Ischaemic stroke is the most common form of stroke, and accounts for 80% of stroke cases. It occurs due to anaemic infarction of the brain, but the underlying cause of the necrosis depends on the type of stroke.

Stroke involving the territory of the internal carotid system, including the anterior and middle cerebral arteries, is called anterior territory stroke. Middle cerebral artery infarct is most common, 2/3 of all strokes. Anterior cerebral artery infarct is rare, ~2% of all strokes. 20% of strokes involve the vertebrobasilar arterial system, called posterior territory stroke.

Types

We can differentiate six types according to etiology:

Large artery stroke
Small artery/lacunar stroke
Embolic stroke
Watershed stroke
Cryptogenic stroke
Stroke due to non-atherosclerotic vascular disease

Large artery stroke

Large artery stroke is due to occlusion of large arteries supplying the brain, most commonly the middle cerebral artery but also the anterior or posterior cerebral artery, internal carotid artery, vertebral artery, etc. Large artery stroke is a CNS manifestation of cardiovascular disease and therefore occurs secondarily to atherosclerotic risk factors like hypertension, dyslipidaemia, etc.

The pathomechanism is similar as for myocardial infarction, with sudden rupture of an atherosclerotic plaque with resulting thrombosis. Large artery stroke has the worst prognosis, as it causes large infarcts (> 1,5 cm in diameter). Infarct can occur in both cortical and subcortical regions.

Small artery stroke

Small artery stroke, also called lacunar stroke, is due to occlusion of the so-called penetrating small arteries or lenticulostriate arteries. These are small arteries which arise at acute angles from larger arteries, which predispose them to turbulence in the context of hypertension. As such, small artery stroke is mostly related to hypertension. Chronic hypertension causes lipohyalinosis of these arteries, eventually causing occlusion.

These arteries are small in diameter and supply subcortical regions. As such, these strokes only affect subcortical structures and therefore don’t cause cortical symptoms like aphasia, and they only cause smaller strokes (< 1,5 cm). Lacunar strokes usually cause one of over 20 combinations of clinical features (syndromes). The most common are:

Only hemiparesis
Only hemisensory loss
Hemiparesis + hemisensory loss
Ataxic hemiparesis
Dysarthria-clumsy hand syndrome (facial and hand weakness + dysarthria)

Embolic stroke

These strokes occur due to embolism, most commonly from the heart or carotid artery. For this reason, everyone with a stroke must be evaluated for sources of embolism. The most common sources are like atrial fibrillation (most common cause), myocardial infarction, endocarditis, or carotid artery stenosis.

These strokes usually affect the cortical surfaces. Multiple emboli may occur simultaneously, causing multiple strokes.

Watershed stroke

A watershed area is a part of the brain which is supplied by the distalmost branches of two separate arteries. If perfusion through one of these two arteries decreases, the watershed area can be safely supplied by the other artery. However, if the perfusion through both arteries decreases, the watershed area is unlikely to receive sufficient perfusion.

Watershed stroke refers to infarction of the watershed region which occurs when there is a sudden decrease in blood flow through both of these arteries. This is usually due to systemic hypoperfusion rather than single artery occlusion. This can occur due to cardiac arrest, severe hypotension, etc.

The clinical features depend on which watershed region is affected:

Stroke in the ACA-MCA watershed region -> sensory loss and paresis in both upper arms, but spares the underarms and lower limbs – also called “man in a barrel” syndrome
Stroke in the MCA-PCA watershed region -> visual loss

Cryptogenic stroke

In cases where the etiology initially cannot be determined, the stroke is called cryptogenic. The underlying etiology is usually paroxysmal atrial fibrillation, patent foramen ovale with paradoxical embolism, or non-atherosclerotic vasculopathy.

Stroke due to non-atherosclerotic vascular disease

Vascular diseases apart from atherosclerotic vascular disease can also cause ischaemic stroke. This is usually due to arterial dissection or vasculitis. The mechanism of ischaemic stroke is either development of thromboembolism or by abnormal haemodynamics.

Arterial dissection which causes stroke most commonly occurs in the internal carotid artery. This can cause stroke even in young people, and can be spontaneous or secondary to trauma.

Clinical features

With regards to stroke, it’s valuable to distinguish clinically whether the stroke affects the anterior or posterior circulation of the brain, and, if possible, which artery specifically. The anterior circulation of the brain consists of the internal carotid arteries, as well as the anterior and middle cerebral arteries. It supplies the majority of both cerebral hemispheres, except the occipital and medial temporal lobes.

The posterior circulation of the brain consists of the vertebral arteries, basilar artery, and posterior cerebral arteries. It supplies the brain stem, cerebellum, thalamus, and occipital cortex. Symptoms of the posterior circulation are covered in topic 26A.

The whole artery need not be affected, as smaller branches of the artery can be obstructed. As such, not all symptoms mentioned below must necessarily occur together. The most commonly affected vessel in ischaemic stroke is the middle cerebral artery.

Symptoms are generally acute and maximal at onset, but sometimes they progress gradually.

Anterior circulation stroke

Symptoms of insufficient blood supply of the carotid artery territory

Contralateral hemianopia
Contralateral hemisensory loss
Contralateral hemiparesis
Aphasia
Gaze palsy toward side of lesion
Contralateral facial palsy
Contralateral pyramidal signs

The combination of hemiparesis, hemisensory loss, and hemianopia is sometimes called “hemi syndrome” in Hungarian literature.

Symptoms of insufficient blood supply of the anterior cerebral artery territory

Contralateral lower extremity weakness

Symptoms of insufficient blood supply of the middle cerebral artery territory

Contralateral upper extremity weakness
Contralateral facial palsy
Aphasia if in dominant hemisphere (usually left)
Hemineglect if in nondominant hemisphere

Posterior circulation stroke

The posterior circulation supplies the brain stem and thalamus (+ cerebellum and occipital cortex), and as such may produce a larger variety of symptoms than anterior circulation strokes. 20% of strokes are posterior circulation strokes.

Symptoms of insufficient blood supply of the vertebrobasilar artery territory

Vertigo
Diplopia
Dysarthria
Contralateral or bilateral hemiparesis/plegia
Contralateral or bilateral hemisensory loss
Bilateral visual changes/hemianopia
Ipsilateral Horner syndrome
Altered consciousness
LMN facial palsy
Dysphagia
Ipsilateral limb ataxia
Alternating brainstem syndrome

Diagnosis and evaluation

As with all acute life-threatening conditions it’s important to assess the stability by ABCDE first. All patients with suspected stroke should be admitted to a stroke unit.

Some patients develop the stroke while sleeping, and only note the symptoms after awakening. This is called a “wake-up stroke”, and for the purposes of treatment we define the onset of the stroke to be the time when the patient was last known to be normal, usually the time they went to bed.

Clinical evaluation

The clinical evaluation of patients with suspected stroke must be rapid and usually takes only a few minutes. This is usually performed with a screening tool like National Institute of Health Stroke Scale (NIHSS), which scores the severity of the stroke based on factors like:

Level of consciousness
Orientation
Ability to perform certain movements, like blinking and squeezing hands
Presence of visual field defect
Presence of facial palsy
Arm drift
Leg drift
Heel-shin test
Sensory loss
Presence of aphasia

The possibility of stroke mimics must always be considered, including:

Recrudescence of old stroke from metabolic or infectious stress
Todd’s paralysis after seizure
Complex migraine
Pseudoseizure, conversion disorder

Diagnostic imaging

The most important and first diagnostic test is native CT. Ischaemia is usually not visible on native CT in the first 6 hours, but intracranial haemorrhage is visible much earlier. Therefore, the goal of native CT is to rule out haemorrhagic stroke. In a patient with clinical features of stroke and no bleeding on CT, ischaemic stroke is presumed. In some cases, the “hyperdense artery” sign can be seen, which is due to a thrombus in the middle cerebral artery.

ECG and labs are important but should not delay the native CT.

The ASPECTS score can be used to score early ischaemic changes on native CT in ischaemic stroke. A score of 10 is a normal native CT, while a score of 0 means that the entire MCA territory is ischaemic.

Vascular imaging

Vascular imaging (CTA/MRA) is performed after or during the initial native CT. Its purpose is to learn more about the type of stroke, and how good the collateral blood supply is. Vascular imaging can detect a large artery occlusion, which is an indication for thrombectomy.

Sometime during the first days after a stroke, a carotid ultrasound must be made to look for carotid atherosclerosis, which can be a source of embolism or thrombosis. Severe carotid artery stenosis can lead to TIA/ischaemic stroke and may therefore be an indication for carotid endarterectomy or stenting.

Perfusion imaging

The penumbra is the brain area around the infarcted brain which is potentially still salvageable if revascularization occurs in time. In some cases, perfusion imaging (CT perfusion or MRI with DWI) is performed to examine the penumbra. This can be useful if the size of the penumbra influences the decision of whether to perform thrombectomy or not.

For example, if there is a large artery occlusion, and the 6 hour time window for thrombectomy has passed, we may perform perfusion imaging to evaluate whether the penumbra is large enough that late thrombectomy is still beneficial.

Cardiac evaluation

If embolic ischaemic stroke is suspected, cardiac investigation is necessary, and includes echocardiography and Holter ECG. These can detect PFO, paroxysmal AF, endocarditis, etc.

Treatment of acute stroke

Thrombolysis

IV thrombolysis with an rtPA like alteplase is the best treatment for ischaemic stroke. It’s indicated for everyone with ischaemic stroke in which it can be performed within 4,5 hours of symptom onset, but the sooner it’s initiated, the better. It can only be performed if haemorrhagic stroke has been ruled out by native CT.

There are some contraindications, like:

Previous intracranial haemorrhage
Intracranial tumour
Recent surgery or trauma
INR > 1,7 or recent treatment with heparin or DOAC

Thrombolysis may “convert” the stroke from ischaemic to haemorrhagic, and it may cause severe bleeds anywhere in the body which are difficult to treat. However, it may also completely reverse the stroke symptoms. As such, it’s difficult but important to select the proper canditates for thrombolysis. Imaging is performed 24 hours after thrombolysis to make sure that haemorrhage conversion did not occur.

In Norway, only approx. 15% of stroke patients receive thrombolytic therapy.

Thrombectomy

Mechanical thrombectomy is indicated if there’s a large artery occlusion visible on vascular imaging. An intravasal catheter is inserted into the femoral artery and led up to the occluded artery in the brain, where the thrombus is removed.

In large artery strokes, thrombolysis is less effective and so thrombectomy may be used. Thrombectomy must be performed within 6 hours of symptom onset, and if they present within 4,5 hours then it should be combined with thrombolysis for best results. If perfusion imaging show a large penumbra, thrombectomy can be performed up to 24 hours after onset.

Aspirin

300 mg ASA is indicated for all cases of ischaemic stroke, but the timing of it depends on whether thrombolysis is performed. If the patient is treated with thrombolysis, aspirin is given after the 24-hour post-thrombolysis imaging has excluded haemorrhage. If the patient does not receive thrombolysis, aspirin is given immediately upon exclusion of haemorrhagic stroke.

Other treatment

If there is a malignant middle cerebral artery infarction, a decompressive hemicranectomy can be performed. This is lifesaving but has high risk of disability.

Supportive treatment is also important. Blood pressure management, blood glucose management, and fluid replacement are necessary. Systolic blood pressure should be kept between 120 mmHg and 220 mmHg.

Prevention

Primary prevention

The primary prevention of stroke is similar to that of all cardiovascular disease. Many major risk factors for CVD are modifiable. 90% of stroke burden globally is due to modifiable risk factors.

Anticoagulation in atrial fibrillation

The CHA2DS2-VASC score is used to determine whether patients with atrial fibrillation should receive anticoagulants or not. The score is like this:

Congestive heart failure – 1 point
Hypertension – 1 point
Age > 75 years – 2 points
Diabetes mellitus – 1 point
Stroke, TIA, or thromboembolism – 2 points
Vascular disease (CAD, PAD, etc.) – 1 point
Age 65 – 74 years – 1 point
Sex Category: female – 1 point

Anticoagulation is indicated if the score is 2 or more in men or 3 or more in women, or if the score is 1 or 2 respectively but 1 of the risk factors is age 65 – 74 (as this is a stronger risk factor). The recommended anticoagulant is a DOAC.

Other primary preventions

Healthy diet – increase intake of
- Fruits and vegetables
- Fibre
- Foods with low glycaemic index and low glycaemic load
- Monounsaturated fat rather than trans or saturated fat
- Omega-3 fatty acids from foods
Smoking cessation
Hypertension – treat
Dyslipidaemia – treat
Increase physical activity
- Moderate intensity exercise for 150 minutes/week OR:
- Vigorous intensity exercise for 75 minutes/week
Weight loss – in cases of overweight or obesity
Treatment of type 2 diabetes

Secondary prevention

Antiplatelet therapy

Should be initiated in all patients after ischaemic stroke. Either aspirin or clopidogrel. Treatment should be initiated as soon as possible of ischaemic stroke onset, except if the patient receives thrombolysis, in which case it should be started 24 hours after.

Cholesterol management

High intensity statins should be initiated in all patients after ischaemic stroke. Statins are beneficial for all patients, possibly even if they don’t have dyslipidaemia, but most patients with ischaemic stroke have dyslipidaemia anyway. The target LDL is 1,4 mM (according to European guidelines. American guidelines target 1.8). If the target isn’t reached with high intensity statins alone and lifestyle changes alone, adjunctive cholesterol lowering drugs should be added.

Blood pressure management

For patients without diabetes, the target is < 140/90 mmHg. For patients with diabetes, the target is < 130/80 mmHg. Both non-pharmacological and pharmacological interventions should be used.

Anticoagulation

Anticoagulation is initiated in all patients with atrial fibrillation after ischaemic stroke. DOACs are preferred.

Carotid surgery

Carotid surgery is indicated for everyone with a 70 – 99% carotid stenosis (1A level recommendation) and suggested for those with 50 – 69% stenosis (2A level recommendation). This involves carotid endarterectomy or carotid artery stenting.

Blood glucose management

For patients with diabetes. Target is < 7% (53 mmol/mol)

Other interventions

Smoking cessation
Reduction of alcohol consumption
Regular physical activity
Mediterranean diet
Salt intake < 2,4 g/day