Flashcards in Geriatrics - Stroke Deck (58):
What are the three main mechanisms of cerebrovascular disease?
Cerebrovascular diseases are subdivided into 3 major categories that include:
Pathophysiologic process that produces CVDs includes:
- reduced blood supply and oxygenation of tissue due to hypoxia, ischaemia and infarction (complication of ischaemia)
- CNS haemorrhage (parenchyma, subarachnoid) from rupture of cerebral vessels
What two mechanisms can derive the brain of oxygen?
The brain is a highly oxygen dependent tissue, and receives 15% of cardiac output. Cerebral blood flow is usually stable over a range of intracranial pressures due to autoregulation of vascular resistance. The brain may be deprived of oxygen in 2 circumstances:
1) FUNCTIONAL hypoxia = caused by low arterial pressure of oxygen (e.g. high altitude), impaired oxygen carrying capacity (e.g. severe anaemia, carbon monoxide poisoning) or inhibition of oxygen use by tissues (e.g. cyanide poisoning)
2) ISCHAEMIA (i.e. stroke) = either transient or permanent due to tissue hypoperfusion, which can be caused by hypotension, vascular occlusion or both
What can cause global ischaemia?
Widespread ischaemic-hypoxic can occur in the setting of severe systemic hypotension, usually when the systolic pressure falls below 50 mmHg, as in cardiac arrest, shock and severe hypotension. The clinical outcome varies with the duration and severity of the insult.
Which neurones are more susceptible to global ischaemic injury?
Neurons are more susceptible to ischaemic injury than are glial cells, and the most susceptible neurones are the pyramidal cells of the hippocampus and neocortex, and Purkinje cells of the cerebellum. In some individuals, even mild or transient global ischaemia insults may cause damage to these vulnerable areas.
In severe global ischaemia, widespread neuronal death occurs irrespective of regional vulnerability. Patients who survive often remain severely neurologically impaired and in a persistent vegetative state. Other patients meet the criteria for brainstem death, including evidence of diffuse cortical injury (isoelectric or "flat" EEG) and brain stem damage, including absent reflexes or respiratory drive. When these patients are sustained on a ventilator the brain gradually undergoes autolysis, leading to "respirator brain".
What are the important morphological features of global ischaemia?
The brain is swollen with wide gyri and narrow sulci.
Features of irreversible ischaemic injury (infarction) are grouped as follows:
- EARLY CHANGES: occurring 12-24 hrs after, include acute neuronal cell change (red neurones). Individual cell bodies are shrunken, along with nuclei. After this, the reaction to tissue damage begins with infiltration of neutrophils
- SUBACUTE CHANGES: occurring at 24 hrs to 2 weeks. Includes necrosis of tissue, influx of macrophages, vascular proliferation and reactive gliosis
- REPAIR: seen after 2 weeks, is characterised by removal of necrotic tissue, loss of organised CNS structure and gliosis. The distribution of neuronal loss in the neocortex is typically uneven, with preservation of some layers and loss of others - termed pseudolaminar necrosis
What are watershed infarcts?
These are wedge shaped areas of infarction that occur in regions of the brain and spinal cord that lie at the most distal portions of arterial territories. They are usually seen after hypotensive episodes. In the cerebral hemispheres, the border zone between the anterior and middle cerebral arteries is at greatest risk. Damage to this region produces a band of necrosis over the cerebral convexivity a few centimetres lateral to the interhemispheric fissure.
What causes focal ischaemia? What is the role of collateral blood flow?
Cerebral arterial occlusion leads first to focal ischaemia then to infarction in the distribution of the affected vessel. The size, location and shape of the infarct and the extent of tissue damage that results can be modified by the presence of tissue collaterals. Specifically, collateral blood flow through the circle of Willis or cortico-leptomeningeal anastamoses can limit damage in some regions. By contrast, there is little collateral flow to structures such as the thalamus, basal ganglia and deep white matter which are supplied by deep penetrating vessels.
What is more common, embolic or thrombotic ischaemia?
Embolic infarctions are more common than infarctions due to thrombosis. Cardiac mural thrombi are a frequent cause of emboli; myocardial dysfunction, valvular disease and atrial fibrillation are important predisposing factors. Thromboemboli also arise in arteries, most often from atheromatous plaques within the carotid arteries or the aortic arch. Other emboli of venous origin cross over to the arterial circulation through cardiac defects and lodge in the brain (paradoxical emboli). These include thromboemboli from deep vein thrombosis and fat emboli (usually following long bone injury). The territory of the middle cerebral artery, a direct extension of the internal carotid artery) is most frequently affected by embolic infarction. Emboli tend to lodge where vessels branch or in areas of stenosis, usually caused by atherosclerosis.
Where do thrombotic occlusions usually occur?
Thrombotic occlusions causing cerebral infarctions usually are superimposed on atherosclerotic plaques. Common sites are around the carotid bifurcation, the origin of the middle cerebral artery, and at either end of the basilar artery. These occlusions may be accompanied by anterograde extension, as well as thrombus fragmentation and distal embolisation.
What are the two types of infarcts?
Infarcts can be divided into two types based on their macroscopic and microscopic appearance. Nonhaemorrhagic infarcts result from acute vascular occlusions (usually caused by atherosclerosis) and can be treated with thrombolytic therapy. This approach is contraindicated in haemorrhagic infarcts, which result from reperfusion of ischaemic tissue either through collaterals or after dissolution of emboli and often produce multiple, sometimes confluent petechial haemorrhages.
Emboli tend to produce haemorrhagic infarcts. Vessel reperfusion after lysis of embolic material causes haemorrhage.
What are common causes of haemorrhagic stroke?
Haemorrhage within the brain is associated with (1) hypertension and other diseases leading to vascular wall injury, (2) structural lesions such as AVMs and cavernous malformations and (3) tumours. Subarachnoid haemorrhage most commonly are caused by a ruptured berry aneurysm but can also occur in other vascular malformations. Subdural or epidural haemorrhages are usually associated with trauma.
What types of patients are most affected by primary brain parenchymal haemorrhage?
Spontaneous intraparenchymal haemorrhages are most common in mid to late adult life, with a peak incidence at about 60 years of age. Most are due to rupture of small intraparenchymal vessels. Hypertension is the leading cause, and brain haemorrhage accounts for roughly 50% of deaths amongst patients with hypertension.
In hypertension, branches of the lenticulostriate vessels develop Charcot-Bouchard microaneurysms. Rupture of these aneurysms produces intracerebral haemorrahage (haematoma). This pushes the brain parenchyma aside.
Which areas of the brain are most vulnerable to intracerebral haemorrhage?
Intracerebral haemorrhage can be devastating when it affects large portions of the brain or extends into the ventricular system. Hypertensive intraparenchymal haemorrhages typically occur in the basal ganglia, thalamus, pons and cerebellum. If the person survives the event, gradual resolution of the haematoma ensues sometimes with considerable clinical improvement.
What is the morphology of intracerebral haemorrhage?
Acute haemorrhages are characterised by extravasated blood, which compresses the adjacent parenchyma. With time, haemorrhages are converted to a cavity with a brown discoloured rim. On microscopic examination, early lesions consist of clotted blood surrounded by brain tissue showing anoxic neuronal and glial changes as well as oedema. Eventually, the oedema resolves and pigment and lipid laden macrophages appear.
What is cerebral amyloid angiopathy?
CAA is a disease in which amyloid peptides, typically the same as those found in Alzheimer's disease, deposit in the walls of medium sized and small caliber meningeal and cortical vessels. The amyloid causes a rigid, pipe-like appearance and stains with Congo red. Amyloid deposition weakens the vessel walls and increases the risk of haemorrhages which differ in the distribution compare to those caused by hypertension. Specifically, CAA associated haemorrhages often occur in the lobes of the cerebral hemispheres (lobar haemorrhages).
What is the most common cause of a subarachnoid haemorrhage?
The most frequent cause of a clinically significant, non traumatic subarachnoid haemorrhage is rupture of a saccular (berry) aneurysm. Haemorrhage into the subarachnoid space also may result from vascular malformation, trauma, rupture of an intracerebral haemorrhage into the ventricular system, haematologic disturbances and tumours.
What precipitates subarachnoid haemorrhage?
Rupture of the saccular aneurysm can occur at any point, but about one third of cases are associated with an increase in intracranial pressure, such as with straining or sexual activity. Blood under arterial pressure is forced into the subarachnoid space, and the patient is stricken with a sudden, excruciating headache and rapidly looses consciousness. Between 25% and 50% die from the initial bleed.
Where is the most common location for aneurysms to develop leading to sub arachnoid haemorrhage?
About 90% of aneurysms occur in the anterior circulation near major arterial branch points. Multiple aneurysms exist in 20-30% of cases. Although they are sometimes referred to as "congenital" they are not present at birth but develop over time due to underlying defects in the vascular media. There is an increased risk of aneurysms in patients with autosomal dominant polycystic kidney disease, as well as those with disorders of extracellular matrix proteins.
The most common site is the anterior communicating artery (40%).
How is aneurysm size related to bleeding risk?
Overally, roughly 1.3% of aneurysms bleed per year with the probability of rupture increasing nonlinearly with size. For example, aneurysms larger than 1cm in diameter have a roughly 50% chance of bleeding each year. In the early period of SAH, there is an additional risk of ischaemic injury from vasospasm of other vessels. Healing and meningeal fibrosis and scarring sometimes obstruct CSF outflow or disrupt absorption leading to hydrocephalus.
What is the morphology of an aneurysm?
An unruptured aneurysm is a thin walled out-pouching of an artery. Beyond the neck of the aneurysm, the muscular wall and intimal elastic lamina are absent, such that the aneurysm sac is lined only by thickened hyalinized intima. The adventitia covering the sac is continuous with that of the parent artery.
What other types of aneurysms can be present other than saccular?
Atherosclerotic, mycotic, traumatic and dissecting aneurysms can also occur intracranially. The last three types (like saccular aneurysms) are most often found in the anterior circulation, whereas atherosclerotic aneurysms frequently involve the basilar artery. Non saccular aneurysms usually caused cerebral infarction due to vascular occlusion rather than haemorrhage.
Name the four different types of vascular malformation
Arteriovenous malformation (AVMs)
AVMs are the most common of these.
What patients are at risk of AVMs?
AVMs affect males twice as frequently as females and most commonly present during ages 10 to 30 years, with seizures, intracranial haemorrhage or SAH. Large AVMs occurring in the newborn can cause high output heart failure because of blood shunting from arteries to veins. The risk of bleeding makes AVMs the most dangerous type of vascular malformation.
Multiple AVMs can be seen in hereditary haemorrhagic telangiectasia, an autosomal dominant condition often associated with mutations affecting the TGF beta pathway.
What is the morphological appearance of AVMs?
AVMs may involve subarachnoid vessels extending into the brain parenchyma or occur exclusively within the brain. On gross inspection, they resemble a tangled meshwork of wormlike vascular channels. Microscopy shows enlarged blood vessels separated by gliotic tissue.
How does hypertension cause cerebrovascular disease?
Hypertension causes hyaline arteriolar sclerosis of the deep penetrating arteries and arterioles that supply the basal ganglia, the hemispheric white matter and the brain stem. Affected arteriolar walls are weakened and are more vulnerable to rupture. In some cases, minute aneurysms (Charcot-Bouchard microaneurysms) form in vessels less than 30 microns in diameter.
Other than massive intracerebral haemorrhage, how else is the brain affected by hypertension?
1) Lacunar infarcts are small cavity infarcts found mostly in the deep grey matter (basal ganglia and thalamus), the internal capsule, and deep white matter and the pons. They are caused by an occlusion of a single penetrating branch of a large cerebral artery.
2) Rupture of small caliber penetrating vessels may occur, leading to development of small haemorrhages. In time, these resorb, leaving behind slit like cavities (slit haemorrhages) surrounded by brownish discolouration.
3) Acute hypertensive encephalopathy most often associated with sustained rises in diastolic pressure to greater than 130 mmHg. It is characterised by increased intracranial pressure and global cerebral dysfunction, manifesting as headache, confusion, vomiting, convulsions, and sometimes coma.
What can cause vasculitis in the CNS?
A variety of inflammatory processes involving blood vessels may compromise blood flow and cause cerebral infarction. Infectious arteritis of small and large vessels was previously seen with syphilis and TB, but now is caused by opportunistic infections (such as aspergillosis, herpes zoster or CMV) arising from the setting of immunosuppression. Some systemic forms of vasculitis such as PAN may involve cerebral vessels and cause single or multiple infarcts throughout the brain.
What is primary angiitis of the CNS?
This is a form of vasculitis involving multiple small to medium sized parenchymal and subarachnoid vessels that is characterised by chronic inflammation, multinucleate giant cells (with or without granuloma formation) and destruction of vessel walls. Affected persons present with a diffuse encephalopathy, often with cognitive dysfunction.
What are the clinical features of stroke?
Acute stroke is characterised by the appearance of rapid (over minutes) focal neurological signs, which can take several forms:
- Speech disturbance
- Visual deficit
- Visuo-spatial disturbance
- Coma (may indicate SAH or intracerebral haemorrhage in the first 24 hours)
How does weakness present in stroke?
Unilateral weakness is the classic presentation of stroke. The weakness starts suddenly and progresses rapidly in a hemiplegic pattern. Reflexes are initially reduced but later tone and reflexes are increased. UMN facial weakness is often present.
What speech disturbances can be present in stroke?
Dysphasia and dysarthria are the usual speech manifestations. Dysphasia indicates dominant frontal (Broca's, motor, expressive) or parietal (Wernicke's, sensory or receptive) lobe damage, while dysarthria is caused by weakness or incoordination of the face and pharyngeal muscles.
Visual disturbances in stroke
Monocular blindess in stroke can be caused by reduced blood flow in the internal carotid or ophthalmic arteries. If transient, this is called amourosis fugax. Ischaemic damage to the occipital lobe or optic tracts causes contralateral hemianopia.
Damage to the non dominant cortex often results in contralateral sensory or visual neglect and apraxia.
Name some structural stroke mimics
Primary cerebral tumours
Metastatic cerebral tumours
Peripheral nerve lesions
Name some functional stroke mimics
Todd's paresis (after epileptic seizure)
Migrainous aura (with or without headache)
How are strokes classified based on their time course?
Transient ischaemic attack (TIA) - symptoms resolve completely within 24 hours. This include amourosis fugax
Stroke - symptoms last >24 hours. With a clear history of rapid onset transient or sustained focal deficit. Alternative diagnoses only account for 5% of cases
Progressing stroke ("stroke in evolution") - focal neurological deficit worsens after the patient first presents. It may be due to the increasing volume of the infarction, haemorrhage or related oedema
Completed stroke - focal deficit persists but is not progressing
How do brainstem infarcts present?
These may result in more severe symptoms including qaudriplegia and lock in syndrome.
The hallmark of brainstem lesions is contralateral motor/ sensory deficits and ipsilateral cranial nerve palsies.
What is a lacunar infarct?
Small infarcts around the basal ganglia, internal capsule, thalamus and pons.
This may result in pure motor, pure sensory, mixed motor and sensory signs or ataxia.
What is the Oxford stroke classification system?
One formal classification system that is sometimes used is the Oxford Stroke Classification (also known as the Bamford Classification), which classifies strokes based on the initial symptoms. A summary is as follows:
The following criteria should be assessed:
1) unilateral hemiparesis and/or hemisensory loss of the face, arm & leg
2) homonymous hemianopia
3) higher cognitive dysfunction e.g. dysphasia
What is a total anterior circulation infarct (TACI, c.15%)?
All 3 features of the Oxford Stroke classification are present. It involves middle and anterior cerebral arteries.
What is a partial anterior circulation infarct (PACI, c. 25%)?
Involves smaller arteries of anterior circulation e.g. upper or lower division of middle cerebral artery.
2 of the criteria are present.
What are posterior circulation infarcts (POCI, c. 25%)?
Involves vertebrobasilar arteries presents with 1 of the following:
1) cerebellar or brainstem syndromes
2) loss of consciousness
3) isolated homonymous hemianopia
What is lateral medullary syndrome?
Lateral medullary syndrome (posterior inferior cerebellar artery)
- aka Wallenberg's syndrome
- ipsilateral: ataxia, nystagmus, dysphagia, facial numbness, cranial nerve palsy e.g. Horner's
- contralateral: limb sensory loss
What is Weber's syndrome?
- ipsilateral III palsy
- contralateral weakness
How does a stroke affecting the anterior inferior cerebellar artery present?
Symptoms are similar to Wallenberg's, but:
Ipsilateral: facial paralysis and deafness
Is it possible to differentiate ischaemic from haemorrhagic strokes based on symptoms?
Whilst symptoms alone cannot be used to differentiate haemorrhagic from ischaemic strokes, patients who've suffered haemorrhages are more likely to have:
- decrease in the level of consciousness: seen in up to 50% of patients with a haemorrhagic stroke
- headache is also much more common in haemorrhagic stroke
- nausea and vomiting is also common
- seizures occur in up to 25% of patients
How should stroke be assessed?
Whilst the diagnosis of stroke may sometimes be obvious in many cases the presenting symptoms may be vague and accurate assessment difficult.
The FAST screening tool (Face/Arms/Speech/Time) is widely known by the general public following a publicity campaign. It has a positive predictive value of 78%.
A variant of FAST called the ROSIER score is useful for medical professionals. It is validated tool recommended by the Royal College of Physicians.
Exclude hypoglycaemia first, then assess the following:
Loss of consciousness or syncope - 1 point
Seizure activity - 1 point
New, acute onset of:
- asymmetric facial weakness + 1 point
- asymmetric arm weakness + 1 point
- asymmetric leg weakness + 1 point
- speech disturbance + 1 point
- visual field defect + 1 point
Score >0 indicates stroke likely.
What investigations are important in suspected stroke?
Patients with suspected stroke need to have emergency neuroimaging. The main cause for urgency is to see whether a patient may be suitable for thrombolytic therapy to treat early ischaemic strokes. The two types of neuroimaging used in this setting are:
What does a haemorrhagic stroke appear like on CT?
Areas of high density represent acute intracerebral haemorrhage. The high density areas (blood) are surrounded by low density areas (oedema). Mass effect can often be seen, with loss of sulci on the side of the haemorrhage and midline shift.
How does cerebral infarction appear on CT?
Acute infarcts appear as low density areas. It causes mass effect with loss of sulci, and sometimes effacement of the horns of the lateral ventricle. Midline shift may also occur.
How are ischaemic strokes managed?
Urgent neuroimaging classifies the stroke as either ischaemic or haemorrhagic. If the stroke is ischaemic, and certain criteria are met, the patient should be offered thrombolysis. Example criteria include:
- patients present with 4.5 hours of onset of stroke symptoms
- the patient has not had a previous intracranial haemorrhage, uncontrolled hypertension, pregnant etc
Once haemorrhagic stroke has been excluded patients should be given aspirin 300mg as soon as possible and antiplatelet therapy should be continued.
Alteplase is currently recommended by NICE.
Should blood pressure be lowered in acute stroke?
No. Blood pressure should not be lowered in the acute phase unless there are complications, e.g. hypertensive encephalopathy.
When should anticoagulation be given in stroke patients with AF?
With regards to atrial fibrillation, the RCP state: 'anticoagulants should not be started until brain imaging has excluded haemorrhage, and usually not until 14 days have passed from the onset of an ischaemic stroke'.
At what level of cholesterol should statins be considered?
If the cholesterol is > 3.5 mmol/l patients should be commenced on a statin. Many physicians will delay treatment until after at least 48 hours due to the risk of haemorrhagic transformation.
What drugs are now given as secondary prevention for stroke?
Clopidogrel is now recommended by NICE ahead of combination use of aspirin plus modified release (MR) dipyridamole in people who have had an ischaemic stroke.
Aspirin plus MR dipyridamole is now recommended after an ischaemic stroke only if clopidogrel is contraindicated or not tolerated, but treatment is no longer limited to 2 years' duration.
MR dipyridamole alone is recommended after an ischaemic stroke only if aspirin or clopidogrel are contraindicated or not tolerated, again with no limit on duration of treatment.
How are haemorrhagic strokes managed?
If imaging confirms a haemorrhagic stroke neurosurgical consultation should be considered for advice on further management. The vast majority of patients however are not suitable for surgical intervention. Management is therefore supportive as per haemorrhagic stroke. Anticoagulants (e.g. warfarin) and antithrombotic medications (e.g. clopidogrel) should be stopped to minimise further bleeding. If a patient is anticoagulated this should be reversed as quickly as possible. Trials have shown improved outcomes in patients who have their blood pressure lowered acutely and this is now part of many protocols for haemorrhagic strokes.
When is endarterectomy considered for stroke/ TIA?
Recommend if patient has suffered stroke or TIA in the carotid territory and are not severely disabled.
Should only be considered if carotid stenosis > 70% according ECST** criteria or > 50% according to NASCET*** criteria.
How are TIAs managed?
Remember with TIAs the, by definition, symptoms last less than 24 hours although in the vast majority of cases the duration is much shorter, typically 1 hour or so. For this reason most patients symptoms will have resolved before they see a doctor.
The treatment of TIAs focuses around reducing the risk of further ischaemic events. NICE currently advocate using a risk based approach based around the ABCD2 prognostic score:
A Age >= 60 years 1
B Blood pressure >= 140/90 mmHg 1
C Clinical features
- Unilateral weakness 2
- Speech disturbance, no weakness 1
D Duration of symptoms
- > 60 minutes 2
- 10-59 minutes 1
Patient has diabetes 1