Clinical Evaluation of Stroke*

*(Contents borrowed from the original Up to Date article, “Overview of the Evaluation of
Stroke” by Louis Caplan, 2012. Further details can be found in Dr Caplan’s article)

The clinical evaluation of a patient with an acute stroke should be broken down into 4 separate
steps

1. Understanding the classification of stroke

2. An initial quick evaluation to stabilize vital signs, determine if intracranial hemorrhage

is present, and decide if thrombolytic therapy is warranted.

3. Forming a hypothesis of stroke etiology based on history, physical examination and

neuroimaging studies.

4. Confirming the precise pathophysiological process with more directed diagnostic

studies.

I. Classification of cerebrovascular disease

 Ischemic infarctions may be caused by pathological process intrinsic to the blood vessels
(such as atherosclerosis, lipohyalinosis, inflammation, amyloid deposition, arterial
dissection, developmental malformation, aneurysmal dilation or venous thrombosis).
 Ischemic infarctions may also originate remotely (such as when an embolus from the
heart or extracranial circulation lodges in an intracranial vessel).
 Ischemic infarctions may also arise from inadequate blood flow due to decreased
cerebral perfusion pressure.
 Intracranial hemorrhage accounts for 20% of cerebrovascular accidents and may arise
from rupture of a vessel within the subarachnoid space or brain parenchyma.

A. Transient Ischemic Attack (TIA)

The definition of a TIA is “a transient episode of neurologic dysfunction caused by focal brain,
spinal cord, or retinal ischemia, without acute infarction”. This definition is tissue based and
not just clinical and replaces the more arbitrary former definition of a reversible ischemic
neurological event lasting less than 24 hours. TIA’s may progress to ischemic strokes, especially
if other risk factors are present. An “ABCD” score may help to predict those at greatest risk.

The ABCD score is calculated based on the following:

Age (≥60 years = 1 point)

Blood pressure elevation when first assessed after TIA (systolic ≥140 mmHg or diastolic ≥90
mmHg = 1 point)

Clinical features (unilateral weakness = 2 points; isolated speech disturbance = 1 point; other =
0 points)

Duration of TIA symptoms (≥60 minutes = 2 points; 10 to 59 minutes = 1 point; <10 minutes = 0
points)

Diabetes (present = 1 point)

The scoring system predicts risk of ischemic infarction within 2 days as follows:

 Score 6 to 7: High two-day stroke risk (8 percent)

 Score 4 to 5: Moderate two-day stroke risk (4 percent)
 Score 0 to 3: Low two-day stroke risk (1 percent)

B. Intracerebral Hemorrhage

Bleeding from arterioles directly into the brain results in a localized hematoma which spreads
along white matter pathways. Neurological symptoms usually increase over minutes to a few
hours. Causes of intracranial hemorrhage include hypertension, trauma, bleeding diatheses,
amyloid angiopathy, sympathomimetic drug use (especially amphetamines and cocaine) and
vascular malformations.

C. Subarachnoid Hemorrhage

Rupture of arterial aneurysms is the major cause of SAH. Following aneurysm rupture, blood is
released directly into the subarachnoid CSF space, rapidly increasing intracranial pressure,
resulting in coma or death if the bleeding continues. Bleeding generally only lasts a few
seconds, but rebleeding is common. Symptoms of SAH begin abruptly and usually consist of a
severe thunderclap headache (“the worst headache of my life”). The onset of headache may or
may not be associated with a brief loss of consciousness, seizures, nausea, vomiting, and/or
nuchal rigidity. There are usually no focal neurological signs at presentation.

D. Ischemia

There are 3 major types of brain ischemia:

 Thrombosis
 Embolism
 Systemic Hypoperfusion
Thrombotic stroke is caused by thrombus formation within an artery that either reduces blood
flow distally in the vessel or breaks of to cause an artery-to-artery embolus. Thrombotic stroke
can further be divided into either large or small vessel disease.

Large vessel thrombotic stroke can originate in either the extracranial or intracranial arterial
system with atherosclerosis the most common cause. Intrinsic lesions in large extracranial and
intracranial arteries cause symptoms by reducing blood flow beyond obstructive lesions, and by
serving as the source of intra-arterial emboli. At times a combination of mechanisms is operant.
Severe stenosis promotes the formation of thrombi which can break off and embolize, and the
reduced blood flow caused by the vascular obstruction makes the circulation less competent at
washing out and clearing these emboli. Pathologies affecting large extracranial vessels include
atherosclerosis, arterial dissection, Takayasu arteritis, giant cell arteritis, and fibromuscular
dysplasia. Pathologies affecting large intracranial vessels include atherosclerosis, arterial
dissection, arteritis or vasculitis, noninflammatory vasculopathy (such as Moyamoya syndrome)
and vasoconstriction.

Small vessel disease refers to penetrating arteries that arise from the distal vertebral artery, the
basilar artery, the MCA, and the circle of Willis arteries. These small arteries thrombose either
due to a lipid hyaline buildup due to hypertension (‘lipohyalinosis”) or from artery-to-artery
embolis of thrombus from more proximal large vessels. Small vessel disease results in small
deep infarcts referred to as lacunes.

Embolic stroke is caused by “debris” originating elsewhere that block arterial access to a
particular brain region. Since the process is not localized as with thrombosis, local therapy only
temporarily solves the problem and further events may occur if the source of the emboli is not
identified and treated.

There are four categories of embolic stroke:

 Known cardioembolic sources

 Possible cardiac or aortic arch source
 Known arterial source
 Truly unknown source after an extensive diagnostic evaluation

The symptoms of an embolic stroke depend upon the region of brain rendered ischemic. The
embolus suddenly blocks the recipient site so that the onset of symptoms is abrupt and usually
maximal at the start. Unlike thrombosis, multiple sites within different vascular territories may
be affected when the source is the heart. Cardioembolic strokes usually occur abruptly,
although they occasionally present with stuttering, fluctuating symptoms. The symptoms may
clear entirely since emboli can migrate and lyse, particularly those composed of thrombus.

Causes of known cardioembolic stroke include atrial fibrillation and paroxysmal atrial
fibrillation, rheumatic mitral or aortic valve disease, bioprosthetic and mechanical heart
valves, atrial or ventricular thrombus, sick sinus syndrome, sustained atrial flutter, recent
myocardial infarction (within one month), chronic myocardial infarction (together with
ejection fraction <28 %), symptomatic congestive heart failure (with ejection fraction <30
%), dilated cardiomyopathy, fibrous nonbacterial endocarditis as found in patients with
systemic lupus (ie, Libman-Sacks endocarditis), antiphospholipid syndrome, and cancer
(marantic endocarditis), infective endocarditis, left atrial myxoma, coronary artery bypass
graft (CABG) surgery.

Causes of possible cardiac or aortic sources of Cardioembolic stroke include mitral annular
calcification, patent foramen ovale (PFO) with or without atrial septal aneurysm, left
ventricular aneurysm without thrombus, complex atheroma in the ascending aorta or
proximal arch.

Known arterial sources include intracranial and extracranial arterial dissections. Arterial
dissections are a common cause of stroke in the young, but may occur at any age.
Dissection occurs when structural integrity of the arterial wall is compromised, allowing
blood to collect between layers as an intramural hematoma. Treatment recommendations
will be discussed below, but depend on whether the dissection is intracranial or extracranial
in origin as well as the amount of time from onset of stroke symptoms to treatment.

Blood disorders — Blood and coagulation disorders are an uncommon primary cause of stroke
and TIA, but they should be considered in patients younger than age 45, patients with a history
of clotting dysfunction, and in patients with a history of cryptogenic stroke. The blood disorders
associated with arterial cerebral infarction include:

 Sickle cell anemia

 Polycythemia vera
 Essential thrombocytosis
 Heparin induced thrombocytopenia
 Protein C or S deficiency, acquired or congenital
 Prothrombin gene mutation
  Factor V Leiden (resistance to activated protein C)
 Antithrombin III deficiency
 Antiphospholipid syndrome
 Hyperhomocysteinemia

Factor V Leiden mutation and prothrombin 20210 mutations are associated mostly with venous
rather than arterial thrombosis. They can result in cerebral venous thrombosis or deep venous
thrombosis with paradoxical emboli. Infectious and inflammatory disease such as pneumonia,
urinary tract infections, Crohn's disease, ulcerative colitis, HIV/AIDS, and cancers result in a rise
in acute phase reactants such as fibrinogen, C-reactive protein, and coagulation factors VII and
VIII. In the presence of an endothelial cardiac or vascular lesion, this increase can promote
active thrombosis and embolism.

Systemic hypoperfusion is a generalized circulatory problem manifesting itself in the brain as

well as in other organs (elevated levels of transaminases, elevation of BUN and creatinine,
oliguria, lactic acidosis, and elevated CPK may be useful markers). Reduced blood flow to the
CNS is more global in patients with systemic hypoperfusion and does not affect isolated
regions. The reduced perfusion can be due to cardiac pump failure caused by cardiac arrest or
arrhythmia, or to reduced cardiac output related to acute myocardial ischemia, pulmonary
embolism, pericardial effusion, or bleeding. Hypoxemia may further reduce the amount of
oxygen carried to the brain.

Symptoms of brain dysfunction typically are diffuse and nonfocal in contrast to the other two
categories of ischemia. Most affected patients have other evidence of circulatory compromise
and hypotension such as pallor, sweating, tachycardia or severe bradycardia, and low blood
pressure. The neurologic signs are typically bilateral, although they may be asymmetric when
there is preexisting asymmetrical craniocerebral vascular occlusive disease.

The most severe ischemia may occur in border zone (watershed) regions between the major
cerebral supply arteries since these areas are most vulnerable to systemic hypoperfusion. The
signs that may occur with border zone infarction include cortical blindness, or at least bilateral
visual loss; stupor; and weakness of the shoulders and thighs with sparing of the face, hands,
and feet (a pattern likened to a "man-in-a-barrel").

II. A. Initial General Assessment

Sudden loss of brain function is the core feature present at the onset of ischemic stroke.
Patients may have other conditions which can mimic stroke and these should be considered as
well. A partial list includes: Post-ictal Todd’s paresis; Metastatic brain tumors; Demyelinating
diseases; Head trauma; Intracerebral hemorrhage; Systemic infections; Toxic-metabolic
disorders; and Conversion disorders. In addition, patients with ischemic stroke may present
concurrently with other serious medical conditions, such as myocardial infarction, or diabetic
ketoacidosis, dehydration, etc. Thus the initial evaluation must be broadly based but rapidly
performed. Goals should include:

 Insuring medical stability

 Quickly reversing conditions contributing to the patient’s problem
 Moving toward uncovering the pathophysiological basis of the patient’s neurological
symptoms

Quickly diagnosing intracerebral or subarachnoid hemorrhage by CT scanning can be lifesaving,

however it is important to assess vital signs before moving the patient to the imaging
department. Vital parameters of particular importance include blood pressure, breathing, and
temperature.

Blood pressure: The mean arterial blood pressure (MAP) is usually elevated in patients
following an acute stroke. This can be due to chronic hypertension (which is an independent
risk factor for both ischemic and hemorrhagic stroke) or part of a physiological response
originating in the CNS to maintain adequate cerebral perfusion pressure (CPP). The goal of
blood pressure management is to maintain adequate perfusion to the ischemic brain tissue.
The pharmacological lowering of blood pressure in the setting of acute ischemic stroke may be
associated with clinical deterioration. For ischemic stroke, it is recommended that
hypertension not be treated acutely unless systolic BP >220mmHg or diastolic BP>120mmHg, or
if the patient has active ischemic coronary disease, heart failure, aortic dissection, hypertensive
encephalopathy, acute renal failure or eclampsia. Blood pressure medications should be held
and restarted 24 hours after the onset of stroke in neurologically stable patients with
preexisting hypertension. Exceptions to this rule include patients with intracranial or
extracranial arterial stenosis who may need to maintain higher blood pressures for as long as 7
to 10 days after infarction. Also, patients who are considered candidates for thrombolytic
therapy need to achieve blood pressures lower than 185/105 mmHg during infusion of tPA as
well as for the next 24 hours.
For patients with intracranial hemorrhage (intracerebral hemorrhage or subarachnoid
hemorrhage), one must weigh risks of further bleeding with risks of reducing cerebral
perfusion. In addition, patients with intracranial hemorrhage may develop increased
intracranial pressure (ICP) due to blood within the cranium. Raised ICP may reduce CPP unless
MAP is increased (recall that CPP=MAP – ICP). Directly measuring ICP directly allows blood
pressure to be reduced as low as possible while still maintaining CPP above 60mmHg.

Intravenous Labetolol is the first line drug of choice for lowering blood pressure in the setting of
stroke since it allows for rapid upward and downward titration of blood pressure. Other agents
include Nitroglycerin Paste and intravenous Nicardipine.

Airway and Breathing: Patients with increased ICP due to intracranial hemorrhage,
vertebrobasilar ischemia, or diffuse cerebral edema can present with a reduced respiratory
drive and/or upper airway obstruction. In addition, hypoventilation may lead to cerebral
vasodilation which further increases ICP. Intubation may be necessary to maintain airway
control and regulate ventilation. Patients who are hypoxic should also receive supplemental
oxygen. Oxygen administration in patients who are not hypoxic is not indicated.

Position of Head: During the acute phase of stroke, the patients head should be midline and
elevated to 30° for patients who have or are at risk for the following conditions:

 Increased ICP (due to large ischemic stroke, intracranial hemorrhage, hydrocephalus,

space occupying lesion, etc)
 Aspiration (patients with dysphagia or diminished consciousness)
 Cardiopulmonary decomensation or oxygen desaturation

Otherwise it is recommended to keep the head of the bed flat for all other patients.

Fever Management: Patients with acute stroke may develop due to central mechanisms or
part of an infectious disease process. Infectious workup should be initiated and empiric
antibiotics may need to be administered until results are in. Regardless of the cause, fever can
worsen brain ischemia and normothermia should be maintained.

Glucose Management: Both hyper and hypoglycemia can increase neurological injury in the
setting of stroke. Hyperglycemia (defined as a blood glucose >126mg/dl) is common in acute
stroke and associated with a poor functional outcome. Hyperglycemia is most commonly
caused by a physiological stress response, though newly diagnosed diabetes may also be a
factor. It is recommended to treat hyperglycemia with insulin possibly for glucose
concentrations >140mg/dl and certainly for >180mg/dl. Hypoglycemia can cause focal
neurological deficits mimicking stroke. Measuring blood glucose should be part of the initial
vital sign evaluation (ABCD’s, Airway, Breathing, Cardiovascular, Dextrose).

History, Physical and Neurological Examinations: The purpose here is to exclude stroke from
stroke mimickers and to quickly establish a baseline neurological examination. Seizures,
syncope, migraine, and hypoglycemia can all mimic stroke. Establishing stroke as the
underlying etiology of the patient’s neurological condition can be challenging in patients with
depressed levels of consciousness and focal neurological findings.

II. B. Urgent neuroimaging to exclude intracranial hemorrhage

Non-contrasted CT should be performed as soon as the patient is medically stable. CT

detection of early ischemic stroke (< 6 hours) findings is about 60% with improved sensitivity
developing over the first 24 hours. The presence of early CT ischemic changes also portends a
worse neurological outcome. Diagnosing an intracerebral hemorrhage or subarachnoid
hemorrhage quickly can be lifesaving.

II. C. Determining if the patient is a candidate for acute thrombolysis therapy.

Once it has been determined that the patient has an acute ischemic stroke, consideration
should be given for thrombolysis. Whenever possible, vascular imaging studies (MRA, CTA,
Doppler ultrasound) should confirm a large vessel thromboembolism. Without a large vessel
occlusion, there is no apparent target for recanalization and many of these patients improve
spontaneously. Also, some patients presenting too late for rTPA may still be candidates for
intravenous or intra-arterial thrombolysis if imaging studies show a significant “at-risk” brain
that is underperfused but not infarcted. With that being said, it is still reasonable to treat with
rTPA eligible patients if neurovascular imaging is not readily available or would delay treatment.

(For treatment indications and contraindications, see “Thrombolysis Guidelines” handout)

III. Forming a Hypothesis of the Stroke Etiology

History

The clinical course of symptom progression may be useful in determining the type of stroke
that the patient has suffered from. For example, embolic strokes usually have an abrupt onset
with maximal neurological deficit at onset. A rapid recovery also supports embolic stroke.
Thrombotic strokes have fluctuating symptoms with a stuttering course. Penetrating artery
occlusions (lacunar strokes) often cause symptoms evolving over hours or days whereas large
vessel ischemia often evolves over a longer period of time. Intracerebral hemorrhage does not
improve in the early phase and tends to be progressive over minutes to hours. Aneurysmal SAH
has a very abrupt onset and focal neurological deficits are uncommon.

Patient demographics can influence the likelihood of specific etiologies for stroke. For example,
most thrombotic and embolic strokes occurring in older individuals are caused by
atherosclerosis. In younger individuals (under 40 years), arteriosclerosis is less common unless
there are multiple risk factors, such as smoking, diabetes, hypertension, hyperlipidemia, or a
strong family history. Hypertensive ICH is more common among African American and Asian
individuals than among Caucasians. Caucasians have a higher incidence of occlusive disease of
the extracranial carotid circulation and vertebral arteries than do other ethnicities.

Hypertension is the most common and important risk factor for stroke with increasing
incidence of both coronary artery disease and stroke with blood pressures that rise above
110/75.

Previous TIA, especially in the same territory as the stroke favors the possibility of a local
arterial thrombosis. Attacks in more than one vascular territory favor embolism from the heart
or aortic arch.

Smoking increases the likelihood of extracranial occlusive vascular disease and more than
doubles the risk of stroke. Smoking cessation results in reduction of stroke risk over time.
Diabetes increases the risk of small vessel occlusive disease. Amphetamine use increases the
risk for both ICH and SAH but not ischemic stroke. Cocaine causes strokes that are often
hemorrhagic, often affecting the posterior circulation intracranial arteries. Heart disease (such
as cardiac valvular disease, prior MI, atrial fibrillation, and endocarditis) increases the risk for
embolic stroke. Stroke during the puerperium increases the risk of stroke due to venous or
arterial thrombosis. Anticoagulants or bleeding diatheses can increases the risk of ICH. The use
of birth control pills is much less of a risk factor with low-dose estrogen containing pills.
Vigorous physical activity or sexual intercourse can be associated with ICH or SAH and not
usually thrombotic stroke. A history of recent head or neck trauma increases the probability of
arterial dissection.

Associated symptoms

Fever raises the possibility of endocarditis. Infectious illness can also raise the levels of acute
phase reactants which may predispose to thrombosis. Headache, seizures, and/or nausea and
vomiting are common with ICH or SAH. Nausea and vomiting may also be a sign of posterior
circulation strokes. Reduced level of consciousness favors SAH or large ischemic strokes with
edema and subfalcine herniation.

Physical Examination

The purpose of the general physical examination is to look for possible underlying causes of
stroke in the patient.

 Absent pulses (lower extremity, radial or carotid) favors a diagnosis of atherosclerosis

with thrombosis, though a sudden-onset cold, blue limb favors embolism. An occlusion
of the common carotid may be picked up by the absence of a carotid pulse. The
presence of a neck bruit also favors partial common carotid or vertebral artery
occlusion. Facial pulses may be lost if there is an ipsilateral common carotid artery
occlusion or even increased if there is an internal carotid artery occlusion (suggesting
more blood being shunted to the external carotid artery circulation).
 Cardiac findings such as atrial fibrillation, murmurs and cardiomegaly may suggest a
cardioembolic source.
 Fundoscopic examination may reveal cholesterol crystals, white intravascular occlusions
(fibrin-platelet embolus), or red clot emboli. Subhyaloid hemorrhage suggests SAH.
Ischemia to the retina may occur with internal carotid artery occlusion affecting the
central retinal artery.

Neurological Examination

Time is of the essence in the hyperacute evaluation of stroke patient as the window of
intervention for thrombolysis is less than 4 ½ hours. The neurological examination should
attempt to confirm the findings from the history and provide a quantifiable measurement of
any neurological deficits that can be followed over time. A quantifiable and validated scoring
system for rating the severity of stroke is the NIH Stroke Scale, which is composed of 11 items
adding to a total score of 0 to 42. The NIHSS has been shown to correlate with functional
outcome for stroke. (See “NIHSS” document in the Stroke Resources Folder).

Certain constellations of neurological deficits will constitute specific stroke syndromes based on
the vascular territories affected. Common stroke syndromes that may be encountered include:

 MCA territory stroke. If involving the dominant hemisphere, aphasia will be present
(receptive, expressive or often both). Contralateral motor and sensory deficit (face,
arm>leg>foot). Complete contralateral hemiplegia if internal capsule involved.
Homonymous hemianopsia. Embolic > atherothrombolic etiology.
 ACA territory stroke. Motor and/or sensory deficit (foot >>face, arm). Grasp and
sucking reflexes. Abulia, paratonic rigidity, gait apraxia. Embolic > atherothrombotic
etiology.
 ICA territory stroke. Combined features of MCA and ACA strokes. Also ipsilateral
amarosis fugax symptoms from central retinal artery involvement. Atherothrombotic >
embolic etiology.
 PCA territory stroke. Homonymous hemianopsia; alexia without agraphia (dominant
hemisphere); visual hallucinations; visual perseverations (calcarine cortex); sensory loss
or spontaneous pain (thalamus); III nerve palsy (cerebral peduncle); upgaze
paresis(midbrain); motor deficit (cerebral peduncle). Embolic > atherothrombotic
etiology.
 Vertebrobasilar territory stroke. Various cranial nerve palsies with crossed sensory
deficits (e.g. decreased pinprick and temperature sensation to ipsilateral face and
contralateral arms and legs); diplopia; vertigo; nausea and vomiting; dysarthria;
dysphagia; pathological hiccups; limb and gait ataxia; motor deficit; impaired LOC (from
the reticular activating system). Bilateral signs suggest basilar artery involvement.
Embolic = atherothrombolic for etiology.
 Penetrating vessel (Lacunar) strokes. Pure motor deficit; pure sensory deficit; pure
motor and sensory deficit; hemiparesis and homolateral ataxia; dysarthria and clumsy
hand. Small artery (Lacunar) infarction.
(for a more complete listing of stroke syndromes, see “Stroke Syndromes” document in the
Stroke Resources folder)

Vascular supply to the brain

Coronal section

ACA Territory Vascular Supply

MCA Territory Vascular Supply

PCA Territory Vascular Supply

Medial Inferior Pontine Syndrome (occlusion of a

paramedian branch of the Basilar artery)

Lateral Inferior Pontine Syndrome (occlusion of the

anterior inferior cerebellar artery)
Medial Midpontine Syndrome
(occlusion of a paramedian branch of
the mid-Basilar artery

Lateral Midpontine Syndrome

(occlusion of a short circumferential
artery)
 Medial Medullary Syndrome (occlusion of Vertebral artery or
branch of Vertebral or lower Basilar artery)

Lateral Medullary Syndrome (occlusion of either Vertebral artery,

Posterior Inferior Cerebellar Artery, or Superior, Middle or Lateral
Medullary arteries)

IV. Confirming the Diagnosis of Stroke

The previous assessment should allow for a presumptive diagnosis of the underlying stroke
pathophysiology. The next phase of the evaluation is to confirm this hypothesis with diagnostic
testing.

A. Embolic Stroke

Embolism is likely in the following circumstances:

 The neurological deficit is sudden in onset and maximal in severity from the beginning
 The region of infarction and degree of deficit are large
 There is a known cardiac or large artery lesion present
 The infarct becomes hemorrhagic on CT or MRI
 There are multiple cortical and/or subcortical infarctions in different vascular territories
 Clinical findings improve quickly
 Posterior circulation strokes
Cardioembolic Stroke

Cardiac evaluation should be performed in all patients with suspected embolic stroke,
especially in those under the age of 45 whether or not they are known to have pre-existing
cardiac disease. Cardiac evaluation should also be considered in patients with occlusive
cerebrovascular disease due to the possible co-occurrence of coronary heart disease and
stroke. The initial evaluation should focus on the presence of cardiac ischemia and arrhythmias
and should include a careful cardiac physical examination and an EKG.

Cardiac Monitoring with an electrocardiogram followed by telemetry or a Holter monitor for 24

hours after ischemic stroke can identify many patients with atrial fibrillation. A normal sinus
rhythm does not exclude atrial fibrillation in all patients as this arrhythmia may be intermittent.

Echocardiography should be performed in all patients with suspected embolic stroke.

Echocardiography should strongly be considered especially in younger patients without obvious
cerebrovascular atherosclerotic disease. The initial study of choice is generally transthoracic
echocardiography (TTE). If the preliminary cardiac evaluation, vascular studies, and TTE fail to
reveal a source for the ischemic stroke, then transesophageal echocardiography (TEE) should be
considered. TEE has advantages of being able to examine the aorta, the atria, and the atrial
septum. It is also the best study to identify clot in the left atrial appendage. The main
disadvantage of TEE is its invasiveness compared to TTE. TTE may be better able to locate left
ventricular thrombi in patients with congestive heart failure or prior myocardial infarction.

Artery-to-Artery Embolic Stroke

The distinction between artery-to-artery and cardioembolic sources of embolism can be

difficult. Suspicion of artery-to-artery embolism arises when pathology in a large vessel is
identified with noninvasive testing. Repetitive ischemic attacks within a single vascular territory
and/or a normal echocardiogram (especially with TEE) also raise suspicion.

B. Large Vessel Atherothrombotic Stroke

Large vessel occlusive strokes are often preceded by TIA’s in the same vascular territory. The
onset of symptoms may or may not be abrupt and the clinical course often fluctuates. The
region of cerebral infarction is often large and includes both cortical and subcortical territories.
The usual source of atherothrombotic stroke is intracranial artery occlusion.

Patients with large vessel atherothrombotic stroke should have both intracranial and extra-
cranial vascular imaging (see “Neuroimaging of the Acute Stroke Patient” below).

C. Small Vessel (Lacunar) Stroke

Most patients with Lacunar infarctions have risk factors for penetrating artery disease such as
hypertension, diabetes mellitus, or polycythemia. Clinical findings on neurological examination
typically conform to one of the well-recognized lacunar stroke syndromes:

 Pure Motor Hemiparesis

 Pure Sensory Stroke
 Dysarthria-Clumsy Hand Syndrome
 Ataxia-Hemiparesis

(For more information about these stroke syndromes, see the “Stroke Syndromes”document in
the Stroke Resources folder)

While most patients with lacunar infarctions with known risk factors won’t have other
identifiable cardiac or large vessel sources, some will have large vessel disease, especially in
patients of Asian ethnicity. Vascular imaging (CTA or MRA) performed at the same time as
brain imaging (CT or MRI) to exclude localized occlusion of a feeding artery, a condition
mimicking lacunar infarction. It is especially important to perform intracranial vascular imaging
in Asians and African Americans as people with these ethnicities commonly have intracranial
large vessel occlusive disease.

Neuroimaging of the Acute Stroke Patient

Neuroimaging studies in the acute stroke setting should be used to rule out hemorrhagic
stroke, assess the degree of brain injury, and to identify the vascular lesion responsible for the
ischemic deficit.

Computed Tomography has several advantages for imaging in the setting of acute stroke. CT is
widely available and has a high rate of speed of acquisition. In the hyperacute phase of stroke,
CT is highly sensitive for confirming or excluding intracranial hemorrhage. Vascular imaging
studies may help define if there is a large vessel thrombus that may be amenable to systemic
intravenous thrombolytic therapy or localized intra-arterial thrombolysis. Vascular imaging of
any sort however should never delay treatment using intravenous tPA for eligible patients.

Non-contrasted CT should be performed as soon as the patient is medically stable. CT

detection of early (<6 hours) ischemic stroke findings is about 60% with improved sensitivity
developing over the first 24 hours. The presence of early CT findings also portends a worse
neurological outcome. Early signs on CT include:

 Hypodensity involving the MCA territory

 Obscuration of the lentiform nuclei (basal ganglia)
 Cortical sulcal effacement
 Focal parenchymal hypodensity
  Loss of the insular ribbon or obscuration of the Sylvian fissure
 Hyperdensity of large vessels (“hyperdense MCA sign”, suggesting a thrombus within
the MCA)
 Loss of grey-white matter differentiation in the basal ganglia

CT Angiography (CTA) is performed by administering a rapid bolus of contrast during image

acquisition of the brain. The procedure requires a large bore peripheral IV, but only requires an
addition 5 to 10 minutes of acquisition time. CTA is very useful for detecting thrombus or
embolus within large intracranial or extracranial arteries, which may guide therapy for intra-
arterial vs intravenous thrombolysis. Using the source images from CTA, one may be able to
detect reduced perfusion to a region of the brain based on reduced uptake of contrast within
the microvasculature of the affected region (a “poor man’s” CT perfusion study).

CT Perfusion studies (CTP) also uses a bolus of contrast which can be done by continuing to
image after a CTA or by giving another separate bolus. CTP requires repeat scanning of select
parts of the brain over and over to track the progress of the contrast bolus through the
vasculature.

Magnetic Resonance Imaging may allow further sub classification of acute stroke patients to
guide intravenous thrombolysis or interventional vascular treatments. Brain MRI that combines
T1, T2, T2 FLAIR, Diffusion-Weighted Imaging (DWI), Perfusion-Weighted Imaging (PWI), and
Gradient Echo (GRE) sequences allows for differentiation of ischemic stroke from intracranial
hemorrhage. GRE sequences picks up acute hemorrhage as well as CT and chronic hemorrhage
even better. In centers with ultrafast MRI imaging protocols, acquisition times may be as short
as 5 minutes, compared to the usual 15 – 20 minutes with conventional MRI.

Diffusion-Weighted Imaging (DWI) measures a signal related to the movement of water

molecules between two closely spaced radiofrequency pulses. In acute stroke, swelling of
ischemic parenchymal cells follows failure of the Na+/K+ ATPase pumps leading to an increased
ratio of intracellular to extracellular volume fractions. DWI picks up signal changes due to
cytotoxic edema as well as T2 signal change from vasogenic edema or gliosis. In order to
account for the “T2 shine-through”, Apparent Diffusion Coeficient (ADC) mapping can be
created by “subtracting” the T2 shine-through from the bright signal on DWI images to leave
behind a darkened signal reflecting pure signal changes from cytotoxic edema. DWI is a
sensitive and specific indicator of acute stroke within 6 hours of symptom onset. In the setting
of TIA’s, DWI may show signal changes predictive of future TIA’s or ischemic stroke in the same
vascular region.

Perfusion-Weighted Imaging (PWI) uses fast MRI techniques to quantify the amount of contrast
agent reaching the brain following a bolus infusion. The course of contrast arrival and washout
allows the construction of regional areas of reduced perfusion (the ischemic penumbra). While
some patients may show a clearly defined area of irreversible infarction on DWI and
surrounding reduced perfusion on PWI, this is not always the case with lots of exceptions.

MR Angiography using time of flight technique is generally adequate for visualizing the
intracranial portions of both the anterior and posterior circulations. These studies do not show
the aortic arch or vertebral artery origins however. For these arteries, contrast bolus MRA may
show vessel patency through these regions. Alternatively duplex and color-flow Doppler can be
used to visualize the origins of the vertebral arteries as well as the extracranial portions of the
carotid arteries.

Carotid Duplex Ultrasound and Transcranial Doppler flow studies are non-invasive methods to
evaluate flow and patency of the extracranial and large intracranial vessels. In some centers,
when combined, they can be just as useful as conventional angiography in determining arterial
lesions amenable to interventional treatment. Carotid Doppler ultrasound occasionally finds
the source of an arterial-to-arterial embolus, but more often it is used as a staging risk factor
for large vessel extracranial carotid artery stenosis. Patients with >70% stenosis ipsilateral to a
anterior circulation large vessel thrombotic stroke may benefit from carotid endarterectomy.

Conventional Angiography remains the gold standard for evaluating the cerebral vessels. It can
determine the degree of arterial stenosis, the presence of dissection, vasculopathy, vasculitis,
or vascular malformations. It can also provide information about collateral flow and perfusion
status. In large vessel occlusion, angiography is more sensitive than non-invasive imaging
techniques and allow for potential “in-situ” treatment, such as intra-arterial thrombolysis.