship with ischaemic stroke, which may be partly obscured because of a negative association with intracerebral haemorrhage. Treatment trials have shown that statin therapy reduces recurrent stroke risk in patients with stroke or TIA.
Other risk factors Migraine, particularly migraine with aura, and the oral contraceptive pill (particularly oestrogen-containing preparations) are risk factors for stroke. Hormone replacement therapy appears to increase the risk, particularly soon after its initiation, perhaps by a prothrombotic mechanism. There is a link between inflammation, infection and stroke. Chronic infection and inflammation can predispose to atherosclerosis and stroke. A number of studies suggest acute infections can cause stroke. There is a strong association between socioeconomic status and stroke risk,
Body mass index and physical exercises Increased body mass index is a risk factor for stroke, partly because of its association with other risk factors such as hypertension and diabetes. Cohort and case-control studies have demonstrated that lack of exercise is associated with increased risk of stroke.
MEDICINE --:-
2
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
although this may be largely confounded by other factors such as smoking and lack of exercise. The relative risks associated with the more important risk factors for stroke are shown in Table 1.
Pathophysiological classification of stroke
Pathology and pathogenesis A pathophysiological classification of stroke (Table 2) is useful to identify the underlying cause of an individual stroke for planning treatment and guiding prognosis.
Category
Disease mechanism
Cerebral ischaemia
Atherothromboembolism C Extracranial carotid and vertebral stenosis C Intracranial stenosis C Aortic arch atheroma Cardioembolism Small vessel disease (lacunar stroke) Arterial dissection C Idiopathic C Secondary to connective tissue disorders Inflammatory vascular disorders C Giant cell arteritis C Systemic lupus erythematosus and other systemic vasculitis C Primary angiitis Haematological disorders C Antiphospholipid syndrome C Other prothrombotic disorders C Cellular disorders Trauma Drug abuse Monogenic causes C CADASIL C Mitochondrial disorders (e.g. MELAS) C Sickle cell disease Infection C Meningitis, especially tuberculosis C HIV Others C Migraine C Contraceptive pill/pregnancy Intracerebral haemorrhage C Small vessel disease and microaneurysms in perforating vessels C Arteriovenous malformations C Amyloid angiopathy C Intracerebral tumours C Cerebral venous thrombosis C Haemostatic factors Anticoagulant and antiplatelet drugs Coagulation disorders Thrombolytic therapy C Drug abuse C Moyamoya syndrome SAH
Cerebral haemorrhage Twenty per cent of stroke is caused by cerebral haemorrhage, of which a quarter is SAH. Subarachnoid haemorrhage: SAH is the spontaneous extravasation of blood into the subarachnoid space when a blood vessel near the surface of the brain leaks (Figure 1b,c). Eighty-five per cent of SAH arises from rupture of saccular aneurysms at the base of the brain, and these have a high risk of early rebleeding. Saccular aneurysms occur most commonly in the anterior communicating artery, internal carotid artery and middle cerebral artery. Most are idiopathic and develop during life rather than being congenital, but there is a significant genetic predisposition. In a minority of cases, they are associated with systemic conditions, including polycystic kidney disease and connective tissue disorders. Ten per cent of SAH are perimesencephalic, with haemorrhage around the ventral midbrain and a normal angiogram. The cause in this subgroup is uncertain but the prognosis is very good. The remaining 5% of SAHs have other causes, including fistulas, arteriovenous malformations and other rare causes. Stroke (a focal deficit) occurs in a minority of cases of SAH. It can be immediate, from a localized haematoma (most commonly with middle cerebral artery aneurysms), or delayed, from secondary vasospasm.
Cerebral haemorrhage
Intracerebral haemorrhage: this can be divided conveniently into lobar haemorrhages, involving the cortex, and subcortical
Well-recognized risk factors for stroke (estimates of relative risk are representative figures derived from different studies of each risk factor) Risk factor
Relative risk of stroke
Age (>75 years versus 55e64 years) Blood pressure (160/95 versus 120/80 mmHg) Smoking (current status) Diabetes mellitus Social class (V versus I) Ischaemic heart disease Heart failure Atrial fibrillation Past TIA Physical activity (little or none versus some) Oral contraceptives
5 7 2 2 1.6 3 5 5 5 2.5 3
MELAS, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes.
Table 2
haemorrhages. Most subcortical haemorrhages occur in the basal ganglia region as a result of hypertension. They frequently coexist with ischaemic small vessel disease and can result from microaneurysms or fragility of the perforating artery vessel walls. Lobar haemorrhages can occur due to bleeding from an underlying lesion such as an arteriovenous malformation or
Table 1
MEDICINE --:-
3
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
a
b
c
Intracerebral haemorrhage. a A primary intracerebral haemorrhage in the left subcortex in a hypertensive individual. Blood appears as high signal on this CT brain scan. b A subarachnoid haemorrhage secondary to a right anterior cerebral artery (ACA) aneurysm. Blood can be seen in both the vicinity of the left anterior cerebral artery (upper arrow) and in the ventricular system (lower arrow). c An angiogram from the patient in b showing the right anterior cerebral artery aneurysm (arrow). There are two other asymptomatic aneurysms.
2008 Hugh Markus
Figure 1
tumour (Figure 1a). They can also occur spontaneously and can be secondary to amyloid angiopathy, sometimes resulting in multiple lobar haemorrhages. This is more common in the elderly, and when it occurs in younger individuals can have a genetic basis.
Ischaemic stroke Eighty per cent of strokes are caused by primary cerebral ischaemia, most commonly large artery disease, small vessel disease and cardioembolism. However, a large number of other diseases occasionally cause ischaemic stroke.
a
b
c
Cerebral small vessel disease. a Disease of the small perforating end-arteries results in small discrete (lacunar) infarcts, as seen on this CT scan, which shows an infarct in the posterior capsule on the left (arrow). This caused a right hemiparesis. b More diffuse disease also results in leukoaraiosis. This develops first in those regions most distant from the vessel origins, i.e. internal watershed or borderzone areas, which are the periventricular regions (lower arrow) and the deep white matter regions. This is best seen as high signal on T2-weighted or FLAIR MRI (this image). The pathological correlate of leukoaraiosis is chronic ischaemic changes with gliosis, neuronal loss and ischaemic demyelination. A lacunar infarct is also shown (upper arrow). c Recent imaging studies with gradient-echo MRI have shown frequent microbleeds (haemosiderin deposition results in areas of signal loss). This is consistent with an increased risk of cerebral haemorrhage in patients with small vessel disease, suggesting subcortical intracerebral haemorrhage and lacunar stroke with leukoaraiosis may be part of the same disease spectrum. Here a number of dark spots or microbleeds can be seen. © 2008 Hugh Markus Figure 2 MEDICINE --:-
4
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
Large artery stroke: about 20% of strokes are caused by large artery disease, most commonly carotid artery stenosis. This usually occurs at the carotid bifurcation but can occur more distally. The primary mechanism is embolism from an ulcerated or eroded stenotic plaque. Large artery stroke can arise from vertebrobasilar stenoses or intracranial stenosis. Large artery disease, particularly if there is a poor collateral supply, occasionally results in haemodynamic stroke. This can occur during a drop in systemic perfusion pressure.
recurrent lacunar stroke, migraine with aura, psychiatric disturbance (usually depression) and dementia. Vasculitis is a rare but important cause of stroke. This can be associated with systemic vasculitis affecting large or small vessels. Isolated central nervous system vasculitis, also called primary angiitis, affects the small arteries and can cause stroke-like episodes and/or dementia. Ischaemic stroke of unknown cause e cryptogenic stroke: in about 20e30% of cases, no underlying cause is found even after detailed investigation. Implantable cardiac monitors may detect short bursts of atrial fibrillation over a period of many months in this patient group,4 suggesting that some embolic stroke (cortical rather than lacunar infarction) of undetermined source has a cardiac source.5 There are ongoing trials of anticoagulation versus antiplatelet agents in this patient group.
Cardioembolic stroke: about a quarter of ischaemic strokes are due to cardioembolism. Important causes include atrial fibrillation with left atrial thrombus, cardiac valve disease, prosthetic cardiac valves, cardiomyopathy and heart failure, and left ventricular thrombus secondary to myocardial infarction. Recent data using indwelling monitors that can detect shorts burst of atrial fibrillation over a period of many months has found that paroxysymal atrial fibrillation is relatively common although the significance of rare short bursts of atrial fibrillation remains to be determined.
Clinical features of stroke Infarction versus haemorrhage Brain CT or MRI is needed to reliably distinguish clinically between cerebral infarction and intracerebral haemorrhage. In contrast, SAH can usually be clinically differentiated by its presentation with sudden-onset (thunderclap) headache and signs of meningism with neck stiffness. Because the management of cerebral haemorrhage and infarction differs markedly, urgent brain imaging is required in all stroke patients (see Stroke: Management of Prevention on pages 000-000 of this issue).
Cerebral small vessel disease: about a quarter of ischaemic strokes are lacunar strokes resulting from small vessel disease.3 The white matter and deep grey matter nuclei are supplied by perforating or penetrating end-arteries arising from the basal intracerebral vessels and cortical vessels. Ischaemia in the territory of one artery results in a small infarction known as a lacuna. The underlying disease mechanisms are poorly understood, but most patients are hypertensive. Some patients have diffuse arteriopathy with thickening of the small arteries, described as lipohyalanosis. In others, microatheroma at the origin of the perforating vessels may be responsible. Lacunar stroke may be accompanied by diffuse white matter ischaemia (seen as low-density on computed tomography (CT) or high density on T2-weighted magnetic resonance imaging (MRI)), referred to as leukoaraiosis (Figure 2). Patients with small vessel disease also have increased risk of intracerebral haemorrhage, and studies using gradient-echo MRI show frequent microbleeds (Figure 2).
Arterial supply of the brain
Posterior cerebral arteries
Carotid siphon (in cavernous sinus) Carotid canal (in petrous bone) Foramen magnum
Basilar artery Vertebral artery External carotid artery Common carotid artery
Other causes of ischaemic stroke: many other diseases can cause ischaemic stroke: Carotid and vertebral dissection is an important cause of stroke in young individuals. A tear in the arterial wall, often following a history of trauma, results in secondary thrombosis and embolic stroke. Intracranial dissection, particularly of the vertebral artery, can also result in SAH. Prothrombotic factors (e.g. lupus anticoagulant, anticardiolipin antibody), the oral contraceptive pill and migraine are all associated with an increased risk of stroke. In young women presenting with stroke, a combination of these is often all that can be found responsible. Genetic diseases can cause stroke, particularly in the young. Sickle cell disease is associated with a significant stroke risk. The most common genetic form of stroke without systemic clinical features is cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). This autosomal dominant disease, caused by NOTCH 3 mutations, results in
MEDICINE --:-
Middle cerebral artery
Anterior cerebral arteries
Right subclavian artery
C1 C2 C3
A
Internal carotid artery
C4 C5
Left subclavian artery
C6 C7 D1
B
C D
Aortic arch The internal carotid artery (anterior circulation) divides from the anterior and middle cerebral arteries. The basilar artery (posterior circulation) divides from the posterior cerebral arteries. The Circle of Willis at the base of the brain provides communication between the different intracerebral vessels via the anterior and posterior communicating arteries. It is variably complete in different people, and this can determine whether carotid occlusion is asymptomatic or results in massive middle cerebral artery infarction. Common extracranial sites of atheroma are shown: A – proximal internal carotid artery, B – common carotid artery origin, C –vertebral artery origin, D – subclavian artery.
Figure 3
5
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
The first branch of the internal carotid artery is the ophthalmic artery. Emboli from a carotid stenosis can therefore cause retinal ischaemia (usually presenting with amaurosis fugax e a curtain descending from above, leading to complete transient loss of vision).
Clinical features of stroke divided according to arterial territory Anterior circulation e carotid territory C Amaurosis fugax/retinal infarction (ophthalmic artery) C Hemiparesis C Hemisensory loss C Hemianopia (optic tract and radiation) C Dysphasia (expressive and/or receptive) if dominant hemisphere C Sensory inattention C Visual inattention C Neglect Posterior circulation e vertebrobasilar territory C Ataxia e cerebellum and brainstem cerebellar connections C Cranial nerve nuclei involvement Diplopia and extraocular eye movement disorders Facial sensory loss Facial palsy e lower motor neurone (affects upper and lower face) Dysphagia Vertigo Hearing disturbance Vomiting Dysarthria Hemiparesis (descending corticospinal tract) e can be bilateral weakness Hemisensory loss (ascending sensory tracts) e can be bilateral sensory loss Hemianopia e occipital lobe involvement Cortical blindness e basilar artery occlusion, causing ischaemia in both occipital cortices
Posterior circulation stroke: the two vertebral arteries and basilar artery comprise the posterior circulation. The basilar artery terminates in the posterior cerebral artery. Posterior cerebral artery infarction results in hemianopia because of occipital cortex involvement. The posterior circulation supplies the brainstem and cerebellum. Infarction can result in hemiparesis or hemisensory loss (involvement of the descending and ascending tracts), ataxia or involvement of cranial nerve nuclei (e.g. vertigo, eye movement abnormalities, facial palsy, tongue weakness, dysphagia). Basilar ischaemia can result in bilateral weakness or sensory loss, or bilateral (complete) visual loss. Lacunar stroke: many lacunar infarcts are asymptomatic, but they can affect clinically eloquent descending or ascending fibres in the white matter or deep grey matter. Symptoms usually occur from infarction in the posterior limb of the internal capsule affecting the corticospinal tract. This results in pure motor stroke (hemiparesis affecting the face, arm and leg). Other lacunar syndromes involve pure sensory stroke and sensorimotor stroke, clumsy hand dysarthria (slight weakness and clumsiness of the hand with slurred speech) and ataxic hemiparesis (ataxia and usually mild hemiparesis affecting the same side). As they spare the cortex, lacunar strokes do not present with features such as neglect or dysphasia. A
KEY REFERENCES 1 Feigin VL, Forouzanfar MH, Krishnamurthi R, et al. Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) and the GBD Stroke Experts Group. Global and regional burden of stroke during 1990e2010: findings from the Global Burden of Disease Study 2010. Lancet 2014; 383: 245e54. 2 National Audit Office. Reducing brain damage: faster access to better stroke care. London: National Audit Office, 2005. 3 Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9: 689e701. 4 Luciano A, Sposato LA. Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and metaanalysis. Lancet Neurol 2010; 14: 377e87. 5 Hart RG, Diener HC, Coutts SB, et al. Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 2014; 13: 429e38.
Table 3
Localizing the lesion The neurological consequences of a stroke depends on the brain region affected. Localization requires knowledge of cerebral arterial anatomy (Figure 3) and location of different functions within the brain. Ischaemic territory strokes can be divided into anterior and posterior circulation stroke (Table 3). Anterior circulation stroke: this refers to stroke in the territory of the carotid arteries, which supply the anterior and middle cerebral arteries. Anterior cerebral artery infarction can be asymptomatic or cause weakness primarily of the leg. Middle cerebral artery stroke can cause: hemiparesis (worse in the arm if infarction is cortical; affecting the arm, face and leg equally if subcortical) hemisensory loss hemianopia (from involvement of the optic radiation) dysphasia (if in the dominant hemisphere) inattention (both visual and sensory) neglect.
MEDICINE --:-
FURTHER READING Markus H, Pereira A, Cloud G. Handbook of stroke medicine. Oxford: Oxford University Press, 2010.
6
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
Stroke: causes and clinical features
Key points C
Stroke is a syndrome, not a specific disease
Hugh Markus
C
It is caused by many different pathologies, some of which require specific treatment
Abstract
C
All result in usually sudden-onset focal loss of neurological function
C
About 80% of strokes are caused by primary cerebral ischaemia, and 20% by cerebral haemorrhage
C
A large number of risk factors, many modifiable, increase stroke risk
Stroke is a clinical syndrome rather than a specific disease. This article reviews risk factors for stroke, and the different pathologies that can cause stroke. Approximately 20% of strokes are due to cerebral haemorrhage, most of which is intracerebral, with a significant minority caused by subarachnoid haemorrhage. The remaining 80% are ischaemic, including large artery disease, cardioembolic and small vessel disease. Differentiation of cerebral ischaemia from haemorrhage is impossible without brain imaging. Assessment of a patient with ischaemic stroke requires knowledge of the cerebral arterial supply and cerebral anatomy to differentiate anterior and posterior territory involvement.
The National Audit Office report in 2005 found that stroke costs the UK National Health Service (NHS) and economy about £7 billion a year: £2.8 billion in direct costs to the NHS, £2.4 billion in informal care costs (e.g. costs of home nursing borne by patients’ families) and £1.8 billion in income lost to productivity and disability.2 Therefore preventive treatments with relative modest benefits in individual patients can have a major effect on public health and healthcare costs. Stroke and cerebrovascular disease is the second leading cause of dementia, and there is increasing evidence that coexisting cerebrovascular increases the risk that someone with Alzheimer’s disease pathology will develop clinical dementia. Stroke is also the most common cause of epilepsy in the elderly.
Keywords Brain imaging; cerebral haemorrhage; cerebral infarction; cerebrovascular disease; pathogenesis; risk factors; stroke; transient ischaemic attack
Introduction Each year over 17 million people worldwide suffer a stroke, with 5 million left significantly disabled; an estimated 34 million people worldwide are living with the effects of stroke.1 In the UK and USA, stroke is the third most common cause of death (>60,000 and 160,000 deaths per annum, respectively) and the leading cause of adult disability. Its incidence rises exponentially with age, and about 25% of men and 20% of women who live to 85 years of age can expect to suffer a stroke. The incidence of stroke is falling in some developed countries (e.g. by 19% from 1990 to 2010 in the UK), but rising in less developed countries, and it is more common in the elderly, who comprise a higher portion of the population in developed countries. This means that the impact of stroke is increasing. A recent study on global burden of stroke between 1990 and 2010 reported a 25% increase in stroke in individuals aged 20e64 years, 113% rise in prevalence of stroke survivors, 70% increase in all strokes and 36% increase in number of deaths caused by stroke. Over 60% of global stroke occurs in people aged <75 years.
Definitions Stroke Stroke is a clinical syndrome characterized by the rapid onset of focal neurological signs, lasting >24 hours or leading to death, with a presumed vascular cause (infarction and/or haemorrhage). Stroke results from a number of different diseases and processes that all cause a sudden-onset disruption of blood supply to a particular part of the brain. About 80% are caused by primary cerebral ischaemia resulting in infarction, while 20% are due to cerebral haemorrhage with intracerebral haemorrhage being much more common than stroke due to subarachnoid haemorrhage (SAH). The subtypes of ischaemic stroke and intracerebral haemorrhage contain multiple pathologies, which may have different risk factor profiles and different treatments.
Hugh Markus MA BM BCh DM FRCP is Professor of Stroke Medicine Neurology at the University of Cambridge, and Honorary Consultant Neurologist at Addenbrooke’s Hospital, Cambridge, UK. He trained in general medicine at Oxford and Nottingham and then in neurology in London. He was Foundation Professor of Neurology at St George’s University of London before moving to his current post in 2013. His research interests include investigating the pathophysiology of, and developing novel treatment approaches for, stroke using both imaging and molecular genetic approaches. He has a particular interest in cerebral small vessel disease and vascular cognitive impairment. Competing interests: none declared.
MEDICINE --:-
Transient ischaemic attack (TIA) TIA has the same definition as stroke except that symptoms last <24 hours. Imaging studies show that patients with TIA frequently suffer cerebral infarction despite complete clinical recovery, particularly when symptoms last hours rather than minutes. This suggests a pathophysiological continuum with stroke, and there are calls for a change in the definition e either to exclude these patients and call this a stroke, or to reduce the duration of symptoms in the definition of a TIA.
1
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
Cerebrovascular disease Cerebrovascular disease includes stroke and other diseases of the blood vessels of the brain, such as vascular dementia. It can be asymptomatic or subclinical (e.g. asymptomatic carotid stenosis or periventricular small vessel disease).
Alcohol Heavy alcohol consumption is a risk factor for stroke, particularly intracerebral haemorrhage, possibly by increasing blood pressure and predisposing to atrial fibrillation. Moderate alcohol consumption may protect against both ischaemic heart disease and stroke although the evidence is not all consistent.
Risk factors Ethnicity There is an increased incidence of stroke in African-Caribbean individuals in the UK and African-Americans compared with white individuals. Intracerebral haemorrhage and small vessel ischaemic stroke are particularly increased, which may relate partly to the increased prevalence and severity of hypertension. In the UK, South-Asian populations have a higher stroke mortality than white individuals, perhaps partly due to increased central obesity, insulin resistance and diabetes mellitus. There are differences in the distribution of stroke subtypes between ethnic groups: for example, intracranial disease is more common in Chinese than white European stroke patients.
Most epidemiological studies, including prospective ones, which provide the most robust data, have been unable to differentiate risk factors for stroke caused by haemorrhage or infarction, let alone different ischaemic stroke subtypes. Most risk factor data therefore apply to the stroke syndrome as a whole. Age Age is the strongest risk factor for both cerebral infarction and primary intracerebral haemorrhage. The risk of stroke in people aged 75e84 years is 25 times the risk for age 45e54 years. Sex Male sex is a risk factor for stroke but, because of their greater life expectancy, more women suffer a stroke.
Homocysteine Very high concentrations of serum homocysteine, associated with the autosomal recessive condition homocysteinuria, are associated with an increased risk of stroke and other arterial thrombosis at a young age. Increasing evidence has recently suggested that a moderately elevated serum homocysteine concentration is associated with stroke on a population basis. Raised serum homocysteine has been associated with endothelial dysfunction. However, randomized trials using B vitamins and folic acid to reduce serum homocysteine have had negative results, although a secondary analysis of the VITATOPS (VITAmins TO Prevent Stroke) study suggested a possible effect in lacunar stroke. A recent large Chinese primary prevention study found vitamins taken to lower homocysteine reduced stroke risk in hypertensive patients.
Blood pressure Increasing blood pressure is a major risk factor for stroke and is strongly and independently associated with both ischaemic and haemorrhagic strokes. The relationship between diastolic blood pressure and subsequent stroke is log-linear throughout the normal range. There is no apparent threshold below which the risk of stroke becomes stable, at least not over the normal range of blood pressure. The increase in stroke risk almost doubles with each 7.5 mmHg increase in diastolic blood pressure. Systolic blood pressure is also a risk factor for stroke. The causal nature of the relationship is strongly supported by randomized controlled trials, demonstrating that stroke can be prevented by treating blood pressure, even at ‘normal’ blood pressure levels.
Vascular disease elsewhere Many cases of stroke result directly or indirectly from atheromatous disease, which also causes ischaemic heart and peripheral vascular disease. It is not surprising that other evidence of cardiovascular disease is a risk factor for stroke. Furthermore, some risk factors, such as hypertension, are risk factors for both stroke and systemic atheroma. An increased risk of stroke has been associated with the presence of ischaemic heart disease, peripheral vascular disease, cardiac failure and atrial fibrillation. The latter is an important, and potentially preventable, cause of stroke. Elderly individuals with atrial fibrillation have an annual stroke risk of 5%.
Smoking Cigarette smoking doubles the risk of stroke. Diabetes mellitus Diabetes also doubles the risk of stroke. It is a risk factor for both carotid atherosclerosis and large vessel disease. Cholesterol Increased total cholesterol and low-density lipoprotein cholesterol are strong risk factors for ischaemic heart disease, but the relationship to stroke appears weaker. However, recent data have shown a relationship with ischaemic stroke, which may be partly obscured because of a negative association with intracerebral haemorrhage. Treatment trials have shown that statin therapy reduces recurrent stroke risk in patients with stroke or TIA.
Other risk factors Migraine, particularly migraine with aura, and the oral contraceptive pill (particularly oestrogen-containing preparations) are risk factors for stroke. Hormone replacement therapy appears to increase the risk, particularly soon after its initiation, perhaps by a prothrombotic mechanism. There is a link between inflammation, infection and stroke. Chronic infection and inflammation can predispose to atherosclerosis and stroke. A number of studies suggest acute infections can cause stroke. There is a strong association between socioeconomic status and stroke risk,
Body mass index and physical exercises Increased body mass index is a risk factor for stroke, partly because of its association with other risk factors such as hypertension and diabetes. Cohort and case-control studies have demonstrated that lack of exercise is associated with increased risk of stroke.
MEDICINE --:-
2
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
although this may be largely confounded by other factors such as smoking and lack of exercise. The relative risks associated with the more important risk factors for stroke are shown in Table 1.
Pathophysiological classification of stroke
Pathology and pathogenesis A pathophysiological classification of stroke (Table 2) is useful to identify the underlying cause of an individual stroke for planning treatment and guiding prognosis.
Category
Disease mechanism
Cerebral ischaemia
Atherothromboembolism C Extracranial carotid and vertebral stenosis C Intracranial stenosis C Aortic arch atheroma Cardioembolism Small vessel disease (lacunar stroke) Arterial dissection C Idiopathic C Secondary to connective tissue disorders Inflammatory vascular disorders C Giant cell arteritis C Systemic lupus erythematosus and other systemic vasculitis C Primary angiitis Haematological disorders C Antiphospholipid syndrome C Other prothrombotic disorders C Cellular disorders Trauma Drug abuse Monogenic causes C CADASIL C Mitochondrial disorders (e.g. MELAS) C Sickle cell disease Infection C Meningitis, especially tuberculosis C HIV Others C Migraine C Contraceptive pill/pregnancy Intracerebral haemorrhage C Small vessel disease and microaneurysms in perforating vessels C Arteriovenous malformations C Amyloid angiopathy C Intracerebral tumours C Cerebral venous thrombosis C Haemostatic factors Anticoagulant and antiplatelet drugs Coagulation disorders Thrombolytic therapy C Drug abuse C Moyamoya syndrome SAH
Cerebral haemorrhage Twenty per cent of stroke is caused by cerebral haemorrhage, of which a quarter is SAH. Subarachnoid haemorrhage: SAH is the spontaneous extravasation of blood into the subarachnoid space when a blood vessel near the surface of the brain leaks (Figure 1b,c). Eighty-five per cent of SAH arises from rupture of saccular aneurysms at the base of the brain, and these have a high risk of early rebleeding. Saccular aneurysms occur most commonly in the anterior communicating artery, internal carotid artery and middle cerebral artery. Most are idiopathic and develop during life rather than being congenital, but there is a significant genetic predisposition. In a minority of cases, they are associated with systemic conditions, including polycystic kidney disease and connective tissue disorders. Ten per cent of SAH are perimesencephalic, with haemorrhage around the ventral midbrain and a normal angiogram. The cause in this subgroup is uncertain but the prognosis is very good. The remaining 5% of SAHs have other causes, including fistulas, arteriovenous malformations and other rare causes. Stroke (a focal deficit) occurs in a minority of cases of SAH. It can be immediate, from a localized haematoma (most commonly with middle cerebral artery aneurysms), or delayed, from secondary vasospasm.
Cerebral haemorrhage
Intracerebral haemorrhage: this can be divided conveniently into lobar haemorrhages, involving the cortex, and subcortical
Well-recognized risk factors for stroke (estimates of relative risk are representative figures derived from different studies of each risk factor) Risk factor
Relative risk of stroke
Age (>75 years versus 55e64 years) Blood pressure (160/95 versus 120/80 mmHg) Smoking (current status) Diabetes mellitus Social class (V versus I) Ischaemic heart disease Heart failure Atrial fibrillation Past TIA Physical activity (little or none versus some) Oral contraceptives
5 7 2 2 1.6 3 5 5 5 2.5 3
MELAS, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes.
Table 2
haemorrhages. Most subcortical haemorrhages occur in the basal ganglia region as a result of hypertension. They frequently coexist with ischaemic small vessel disease and can result from microaneurysms or fragility of the perforating artery vessel walls. Lobar haemorrhages can occur due to bleeding from an underlying lesion such as an arteriovenous malformation or
Table 1
MEDICINE --:-
3
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
a
b
c
Intracerebral haemorrhage. a A primary intracerebral haemorrhage in the left subcortex in a hypertensive individual. Blood appears as high signal on this CT brain scan. b A subarachnoid haemorrhage secondary to a right anterior cerebral artery (ACA) aneurysm. Blood can be seen in both the vicinity of the left anterior cerebral artery (upper arrow) and in the ventricular system (lower arrow). c An angiogram from the patient in b showing the right anterior cerebral artery aneurysm (arrow). There are two other asymptomatic aneurysms.
2008 Hugh Markus
Figure 1
tumour (Figure 1a). They can also occur spontaneously and can be secondary to amyloid angiopathy, sometimes resulting in multiple lobar haemorrhages. This is more common in the elderly, and when it occurs in younger individuals can have a genetic basis.
Ischaemic stroke Eighty per cent of strokes are caused by primary cerebral ischaemia, most commonly large artery disease, small vessel disease and cardioembolism. However, a large number of other diseases occasionally cause ischaemic stroke.
a
b
c
Cerebral small vessel disease. a Disease of the small perforating end-arteries results in small discrete (lacunar) infarcts, as seen on this CT scan, which shows an infarct in the posterior capsule on the left (arrow). This caused a right hemiparesis. b More diffuse disease also results in leukoaraiosis. This develops first in those regions most distant from the vessel origins, i.e. internal watershed or borderzone areas, which are the periventricular regions (lower arrow) and the deep white matter regions. This is best seen as high signal on T2-weighted or FLAIR MRI (this image). The pathological correlate of leukoaraiosis is chronic ischaemic changes with gliosis, neuronal loss and ischaemic demyelination. A lacunar infarct is also shown (upper arrow). c Recent imaging studies with gradient-echo MRI have shown frequent microbleeds (haemosiderin deposition results in areas of signal loss). This is consistent with an increased risk of cerebral haemorrhage in patients with small vessel disease, suggesting subcortical intracerebral haemorrhage and lacunar stroke with leukoaraiosis may be part of the same disease spectrum. Here a number of dark spots or microbleeds can be seen. © 2008 Hugh Markus Figure 2 MEDICINE --:-
4
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
Large artery stroke: about 20% of strokes are caused by large artery disease, most commonly carotid artery stenosis. This usually occurs at the carotid bifurcation but can occur more distally. The primary mechanism is embolism from an ulcerated or eroded stenotic plaque. Large artery stroke can arise from vertebrobasilar stenoses or intracranial stenosis. Large artery disease, particularly if there is a poor collateral supply, occasionally results in haemodynamic stroke. This can occur during a drop in systemic perfusion pressure.
recurrent lacunar stroke, migraine with aura, psychiatric disturbance (usually depression) and dementia. Vasculitis is a rare but important cause of stroke. This can be associated with systemic vasculitis affecting large or small vessels. Isolated central nervous system vasculitis, also called primary angiitis, affects the small arteries and can cause stroke-like episodes and/or dementia. Ischaemic stroke of unknown cause e cryptogenic stroke: in about 20e30% of cases, no underlying cause is found even after detailed investigation. Implantable cardiac monitors may detect short bursts of atrial fibrillation over a period of many months in this patient group,4 suggesting that some embolic stroke (cortical rather than lacunar infarction) of undetermined source has a cardiac source.5 There are ongoing trials of anticoagulation versus antiplatelet agents in this patient group.
Cardioembolic stroke: about a quarter of ischaemic strokes are due to cardioembolism. Important causes include atrial fibrillation with left atrial thrombus, cardiac valve disease, prosthetic cardiac valves, cardiomyopathy and heart failure, and left ventricular thrombus secondary to myocardial infarction. Recent data using indwelling monitors that can detect shorts burst of atrial fibrillation over a period of many months has found that paroxysymal atrial fibrillation is relatively common although the significance of rare short bursts of atrial fibrillation remains to be determined.
Clinical features of stroke Infarction versus haemorrhage Brain CT or MRI is needed to reliably distinguish clinically between cerebral infarction and intracerebral haemorrhage. In contrast, SAH can usually be clinically differentiated by its presentation with sudden-onset (thunderclap) headache and signs of meningism with neck stiffness. Because the management of cerebral haemorrhage and infarction differs markedly, urgent brain imaging is required in all stroke patients (see Stroke: Management of Prevention on pages 000-000 of this issue).
Cerebral small vessel disease: about a quarter of ischaemic strokes are lacunar strokes resulting from small vessel disease.3 The white matter and deep grey matter nuclei are supplied by perforating or penetrating end-arteries arising from the basal intracerebral vessels and cortical vessels. Ischaemia in the territory of one artery results in a small infarction known as a lacuna. The underlying disease mechanisms are poorly understood, but most patients are hypertensive. Some patients have diffuse arteriopathy with thickening of the small arteries, described as lipohyalanosis. In others, microatheroma at the origin of the perforating vessels may be responsible. Lacunar stroke may be accompanied by diffuse white matter ischaemia (seen as low-density on computed tomography (CT) or high density on T2-weighted magnetic resonance imaging (MRI)), referred to as leukoaraiosis (Figure 2). Patients with small vessel disease also have increased risk of intracerebral haemorrhage, and studies using gradient-echo MRI show frequent microbleeds (Figure 2).
Arterial supply of the brain
Posterior cerebral arteries
Carotid siphon (in cavernous sinus) Carotid canal (in petrous bone) Foramen magnum
Basilar artery Vertebral artery External carotid artery Common carotid artery
Other causes of ischaemic stroke: many other diseases can cause ischaemic stroke: Carotid and vertebral dissection is an important cause of stroke in young individuals. A tear in the arterial wall, often following a history of trauma, results in secondary thrombosis and embolic stroke. Intracranial dissection, particularly of the vertebral artery, can also result in SAH. Prothrombotic factors (e.g. lupus anticoagulant, anticardiolipin antibody), the oral contraceptive pill and migraine are all associated with an increased risk of stroke. In young women presenting with stroke, a combination of these is often all that can be found responsible. Genetic diseases can cause stroke, particularly in the young. Sickle cell disease is associated with a significant stroke risk. The most common genetic form of stroke without systemic clinical features is cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). This autosomal dominant disease, caused by NOTCH 3 mutations, results in
MEDICINE --:-
Middle cerebral artery
Anterior cerebral arteries
Right subclavian artery
C1 C2 C3
A
Internal carotid artery
C4 C5
Left subclavian artery
C6 C7 D1
B
C D
Aortic arch The internal carotid artery (anterior circulation) divides from the anterior and middle cerebral arteries. The basilar artery (posterior circulation) divides from the posterior cerebral arteries. The Circle of Willis at the base of the brain provides communication between the different intracerebral vessels via the anterior and posterior communicating arteries. It is variably complete in different people, and this can determine whether carotid occlusion is asymptomatic or results in massive middle cerebral artery infarction. Common extracranial sites of atheroma are shown: A – proximal internal carotid artery, B – common carotid artery origin, C –vertebral artery origin, D – subclavian artery.
Figure 3
5
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006
STROKE
The first branch of the internal carotid artery is the ophthalmic artery. Emboli from a carotid stenosis can therefore cause retinal ischaemia (usually presenting with amaurosis fugax e a curtain descending from above, leading to complete transient loss of vision).
Clinical features of stroke divided according to arterial territory Anterior circulation e carotid territory C Amaurosis fugax/retinal infarction (ophthalmic artery) C Hemiparesis C Hemisensory loss C Hemianopia (optic tract and radiation) C Dysphasia (expressive and/or receptive) if dominant hemisphere C Sensory inattention C Visual inattention C Neglect Posterior circulation e vertebrobasilar territory C Ataxia e cerebellum and brainstem cerebellar connections C Cranial nerve nuclei involvement Diplopia and extraocular eye movement disorders Facial sensory loss Facial palsy e lower motor neurone (affects upper and lower face) Dysphagia Vertigo Hearing disturbance Vomiting Dysarthria Hemiparesis (descending corticospinal tract) e can be bilateral weakness Hemisensory loss (ascending sensory tracts) e can be bilateral sensory loss Hemianopia e occipital lobe involvement Cortical blindness e basilar artery occlusion, causing ischaemia in both occipital cortices
Posterior circulation stroke: the two vertebral arteries and basilar artery comprise the posterior circulation. The basilar artery terminates in the posterior cerebral artery. Posterior cerebral artery infarction results in hemianopia because of occipital cortex involvement. The posterior circulation supplies the brainstem and cerebellum. Infarction can result in hemiparesis or hemisensory loss (involvement of the descending and ascending tracts), ataxia or involvement of cranial nerve nuclei (e.g. vertigo, eye movement abnormalities, facial palsy, tongue weakness, dysphagia). Basilar ischaemia can result in bilateral weakness or sensory loss, or bilateral (complete) visual loss. Lacunar stroke: many lacunar infarcts are asymptomatic, but they can affect clinically eloquent descending or ascending fibres in the white matter or deep grey matter. Symptoms usually occur from infarction in the posterior limb of the internal capsule affecting the corticospinal tract. This results in pure motor stroke (hemiparesis affecting the face, arm and leg). Other lacunar syndromes involve pure sensory stroke and sensorimotor stroke, clumsy hand dysarthria (slight weakness and clumsiness of the hand with slurred speech) and ataxic hemiparesis (ataxia and usually mild hemiparesis affecting the same side). As they spare the cortex, lacunar strokes do not present with features such as neglect or dysphasia. A
KEY REFERENCES 1 Feigin VL, Forouzanfar MH, Krishnamurthi R, et al. Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) and the GBD Stroke Experts Group. Global and regional burden of stroke during 1990e2010: findings from the Global Burden of Disease Study 2010. Lancet 2014; 383: 245e54. 2 National Audit Office. Reducing brain damage: faster access to better stroke care. London: National Audit Office, 2005. 3 Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9: 689e701. 4 Luciano A, Sposato LA. Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and metaanalysis. Lancet Neurol 2010; 14: 377e87. 5 Hart RG, Diener HC, Coutts SB, et al. Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 2014; 13: 429e38.
Table 3
Localizing the lesion The neurological consequences of a stroke depends on the brain region affected. Localization requires knowledge of cerebral arterial anatomy (Figure 3) and location of different functions within the brain. Ischaemic territory strokes can be divided into anterior and posterior circulation stroke (Table 3). Anterior circulation stroke: this refers to stroke in the territory of the carotid arteries, which supply the anterior and middle cerebral arteries. Anterior cerebral artery infarction can be asymptomatic or cause weakness primarily of the leg. Middle cerebral artery stroke can cause: hemiparesis (worse in the arm if infarction is cortical; affecting the arm, face and leg equally if subcortical) hemisensory loss hemianopia (from involvement of the optic radiation) dysphasia (if in the dominant hemisphere) inattention (both visual and sensory) neglect.
MEDICINE --:-
FURTHER READING Markus H, Pereira A, Cloud G. Handbook of stroke medicine. Oxford: Oxford University Press, 2010.
6
Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Markus H, Stroke: causes and clinical features, Medicine (2016), http://dx.doi.org/10.1016/ j.mpmed.2016.06.006