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Stroke: Classification and diagnosis

Article  in  Pharmaceutical Journal · January 2018

DOI: 10.1211/CP.2018.20204150

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Stroke: classification and diagnosis
pharmaceutical-journal.com/learning/cpd-article/stroke-classification-and-diagnosis/20204150.cpdarticle

Clinical Pharmacist 10 JAN 2018 By Paresh Parmar

In light of the many pressures currently facing the NHS, as well as an ever increasing ageing
population, pharmacists and healthcare professionals should be aware of the risk factors for
stroke, its classification and diagnosis.

Source: Zephyr / Science Photo Library

Strokes can be classified into two main types: ischaemic (caused by a clot), or haemorrhagic (caused by a
bleed). In the image, a 3D scan showing haemorrhagic stroke.

Stroke was first described more than 2,400 years ago as apoplexy, which means “struck down
by violence”. As stroke is of sudden onset and often causes paralysis, this description is apt[1].
In 1658, Jacob Wepfer studied apoplexy post mortem, and was the first to identify that
apoplexy could result from either bleeding in the brain (haemorrhagic stroke) or the blockage
of one of the main arteries to the brain (ischaemic stroke)[2].
In 2015, stroke was the second largest cause of death (after ischaemic heart disease), and
accounted for 6.3 million deaths globally. Of these, ischaemic stroke was responsible for
around 3 million deaths, and haemorrhagic stroke for 3.3 million deaths[3].
There has been a 21% reduction in the number of strokes globally[3]; however, in the UK, even
though the number of strokes has reduced from 152,000 in 2013 to 100,000 in 2015[4], stroke
currently is the fourth largest cause of death. The 100,000 strokes that occur each year in the
UK equate to one stroke occurrence every five minutes [5]. One in eight strokes are fatal within
the first 30 days[5], the risk of recurrent stroke is greatest within the first 30 days of having a
stroke, and two-thirds of all stroke survivors will have some form of disability [5].
The best predictors of stroke recovery at three months are the initial neurological deficit (e.g.
weakness of side of face, and/or arm, and/or leg; loss of sensations; loss of visual field; slurred
speech) and age. Other factors include high blood glucose concentrations, body temperature,
and previous stroke, which can result in poorer prognosis[6].

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The estimated economic cost of stroke in the UK each year is around £9bn, with direct costs of
around £4.3bn, informal care costs of around £2.4bn and loss of productivity of around
£1.3bn[5]. When looking at treatments, the initial cost of a single thrombolysis treatment is
£480, with a day on a hyperacute stroke unit costing on average £583[7],[8]. On average, the
cost of care for each stroke patient is around £22,000, which includes acute care and
rehabilitation[9].
In light of the many pressures currently facing the NHS, as well as an ever increasing ageing
population, pharmacists and healthcare professionals should be aware of the risk factors for
stroke, its classification and diagnosis, as outlined in this article.

Stroke types and causes

Strokes can be classified into two main types: ischaemic (i.e. caused by a clot in a blood vessel
in the brain), or haemorrhagic (i.e. caused by a bleed in the brain)[5]. These two main
classifications allow further classification into subtypes (see Figure 1).

Figure 1: Classification of strokes

Strokes can be divided into ischaemic and primary haemorrhagic strokes, which can then be divided into
further subcategories. Haemorrgahic stroke accounts for 15% of all strokes.

Ischaemic stroke is defined as an episode of neurological dysfunction caused by focal

cerebral, spinal, or retinal infarction with symptoms persisting for more than 24 hours,
whereas a transient ischaemic attack (TIA) is defined as a “transient episode of neurological
dysfunction caused by focal brain, spinal cord or retinal ischaemia without acute
infarction”[10],[11]. TIAs are typically referred to as mini-strokes with symptoms being
transient (i.e. lasting from minutes to hours but less than 24 hours)[5].
There are two different types of haemorrhagic stroke: subarachnoid haemorrhage (SAH),
which comprises around 5% of all strokes, and intracerebral haemorrhage (ICH), which
accounts for around 10% of all strokes. SAH is the result of a haemorrhage from a cerebral
blood vessel, aneurysm or vascular malformation into the subarachnoid space, the space
surrounding the brain where blood vessels lie between the arachnoid and pia mater (see Figure
2).

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 Figure 2: A brain and skull cross section showing the different anatomical layers
Source: Claus Lunau / Science Photo Library

Subarachnoid haemorrhage is the result of a haemorrhage from a cerebral blood vessel, aneurysm or
vascular malformation into the subarachnoid space, the space surrounding the brain where blood vessels lie
between the arachnoid and pia mater.

In SAH, patients typically experience the sudden onset of severe headache and vomiting, with
non-focal neurological signs that may include loss of consciousness and neck stiffness[12].
Stroke caused by ICH is defined as “rapidly developing clinical signs of neurological
dysfunction attributable to a focal collection of blood within the brain parenchyma or
ventricular system that is not caused by trauma”[10].
ICH occurs spontaneously or when a weakened blood vessel within the brain bursts, allowing
blood to leak, increasing intracranial pressure, causing damage to the brain cells surrounding
the blood. Growth of the haematoma volume is associated with a poorer functional outcome
and increased mortality rate[13].
To assist with the clinical diagnosis of stroke, three questions must be answered:
1. Is the process vascular or a stroke-like mimic?
2. If a vascular process, then where in the central nervous system (CNS) is the abnormality,
and which blood vessels supply that area?
3. What is the disease mechanism (i.e. ischaemic or haemorrhagic)?
Clinicians should determine whether these findings could be caused by a non-vascular process
(e.g. a brain tumour, metabolic disorder, infection, demyelination, intoxication or traumatic
injury) that mimics stroke. Bedside clinical assessment to determine the stroke mechanism
should include past and present personal and family illnesses; the presence and nature of past
strokes and/or TIAs; activity at the onset of the stroke; temporal course and progression of the
focal symptoms and findings; and accompanying symptoms (e.g. headache, vomiting and
decreased level of consciousness)[4]. Determination of the stroke location is most often made
by assimilating all the available information, which includes the physical neurological
symptoms, as well as findings from brain imaging scans.

Stroke classification: mechanisms and brain territory

Ishaemic stroke

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A system for categorisation of ischaemic stroke subtypes, mainly based on aetiology and the
mechanism, leading to the vessel occlusion, was developed for Trial of Org 10172 in Acute
Stroke Treatment (TOAST)[14]. This information is important in everyday management, as it
should influence both the acute and secondary prevention strategies.
The TOAST classification is the most widely used and includes:
1. Large-vessel atherothrombosis;
2. Cardioembolism;
3. Small-vessel disease;
4. Other determined causes;
5. Undetermined causes.
The undetermined causes also include cases involving more than one primary
mechanism[14],[15].
Large vessel atherothrombosis refers to the formation of lipid-laden atherosclerotic plaques
on the inner wall of a large vessel and can affect both extracranial and intracranial arteries[15].
The most common sites for formation of atherosclerotic plaques include where the common
carotid arteries split, the start of the vertebral arteries and the course of the middle cerebral
artery[16]. In atheroembolism, a thrombus forms on the wall of a blood vessel, breaks apart and
sheds pieces of clot, which are carried downstream and lodge in smaller arterial branches,
resulting in multiple smaller strokes within the expected territory of the parent vessel[17].
Cardioembolism occurs as a result of blood clots, which may have formed within the heart,
breaking loose, entering the circulation and then becoming lodged downstream in a cerebral
artery. Clots can form within the heart because of intracardiac stasis of blood (e.g. atrial
fibrillation) or as a result of adhering to a thrombogenic device or lesion (e.g. an implanted
prosthetic valve)[18],[19].
Small-vessel disease refers to occlusive disease involving the microcirculation of the brain.
Common locations for small-vessel disease include deep areas of the hemispheric white
matter; the region of white matter known as the internal capsule, next to the proximal middle
cerebral artery and supplied with blood by its penetrating branches; the pons in the mid-
brainstem, supplied by penetrators arising from the basilar artery; and the thalamus, reliant
primarily on branches of the posterior cerebral arteries [20]. Infarctions in these regions are
small (<1.5cm) and depending on the location within the brain, usually produce one of the
classic lacunar syndromes[21]:
1. Pure motor symptoms (usually face and arm, or arm and leg, comprising 33–50% of all
small-vessel strokes)[22];
2. Pure sensory;
3. Mixed sensorimotor;
4. Ataxic hemiparesis (weakness of one side with disproportionate clumsiness [ataxia] of the
same side);
5. Clumsy hand dysarthria, clumsiness of either hand, which is out of proportion to any
weakness of the limb, combined with slurred speech[23].
Other determined causes include strokes caused by extracranial arterial dissections, non-
atheroscleotic vasculopathies, hypercoagulable states or haematologic disorders[14].

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Undetermined causes include patients in whom a complete screening workup for cardiac
conduction or structural abnormalities, intracranial or extracranial large-artery stenosis,
coagulopathy, and other conditions do not reveal any cause[24],[25]. Around 40% of ischaemic
strokes are of undetermined cause [26].The stroke may be considered to be cryptogenic after
standard assessments when clinical examination and neuroimaging suggest a superficial or
large, deep cerebral infarct, but none of the above routine vessel-imaging, cardiac or
haematologic tests have revealed a probable cause of the stroke[27]. Cryptogenic embolism has
recently been given the term Embolic Stroke of Unknown Source (ESUS) [28].
The Oxfordshire Community Stroke Project (OCSP), also known as Oxfordshire or Bamford’s
classification (see Box 1), relies exclusively on clinical findings to classify the stroke
according to the brain territory involved and can be completed in the Accident and Emergency
room[29]. The Oxfordshire classification describes four syndromes that are either ischaemic or
haemorrhagic (e.g. total anterior circulation syndrome [TACS], if ischaemic, is TACI, or if
haemorrhagic, is TACH).

This classification, also known as Oxfordshire or Bamford’s classification, relies

exclusively on clinical findings. It classifies strokes according to the brain territory
involved and can be completed in the Accident and Emergency room.
Total anterior circulation syndrome (TACS) includes all of:
Unilateral motor, sensory deficit, or both affecting at least two of face, arm and leg;
Higher cerebral dysfunction (e.g. dysphagia [swallowing disorder], dyspraxia
[coordination disorder], neglect, dyscalculia [difficulty in understanding numbers];
Homonymous hemianopia.

If consciousness is impaired, higher cerebral dysfunction and visual fields are assumed.
Partial anterior circulation syndrome (PACS):
Two of the three components of TACS or pure higher cortical dysfunction, or pure motor
or sensory deficit, but not as extensive as for lacunar syndromes (see below).
Lacunar syndrome (LACS):
Pure motor or pure sensory deficit affecting at least two of face, arm or leg;
Sensorimotor deficit;
Ataxic hemiparesis;
Dysarthria (slurred speech), clumsy hand syndrome;
Acute onset movement disorder.

Posterior circulation syndrome (POCS):

Isolated heminopia;
Brain stem signs;
Cerebellar ataxia (inability to coordinate balance, gait, extremity and eye
movements).

One-year mortality in the OCSP classification for the 60–70% of patients with TACS is
higher than for those patients with partial anterior circulation syndrome (PACS) and posterior
circulation syndrome (POCS; around 15–23%), which, in turn, is higher than for patients with
lacunar syndrome (LACS; 10–15%)[30],[31].

Risk factors

[32],[33] 5/15
Risk factors for stroke are classified as modifiable or non-modifiable (see Table 1)[32],[33].
Common modifiable risk factors that are less specific and more prevalent include
hypertension, diabetes and smoking, which all affect health in several ways and provide
opportunities to modify risk in large numbers of people. Other specific risk factors that are
less prevalent include atrial fibrillation and TIAs[34]. Non-modifiable risk factors include age
(stroke risk doubling with each decade of life after the age of 55 years), gender (more men
have strokes than women; however, more women die of strokes) and genetic factors (e.g.
Fabry’s disease)[35].

Ishaemic Haemorrhagic

Modifiable factors Cardiac disease Anticoagulation

History of hypertension Hypertension

Diabetes Heavy drinking

Hypercholesterolaemia Illegal drug use (especially cocaine and crystal

meth)

Transient ishaemic attack Thrombolytic therapy

Cigarette smoking

Hyperhomocysteinemia

Mitral stenosis

Obesity and low physical

activity

Non-modifiable Age Age

factors

Gender Race/ethnicity

Hereditary/familial factors Amyloid angiopathy

Race/ethnicity

Geographic location

Table 1: Risk factors for ishaemic stroke and haemorrhagic stroke

Haemorrhagic stroke
The primary pathology of haemorrhagic stroke is an area of bleeding that directly causes
damage to the brain tissue. A third of patients presenting with ICH will, within the first few
hours, have rapidly expanding haematomas. This, together with age and neurological deficit,
is predictive of poor outcome at three months[36].
The leaking blood results in the displacement and compression of nearby tissue, which
eventually dissects into ventricles and subarachnoid space. Patients may also present with
additional symptoms of severe headache (due to increased intracranial pressure or meningeal
irritation), lower Glasgow Coma Scale (GCS), vomiting, neck stiffness and coma.

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Hypertension is the most powerful modifiable risk factor for ICH. A significant proportion of
hypertensive haemorrhages occur due to non-adherence of antihypertensive medication, which
can be intentional or unintentional, or as a result of illicit catecholaminergic drug use (e.g.
cocaine or methamphetamine) [37].
A large proportion of patients with ICH are taking anticoagulants, usually prescribed for
primary or secondary prevention of cardioembolic stroke in the setting of valvular heart
disease or atrial fibrillation, or for the prevention or treatment of deep vein thrombosis or
pulmonary embolism. Anticoagulant-related ICH accounts for up to 19% of all ICH cases and
antithrombotic-associated-ICH comprises 12–20% of patients with ICH[38],[39],[40],[41].
The risk of in​tracerebral bleeding is reduced in patients with atrial fibrillation who are treated
with direct oral anticoagulants (DOACs) compared with patients treated with warfarin[42].

Haemorrhagic conversion of ischaemic stroke

This may occur after thrombolytic drugs (alteplase) are administered to patients with an
ischaemic stroke or where a patient has a large cerebral clot, which tends to be more common
with cardioembolic strokes[43]. The major adverse effect of thrombolysis is symptomatic
intracerebral haemorrhage, observed in around 6–7% of cases. The risk of symptomatic ICH
increases with age, high blood pressure, very severe neurological deficits, severe
hyperglycaemia, and possibly, with early ischaemic changes on computed tomography (CT)
scans[44],[45].

Stroke screening tests

FAST

In February 2009, the Department of Health launched the “Act FAST” campaign to raise
awareness about the signs of stroke and encourage people to call 999 immediately, so that
those experiencing a stroke can be treated within 4.5 hours of onset, when they have a greater
chance of receiving thrombolysis[46],[47].
FAST is a simple mnemonic that anyone can use and helps to identify the key symptoms of
stroke. These are:
F acial weakness
Can the person smile?
Has their mouth or eye drooped?
A rm weakness
Can the person raise both arms?
S peech problems
Can the person speak clearly and understand what you say?
T ime
Time to call 999.

Even if a person only has one of these symptoms, they or a bystander should call for an
ambulance as soon as possible. As part of the patient assessment, ambulance crews monitor
the patient’s blood pressure and blood sugar, and conduct an electrocardiogram (ECG). The
FAST campaign led to a fall in the delay to seek and receive medical attention after a major
stroke in the UK. Patients who were FAST+ were taken to hospital quicker and if a stroke was
confirmed, patients have been treated more effectively [48],[49].

ROSIER scale
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The ‘Recognition of stroke in emergency room’ (ROSIER) scale is designed for use in
emergency departments[50]. It is more in-depth than the FAST test and includes screening for
common conditions that can mimic stroke, such as hypoglycaemia. Points are allocated based
on presenting symptoms (see Table 2).

Symptoms Points

Loss of consciousness or syncope -1

Seizure activity -1

New acute onset:

Asymmetric facial weakness +1

Asymmetric arm weakness +1

Asymmetric leg weakness +1

Speech disturbance +1

Visual field defect +1

Table 2: The ‘Recognition of stroke in emergency

room’ (ROSIER) scale

A stroke is likely if a person scores >0 in the absence of hypoglycaemia.

The ROSIER scale can be completed in less than five minutes; however, it is not used very
often, since every minute counts, especially if a patient is a candidate for thrombolysis.

Time is brain
The human brain is densely packed with a vast network of neurons, synapses and nerve fibres.
There are around 130 billion neurons in human brain; however, for every minute that a patient
with an ischaemic stroke is untreated, 1.9 million neurons, 14 billion synapses and 12km (7.5
miles) of myelinated fibres are destroyed. The phrase “time is brain” is apt because strokes
are medical emergencies that require urgent treatment[51]. Prompt treatment with thrombolysis
within 4.5 hours significantly improved clinical outcomes in patients with acute ischaemic
stroke by reducing further neuronal destruction [48].

Computed tomography versus magnetic resonance imaging

scans
Clinically, it is impossible to reliably distinguish cerebral infarction from intracerebral
haemorrhage; this can be achieved only with non-contrast CT or magnetic resonance imaging
(MRI) of the brain.
After obtaining a clear history of the onset of the symptoms and the clinical examination of
the patient, the suspected stroke patient is sent for brain imaging. A CT scan can quickly
exclude the presence of haemorrhage and in potential thrombolysis candidates, contribute
towards decreasing the door-to-needle time for thrombolysis. A delay in CT scanning results
in a longer door-to-needle time, which adversely affects a patient because of greater loss of
brain neurons.

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The absence of haemorrhage on the CT scan supports the diagnosis of an ischaemic event, and
some evidence of ischaemia may be observed on CT; however, the diagnosis of an ischaemic
stroke is based on the clinical examination, as a clot is not always observed on a CT scan.
CT scans are faster, more readily available, less expen​sive than MRI scans, and can be
performed on patients with implanted devices (e.g. pacemakers) and on patients who are
claustro​phobic.
On an uncoloured CT scan a clot shows as a hyperdense sign (i.e. will look whiter than normal
tissue), reflecting the arterial territory involved. Figure 3 shows a coloured CT scan where the
blood vessels are shown white and the clot is shown dark in the circle. The hyperdense vessel
sign and signs related to the loss of contrast between the grey and white matter (e.g. the
insular ribbon sign and lentiform obscuration) are all examples of signs of acute ischaemia on
CT[52].

Figure 3: Middle cerebral artery clot on computed tomography (CT) scan

Source: Zephyr / Science Photo Library

Coloured computed tomography (CT) scan of an axial section through the brain of a 53-year-old patient
affected by hemiplegia (paralysis) of the right side of the body following a stroke. A thrombosis is visible at the
termination of the left internal carotid artery.

Neuroimaging also serves to exclude other pathologies that may resemble stroke clinically.
These stroke mimics include, haemorrhagic neoplasms, encephalitis, multiple sclerosis,
postictal (Todd’s) paresis, some types of migraine, intoxications, hypertensive
encephalopathy, and hyper- or hypo-glycaemia [52].
An acute haemorrhage on CT is clearly visible in the acute phase, as high attenuation. This
appearance remains reliable for around 72 hours. By day 10, the haemorrhage becomes
hypodense and becomes indistinguishable from an infarct[53],[54].
Multimodal MRI sequences, particularly diffusion-weighted images, depict anatomy in greater
detail than non-con​trast CT; however, MRI is more time-consuming than CT scanning and is,
therefore, not appropriate for the initial assessment of patients who may be eligible for
thrombolysis. MRI is more sensitive in detecting early ischaemia and it allows for
differentiation between old and new ischaemia[55]. MRI is preferred for the investigation of
TIA[56].
The major drawback of CT is the high radiation dose, while with MRI it is more complicated
and time consuming[52].

Role of the pharmacy team on the acute stroke unit

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The pharmacy team, which includes specialist stroke pharmacists and pharmacy
technicians, plays an integral role in the multidisciplinary stroke team (MDT) in assessing
the stroke patient’s physical and cognitive disabilities, and in managing their medication.
Knowing what type of stroke a patient has, whether it is total anterior circulation syndrome
(TACS), partial anterior circulation syndrome (PACS), posterior circulation syndrome
(POCS) or lacunar syndrome (LACS), and the MDT’s description of the patient’s
symptoms and deficits, can assist the pharmacist in assessing the patient’s disability and
medication challenges (e.g. dysphagia, aphasia, administration and adherence).
For example, if a patient has TACS, then they will have the following symptoms:
Unilateral weakness and/or sensory deficit of face, arm and leg;
Homonymous hemianopia (see Figure 4);
Higher cerebral dysfunction like dysphasia, visuospatial disorder.

Figure 4: Homonymous
hemianopia as a result of a
cerebrovascular event
Source: Shutterstock.com / MAG

Homonymous hemianopia is
hemianopic visual field loss on the
same side of both eyes.
Homonymous hemianopia occurs
because the right half of the brain
has visual pathways for the left
hemifield of both eyes, and the left
half of the brain has visual
pathways for the right hemifield of
both eyes. When one of these
pathways is damaged, the
corresponding visual field is lost.

The degree of the patient’s

stroke symptoms is linked to
the location and size of the
infarct/haemorrhage.
If the patient has a left-sided homonymous hemianopia, it would be advisable for
pharmacists and healthcare professionals, when communicating with the patient, to stand
on the patient’s right side. This would allow for the patient to see them and allow for an
enhanced patient consultation. Speech and language therapists (SLTs) are able to guide
healthcare professionals on using appropriate techniques and tools when communicating
with aphasic patients. SLTs are able to assess the patient for dysphagia and recommend
fluid consistency and food texture to allow for safe swallowing. Using this information,
pharmacists can amend oral medication formulations to allow for the safe and appropriate
administration of oral medication where necessary[57].
With upper limb hemiparesis, assessing the strength and tone of the patient’s arm and hand
will provide evidence as to whether the patient would manage administering oral
medication to themselves, taking into account any cognitive impairment post-stroke.

Financial and conflicts of interest disclosure:

The author has no relevant affiliations or financial involvement with any organisation or
entity with a financial interest in or financial conflict with the subject matter or materials
discussed in the manuscript. No writing assistance was used in the production of this
manuscript.
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