Ischemic stroke

Ischaemic stroke results from a sudden cessation of adequate amounts of blood reaching parts of the brain. Ischaemic strokes can be divided according to territory affected or mechanism.

Epidemiology

Stroke is the second most common cause of morbidity worldwide (after myocardial infarction) and is the leading cause of acquired disability ².

Risk factors for ischaemic stroke largely mirror the risk factors for atherosclerosis, and include age, gender, family history, smoking, hypertension, hypercholesterolaemia and diabetes.

Clinical presentation

An ischaemic stroke typically presents with rapid onset neurological deficit, which is determined by the area of brain that is involved. The symptoms often evolve over hours, and may worsen or improve, depending on the fate of the ischaemic penumbra. 

The vascular territory affected will determine exact symptoms and clinical behaviour of the lesion:

• anterior cerebral artery infarct
• middle cerebral artery infarct
• posterior cerebral artery infarct
• lacunar infarct
• cerebellar infarct
• brainstem infarct:
  • midbrain infarct
  • pontine infarct
  • medullary infarct

Pathophysiology

Interruption of blood flow through an intracranial artery leads to deprivation of oxygen and glucose in the supplied vascular territory. This initiates a cascade of events at a cellular level which, if circulation is not re-established in time, will lead to cell death, mostly through liquefactive necrosis.

The mechanism of vessel obstruction is important in addressing therapeutic manoeuvres to both attempt to reverse or minimise the effects and to prevent future infarcts. 

Examples include:

• embolism:
  • cardiac embolism:
    • atrial fibrillation
    • ventricular aneurysm
    • endocarditis
  • paradoxical embolism
  • atherosclerotic embolism
  • fat embolism
  • air embolism
• thrombosis:
  • perforator thrombosis: lacunar infarct
  • acute plaque rupture with overlying thrombosis
• arterial dissection

Global cerebral hypoxia (as is seen in drowning or asphyxiation) is, usually, considered separately.

Radiographic features

In many institutions with active stroke services which provide reperfusion therapies a so-called code stroke aimed at expediting diagnosis and treatment of patients will include a non-contrast CT brain, CT perfusion and CT angiography. 

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Non-contrast CT brain

Non-contrast CT of the brain remains the mainstay of imaging in the setting on an acute stroke.   It is fast, inexpensive and readily available. Its main limitation however is the limited sensitivity in the acute setting. Detection depends on the territory, the experience of the interpreting radiologist and of course the time of the scan from onset of symptoms. Whether tissue is supplied by end arteries (e.g. lenticulostriate arteries) or has collateral supply (much of the cerebral cortex) will influence how quickly cytotoxic oedema develops ⁶.  For example detection of MCA territory infarct has been shown to be approximately 60-70% in the first 6 hours ³, although changes in the deep grey matter nuclei (especially lentiform nucleus) can be visible within 1 hour of occlusion in up to 60% of patients ⁶. 

The goals of CT in the acute setting are:  

1. exclude intracranial haemorrhage, which would preclude thrombolysis;
2. look for any "early" features of infarction
3. exclude other intracranial pathologies that may mimic a stroke, such as tumour

Immediate

The earliest CT sign visible is a hyperdense segment of a vessel, representing direct visualisation of the intravascular thrombus / embolus and as such is visible immediately ⁷. Although this can be seen in any vessel, it is most often observed in the middle cerebral artery (see hyperdense middle cerebral artery sign). 

Early (1-3 hours) (also known as hyperacute phase)

Within the first few hours a number of signs are visible depending on the site of occlusion and the presence of collateral flow. Early features include:

• loss of grey-white matter differentiation, and hypoattenuation of deep nuclei:
  • lentiform nucleus,  changes seen as early as 1 hour after occlusion,  visible in 75% of patients at 3 hours ⁶
• cortical hypodensity with associated parenchymal swelling with resultant gyral effacement
  • cortex which has poor collateral supply (e.g. insular ribbon) is more vulnerable ⁶. 

First week

With time the hypo-attenuation and swelling become more marked resulting in significant mass effect. This is a major cause of secondary damage in large infarcts. 

Second to third week

As time goes on the swelling starts to subside and small amounts of cortical petechial haemorrhages (not to be confused with haemorrhagic transformation) results in elevation of the attenuation of the cortex. This is known as the CT fogging phenomenon ⁵. Imaging a stroke at this time can be misleading as the affected cortex will appear near normal. 

Months

Later still the residual swelling passes, and gliosis sets in eventually appearing as a region of low density with negative mass effect. Cortical mineralisation can also sometimes be seen appearing hyperdense. 

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CT perfusion

CT perfusion has emerged as a critical tool in selecting patients for reperfusion therapy as well as increasing the accurate diagnosis of ischaemic stroke among non-expert readers four fold compared to routine non-contrast CT ⁹. 

It allows both the core of the infarct (that part destined to never recover regardless of reperfusion) to be identified as well as the surrounding penumbra (the region which although ischaemic has yet to go on to infarct and can be potentially salvaged). 

The key to interpretation is understanding a number of perfusion parameters:

• cerebral blood volume (CBV)
• cerebral blood flow (CBF)
• mean transit time (MTT) 
• time to peak (TPP)

Areas which demonstrate matched defects in CBV and MTT represent the unsalvageable infarct core, whereas areas which have prolonged MTT but preserved CBV are considered to be the ischaemic penumbra ⁹. 

These factors will be discussed further separately. See CT perfusion. 

CT angiography

• may identify thrombus within an intracranial vessel, and may guide intra-arterial thrombolysis or clot retrieval. 
• evaluation of the carotid and vertebral arteries in the neck 
  • establishing stroke aetiology (eg. atherosclerosis, dissection)
  • access limitation for endovascular treatment (e.g. tortuosity, stenosis)

MRI

MRI is more time consuming and less available than CT, but has significantly higher sensitivity and specificity in the diagnosis of acute ischaemic infarction in the first few hours after onset.

• diffusion weighted imaging (DWI) / ADC:
  • diffusion restriction may be seen within minutes following the onset of ischaemia ⁴ 
  • correlates well with infarct core
  • for detailed discussion of DWI and ADC in stroke see diffusion weighted MRI in acute stroke
• T2-weighted imaging and FLAIR:
  • less sensitive than DWI in the first few hours to parenchymal change
  • loss of normal signal void in large arteries may be visible immediately
  • after 6-12 hours infarcted tissue becomes high signal ¹⁰
  • sulcal effacement and mass effect develop and become maximal in the first few days
  • fogging: between 1-4 weeks (peak 2-3 weeks) infiltration of inflammatory cells may reduce T2 signal such that it becomes relatively isointense to normal parenchyma. 
• T1
  • low intensity roughly mirrors high T2 / FLAIR signal
  • cortical laminar necrosis or pseudolaminar necrosis may be seen as a ribbon of intrinsic high T1 signal, usually after 2 weeks (although it can be seen earlier) ¹⁰
• T1 C+:
  • arterial enhancement (aka intravascular enhancement):
    • can be seen very early (0-2 hours) although it is more common at about day 3
    • lasts approximately 1 week ¹⁰
    • seen in ~50% of cases
  • parenchymal enhancement:
    • usually begins towards the end of the first week ¹⁰ 
    • usually lasts less than 12 weeks; if longer than this the presence of an underlying lesion should be considered ¹⁰
  • meningeal enhancement ¹⁰:
    • uncommon
    • seen in the first week, typically 1-3 days
    • usually fades by the start of the second week
• GRE/SWI:
  • highly sensitive in the detection of haemorrhage

Treatment and prognosis

In the past treatment for ischaemic stroke was supportive, and the earliest improvements in patient outcome were in dedicated stroke unit care and attempts at preventing the numerous complications which are encountered by patients with neurological impairment (e.g. aspiration pneumonia, pressure ulcers etc.). 

Neurosurgical intervention can also allow patients to survive the period of maximal swelling by performing decompressive craniectomies (with or without duroplasty). 

More recently various reperfusion therapies have been developed including: 

1. intravenous or intra-arterial thrombolysis (e.g. stroptokinase, rtPA)
2. mechanical thrombectomy

Regardless of the therapy, early presentation and triage are essential if any outcome gains are to be had. 

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