Overview of the evaluation of stroke

Author:
Louis R Caplan, MD
Section Editor:
Scott E Kasner, MD
Deputy Editor:
John F Dashe, MD, PhD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2021. | This topic last updated: Aug 03, 2021.
INTRODUCTION The symptoms of brain ischemia may be transient, lasting seconds
to minutes, or may persist for longer periods of time. Symptoms and signs remain
indefinitely if the brain becomes irreversibly damaged and infarction occurs.
Unfortunately, neurologic symptoms do not accurately reflect the presence or absence
of infarction, and the tempo of the symptoms does not indicate the cause of the
ischemia [1,2]. This is a critical issue because treatment depends upon accurately
identifying the cause of symptoms.

An overview of the evaluation of patients who present with neurologic symptoms that
may be consistent with stroke is discussed here. This evaluation includes the following:

●Understanding the classification of stroke

●An initial quick evaluation to stabilize vital signs, determine if intracranial
hemorrhage is present, and, in patients with ischemic stroke, decide if reperfusion
therapy is warranted (see "Initial assessment and management of acute stroke")
●Forming a hypothesis of the stroke etiology based upon the history, physical
examination, and initial brain imaging study (usually a noncontrast head CT scan)
●Confirming the precise pathophysiologic process with more directed diagnostic
testing
The approach to patients with transient brain ischemia is reviewed separately.
(See "Initial evaluation and management of transient ischemic attack and minor
ischemic stroke".)
CLASSIFICATION Cerebrovascular disease is caused by one of several
pathophysiologic processes (table 1) involving the blood vessels of the brain:
●The process may be intrinsic to the vessel, as in atherosclerosis, lipohyalinosis,
inflammation, amyloid deposition, arterial dissection, developmental malformation,
aneurysmal dilation, or venous thrombosis.
●The process may originate remotely, as occurs when an embolus from the heart
or extracranial circulation lodges in an intracranial vessel.
●The process may result from inadequate cerebral blood flow due to decreased
perfusion pressure or increased blood viscosity.
●The process may result from rupture of a vessel in the subarachnoid space or
intracerebral tissue.

The first three processes can lead to transient brain ischemia (transient ischemic attack
[TIA]) or permanent brain infarction (ischemic stroke), while the fourth results in either
subarachnoid hemorrhage or an intracerebral hemorrhage (primary hemorrhagic stroke).
Approximately 80 percent of strokes are due to ischemic cerebral infarction and 20
percent to brain hemorrhage.

Transient brain ischemia — TIA is now defined as a transient episode of neurologic

dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute
infarction. This tissue-based definition of TIA relies on the absence of end-organ injury
as assessed by imaging or other techniques. The proposed advantages of the tissue-
based definition are that the defined end point is biological (tissue injury) rather than
arbitrary (24 hours). (See "Definition, etiology, and clinical manifestations of transient
ischemic attack", section on 'Definition of TIA'.)
The approach to patients with TIA is reviewed separately. (See "Initial evaluation and
management of transient ischemic attack and minor ischemic stroke".)
Intracerebral hemorrhage — Bleeding in intracerebral hemorrhage (ICH) is usually
derived from arterioles or small arteries. The bleeding is directly into the brain, forming a
localized hematoma which spreads along white matter pathways. Accumulation of blood
occurs over minutes or hours; the hematoma gradually enlarges by adding blood at its
periphery like a snowball rolling downhill. The most common causes of ICH are
hypertension, trauma, bleeding diatheses, amyloid angiopathy, illicit drug use (mostly
amphetamines and cocaine), and vascular malformations. Less frequent causes include
bleeding into tumors, aneurysmal rupture, and vasculitis. Neurologic symptoms usually
increase gradually over minutes or a few hours. (See "Spontaneous intracerebral
hemorrhage: Pathogenesis, clinical features, and diagnosis" and "Clinical diagnosis of
stroke subtypes".)
Subarachnoid hemorrhage — Rupture of arterial aneurysms is the major cause of
subarachnoid hemorrhage (SAH). Aneurysm rupture releases blood directly into the
cerebrospinal fluid (CSF) under arterial pressure. The blood spreads quickly within the
CSF, rapidly increasing intracranial pressure. Death or deep coma ensues if the
bleeding continues. The bleeding usually lasts only a few seconds but rebleeding is
common. With causes of SAH other than aneurysm rupture (eg, vascular malformations,
bleeding diatheses, trauma, amyloid angiopathy, and illicit drug use), the bleeding is
less abrupt and may continue over a longer period of time.
Symptoms of SAH begin abruptly, occurring at night in 30 percent of cases. The primary
symptom is a sudden, severe headache (97 percent of cases) classically described as
the "worst headache of my life." The headache is lateralized in 30 percent of patients,
predominantly to the side of the aneurysm. The onset of the headache may or may not
be associated with a brief loss of consciousness, seizure, nausea, vomiting, focal
neurologic deficit, or stiff neck (figure 1) [3]. There are usually no important focal
neurologic signs at presentation unless bleeding occurs into the brain and CSF at the
same time (meningocerebral hemorrhage). (See "Aneurysmal subarachnoid
hemorrhage: Clinical manifestations and diagnosis".)
Ischemia — There are three main subtypes of brain ischemia:
●Thrombosis
●Embolism
●Systemic hypoperfusion
Thrombotic stroke — Thrombotic strokes are those in which the pathologic process
giving rise to thrombus formation in an artery produces a stroke either by reduced blood
flow distally (low flow) or by an embolic fragment that breaks off and travels to a more
distant vessel (artery-to-artery embolism). All thrombotic strokes can be divided into
either large or small vessel disease (table 2).
●Large vessel disease includes both the extracranial and intracranial arterial
system; atherothrombosis is by far the most common pathologic process.
(See "Pathophysiology of symptoms from carotid atherosclerosis" and "Intracranial
large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis".)
●Small vessel disease refers specifically to penetrating arteries that arise from the
distal vertebral artery, the basilar artery, the middle cerebral artery stem, and the
arteries of the circle of Willis. These arteries thrombose due to atheroma formation
at their origin or in the parent large artery, or due to lipohyalinosis (a lipid hyaline
build-up distally secondary to hypertension). Penetrating artery (small vessel)
disease can result in small deep infarcts usually referred to as lacunes.
(See "Lacunar infarcts".)
Embolic stroke — Embolism refers to particles of debris originating elsewhere that
block arterial access to a particular brain region. Since the process is not local (as with
thrombosis), local therapy only temporarily solves the problem; further events may
occur if the source of embolism is not identified and treated.
Embolic strokes are divided into four categories (table 2). (See "Etiology, classification,
and epidemiology of stroke".)
●Those with a known source that is cardiac
●Those with a possible cardiac or aortic source based upon transthoracic and/or
transesophageal echocardiographic findings
●Those with an arterial source
●Those with a truly unknown source in which these tests are negative or
inconclusive
Systemic hypoperfusion — Systemic hypoperfusion is a more general circulatory
problem, manifesting itself in the brain and perhaps other organs. 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. (See "Clinical diagnosis of stroke subtypes".)
INITIAL GENERAL ASSESSMENT Sudden loss of focal brain function is the
core feature of the onset of ischemic stroke. However, patients with conditions other
than brain ischemia can present in a similar fashion (table 3). In addition, patients who
have an ischemic stroke may present with other serious medical conditions. Thus, the
initial evaluation requires a rapid but broad assessment. The goals in this initial phase
include:
●Ensuring medical stability
●Quickly reversing any conditions that are contributing to the patient's problem
●Moving toward uncovering the pathophysiologic basis of the patient's neurologic
symptoms.
Diagnosing an intracerebral or subarachnoid hemorrhage as soon as possible can be
lifesaving and prevent or minimize permanent neurologic damage. The history may
provide clues to these diagnoses, but early triage of the patient to CT scan or MRI is
critical. However, it is important to assess and optimize vital physiologic
function before sending the patient for an imaging study. (See "Initial assessment and
management of acute stroke".)
Vital signs — Parameters of particular concern in patients with stroke include blood
pressure, breathing, and temperature.
Blood pressure — The mean arterial blood pressure (MAP) is usually elevated in
patients with an acute stroke. This may be due to chronic hypertension, which is a major
risk factor for ischemic stroke. However, an acute elevation in blood pressure often
represents an appropriate response to maintain brain perfusion. The decision to treat
requires a balance between the potential danger of severe increases in blood pressure,
and a possible decline in neurologic functioning when blood pressure is lowered.
(See "Initial assessment and management of acute stroke", section on 'Blood pressure
management'.)
Breathing — Patients with increased intracranial pressure (ICP) due to hemorrhage,
vertebrobasilar ischemia, or bihemispheric ischemia can present with a decreased
respiratory drive or muscular airway obstruction. Hypoventilation, with a resulting
increase in the partial pressure of carbon dioxide, may lead to cerebral vasodilation
which further elevates ICP.

Intubation may be necessary to restore adequate ventilation and to protect the airway.
This is especially important in the presence of vomiting, which occurs commonly with
increased ICP, vertebrobasilar ischemia, and intracranial hemorrhage.

Fever — Fever may occur in patients with an acute stroke and can worsen brain
ischemia [4]. Normothermia should be maintained for at least the first several days after
an acute stroke. (See "Initial assessment and management of acute stroke", section on
'Fever'.)
History and physical examination — The history and physical examination should be
used to distinguish between other disorders in the differential diagnosis of stroke (table
3). As examples, seizures, syncope, migraine, and hypoglycemia can mimic acute
ischemia. The most difficult cases involve patients with focal signs and altered level of
consciousness. It is important to ask the patient or a relative whether the patient takes
insulin or oral hypoglycemic agents, has a history of a seizure disorder or drug overdose
or abuse, medications on admission, recent trauma, or hysteria (see "Differential
diagnosis of transient ischemic attack and acute stroke"). The history is also important
in separating ischemia from hemorrhage and distinguishing between subtypes of
ischemia and hemorrhage.
Ischemia versus hemorrhage — Noncontrast computed tomography (CT) is typically
the first diagnostic study in patients with suspected stroke. The main advantages of CT
are widespread access and speed of acquisition. CT is highly sensitive for the diagnosis
of hemorrhage in the acute setting [5]. Intracerebral hemorrhages are evident almost
instantly after onset as focal white hyperdense lesions within the brain parenchyma.
(See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and
diagnosis", section on 'Head CT'.)
Intracerebral hemorrhages can also be defined by MRI; the use of susceptibility
sequences improves the sensitivity of MRI for early detection of hemorrhage. Gradient-
echo images can also show the presence of old hemorrhages since this technique is
very sensitive to hemosiderin, which can remain in old hemorrhages indefinitely.
(See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and
diagnosis", section on 'Brain MRI'.)
Small subarachnoid hemorrhages can be missed by either CT or MRI. Lumbar puncture
may be needed to make the diagnosis in such patients. (See "Aneurysmal subarachnoid
hemorrhage: Clinical manifestations and diagnosis", section on 'Lumbar puncture'.)
MRI is more sensitive than CT for the early diagnosis of brain infarction, although CT
may identify subtle indicators of infarction within six hours of stroke onset in a significant
number of patients (see "Neuroimaging of acute ischemic stroke", section on 'Early
infarct signs'). Fluid-attenuated inversion recovery (FLAIR) MRI sequences and
diffusion-weighted images (DWI-MRI) are especially useful in showing infarcts early
after the onset of symptoms. In patients with ischemia who do not yet have brain
infarction, both CT and MRI may be normal. (See "Neuroimaging of acute ischemic
stroke", section on 'Magnetic resonance imaging'.)
Is the patient a candidate for reperfusion? — Timely restoration of blood flow is the
most effective maneuver for salvaging ischemic brain tissue that is not already infarcted.
Removal of occlusive intracranial thrombi must be accomplished quickly, since the
benefit of reperfusion therapy for ischemic stroke decreases in a continuous fashion
over time. An important aspect of the hyperacute phase of stroke assessment is to
determine if the patient is eligible for intravenous thrombolysis and/or mechanical
thrombectomy:
●Intravenous thrombolytic therapy with alteplase (recombinant tissue-type
plasminogen activator or rt-PA) improves outcomes in patients with acute
ischemic stroke who can be treated within 3 to 4.5 hours from stroke onset and
meet additional eligibility criteria (table 4). This issue is discussed in detail
separately. (See "Approach to reperfusion therapy for acute ischemic stroke",
section on 'Alteplase'.)
●Intra-arterial mechanical thrombectomy using a second-generation stent retriever
device can improve outcomes for well-selected patients with ischemic stroke
caused by a large artery occlusion in the proximal anterior circulation when started
up to 24 hours from the time last seen. This therapy is reviewed in detail
elsewhere. (See "Mechanical thrombectomy for acute ischemic stroke".)
DETERMINING A PRESUMPTIVE DIAGNOSIS OF STROKE
SUBTYPE After completing the initial assessment, the goal of the subsequent
evaluation is to determine the underlying pathophysiology of the stroke in order to guide
therapy (table 1). This part of the discussion assumes that patients with subarachnoid
hemorrhage have already been identified by the initial history and physical examination
and noncontrast head CT (with or without lumbar puncture). A review of the clinical
features and diagnosis of subarachnoid hemorrhage is found separately.
(See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)
In addition, the presence of intracerebral hemorrhage should already be evident by this
phase of the evaluation; the diagnostic evaluation in these patients is reviewed
elsewhere. (See 'Evaluation of patients with intracerebral hemorrhage' below.)
In practice, then, this second stage of evaluation is focused upon distinguishing
between embolic and thrombotic strokes; in patients with the latter, it is worth
differentiating between large vessel and small vessel (penetrating artery or lacunar)
infarcts since the causes, outcomes, and treatments are different. Some patients will
have more than one potential etiology for stroke, although the majority will have only
one predominant cause [6]. (See "Etiology, classification, and epidemiology of
stroke" and "Clinical diagnosis of stroke subtypes".)

A presumptive diagnosis of the stroke subtype can be made following a thorough history,
physical examination, and imaging study such as CT or MRI. However, confirmation of
the diagnosis requires more extensive testing.

A history of carotid stenosis is a significant risk factor for large artery thrombotic stroke,
but these patients need to have other stroke subtypes considered in the differential
diagnosis. In the North American Symptomatic Carotid Endarterectomy Trial (NASCET),
of patients with 70 to 99 percent stenosis who subsequently had an ischemic stroke, 20
and 45 percent of strokes that occurred in the territory of symptomatic and
asymptomatic carotid arteries, respectively, were unrelated to carotid stenosis [7].
History — A number of features in the clinical history may be useful in determining the
type of stroke:
●Clinical course
●Ecology
●Previous transient ischemic attack (TIA)
●Activity at the onset or just before the stroke
●Associated symptoms
Clinical course — The most important historical item for differentiating stroke subtypes
is the pace and course of the symptoms and signs and their clearing [8]. Each subtype
has a characteristic course.
●Embolic strokes most often occur suddenly (figure 2). The deficits indicate focal
loss of brain function that is usually maximal at onset. Rapid recovery also favors
embolism.
●Thrombosis-related symptoms often fluctuate, varying between normal and
abnormal or progressing in a stepwise or stuttering fashion with some periods of
improvement (figure 3).
●Penetrating artery occlusions usually cause symptoms that develop during a
period of hours or at most a few days (figure 4), compared with large artery-
related brain ischemia, which can evolve over a longer period.
●Intracerebral hemorrhage (ICH) does not improve during the early period; it
progresses gradually during minutes or a few hours (figure 5).
●Aneurysmal subarachnoid hemorrhage (SAH) develops in an instant. Focal brain
dysfunction is less common.
Patients often do not give a specific history regarding the course of neurologic
symptoms. I may ask if the patient could walk, talk, use the phone, use the hand, etc, as
the events developed after the first symptoms occurred [8].
Ecology — Ecology refers to known demographic and historical features that provide
probabilities of the patient having one or more of the stroke subtypes. Age, sex, and
race are important demographic variables known to the clinician before taking the
history [9].
●Most thrombotic and embolic strokes related to atherosclerosis occur in older
patients. Individuals under age 40 rarely have severe atherosclerosis unless they
also have major risk factors such as diabetes, hypertension, hyperlipidemia,
 smoking, or a strong family history. In contrast, cardiac-origin embolism is
common in young people who are known to have heart disease.
●Hypertensive ICH is more common among blacks and individuals of Asian
descent than among whites.
●Premenopausal women have a lower frequency of atherosclerosis than men of
similar age unless they have major stroke risk factors. Even after adjusting for age,
the incidence of atherosclerotic stroke is four times higher in men [10].
●Blacks, Asians, and women have a lower incidence of occlusive disease of the
extracranial carotid and vertebral arteries than white men.
Hypertension is the most common and most important stroke risk factor, including
isolated systolic hypertension (see "Overview of secondary prevention of ischemic
stroke", section on 'Hypertension'). Epidemiologic studies show that there is a gradually
increasing incidence of both coronary disease and stroke as the blood pressure rises
above 110/75 mmHg (figure 6) [11,12]. However, these observations do not prove a
causal relationship, since increasing blood pressure could be a marker for other risk
factors such as increasing body weight, which is associated with dyslipidemia, glucose
intolerance, and the metabolic syndrome. The best evidence for a causal role of
increasing blood pressure in cardiovascular complications is an improvement in
outcome with antihypertensive therapy. This evidence is reviewed elsewhere.

Chronic hypertension is a risk factor for both thrombotic extracranial and intracranial
large artery disease and penetrating artery disease. Conversely, the absence of a
history of hypertension or of present hypertension reduces the likelihood of penetrating
artery disease.

Smoking increases the likelihood of extracranial occlusive vascular disease, more than
doubling the risk of stroke [13]. The risk of ischemic stroke decreases over time after
smoking cessation. In one series of middle-aged women, for example, the excess risk
among former smokers largely disappeared two to four years after cessation [13].
(See "Cardiovascular risk of smoking and benefits of smoking cessation".)

Several other risk factors for stroke have been identified:

●Diabetes increases the likelihood of large and small artery occlusive disease.
●The use of amphetamines increases the likelihood of both ICH and SAH but not
brain ischemia.
●Cocaine-related strokes are often hemorrhagic (ICH and SAH), due to
aneurysms and vascular malformations [14]. Cocaine is also associated with brain
ischemia, especially involving the posterior circulation intracranial arteries; this is
probably due to vasoconstriction.
●Heart disease, including cardiac valvular disease, prior myocardial infarction,
atrial fibrillation, and endocarditis, increases the probability of a stroke due to
embolism.
●Stroke during the puerperium has an increased likelihood of being related to
venous or arterial thrombosis.
 ●The presence of a known bleeding disorder or prescription of warfarin or other
anticoagulants predisposes to hemorrhage, into either the brain or the
cerebrospinal fluid (CSF).
The link between stroke and oral contraceptive use has been a controversial issue.
Initial studies suggesting this association were performed with oral contraceptives
containing higher doses of estrogen; the risk may not be as great with current low dose
oral contraceptives. (See "Combined estrogen-progestin contraception: Side effects and
health concerns", section on 'Cardiovascular effects'.)

The presence of these risk factors increases the odds that a stroke is due to a particular
mechanism, but the clinician cannot make a firm diagnosis simply on the basis of
probability. As examples: some conditions such as hypertension predispose to more
than one subtype (thrombosis, intracranial hemorrhage); the presence of a prior
myocardial infarction increases the likelihood of cardiac origin embolism, but also
increases the likelihood of carotid and vertebral artery neck occlusive disease
(thrombosis); and an older patient with severe atherosclerosis may also harbor an
unexpected cerebral aneurysm.

Previous transient ischemic attack — A history of TIA (especially more than one) in
the same territory as the stroke strongly favors the presence of a local vascular lesion
(thrombosis). Attacks in more than one vascular territory suggest brain embolism from
the heart or aorta. TIAs are not a feature of brain hemorrhage.

Patients often will not volunteer a prior history of symptoms consistent with a TIA. Many
patients, for example, do not relate prior hand or eye problems to subsequent leg
problems. Thus, the physician must ask directly about specific symptoms. "Did your arm,
hand, or leg ever transiently go numb?" "Did you ever have difficulty speaking?" "Did
you ever lose vision? If so, in which part of your vision? Was it in one eye and, if so,
which one?"

Activity at the onset or just before the stroke — Hemorrhages (ICH and SAH) can
be precipitated by sex or other physical activity, while thrombotic strokes are unusual
under these circumstances. Trauma before the stroke suggests traumatic dissection or
occlusion of arteries or traumatic brain hemorrhage. Sudden coughing and sneezing
sometimes precipitates brain embolism. Similarly, getting up during the night to urinate
seems to promote brain embolism (a matutinal embolus).
Associated symptoms — The presence of certain associated symptoms is suggestive
of specific stroke subtypes.
●Fever raises the suspicion of endocarditis and resulting embolic stroke.
●Infections activate acute phase blood reactants, thereby predisposing to
thrombosis.
●Headache is typically a feature of hemorrhagic strokes, but some patients have
headaches in the prodromal period before thrombotic strokes.
●Vomiting is common in patients with ICH, SAH, and posterior circulation large
artery ischemia (figure 1).
●Seizures are most often seen in patients with lobar ICH or brain embolism; they
are rare in patients with acute thrombosis [15].
 ●Reduced alertness favors the presence of hemorrhage. Accompanying
neurologic signs are suggestive of ICH, while the absence of focal signs suggests
SAH. Loss of consciousness is also common in patients with thrombotic and
embolic strokes that are large or involve the posterior circulation large arteries.
Physical examination — Important clues in the general physical examination include
the following:
●Absent pulses (inferior extremity, radial, or carotid) favors a diagnosis of
atherosclerosis with thrombosis, although the sudden onset of a cold, blue limb
favors embolism.
●The internal carotid arteries in the neck cannot be reliably palpated but, in some
patients, occlusion of the common carotid artery in the neck can be diagnosed by
the absence of a carotid pulse.
●The presence of a neck bruit suggests the presence of occlusive extracranial
disease, especially if the bruit is long, focal, and high pitched.
●Palpating the facial pulses is helpful in diagnosing common carotid and internal
carotid artery occlusions and temporal arteritis. The facial pulses on the side of the
occlusion are often lost with common carotid artery occlusions. In contrast, some
patients with internal carotid artery occlusion will have increased facial pulses on
the side of the occlusion because collateral channels develop between the
external carotid artery facial branches and the carotid arteries intracranially. In
patients with temporal arteritis, the temporal arteries are often irregular and have
sausage-shaped areas of dilatation, may be tender, and are often pulseless.
●Cardiac findings, especially atrial fibrillation, murmurs, and cardiac enlargement,
favor cardiac-origin embolism. (See "Auscultation of cardiac murmurs in adults".)
●Careful examination of the optic fundus may reveal a cholesterol crystal, white
platelet-fibrin, or red clot emboli. Subhyaloid hemorrhages in the eye suggest a
suddenly developing brain or subarachnoid hemorrhage. When the carotid artery
is occluded, the iris may appear speckled and the ipsilateral pupil can become
dilated and poorly reactive. The retina in that circumstance may also show
evidence of chronic ischemia (venous stasis retinopathy).
Neurologic examination — The patient's account of his or her neurologic symptoms
and the neurologic signs found on examination tell more about the location of the
process in the brain than the particular stroke subtype. The blood supply to various
parts of the brain and associated neurologic findings are shown in the figures (figure 7A-
G).
Nevertheless, some constellations of symptoms and signs occasionally suggest a
specific process (table 5).
●Weakness of the face, arm, and leg on one side of the body unaccompanied by
sensory, visual, or cognitive abnormalities (pure motor stroke) favors the presence
of a thrombotic stroke involving penetrating arteries or a small ICH.
●Large focal neurologic deficits that begin abruptly or progress quickly are
characteristic of embolism or ICH.
●Abnormalities of language suggest anterior circulation disease, as does the
presence of motor and sensory signs on the same side of the body (figure 8).
●Vertigo, staggering, diplopia, deafness, crossed symptoms (one side of the face
and other side of the body), bilateral motor and/or sensory signs, and hemianopia
 or bilateral visual field loss suggest involvement of the posterior circulation.
(See "Posterior circulation cerebrovascular syndromes".)
●The sudden onset of impaired consciousness in the absence of focal neurologic
signs is characteristic of SAH.
Imaging studies — Brain imaging and a comprehensive neurovascular evaluation
should be obtained for most patients suspected of having acute ischemic stroke or
transient ischemic attack. Neurovascular imaging is important to determine the potential
sources of embolism or low flow in ischemic stroke and to detect possible aneurysms or
vessel malformations in hemorrhagic stroke. (See "Neuroimaging of acute ischemic
stroke".)

The location and size of a brain infarct on CT or MRI may further aid in distinguishing
between stroke subtypes.

●Small subcortical (deep) infarcts are most commonly located in the basal ganglia,
internal capsule, thalamus, and pons. They are potentially within the blood supply
of a single penetrating artery. The most common cause of a small deep infarct is
lacunar infarction due to degenerative changes in the penetrating arteries.
●Rostral brainstem (midbrain and thalamus), occipital lobe, and cerebellar infarcts
are most commonly caused by brain embolism. (See "Posterior circulation
cerebrovascular syndromes".)

On the other hand, large subcortical infarcts, infarcts that are limited to the cerebral
cortex, and infarcts that are both cortical and subcortical are commonly caused by
thrombosis or embolism.

CONFIRMING THE DIAGNOSIS The previous assessment should allow the

formation of a presumptive diagnosis of the underlying stroke pathophysiology. The next
phase of the evaluation is to confirm this hypothesis with diagnostic tests.
Embolic stroke — Embolism is especially likely in the following circumstances:
●The onset is sudden and the neurologic deficit is maximal from the beginning
●The infarct and deficit are large
●There is a known cardiac or large artery lesion present
●The infarct is or becomes hemorrhagic on CT or MRI
●There are multiple cortical or cortical/subcortical infarcts in different vascular
territories
●Clinical findings improve quickly (so-called "spectacular shrinking deficit") [16]
In addition, embolic stroke is common in patients who have had a posterior circulation
stroke; in a registry of 361 patients who had vertebrobasilar strokes or transient
ischemic attacks (TIAs) and were admitted to a university hospital, 41 percent had an
embolic event [17].
A possible cardiac source should be considered in all patients with suspected embolic
stroke, particularly in patients under age 45, whether or not they have clinical evidence
of heart disease. This issue is discussed below. (See 'Cardiac evaluation' below.)
Vascular studies — The extracranial and intracranial arteries are also common
sources of brain embolism and should be studied. (See "Etiology, classification, and
epidemiology of stroke".)
 ●Ifthe infarct and brain symptoms are within the anterior circulation (carotid artery
supply), then the extracranial and intracranial carotid arteries, and the middle and
anterior cerebral artery branches should be the focus of the examinations.
●When the infarct is within the posterior circulation (vertebrobasilar system), the
extracranial and intracranial vertebral arteries, the basilar artery, and the posterior
cerebral arteries should be the focus of the vascular investigations.
The anterior circulation can be studied using duplex ultrasound of the neck and
transcranial Doppler (TCD) of the intracranial arteries [18,19]. B-mode images of the
carotid artery also demonstrate the degree of stenosis and irregularities or ulcerations
within plaques. (See "Pathophysiology of symptoms from carotid atherosclerosis",
section on 'Plaque morphology and pathology'.)

Alternatively, CT angiography (CTA) or MR angiography (MRA) of the neck and head

arteries may be sufficient. Conventional angiography is performed when the screening
tests do not fully define the lesion and more characterization is warranted, and when
surgery or interventional treatment through an arterial catheter (angioplasty or intra-
arterial thrombolysis) may be indicated.

Within the posterior circulation, duplex and color-flow Doppler investigation of the
origins of the vertebral arteries [20] and ultrasound of the subclavian arteries (especially
when the radial pulse or blood pressure on one side is lower than the other) can detect
lesions of the proximal portion of the vertebral arteries. Atherosclerosis most often
affects this proximal region. The ultrasonographer can then insonate over the rest of the
vertebral artery in the neck using a continuous-wave Doppler to detect the direction of
flow within the artery (craniad as would be normal, or reversed or to-and-fro flow
suggesting proximal obstruction).
CTA and MRA of the neck vertebral arteries are also helpful, but these tests may not
adequately show the origins of the vertebral arteries [21]. The clinician must be certain
that the films are adequate to see the complete extracranial and intracranial
vertebrobasilar system.
An important advance in the detection of brain embolism is monitoring by TCD [22].
Emboli that pass under ultrasound probes make a high-pitched chirp and are recorded
as high-intensity transient signals (HITS). The location and pattern of these emboli can
help define the presence of embolism and give clues as to the source. TCD monitoring
can also help to assess the effectiveness of treatment.
Artery-to-artery versus cardiac sources of embolism — The distinction between
artery-to-artery and non-artery-to-artery sources of embolism can be difficult. Suspicion
of the former typically arises once vascular pathology in a large vessel has been
identified (eg, with noninvasive testing). Repetitive spells within a single vascular
territory are also suggestive of an artery-to-artery source, as is a normal
echocardiogram. However, caution must be used in interpreting the results of a
transthoracic echocardiogram. As previously mentioned, this study can exclude a
cardiomyopathy and most atrial and mitral valve pathology, but may miss other potential
embolic sources such as clot in the atrial appendage, a patent foramen ovale, mitral
valve lesions, and aortic atherosclerosis. Transesophageal echocardiography is better
for identifying these lesions.
Small vessel (lacunar) stroke — Most patients with lacunar infarcts have risk factors
for penetrating artery disease (eg, hypertension, diabetes mellitus, or polycythemia).
The clinical findings typically conform to one of the well-recognized lacunar syndromes:
pure motor hemiparesis, pure sensory stroke, dysarthria-clumsy hand, or ataxic
hemiparesis. (See "Lacunar infarcts".)
Further testing is of low yield in patients suspected of having a lacunar infarction who
have the typical risk factors, clinical neurologic findings, and characteristic brain imaging
(eg, small subcortical infarct). On the other hand, some patients seen within the first few
hours after symptom onset with clinical findings suggestive of lacunar infarction are
found to have large artery disease; this has been particularly true for patients of Asian
origin [23]. Vascular imaging (CTA or MRA) can be performed at the same time as brain
imaging (CT or MRI) to exclude occlusion of the parent feeding artery, a condition that
can mimic a lacunar infarct. (See "Lacunar infarcts", section on 'Evaluation and
diagnosis'.)
It is particularly important to perform intracranial vascular imaging in blacks and persons
of Asian descent, since intracranial large artery occlusive disease is common in these
patients. An alternative diagnostic test to exclude intracranial occlusive disease is TCD,
a technique that measures the blood flow velocities in the large intracranial arteries
using an ultrasound probe placed over the orbit, temporal bone, and foramen magnum
[18]. (See "Neuroimaging of acute ischemic stroke", section on 'Transcranial Doppler'.)
Large vessel atherothrombotic stroke — Large vessel atherothrombotic strokes are
often preceded by TIAs, and the onset may or may not be abrupt. The course of
neurologic symptoms and signs fluctuates or is progressive in development. Infarcts
that are large and subcortical are usually caused by occlusion of intracranial arteries.
Patients with suspected large vessel atherothrombotic strokes need to have both
intracranial and extracranial vascular testing. Extracranial vascular testing can be
performed with MRA, CTA, or duplex carotid ultrasound. All are reliable and specific for
detecting important severe occlusive lesions in the extracranial carotid arteries.
Ultrasound devices such as color-flow Doppler imaging and power Doppler improve the
resolution and quantification of carotid artery lesions. (See "Evaluation of carotid artery
stenosis".)
One approach to patients with suspected carotid artery stenosis is to first perform
carotid duplex ultrasound. Patients with stenoses less than 50 percent are followed with
serial examinations, usually on an annual basis to determine if there is progression.
Transcranial Doppler and either MRA or CTA should be performed if the carotid
stenosis is greater than 50 percent on the duplex ultrasound. Both MRA and CTA
accurately define abnormalities within the carotid and vertebral arteries in the neck and
their intracranial branches. MRI can be performed at the same time as MRA; the
presence or absence of a brain infarct can help determine treatment. (See "Evaluation
of carotid artery stenosis".)

Head CT and CTA are acceptable alternatives to MRI and MRA and may be more
available than MR in some centers. Head CT and CTA should be done if MRI and MRA
are contraindicated or impractical.

Conventional angiography is rarely performed; indications include patients who cannot

tolerate an MRA or CTA, patients with discrepant CTA/MRA and ultrasound findings,
and patients with suspected nonatherosclerotic disease (eg, dissection, fibromuscular
dysplasia).

Patients with carotid artery stenosis who have had nondisabling strokes may be
candidates for carotid endarterectomy or carotid artery stenting. (See "Management of
symptomatic carotid atherosclerotic disease".)
CARDIAC EVALUATION A cardiac evaluation is important in most patients with
brain ischemia [24]. Not only are cardiac and aortic origin emboli common, but many
patients with cerebrovascular occlusive disease have concurrent coronary heart disease
that can lead to significant morbidity and mortality [25-28]. The basic evaluation includes
a thorough history focusing on the presence of cardiac ischemia and arrhythmias, a
careful cardiac examination, and an electrocardiogram.
Monitoring for subclinical atrial fibrillation — All patients with ischemic stroke should
have cardiac monitoring for at least the first 24 hours after stroke onset to look for
subclinical atrial fibrillation (AF) [29]. In addition, we suggest ambulatory cardiac
monitoring for several weeks (eg, 30 days) for patients with a cryptogenic ischemic
stroke or transient ischemic attack (TIA). These patients are characterized by brain
ischemia not attributable to a definite source of cardioembolism, large artery
atherosclerosis, or small artery disease despite extensive vascular and cardiac
evaluation, including no evidence of AF on standard 12-lead electrocardiogram (ECG)
and 24-hour cardiac monitoring (see "Cryptogenic stroke").
Prolonged cardiac event monitoring increase the detection of subclinical AF in patients
with TIA or acute ischemic stroke who present with sinus rhythm [30-35]. In contrast,
subclinical AF, if transient, infrequent, and largely asymptomatic, may be undetected on
standard cardiac monitoring such as continuous telemetry and 24- or 48-hour Holter
monitors. This issue is illustrated by the following observations among trials of patients
without an identified mechanism for stroke or TIA:
●In The CRYSTAL AF trial, 441 patients with cryptogenic stroke and no evidence
of AF during at least 24 hours of ECG monitoring were randomly assigned to
prolonged ambulatory cardiac monitoring with a subcutaneous insertable cardiac
monitor (also sometimes referred to as implantable cardiac monitor or implantable
loop recorder) recorder or to a control group with conventional follow-up [30]. At
six months, AF detection was significantly higher in the monitored group (8.9
percent, versus 1.4 percent in the control group, hazard ratio [HR] 6.4, 95% CI
1.9-21.7).
●In the EMBRACE trial, 572 patients who had a cryptogenic stroke or TIA (with no
AF after 24-hour cardiac monitoring) in the previous six months were randomly
assigned to additional ambulatory monitoring with a 30-day external loop recorder
(intervention group) or a 24-hour Holter monitor (control group) [31]. At study end,
the rate of AF detection was significantly greater in the intervention group (16.1
percent, versus 3.2 percent in the control group, 95% CI 8.0-17.6).
●The PER DIEM trial randomly assigned 300 patients within six months of
ischemic stroke and no known AF (66 percent had a cryptogenic stroke) in a 1:1
ratio to monitoring with either an insertable cardiac monitor (placed for one year)
or an external loop recorder (worn for four weeks) [34]. At 12 months, detection of
new AF lasting more than two minutes was observed in a greater number of
 patients in the insertable cardiac monitor group compared with the external loop
recorder group (15.3 versus 4.7 percent, absolute difference 10.7 percent, 95% CI
4.0-17.3 percent).
Long-term cardiac monitoring can detect subclinical AF even among patients with a
known mechanism for ischemic stroke. The STROKE-AF trial randomly assigned 492
patients with ischemic stroke attributed to large vessel or small vessel disease in a 1:1
ratio to monitoring with an insertable cardiac monitor or to site-specific usual care
(external cardiac monitoring with ECG, Holter, telemetry, or event recorders) [35]. At 12
months, detection of AF lasting more than 30 seconds was higher in the insertable
cardiac monitor group compared with the usual care group (12.1 versus 1.8 percent,
absolute difference approximately 10.3 percent, HR 7.4, 95% CI 2.6-21.3).
These results parallel other data showing that prolonged cardiac event monitoring
increases the detection of subclinical AF [32,36-40]. Such monitoring may then reduce
the risk of recurrent ischemic stroke by prompting the appropriate use of long-term
anticoagulation [41]. However, rigorous evidence is lacking that anticoagulation of
subclinical AF improves outcomes for patients initially diagnosed with cryptogenic stroke
[42]. The approach to treatment of subclinical AF detected on monitoring is reviewed
separately. (See "Cryptogenic stroke", section on 'Occult or subclinical atrial fibrillation
on monitoring'.)
In addition, the minimum duration of time (in minutes) of the episodes of AF that
increases the risk of thrombus formation in the atria and thereby increases the risk of
cardioembolic stroke has not been firmly established. (See "Stroke in patients with atrial
fibrillation", section on 'Long-term anticoagulation'.)
The optimal cardiac monitoring method (ie, continuous telemetry, ambulatory
electrocardiography, serial electrocardiography, transtelephonic ECG monitoring, or
insertable cardiac monitor) is uncertain. (See "Ambulatory ECG monitoring".)
Other potential indicators that may predict which patients have or are likely to develop
atrial fibrillation include determination of the left atrial appendage ejection fraction by
transesophageal echocardiography [43] and demonstration of an atrial fibrillation
phenotype on left atrial appendage pulse wave Doppler even when the surface ECG
shows normal sinus rhythm [44]. In addition, measurements of B-type (brain) natriuretic
protein (BNP) and the N-terminal fragment of BNP indicate that these values are
elevated in patients with atrial fibrillation who have cardiogenic embolism, even in those
with normal ventricular function, when compared with patients who have noncardiogenic
stroke (see "Blood biomarkers for stroke", section on 'Cardioembolic stroke'). These
measurements in patients with normal cardiac ventricular function might identify those
who have intermittent atrial fibrillation or are prone to develop it. Further research is
needed to confirm whether these indicators are clinically useful.
Atrial cardiopathy characterized by a large left atrium and abnormal function and
morphology of the left atrium and left atrial appendage can predispose to thrombus
formation even without atrial fibrillation. (See "Cryptogenic stroke", section on 'Atrial
cardiopathies'.)
Echocardiography — All patients with suspected embolic stroke should have an
echocardiogram. The choice between transthoracic echocardiography (TTE) and
transesophageal echocardiography (TEE) as the initial imaging test to identify a source
of embolism should be individualized on a case-by-case basis. (See "Echocardiography
in detection of cardiac and aortic sources of systemic embolism".)

TTE is the preferred initial test for the majority of patients with a suspected cardiac or
aortic source of emboli, including:

●Patients ≥45 years with a neurologic event and no identified disease on

neurovascular imaging studies
●Patients with a high suspicion of left ventricular thrombus
●Patients in whom TEE is contraindicated (eg, esophageal stricture, unstable
hemodynamic status) or who refuse TEE

TEE is the preferred initial test to localize the source of embolism in the following
circumstances:

●Patients <45 years without known cardiovascular disease (ie, absence of

myocardial infarction or valvular disease history)
●Patients with a high pretest probability of a cardiac embolic source in whom a
negative TTE would be likely to be falsely negative
●Patients with atrial fibrillation and suspected left atrial or left atrial appendage
thrombus, especially in the absence of therapeutic anticoagulation, but only if the
TEE would impact management
●Patients with a mechanical heart valve
●Patients with suspected aortic pathology
Transesophageal versus transthoracic echo — While TTE and TEE have
advantages and disadvantages, both are effective diagnostic tests with a role in the
evaluation of suspected cardioaortic source of embolism. In most patients, TEE yields
higher quality images and has a greater sensitivity and specificity than TTE, but a few
conditions (eg, left ventricular thrombus) are better seen on TTE. However, TEE is an
uncomfortable invasive procedure that may not be tolerated by very ill patients.
Because it is less invasive and readily available in most institutions, TTE is often
reasonable as the initial test of choice.
A TEE is often performed to examine the atria, atrial septal region, and the aorta if the
TTE and preliminary cardiac and vascular imaging tests do not clarify the cause of brain
ischemia [45,46]. (See "Initial evaluation and management of transient ischemic attack
and minor ischemic stroke".)
A TEE is the best test to exclude significant ascending aortic atheromatous disease. It is
also the best test to look for evidence of patent foramen ovale (PFO) or atrial septal
aneurysm, conditions that can cause otherwise cryptogenic stroke.
(See "Thromboembolism from aortic plaque" and "Embolism from atherosclerotic plaque:
Atheroembolism (cholesterol crystal embolism)" and "Atrial septal abnormalities (PFO,
ASD, and ASA) and risk of cerebral emboli
TEE is also the best way to identify clot in the left atrial appendage. These emboli are 3
mm or less in diameter and are usually beyond the resolution of the transthoracic
echocardiographic ultrasound probe. In contrast, left ventricular thrombi in patients with
congestive heart failure or a previous myocardial infarction are best seen with TTE
since the true left ventricular apex is not well seen on TEE. (See "Echocardiography in
detection of cardiac and aortic sources of systemic embolism".)
BLOOD TESTS A number of blood tests may be indicated in select patients with
brain ischemia or hemorrhage, including [29,47]:
●Blood glucose
●Complete blood count, including hemoglobin, hematocrit, white blood cell count,
and platelet count
●Prothrombin time, international normalized ratio (INR), and activated partial
thromboplastin time
●Thrombin time and/or ecarin clotting time if patient is known or suspected to be
taking a direct thrombin inhibitor or a direct factor Xa inhibitor
●Blood lipids, including total, high-density lipoprotein (HDL), and low-density
lipoprotein (LDL) cholesterol, and triglycerides
D-dimer and fibrinogen levels may be helpful in detecting patients whose brain ischemia
can be related to cancer or inflammatory disease. (See "Blood biomarkers for stroke".)
Hypercoagulable studies — While hypercoagulable states are sometimes found in
patients who have had an ischemic stroke, widespread testing for these disorders is
limited by a number of factors including a relatively low prevalence of thrombophilias
and alteration of the sensitivity and specificity of the tests involved in the setting of an
acute ischemic event and in patients taking heparin or warfarin [48]. Furthermore, it
remains unclear if the inherited thrombophilias directly predispose to stroke as they do
to venous thrombosis.
A case-control study found that one in seven patients with a first ever acute ischemic
stroke tested positive for one of the inherited thrombophilias, but that the relationship
was likely to be coincidental rather than causal in almost all cases [49]. In a systematic
review, the prevalence of inherited deficiencies of protein C, protein S, antithrombin III,
or plasminogen was low in unselected patients with ischemic stroke [50]. The pretest
probabilities of other coagulation defects in these patients were as follows:
●Lupus anticoagulant 3 percent (8 percent in patients ≤50 years)
●Anticardiolipin antibodies 17 percent (21 percent in patients ≤50 years)
●Activated protein C resistance/factor V Leiden mutation 7 percent (11 percent in
patients ≤50 years)
●Prothrombin mutation 5 percent (6 percent in patients ≤50 years)

The posttest probabilities of these abnormalities increased with increasing pretest

probability and features of the patients' history and clinical presentation.

In the absence of definitive data, it is my practice to obtain testing for hypercoagulable

conditions in patients who have:

●A personal or family history of systemic thromboses

●No clear etiology for ischemic stroke or transient ischemic attack (TIA), despite
cardiac and vascular imaging, especially when involving young patients
●Clinical findings that suggest systemic lupus erythematosus or the
antiphospholipid antibody syndrome
Antiphospholipid antibodies — The role of antiphospholipid antibodies (aPL) in the
pathogenesis of ischemic stroke remains unclear. Transient elevations of aPL or lupus
anticoagulants can be seen in the setting of acute stroke. Thus, elevated levels may
simply be a sequel to stroke and not related to its cause. On the other hand, aPL may
be associated with thrombosis or a cardiac valve abnormality that is the cause of stroke.
The evidence is conflicting as to how to interpret positive aPL assays among the full
complement of ischemic stroke patients, as illustrated by the following reports [51,52]:
●A large, prospective, cohort study (APASS) of 1770 patients with ischemic stroke
found that the presence of aPL, either LA or aCL, did not predict increased risk for
subsequent vascular ischemic events, including ischemic stroke; did not confer
increased risk for subgroups of patients younger than 55 years or those with
cryptogenic stroke; and did not predict a differential response
to aspirin or warfarin therapy [51]. A small subgroup (120) positive for both LA and
ACL had a tendency toward higher risk of vascular occlusive events at two years
than those without aPL (31.7 versus 24 percent). (See "Clinical manifestations of
antiphospholipid syndrome", section on 'Neurologic involvement'.)
●In patients with systemic lupus erythematosus, one study found that the levels of
both aCL binding to beta 2 glycoprotein I, and anti-phosphatidylserine antibodies
binding to prothrombin were significantly higher in patients with a history of
cerebral infarction compared with those who had no history of cerebral infarction
[53]. Furthermore, lupus patients who were positive for both of these antibodies
had a 77 percent prevalence of cerebral infarction (odds ratio 30.0, 95% CI 11-86).
The presence of either antibody alone was not associated with a significantly
increased stroke risk.
●In 2712 women and 2262 men in the Framingham Heart Study cohort who were
free of stroke or TIA at the time of their baseline examination and were followed
for 11 years, elevated serum concentrations of ACL independently and
significantly predicted the risk of first ischemic stroke or TIA in women but not men
[52].

In the absence of definitive data, we recommend obtaining antiphospholipid antibody

testing in patients who have:

●A history of lupus or symptoms compatible with lupus

●Features that suggest the antiphospholipid syndrome such as miscarriages,
venous thrombosis, or migraine headaches
●Cryptogenic stroke or TIA at a young age
Others — Plasma fibrinogen levels are risk factors for coronary heart disease and
stroke [54,55]. However, the routine use of fibrinogen as a cardiovascular risk marker is
limited by measurement variability. If fibrinogen is used clinically, three measurements
should be obtained at each venipuncture and a minimum of two sets of fibrinogen
measurements are needed. An elevated fibrinogen concentration may make a
difference in the selection of cholesterol lowering medications in patients with
hyperlipidemia.

Other studies may include hemoglobin electrophoresis in patients suspected of having a

hemoglobinopathy, and an erythrocyte sedimentation rate, tests for Lyme disease,
syphilis, and HIV infection in selected patients.
EVALUATION OF PATIENTS WITH INTRACEREBRAL
HEMORRHAGE CT scans usually define the size and location of intracerebral
hemorrhage (ICH) and the presence of intraventricular blood [56]. Mass effect caused
by the intracerebral mass, shift of midline structures, herniation of brain contents from
one compartment to another, and the presence of hydrocephalus are also easily seen
on CT. MRI with echo-planar T2*-weighted (susceptibility) images can also show
hemorrhages soon after the onset of symptoms. Microbleeds (tiny older hemorrhages)
are shown using this technique and can be clues to the presence of cerebral amyloid
angiopathy. It is not necessary to perform both CT and MRI to exclude hemorrhage if
echo-planar MRI scanning is available. A detailed description of the MRI characteristics
of hyperacute ICH is found separately. (See "Spontaneous intracerebral hemorrhage:
Pathogenesis, clinical features, and diagnosis", section on 'Brain MRI'.)

Vascular malformations and brain tumor are better visualized on MRI. Echo-planar MRI
can also show old hemorrhages not visible on CT scans. The location and appearance
of the lesion as well as the history of the patient (eg, race, blood pressure, presence of
known bleeding disorder, use of drugs) help determine the choice of additional
diagnostic studies.

●Hypertensive ICH – No further diagnostic tests are necessary in the severely

hypertensive patient with a well circumscribed and homogeneous hematoma that
is located in a typical location for hypertensive ICH (eg, putamen/internal capsule,
caudate nucleus, thalamus, pons, or cerebellum); the clinician can be confident
that the patient has a hypertensive hemorrhage in this circumstance
(see "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and
diagnosis"). Similarly, a traumatic etiology can be diagnosed with confidence in
the patient who has had recent trauma and lesions in the appropriate location and
with the appearance of contusion and traumatic hemorrhages (eg, anterior and/or
orbital frontal lobes and temporal lobes at the surface).
●Bleeding disorder – Evaluation for a bleeding disorder (platelet count,
prothrombin time, international normalized ratio (INR), activated partial
thromboplastin time for all patients, and thrombin time and/or ecarin clotting time if
the patient is known or suspected to be taking a direct thrombin inhibitor or a
direct factor Xa inhibitor) should be performed in every patient with an intracranial
hemorrhage, especially if the cause is not immediately clear. A bleeding tendency
can cause or contribute to bleeding initiated by other etiologies. (See "Approach to
the adult with a suspected bleeding disorder".)
Iatrogenic prescription of anticoagulants is the most common bleeding disorder
contributing to brain hemorrhages. Oral anticoagulant-related intracerebral
hemorrhage is often lobar [57]. Compared with spontaneous intracerebral
hemorrhages, anticoagulant-related hemorrhages are larger and associated with
greater hematoma expansion and mortality [57,58]. (See "Risks and prevention of
bleeding with oral anticoagulants".)
●Lobar or atypical hemorrhage – Amyloid angiopathy, bleeding into a tumor,
and vascular malformations are likely etiologies of hemorrhages that are lobar or
atypical in appearance.
 •Cerebral amyloid angiopathy – Hemorrhages related to amyloid angiopathy
are usually lobar and have a predilection to cluster in posterior brain regions,
including the parietal and occipital lobes. The hemorrhages are usually multiple.
T2* weighted (susceptibility) MRI images may show the presence of old small
hemorrhages ("microbleeds"). Patients with amyloid angiopathy are typically
over the age of 60 years. (See "Cerebral amyloid angiopathy".)
•Vascular malformation or brain tumor – Other bleeding lesions should be
excluded in patients under the age of 60 if the blood pressure is not sufficiently
elevated to make a firm diagnosis of hypertensive lobar hemorrhage. A repeat
MRI after the blood has been reabsorbed (four to eight weeks) may show
residual vascular malformations or a brain tumor. Vascular imaging using CT
angiography (CTA) or MR angiography (MRA) of the intracranial circulation is
useful as a screening test for vascular malformations and aneurysms. Contrast
angiography by arterial catheterization may be necessary in patients with a
CTA or MRA suggestive of vascular malformation. (See "Vascular
malformations of the central nervous system" and "Brain arteriovenous
malformations".)
•Cocaine use – Patients with intracerebral hemorrhage after cocaine use (but
not amphetamines) have a relatively high incidence of underlying aneurysms
and vascular malformations. They require vascular imaging tests (eg, CTA,
MRA, and/or conventional angiography).
SUMMARY AND RECOMMENDATIONS
●Cerebrovascular disease is caused by one of several pathophysiologic processes
(table 1 and table 2) involving the blood vessels of the brain.
(See 'Classification' above.)
●Sudden loss of focal brain function is the core feature of the onset of ischemic
stroke. However, patients with conditions other than stroke can present in a similar
fashion (table 3). The initial evaluation requires a rapid but broad assessment to
stabilize vital signs, determine if intracranial hemorrhage is present, and decide if
reperfusion therapy with intravenous thrombolysis (table 4) or mechanical
thrombectomy is warranted for patients with ischemic stroke. (See 'Initial general
assessment' above and 'Is the patient a candidate for reperfusion?' above.)
●After completing the initial assessment, the goal of the subsequent evaluation is
to determine the underlying pathophysiology of the stroke based upon the history,
physical examination, and initial neuroimaging study (table 1). Certain
constellations of symptoms and signs can suggest a specific ischemic process
(table 5). (See 'Determining a presumptive diagnosis of stroke subtype' above.)
●Confirming the precise pathophysiologic process is aided by more directed
diagnostic testing, including cardiac studies and neurovascular imaging.
(See 'Confirming the diagnosis' above.)
●Cardiac monitoring for at least the first 24 hours after the onset of ischemic stroke
is useful to look for arrhythmias. For patients with a cryptogenic ischemic stroke or
transient ischemic attack (TIA) and no evidence of atrial fibrillation on
electrocardiogram (ECG) and 24-hour cardiac monitoring, we suggest ambulatory
cardiac monitoring for several weeks. All patients with suspected embolic stroke
 should have an echocardiogram. (See 'Cardiac evaluation' above
and 'Echocardiography' above.)
●A number of blood tests are indicated in patients with brain ischemia, including a
complete blood count, platelet count, prothrombin time and partial thromboplastin
time, and serum lipids. However, indications to test for hypercoagulable disorders
are limited. Furthermore, it remains unclear if the inherited thrombophilias directly
predispose to arterial stroke as they do to venous thrombosis. (See 'Blood
tests' above.)
●Evaluation for a bleeding disorder (platelet count, prothrombin time, activated
partial thromboplastin time for all patients, and thrombin time and/or ecarin clotting
time if the patient is known or suspected to be taking a direct thrombin inhibitor or
a direct factor Xa inhibitor) should be performed in every patient with an
intracranial hemorrhage. (See 'Evaluation of patients with intracerebral
hemorrhage' above.)

Pathophysiologic ischemic stroke classification

Large vessel atherothrombotic stroke

More common

Bifurcation of the common carotid artery

Siphon portion of the common carotid artery

Middle cerebral artery stem

Intracranial vertebral arteries proximal to middle basilar artery

Origin of the vertebral arteries

Less common

Origin of the common carotid artery

Posterior cerebral artery stem

Origin of the major branches of the basilar-vertebral arteries

Origin of the branches of the anterior, middle, and posterior cerebral arteries

Small vessel (lacunar) stroke

Mechanism

Lipohyalinotic occlusion
 Less frequently proximal atherothrombotic occlusion

Least likely embolic occlusion

Most common locations

Penetrating branches of the anterior, middle, and posterior cerebral and basilar arteries

Cardioaortic embolic stroke

Cardiac sources definite - antithrombotic therapy generally used

Left atrial thrombus

Left ventricular thrombus

Atrial fibrillation and paroxysmal atrial fibrillation

Sustained atrial flutter

Recent myocardial infarction (within one month)

Rheumatic mitral or aortic valve disease

Bioprosthetic and mechanical heart valve

Chronic myocardial infarction with ejection fraction <28 percent

Symptomatic heart failure with ejection fraction <30 percent

Dilated cardiomyopathy

Cardiac sources definite - anticoagulation hazardous

Bacterial endocarditis (exception nonbacterial)

Atrial myxoma

Cardiac sources possible

Mitral annular calcification

Patent foramen ovale

Atrial septal aneurysm

Atrial septal aneurysm with patent foramen ovale

 Left ventricular aneurysm without thrombus

Isolated left atrial spontaneous echo contrast ("smoke") without mitral stenosis or atrial fibrillation

Mitral valve strands

Ascending aortic atheromatous disease (>4 mm)

True unknown source embolic stroke

Other

Dissection

Moyamoya

Binswanger's disease

Primary thrombosis

Cerebral mass
Graphic 55099 Version 4.0
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Characteristics of stroke subtypes

Stroke type Clinical course Risk factors Other clues

Intracerebral Gradual onset and progression
hemorrhage during minutes or hours in
most patients, but may present
abruptly with maximal deficit
at onset.
Hypertension, trauma, bleeding diatheses, May be precipitated
illicit drugs (eg, amphetamines, cocaine), by sex or other
vascular malformations. More common in physical activity.
Black people and Asian people than in Patient may have
White people. reduced alertness.

Subarachnoid Abrupt onset of sudden,
hemorrhage severe headache. Focal brain
dysfunction less common than
with other types.
Smoking, hypertension, moderate to heavy May be precipitated
alcohol use, genetic susceptibility (eg, by sex or other
polycystic kidney disease, family history physical activity.
of subarachnoid hemorrhage) and Patient may have
sympathomimetic drugs (eg, cocaine) reduced alertness.

Ischemic Stuttering progression with Atherosclerotic risk factors (age, smoking, May have neck
(thrombotic) periods of improvement. diabetes mellitus, etc). Males affected bruit.
Lacunes develop over hours more commonly than females. May have
 or at most a few days; large history of TIA.
artery ischemia may evolve
over longer periods.

Ischemic Sudden onset with deficit Atherosclerotic risk factors as listed above. Can be precipitated
(embolic) maximal at onset. Clinical Males affected more commonly than by getting up at
findings may improve females. History of heart disease (valvular, night to urinate or
quickly. atrial fibrillation, endocarditis). sudden coughing or
sneezing.

Etiology, classification, and epidemiology of stroke

Author:
Louis R Caplan, MD
Section Editor:
Scott E Kasner, MD
Deputy Editor:
John F Dashe, MD, PhD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2021. | This topic last updated: Oct 06, 2021.
INTRODUCTION The two broad categories of stroke, hemorrhage and ischemia, are
diametrically opposite conditions: hemorrhage is characterized by too much blood within
the closed cranial cavity, while ischemia is characterized by too little blood to supply an
adequate amount of oxygen and nutrients to a part of the brain [1].
Each of these categories can be divided into subtypes that have somewhat different
causes, clinical pictures, clinical courses, outcomes, and treatment strategies. As an
example, intracranial hemorrhage can be caused by intracerebral hemorrhage (ICH,
also called parenchymal hemorrhage), which involves bleeding directly into brain tissue,
and subarachnoid hemorrhage (SAH), which involves bleeding into the cerebrospinal
fluid that surrounds the brain and spinal cord [1].
This topic will review the classification of stroke. The clinical diagnosis of stroke
subtypes and an overview of stroke evaluation are discussed separately. (See "Clinical
diagnosis of stroke subtypes" and "Overview of the evaluation of stroke".)
DEFINITIONS Stroke is classified into two major types:
●Brain ischemia due to thrombosis, embolism, or systemic hypoperfusion
●Brain hemorrhage due to intracerebral hemorrhage (ICH) or subarachnoid
hemorrhage (SAH)

A stroke is the acute neurologic injury that occurs as a result of one of these pathologic
processes. Approximately 80 percent of strokes are due to ischemic cerebral infarction
and 20 percent to brain hemorrhage.
An infarcted brain is pale initially. Within hours to days, the gray matter becomes
congested with engorged, dilated blood vessels and minute petechial hemorrhages.
When an embolus blocking a major vessel migrates, lyses, or disperses within minutes
to days, recirculation into the infarcted area can cause a hemorrhagic infarction and
may aggravate edema formation due to disruption of the blood-brain barrier.

A primary ICH damages the brain directly at the site of the hemorrhage by compressing
the surrounding tissue. Physicians must initially consider whether the patient with
suspected cerebrovascular disease is experiencing symptoms and signs suggestive of
ischemia or hemorrhage.

The great majority of ischemic strokes are caused by a diminished supply of arterial
blood, which carries sugar and oxygen to brain tissue. Another cause of stroke that is
difficult to classify is stroke due to occlusion of veins that drain the brain of blood.
Venous occlusion causes a backup of fluid resulting in brain edema, and in addition it
may cause both brain ischemia and hemorrhage into the brain.

BRAIN ISCHEMIA There are three main subtypes of brain ischemia [2]:
●Thrombosis (see 'Thrombosis' below) generally refers to local in situ obstruction
of an artery. The obstruction may be due to disease of the arterial wall, such as
arteriosclerosis, dissection, or fibromuscular dysplasia; there may or may not be
superimposed thrombosis.
●Embolism (see 'Embolism' below) refers to particles of debris originating
elsewhere that block arterial access to a particular brain region [3]. Since the
process is not local (as with thrombosis), local therapy only temporarily solves the
problem; further events may occur if the source of embolism is not identified and
treated.
●Systemic hypoperfusion (see 'Systemic hypoperfusion' below) is a more general
circulatory problem, manifesting itself in the brain and perhaps other organs.
Blood disorders (see 'Blood disorders' below) are an uncommon primary cause of
stroke. However, increased blood coagulability can result in thrombus formation and
subsequent cerebral embolism in the presence of an endothelial lesion located in the
heart, aorta, or large arteries that supply the brain.
Transient ischemic attack (TIA) is defined clinically by the temporary nature of the
associated neurologic symptoms, which last less than 24 hours by the classic definition.
The definition is changing with recognition that transient neurologic symptoms are
frequently associated with permanent brain tissue injury. The definition of TIA is
discussed in more detail separately. (See "Definition, etiology, and clinical
manifestations of transient ischemic attack", section on 'Definition of TIA'.)
Thrombosis — Thrombotic strokes are those in which the pathologic process giving
rise to thrombus formation in an artery produces a stroke either by reduced blood flow
distally (low flow) or by an embolic fragment that breaks off and travels to a more distant
vessel (artery-to-artery embolism). Thrombotic strokes can be divided into either large
or small vessel disease (table 1). These two subtypes of thrombosis are worth
distinguishing since the causes, outcomes, and treatments are different.
Large vessel disease — Large vessels include both the extracranial (common and
internal carotids, vertebral) and intracranial arterial system (Circle of Willis and proximal
branches) (figure 1 and figure 2).

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
●Dissection
●Takayasu arteritis
●Giant cell arteritis
●Fibromuscular dysplasia

Pathologies affecting large intracranial vessels include:

●Atherosclerosis
●Dissection
●Arteritis/vasculitis
●Noninflammatory vasculopathy
●Moyamoya syndrome
●Vasoconstriction

Atherosclerosis is by far the most common cause of in situ local disease within the large
extracranial and intracranial arteries that supply the brain. White platelet-fibrin and red
erythrocyte-fibrin thrombi are often superimposed upon the atherosclerotic lesions, or
they may develop without severe vascular disease in patients with hypercoagulable
states. Vasoconstriction (eg, with migraine) is probably the next most common, followed
in frequency by arterial dissection (a disorder much more common than previously
recognized) and traumatic occlusion. Fibromuscular dysplasia is an uncommon
arteriopathy, while arteritis is frequently mentioned in the differential diagnosis, but it is
an extremely rare cause of thrombotic stroke.

Aortic disease is really a form of proximal extracranial large vessel disease, but it is
often considered together with cardioembolic sources because of anatomic proximity.
(See 'Aortic atherosclerosis' below.)
Identification of the specific focal vascular lesion, including its nature, severity, and
localization, is important for treatment since local therapy may be effective (eg, surgery,
angioplasty, intraarterial thrombolysis). It should be possible clinically in most patients to
determine whether the local vascular disease is within the anterior (carotid) or posterior
(vertebrobasilar) circulation and whether the disorder affects large or penetrating
arteries. (See "Clinical diagnosis of stroke subtypes", section on 'Neurologic
examination'.)
Delivery of adequate blood through a blocked or partially blocked artery depends upon
many factors, including blood pressure, blood viscosity, and collateral flow. Local
vascular lesions also may throw off emboli, which can cause transient symptoms. In
patients with thrombosis, the neurologic symptoms often fluctuate, remit, or progress in
a stuttering fashion (figure 3). (See "Clinical diagnosis of stroke subtypes", section on
'Clinical course' and "Definition, etiology, and clinical manifestations of transient
ischemic attack", section on 'Mechanisms and clinical manifestations'.)
Small vessel disease — Small vessel disease affects the intracerebral arterial system,
specifically penetrating arteries that arise from the distal vertebral artery, the basilar
artery, the middle cerebral artery stem, and the arteries of the circle of Willis. These
arteries thrombose due to:
●Lipohyalinosis (a lipid hyaline build-up distally secondary to hypertension) and
fibrinoid degeneration
●Atheroma formation at their origin or in the parent large artery
The most common cause of obstruction of the smaller arteries and arterioles that
penetrate at right angles to supply the deeper structures within the brain (eg, basal
ganglia, internal capsule, thalamus, pons) is lipohyalinosis (ie, blockage of an artery by
medial hypertrophy and lipid admixed with fibrinoid material in the hypertrophied arterial
wall). A stroke due to obstruction of these vessels is referred to as a lacunar stroke
(see "Lacunar infarcts"). Lipohyalinosis is most often related to hypertension, but aging
may play a role.
Microatheromas can also block these small penetrating arteries, as can plaques within
the larger arteries that block or extend into the orifices of the branches (called
atheromatous branch disease) [1].
Penetrating artery occlusions usually cause symptoms that develop during a short
period of time, hours or at most a few days (figure 4), compared with large artery-related
brain ischemia, which can evolve over a longer period.
Embolism — Embolic strokes are divided into four categories (table 1).
●Those with a known source that is cardiac
●Those with a possible cardiac or aortic source based upon transthoracic and/or
transesophageal echocardiographic findings
●Those with an arterial source (artery to artery embolism)
●Those with a truly unknown source in which tests for embolic sources are
negative
The symptoms depend upon the region of brain rendered ischemic [4,5]. The embolus
suddenly blocks the recipient site so that the onset of symptoms is abrupt and usually
maximal at the start (figure 5). Unlike thrombosis, multiple sites within different vascular
territories may be affected when the source is the heart (eg, left atrial appendage or left
ventricular thrombus) or aorta. Treatment will depend upon the source and composition
of the embolus. (See "Secondary prevention for specific causes of ischemic stroke and
transient ischemic attack".)

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. When this occurs, infarction
generally also occurs but is silent; the area of infarction is smaller than the area of
ischemia that gave rise to the symptoms. This process is often referred to as a TIA due
to embolism, although it is more correctly termed an embolic infarction or stroke in
which the symptoms clear within 24 hours.

Cardioembolic strokes can be divided into those with a known source and those with a
possible cardiac or ascending aortic source based upon transthoracic and/or
transesophageal echocardiographic findings [3].
High-risk cardiac source — The diagnosis of embolic strokes with a known cardiac
source is generally agreed upon by physicians (table 2) [6,7]; included in this category
are those due to:
●Atrial fibrillation and paroxysmal atrial fibrillation
●Rheumatic mitral or aortic valve disease
●Bioprosthetic and mechanical heart valves
●Atrial or ventricular thrombus
●Sinus node dysfunction
●Sustained atrial flutter
●Recent myocardial infarction (within one month)
●Chronic myocardial infarction together with ejection fraction <28 percent
●Symptomatic congestive heart failure with ejection fraction <30 percent
●Dilated cardiomyopathy
●Fibrous nonbacterial endocarditis as found in patients with systemic lupus (ie,
Libman-Sacks endocarditis), antiphospholipid syndrome, and cancer (marantic
endocarditis)
●Infective endocarditis
●Papillary fibroelastoma
●Left atrial myxoma
●Coronary artery bypass graft (CABG) surgery
With CABG, for example, the incidence of postoperative neurologic sequelae is
approximately 2 to 6 percent, most of which is due to stroke [8]. Atheroemboli
associated with ascending aortic atherosclerosis is probably the most common cause.
(See "Neurologic complications of cardiac surgery".)
Potential cardiac source — Embolic strokes considered to have a potential cardiac
source (table 2) are ones in which a possible source is detected (usually) by
echocardiographic methods [6,7,9], including:
●Mitral annular calcification
●Patent foramen ovale
●Atrial septal aneurysm
●Atrial septal aneurysm with patent foramen ovale
●Atrial cardiopathy (large or malfunctioning left atrium)
●Left ventricular aneurysm without thrombus
●Isolated left atrial smoke on echocardiography (no mitral stenosis or atrial
fibrillation)
●Complex atheroma in the ascending aorta or proximal arch (see 'Aortic
atherosclerosis' below)
In this group, the association of the cardiac or aortic lesion and the rate of embolism is
often uncertain, since some of these lesions do not have a high frequency of embolism
and are often incidental findings unrelated to the stroke event [10]. Thus, they are
considered potential sources of embolism. A truly unknown source represents embolic
strokes in which no clinical evidence of heart disease is present (table 1).
Aortic atherosclerosis — In longitudinal population studies with nonselected patients,
complex aortic atherosclerosis does not appear to be associated with any increased
primary ischemic stroke risk [11-13]. However, most studies evaluating secondary
stroke risk have found that complex aortic atherosclerosis is a risk factor for recurrent
stroke [14-17].

The range of findings is illustrated by the following studies:

●A prospective case-control study examined the frequency and thickness of

atherosclerotic plaques in the ascending aorta and proximal arch in 250 patients
admitted to the hospital with ischemic stroke and 250 consecutive controls, all
over the age of 60 years [15]. Atherosclerotic plaques ≥4 mm in thickness were
found in 14 percent of patients compared with 2 percent of controls, and the odds
ratio for ischemic stroke among patients with such plaques was 9.1 after
adjustment for atherosclerotic risk factors. In addition, aortic atherosclerotic
plaques ≥4 mm were much more common in patients with brain infarcts of
unknown cause (relative risk 4.7).
●In contrast, a population-based study of 1135 subjects who had transesophageal
echocardiography (TEE) found that complex atherosclerotic plaque (>4 mm with
or without mobile debris) in the ascending and transverse aortic arch was not a
significant risk factor for cryptogenic ischemic stroke or TIA after adjusting for age,
sex, and other clinical risk factors [12]. However, there was an association
between complex aortic plaque and noncryptogenic stroke. The investigators
concluded that complex aortic arch debris is a marker for the presence of
generalized atherosclerosis.

Methodologic differences are a potential explanation for the discrepant results of these
reports assessing the risk of ischemic stroke related to aortic atherosclerosis, as the
earlier case-control studies may have been skewed by selection and referral bias.
However, many patients with aortic atherosclerosis also have cardiac or large artery
lesions, a problem that may confound purely epidemiologic studies.

In the author's opinion, there is no question that large protruding plaques in the
ascending aorta and arch, particularly mobile plaques, are an important cause of stroke
[18].
Systemic hypoperfusion — Reduced blood flow 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 borderzone 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").

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 [10]. 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. (See "Cerebral venous thrombosis:
Etiology, clinical features, and diagnosis".)

Infectious and inflammatory disease such as pneumonia, urinary tract infections, Crohn
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.

TOAST classification — The TOAST classification scheme for ischemic stroke is

widely used and has good interobserver agreement [19]. The TOAST system (table 3)
attempts to classify ischemic strokes according to the major pathophysiologic
mechanisms that are recognized as the cause of most ischemic strokes (table 1). It
assigns ischemic strokes to five subtypes based upon clinical features and the results of
ancillary studies including brain imaging, neurovascular evaluations, cardiac tests, and
laboratory evaluations for a prothrombotic state.

The five TOAST subtypes of ischemic stroke are:

●Large artery atherosclerosis

 ●Cardioembolism
●Small vessel occlusion
●Stroke of other determined etiology
●Stroke of undetermined etiology
The last subtype, stroke of undetermined etiology, involves cases where the cause of a
stroke cannot be determined with any degree of confidence, and by definition includes
those with two or more potential causes identified, those with a negative evaluation, and
those with an incomplete evaluation. (See "Cryptogenic stroke".)
SSS-TOAST and CCS classification — Since the original TOAST classification
scheme was developed in the early 1990s, advances in stroke evaluation and
diagnostic imaging have allowed more frequent identification of potential vascular and
cardiac causes of stroke [6]. These advances could cause an increasing proportion of
ischemic strokes to be classified as "undetermined" if the strict definition of this category
(cases with two or more potential causes) is applied.
As a result, an evidenced-based modification of the TOAST criteria called SSS-TOAST
was developed [6]. The SSS-TOAST system divides each of the original TOAST
subtypes into three subcategories as "evident," "probable," or "possible" based upon the
weight of diagnostic evidence as determined by predefined clinical and imaging criteria.
In a further refinement, an automated version of the SSS-TOAST called the Causative
Classification System (CCS) was devised (table 4) to improve its usefulness and
accuracy for stroke subtyping [20]. The CCS is a computerized algorithm that consists
of questionnaire-style classification scheme. The CCS appears to have good inter-rater
reliability among multiple centers [21]. It is available online
at https://ccs.mgh.harvard.edu/ccs_title.php.
The overall agreement between the original TOAST and CCS classification systems
appears to be moderate at best, suggesting that two methods often classify stroke
cases into different categories despite having categories with similar names [22].
BRAIN HEMORRHAGE There are two main subtypes of brain hemorrhage [2]:
●Intracerebral hemorrhage (ICH) refers to bleeding directly into the brain
parenchyma
●Subarachnoid hemorrhage (SAH) refers to bleeding into the cerebrospinal fluid
within the subarachnoid space that surrounds the brain
Intracerebral hemorrhage — Bleeding in ICH is usually derived from arterioles or
small arteries. The bleeding is directly into the brain, forming a localized hematoma that
spreads along white matter pathways. Accumulation of blood occurs over minutes or
hours; the hematoma gradually enlarges by adding blood at its periphery like a snowball
rolling downhill. The hematoma continues to grow until the pressure surrounding it
increases enough to limit its spread or until the hemorrhage decompresses itself by
emptying into the ventricular system or into the cerebrospinal fluid (CSF) on the pial
surface of the brain [23,24].
The most common causes of ICH are hypertension, trauma, bleeding diatheses,
amyloid angiopathy, illicit drug use (mostly amphetamines and cocaine), and vascular
malformations [23,24] (see "Spontaneous intracerebral hemorrhage: Pathogenesis,
clinical features, and diagnosis"). Less frequent causes include bleeding into tumors,
aneurysmal rupture, and vasculitis.
The earliest symptoms of ICH relate to dysfunction of the portion of the brain that
contains the hemorrhage [23,24]. As examples:
●Bleeding into the right putamen and internal capsule region causes left limb
motor and/or sensory signs
●Bleeding into the cerebellum causes difficulty walking
●Bleeding into the left temporal lobe presents as aphasia
The neurologic symptoms usually increase gradually over minutes or a few hours. In
contrast to brain embolism and SAH, the neurologic symptoms related to ICH may not
begin abruptly and are not maximal at onset (figure 6) (and see below).
Headache, vomiting, and a decreased level of consciousness develop if the hematoma
becomes large enough to increase intracranial pressure or cause shifts in intracranial
contents (figure 7) [23,24]. These symptoms are absent with small hemorrhages; the
clinical presentation in this setting is that of a gradually progressing stroke.

ICH destroys brain tissue as it enlarges. The pressure created by blood and
surrounding brain edema is life threatening; large hematomas have a high mortality and
morbidity. The goal of treatment is to contain and limit the bleeding. Recurrences are
unusual if the causative disorder is controlled (eg, hypertension or bleeding diathesis).

Subarachnoid hemorrhage — The two major causes of SAH are rupture of arterial
aneurysms that lie at the base of the brain and bleeding from vascular malformations
that lie near the pial surface. Bleeding diatheses, trauma, amyloid angiopathy, and illicit
drug use are less common. (See "Aneurysmal subarachnoid hemorrhage: Clinical
manifestations and diagnosis".)

Rupture of an aneurysm releases blood directly into the CSF under arterial pressure.
The blood spreads quickly within the CSF, rapidly increasing intracranial pressure.
Death or deep coma ensues if the bleeding continues. The bleeding usually lasts only a
few seconds but rebleeding is very common. With causes of SAH other than aneurysm
rupture, the bleeding is less abrupt and may continue over a longer period of time.

Symptoms of SAH begin abruptly in contrast to the more gradual onset of ICH. The
sudden increase in pressure causes a cessation of activity (eg, loss of memory or focus
or knees buckling). Headache is an invariable symptom and is typically instantly severe
and widespread; the pain may radiate into the neck or even down the back into the legs.
Vomiting occurs soon after onset. There are usually no important focal neurologic signs
unless bleeding occurs into the brain and CSF at the same time (meningocerebral
hemorrhage). Onset headache is more common than in ICH, and the combination of
onset headache and vomiting is infrequent in ischemic stroke (figure 7) [25].
(See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)
Approximately 30 percent of patients have a minor hemorrhage manifested only by
sudden and severe headache (the so-called sentinel headache) that precedes a major
SAH (figure 7) [25]. The complaint of the sudden onset of severe headache is
sufficiently characteristic that SAH should always be considered. In a prospective study
of 148 patients presenting with sudden and severe headache, for example, SAH was
present in 25 percent overall and 12 percent in patients in whom headache was the only
symptom [26].
The goal of treatment of SAH is to identify the cause and quickly treat it to prevent
rebleeding. The other goal of treatment is to prevent brain damage due to delayed
ischemia related to vasoconstriction of intracranial arteries; blood within the CSF
induces vasoconstriction, which can be intense and severe. The treatment of SAH is
discussed separately. (See "Aneurysmal subarachnoid hemorrhage: Treatment and
prognosis".)
EPIDEMIOLOGY Globally, ischemia accounts for 62 percent, intracerebral
hemorrhage 28 percent, and subarachnoid hemorrhage 10 percent of all incident
strokes, reflecting a higher incidence of hemorrhagic stroke in low- and middle-income
countries [27,28]. In the United States, the proportion of all strokes due to ischemia,
intracerebral hemorrhage, and subarachnoid hemorrhage is 87, 10, and 3 percent,
respectively [29].
The lifetime risk of stroke for adult men and women (25 years of age and older) is
approximately 25 percent [30]. The highest risk of stroke is found in East Asia, Central
Europe, and Eastern Europe. Worldwide, stroke is the second most common cause of
mortality and the second most common cause of disability [31]. In China, which has the
greatest burden of stroke in the world, the age-standardized prevalence, incidence, and
mortality rates are estimated to be 1115, 247, and 115 per 100,000 person-years,
respectively [32]. These data suggest that the stroke prevalence in China is relatively
low compared with the prevalence in high-income countries, but the stroke incidence
and mortality rates in China are among the highest in the world. While the incidence of
stroke is decreasing in high-income countries, including the United States [33-35], the
incidence is increasing in low-income countries [36]. The overall rate of stroke-related
mortality is decreasing in high and low income countries, but the absolute number of
people with stroke, stroke survivors, stroke-related deaths, and the global burden of
stroke-related disability is high and increasing [37].
In the United States, the annual incidence of new or recurrent stroke is about 795,000,
of which about 610,000 are first-ever strokes, and 185,000 are recurrent strokes [29].
There is a higher regional incidence and prevalence of stroke and a higher stroke
mortality rate in the southeastern United States (sometimes referred to as the "stroke
belt") than in the rest of the country [38-42].
Men have a higher incidence of stroke than women at younger but not older ages [29].

Black and Hispanic Americans have an increased risk of stroke compared with White
Americans, as illustrated by the following observations:

●The Northern Manhattan Study reported that the age-adjusted incidence of first
ischemic stroke among White, Hispanic, and Black Americans was 88, 149, and
191 per 100,000 respectively [43]. Among Black compared with White Americans,
the relative rate of stroke attributed to intracranial atherosclerosis, extracranial
atherosclerosis, lacunes, and cardioembolism was 5.85, 3.18, 3.09, and 1.58
respectively. Among Hispanic compared with White Americans, the relative rate of
stroke attributed to intracranial atherosclerosis, extracranial atherosclerosis,
lacunes, and cardioembolism was 5.00, 1.71, 2.32, and 1.42.
●The Greater Cincinnati/Northern Kentucky Stroke Study showed that small vessel
strokes and strokes of undetermined origin were nearly twice as common, and
 large vessel strokes were 40 percent more common, among Black compared with
White patients [44]. The incidence of cardioembolic strokes was not significantly
different.
●An increased incidence of stroke has also been found among Mexican
Americans compared with non-Hispanic White Americans [45].

Initial assessment and management of acute stroke

Authors:
Jamary Oliveira-Filho, MD, MS, PhD
Michael T Mullen, MD
Section Editors:
Scott E Kasner, MD
Jonathan A Edlow, MD, FACEP
Deputy Editor:
John F Dashe, MD, PhD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2021. | This topic last updated: Mar 05, 2021.
INTRODUCTION The subacute and long-term assessment and management of
patients who have suffered a stroke includes physical therapy and testing to determine
the precise etiology of the event so as to prevent recurrence. The acute management
differs. Immediate goals include minimizing brain injury, treating medical complications,
and moving toward uncovering the pathophysiologic basis of the patient's symptoms.
Patient assessment and management during the acute phase (first few hours) of an
ischemic stroke will be reviewed here. Use of thrombolytic therapy, endovascular
thrombectomy, treatment of patients not eligible for reperfusion therapy, the clinical
diagnosis of various types of stroke, and the subacute and long-term assessment of
patients who have had a stroke are discussed separately. (See "Approach to
reperfusion therapy for acute ischemic stroke" and "Early antithrombotic treatment of
acute ischemic stroke and transient ischemic attack" and "Clinical diagnosis of stroke
subtypes" and "Overview of the evaluation of stroke".)
INITIAL ASSESSMENT Sudden loss of focal brain function is the core feature of
the onset of ischemic stroke. However, patients with conditions other than brain
ischemia may present in a similar fashion (table 1). (See "Differential diagnosis of
transient ischemic attack and acute stroke".)

In addition, patients suffering a stroke may present with other serious medical
conditions. Thus, the initial evaluation requires a rapid but broad assessment.

The goals in the initial phase include:

●Ensuring medical stability, with particular attention to airway, breathing, and

circulation
●Quickly reversing any conditions that are contributing to the patient's problem
●Determining if patients with acute ischemic stroke are candidates for intravenous
thrombolytic therapy (table 2) or endovascular thrombectomy (see "Approach to
reperfusion therapy for acute ischemic stroke")
 ●Moving toward uncovering the pathophysiologic basis of the patient's neurologic
symptoms
Time is of the essence in the hyperacute evaluation of stroke patients. The history,
physical examination, serum glucose, oxygen saturation, and a noncontrast computed
tomography (CT) scan are sufficient in most cases to guide acute therapy
(see 'Immediate laboratory studies' below). Other tests are considered based upon
individual patient characteristics, but the absence or unavailability of any additional tests
need not be a reason to delay therapy if otherwise indicated.
Airway, breathing and circulation — Assessing vital signs and ensuring stabilization
of airway, breathing, and circulation is part of the initial evaluation of all patients with
critical illness, including those with stroke [1]. Patients with decreased consciousness or
bulbar dysfunction may be unable to protect their airway, and those with increased
intracranial pressure due to hemorrhage, vertebrobasilar ischemia, or bihemispheric
ischemia can present with vomiting, decreased respiratory drive, or muscular airway
obstruction. Hypoventilation, with a resulting increase in carbon dioxide, may lead to
cerebral vasodilation and elevate intracranial pressure.
In these cases, intubation may be necessary to restore adequate ventilation and to
protect the airway from aspiration. Patients with adequate ventilation should have the
oxygen saturation monitored. Patients who are hypoxic should receive supplemental
oxygen to maintain oxygen saturation >94 percent [1]. Supplemental oxygen should not
routinely be given to nonhypoxic patients with acute ischemic stroke.
History and physical — Establishing the time of ischemic stroke symptom onset is
critical because it is the main determinant of eligibility for treatment with intravenous
thrombolysis (table 2) and endovascular thrombectomy [2]. For patients who are unable
to provide a reliable onset time, symptom onset is defined as the time the patient was
last known to be normal or at baseline neurologic status [1]. At times, information from
family members, co-workers, or paramedics (who interviewed witnesses to the onset)
may establish the time the patient was last known to be normal. For patients presenting
within the therapeutic window for intravenous thrombolysis (less than 4.5 hours from
symptom onset) or mechanical thrombectomy (less than 24 hours from symptom onset),
the history needs to be accurate but rapid; contraindications to thrombolytic treatment
should also be assessed (table 2). (See "Approach to reperfusion therapy for acute
ischemic stroke", section on 'Rapid evaluation'.)
The history and physical examination should be used to distinguish between other
disorders in the differential diagnosis of brain ischemia (table 1). As examples, seizures,
syncope, migraine, hypoglycemia (see 'Hypoglycemia' below), hyperglycemia, or drug
toxicity can mimic acute ischemia [1]. The most difficult cases involve patients with the
combination of focal signs and altered level of consciousness. It is important to ask the
patient, relative, or any reliable informant whether the patient takes insulin or oral
hypoglycemic agents, has a history of epilepsy, drug overdose or abuse, or recent
trauma. (See "Differential diagnosis of transient ischemic attack and acute stroke".)
Diagnosing an intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) as
soon as possible can be lifesaving [3,4]. The history may be helpful in this regard. The
presence of acute onset headache and vomiting favor the diagnosis of ICH or SAH
compared with a thromboembolic stroke (figure 1), while the abrupt onset of impaired
cerebral function without focal symptoms favors the diagnosis of SAH. Another
important element of the history is whether the patient takes anticoagulant drugs. Even
with these clues, diagnosing intracranial hemorrhage on clinical grounds is very
imprecise, so early neuroimaging with a CT or magnetic resonance imaging (MRI) scan
is critical. CT is preferred at most centers, as it can be obtained very rapidly and is
effective at distinguishing between ischemic and hemorrhagic stroke
(see "Neuroimaging of acute ischemic stroke"). It is important to assess and stabilize
vital physiologic functions before sending the patient for an imaging study.
The physical examination should include careful evaluation of the neck and retroorbital
regions for vascular bruits, and palpation of pulses in the neck, arms, and legs to
assess for their absence, asymmetry, or irregular rate. The heart should be auscultated
for murmurs (see "Auscultation of cardiac murmurs in adults"). The lungs should be
assessed for abnormal breath sounds, bronchospasm, fluid overload, or stridor.

The skin should be examined for signs of endocarditis, cholesterol emboli, purpura,
ecchymoses, or evidence of recent surgery or other invasive procedures, particularly if
reliable history is not forthcoming. The funduscopic examination may be helpful if there
are cholesterol emboli or papilledema. The head should be examined for signs of
trauma. A tongue laceration may suggest a seizure.

In cases where there is a report or suspicion of a fall, the neck should be immobilized
until evaluated radiographically for evidence of serious trauma. Examination of the
extremities is important to look for evidence of systemic arterial emboli, distal ischemic,
cellulitis, and deep vein thrombosis; the latter should raise the possibility that the patient
is receiving anticoagulant treatment.

Neurologic evaluation — Ischemia in different vascular territories presents with

specific syndromes (table 3). The history should focus upon the time of symptom onset,
the course of symptoms over time, possible embolic sources, possible recent trauma
(which could either represent a contraindication to intravenous thrombolysis or suggest
an arterial dissection as a cause), conditions in the differential diagnosis, and
concomitant diseases. (See "Clinical diagnosis of stroke subtypes".)
The neurologic examination should attempt to confirm the findings from the history and
provide a quantifiable examination for further assessment over time. Many scales are
available that provide a structured, quantifiable neurologic examination. One of the most
widely used and validated scales is the National Institutes of Health Stroke Scale
(NIHSS), composed of 11 items (table 4) adding up to a total score of 0 to 42 (calculator
1); defined cutpoints for mild, moderate, and severe stroke are not well established, but
cut-points of NIHSS score <5 for mild, 5 to 9 for moderate, and ≥10 for severe stroke
may be reasonable.
The three most predictive examination findings for the diagnosis of acute stroke are
facial paresis, arm drift/weakness, and abnormal speech (a combination of dysarthria
and language items derived from the NIHSS) [5,6]. The NIHSS score on admission has
been correlated to stroke outcome (table 5) [7,8], and its use is recommended for all
patients with suspected stroke [9]. The NIHSS does not capture all stroke-related
impairments, particularly with posterior circulation strokes. (See "Use and utility of
stroke scales and grading systems", section on 'NIHSS'.)
Immediate laboratory studies — Urgent brain imaging with CT or MRI is mandatory in
all patients with sudden neurologic deterioration or acute stroke.
(See 'Neuroimaging' below.)
All patients with suspected stroke should have the following studies urgently as part of
the acute stroke evaluation [1,3]:
●Noncontrast brain CT or brain MRI
●Finger stick blood glucose
●Oxygen saturation
Other immediate tests for the evaluation of ischemic and hemorrhagic stroke include the
following [1,3]:
●Electrocardiogram (this should not delay the noncontrast brain CT)
●Complete blood count including platelets
●Troponin
●Prothrombin time and international normalized ratio (INR)
●Activated partial thromboplastin time
●Ecarin clotting time, thrombin time, or appropriate direct factor Xa activity assay if
known or suspected that the patient is taking direct thrombin inhibitor or direct
factor Xa inhibitor and is a candidate for thrombolytic therapy with alteplase
However, thrombolytic therapy for acute ischemic stroke (see 'Acute therapy' below)
should not be delayed while awaiting the results of hematologic studies unless the
patient has received anticoagulants or there is suspicion of a bleeding abnormality or
thrombocytopenia. The only test that is mandatory before initiation of
intravenous alteplase is blood glucose [1].
The following laboratory studies may be appropriate in selected patients [1,3,4]
●Serum electrolytes, urea nitrogen, creatinine
●Liver function tests
●Toxicology screen
●Blood alcohol level
●Pregnancy test in women of childbearing potential
●Arterial blood gas if hypoxia is suspected
●Chest radiograph if lung disease is suspected
●Lumbar puncture if subarachnoid hemorrhage is suspected and head CT scan is
negative for blood; note that lumbar puncture will preclude administration of
intravenous alteplase (tPA), though tPA should not be given if there is suspicion
for subarachnoid hemorrhage as the cause of the symptoms
●Electroencephalogram if seizures are suspected
Chest radiography, urinalysis and blood cultures are indicated if fever is present. We
also suggest blood for type and cross match in case fresh frozen plasma is needed to
reverse a coagulopathy if ICH is present. (See "Spontaneous intracerebral hemorrhage:
Pathogenesis, clinical features, and diagnosis".)
In order to limit medication dosage errors, particularly with the use of alteplase, an
accurate body weight should be obtained early during the urgent evaluation [10].
Neuroimaging — In the evaluation of the acute stroke patient, imaging studies are
necessary to exclude hemorrhage as a cause of the deficit, and they are useful to
assess the degree of brain injury and to identify the vascular lesion responsible for the
ischemic deficit. Advanced CT and MRI technologies may be able to distinguish
between brain tissue that is irreversibly infarcted and that which is potentially
salvageable, thereby allowing better selection of patients who are likely to benefit from
therapy. This topic is discussed separately. (See "Neuroimaging of acute ischemic
stroke".)
Cardiac studies — Electrocardiography (ECG) is important for detecting signs of
concomitant acute cardiac ischemia. This test is particularly important in the setting of
stroke, as patients with ischemic stroke frequently harbor coronary artery disease but
may not be able to report chest pain.

Stroke alone can be associated with ECG changes. The sympathetic response to stroke
can lead to demand-induced myocardial ischemia. In large strokes, especially
subarachnoid hemorrhage, there are centrally mediated changes in the ECG.

The ECG and cardiac monitoring are important for the detection of chronic or
intermittent arrhythmias that predispose to embolic events (eg, atrial fibrillation) and for
detecting indirect evidence of atrial/ventricular enlargement that may predispose to
thrombus formation. Current guidelines recommend cardiac monitoring for at least the
first 24 hours after the onset of ischemic stroke to look for atrial fibrillation (AF) or atrial
flutter [1]. However, paroxysmal AF may be undetected on standard cardiac monitoring
such as continuous telemetry and 24- or 48-hour Holter monitors. Extended cardiac
event monitoring for patients with ischemic stroke or transient ischemic attack (TIA) who
present with sinus rhythm can significantly increase the detection of occult AF. Such
monitoring may reduce the risk of recurrent ischemic stroke by prompting the
appropriate use of long-term anticoagulation. The optimal monitoring method –
continuous telemetry, ambulatory electrocardiography, serial electrocardiography,
transtelephonic ECG monitoring, or insertable cardiac monitors (ICMs; also sometimes
referred to as implantable cardiac monitor or implantable loop recorder) – is uncertain,
though longer durations of monitoring are likely to obtain the highest diagnostic yield.
(See "Overview of the evaluation of stroke", section on 'Monitoring for subclinical atrial
fibrillation' and "Stroke in patients with atrial fibrillation", section on 'Long-term
anticoagulation'.)
Transthoracic and transesophageal echocardiography adequately detect cardiogenic
and aortic sources for cerebral embolism other than atrial fibrillation
(see "Echocardiography in detection of cardiac and aortic sources of systemic
embolism"). However, their use can be postponed to later in the hospitalization, when
the patient is in a more stable clinical condition. Exceptions include patients with a
moderate or high suspicion of endocarditis, where echocardiography may provide
confirmation of the diagnosis. (See "Clinical manifestations and evaluation of adults with
suspected left-sided native valve endocarditis", section on
'Echocardiography' and "Overview of the evaluation of stroke", section on 'Cardiac
evaluation'.)
STROKE MANAGEMENT ISSUES In addition to stabilization of airway,
breathing, and circulation, and rapid neurologic evaluation discussed above, early key
management issues that often arise in acute stroke include blood pressure control
(see 'Blood pressure management' below), fluid management (see 'Fluids' below),
treatment of abnormal blood glucose levels (see 'Hypoglycemia' below
and 'Hyperglycemia' below), swallowing assessment (see 'Swallowing
assessment' below), and treatment of fever and infection (see 'Fever' below). Care in a
dedicated stroke unit (see 'Stroke unit care' below) is associated with better outcomes.
Fluids — Intravascular volume depletion is frequent in the setting of acute stroke,
particularly in older adult patients [11], and may worsen cerebral blood flow. For most
patients with acute stroke and volume depletion, isotonic saline without dextrose is the
agent of choice for intravascular fluid repletion and maintenance fluid therapy [12]. In
general, it is best to avoid excess free water (eg, as in ½ isotonic saline) because
hypotonic fluids may exacerbate cerebral edema in acute stroke and are less useful
than isotonic solutions for replacing intravascular volume. In addition, it is best to avoid
fluids containing glucose, which may exacerbate hyperglycemia. However, fluid
management must be individualized based on cardiovascular status, electrolyte
disturbances, and other conditions that may perturb fluid balance. (See "Maintenance
and replacement fluid therapy in adults".)
In particular, hyponatremia following subarachnoid hemorrhage may be due to
inappropriate secretion of antidiuretic hormone (SIADH) or rarely, to cerebral salt
wasting; these are physiologically distinct and are treated differently, as discussed
separately. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis",
section on 'Hyponatremia'.)
Hypoglycemia — Hypoglycemia can cause focal neurologic deficits mimicking stroke,
and severe hypoglycemia alone can cause neuronal injury. It is important to check the
blood sugar and rapidly correct low serum glucose (<60 mg/dL [3.3 mmol/L]) at the first
opportunity [1].
Hyperglycemia — Hyperglycemia, generally defined as a blood glucose level >126
mg/dL (>7.0 mmol/L), is common in patients with acute stroke and is associated with
poor functional outcome [13-18]. In a series of 59 patients with acute ischemic stroke,
admission hyperglycemia was present in 32 percent of patients without diabetes and 81
percent of patients with diabetes [19]. Stress hyperglycemia may be the most common
cause [15], although newly diagnosed diabetes is also important [16]. Hyperglycemia
may augment brain injury by several mechanisms, including increased tissue acidosis
from anaerobic metabolism, free radical generation, and increased blood brain barrier
permeability [20-22].
In light of these observations, it is reasonable to treat severe hyperglycemia in the
setting of acute stroke. The American Heart Association/American Stroke Association
guidelines for acute ischemic stroke recommend treatment for hyperglycemia to achieve
serum glucose concentrations in the range of 140 to 180 mg/dL (7.8 to 10 mmol/L) [1].
The European Stroke Initiative guidelines recommend treatment for glucose >180
mg/dL (>10 mmol/L) [23].
Tighter control of glucose with intravenous insulin does not improve functional outcome
in patients with acute ischemic stroke. The multicenter SHINE trial randomly assigned
over 1100 adults with hyperglycemia and acute ischemic stroke to either intensive
treatment of hyperglycemia (continuous insulin infusion with a target blood glucose
concentration of 80 to 130 mg/dL) or standard treatment (subcutaneous insulin on a
sliding scale with a target glucose of 80 to 179 mg/dL) [24]. At 90 days, there was no
difference in the proportion of patients achieving a favorable functional outcome
between the intensive and standard treatment groups (20.5 versus 21.6 percent). In
addition, treatment withdrawal for hypoglycemia or other adverse events was more
common in the intensive treatment group (11.2 versus 3.2 percent). Similarly, a 2014
systematic review identified 11 controlled trials involving nearly over 1500 adults with
acute ischemic stroke who were randomly assigned to either intensively monitored
insulin infusion therapy or to usual care; there was no difference between the treatment
and control groups for the combined outcome of death or dependency, and no
difference between groups for the outcome of final neurologic deficit [25]. In addition,
the intervention group had a higher rate of symptomatic hypoglycemia.
Swallowing assessment — Dysphagia is common after stroke and is a major risk
factor for developing aspiration pneumonia. It is important to assess swallowing function
prior to administering oral medications or food. Thus, prevention of aspiration in patients
with acute stroke includes initial nulla per os (NPO) status until swallowing function is
evaluated. (See "Complications of stroke: An overview", section on 'Dysphagia'.)
Note that aspirin, if and when indicated, can be given rectally.
Head and body position — During the acute phase of stroke, the position of the
patient and the head of bed should be individualized with respect to the risk of elevated
intracranial pressure and aspiration, and the presence of comorbid cardiopulmonary
disease [26]. We recommend keeping the head in neutral alignment with the body and
elevating the head of the bed to 30 degrees for patients in the acute phase of stroke
who are at risk for any of the following problems:
●Elevated intracranial pressure (ie, intracerebral hemorrhage, cerebral edema >24
hours from stroke onset in patients with large ischemic infarction)
●Aspiration (eg, those with dysphagia and/or diminished consciousness)
●Cardiopulmonary decompensation or oxygen desaturation (eg, those with chronic
cardiac and pulmonary disease)

In the absence of these problems, we suggest keeping the head of bed in the position
that is most comfortable for the patient. In addition, a cervical collar or a central
intravenous line dressings, if present, should be loose enough so that they do not
occlude venous outflow from the head.

A number of reports suggest that cerebral perfusion is maximal when patients are in the
horizontal position [27-29]. As an example, in a study involving 20 patients with
moderately severe ischemic stroke in the middle cerebral artery (MCA) territory, mean
flow velocity in the MCA measured by transcranial Doppler increased by an average of
20 percent when the head-of-bed elevation decreased from 30 to 0 degrees, and by an
average of 12 percent when head-of-bed elevation decreased from 30 to 15 degrees
[28]. Furthermore, some patients with acute ischemic stroke may develop increased
ischemic symptoms upon standing, sitting, or elevating the head of the bed, due to
reduction in flow through stenotic vessels or collateral pathways [30,31]. Thus, some
stroke experts have favored a supine position is preferred for nonhypoxic patients with
acute ischemic stroke who are able to tolerate lying flat. When done, keeping the patient
flat is a temporary measure that should be discontinued in most patients after 24 to 48
hours.
Nevertheless, the benefit of maintaining the head flat in this setting remains unproven
[32]. In the HeadPoST controlled trial of over 11,000 subjects with acute stroke (85
percent ischemic) who were randomly assigned to either a lying-flat position or a sitting-
up position with the head elevated to at least 30 degrees, there was no difference
between treatment groups in disability outcomes, mortality, or serious adverse events
[33].
Mobilization of stable patients after 24 hours may lessen the likelihood of major
complications such as pneumonia, deep vein thrombosis, pulmonary embolism, and
pressure sores after stroke. Exceptions may include those who exhibit neurologic
deterioration upon assuming more upright postures. In addition, there is a potential
increased risk of aspiration if a flat position is maintained for a prolonged period [34].
However, very early mobilization, within 24 hours of symptom onset, may be harmful
[35]. The multicenter randomized AVERT trial, with over 2000 patients, evaluated a
protocol of very early mobilization, which was started within 24 hours of stroke onset
and consisted of frequent out-of-bed activity including sitting, standing, and walking.
Compared with usual care, very early mobilization and early rehabilitative therapies
reduced the odds of a favorable outcome at three months [36].
Fever — Fever has special significance in patients presenting with acute neurologic
deterioration. Both problems may occur in patients with a primary central nervous
system infection such as meningitis, subdural empyema, brain abscess, and infective
endocarditis. These conditions need to be excluded as the etiology of fever. In addition,
common etiologies of fever including aspiration pneumonia and urinary tract infection
should also be excluded.
Fever may contribute to brain injury in patients with an acute stroke. This concept has
been demonstrated in animal models in which ischemic injury is increased in the
presence of elevated temperature. Hyperthermia may act via several mechanisms to
worsen cerebral ischemia [37]:
●Enhanced release of neurotransmitters
●Exaggerated oxygen radical production
●More extensive blood-brain barrier breakdown
●Increased numbers of potentially damaging ischemic depolarizations in the focal
ischemic penumbra
●Impaired recovery of energy metabolism and enhanced inhibition of protein
kinases
●Worsening of cytoskeletal proteolysis
Fever is associated with unfavorable outcomes in human studies of stroke [38-41]. One
meta-analysis analyzed fever and outcome in patients with neurologic injury, including
hemorrhagic and/or ischemic stroke [38]. Fever was significantly associated with
increased mortality rates, greater disability, more dependence, worse functional
outcome, greater severity, and longer intensive care unit and hospital stays. These
results were consistent for overall pooled data and for subgroups limited to studies of
patients with hemorrhagic, ischemic, or all stroke types. A subsequent meta-analysis
found that fever within 24 hours of hospital admission in patients with ischemic stroke
was associated with a two-fold increase in the odds of mortality at one month after
stroke onset [41].
Treatment — The source of fever should be investigated and treated, and antipyretics
should be used to lower temperature in febrile patients with acute stroke. We suggest
maintaining normothermia for at least the first several days after an acute stroke [37].
However, the clinical utility of this approach has not been established.
 ●The Paracetamol (Acetaminophen) In Stroke (PAIS) trial evaluated 1400 adults
no later than 12 hours after symptom onset of acute ischemic stroke or
intracerebral hemorrhage [42]. Included patients had a body temperature of 36 to
39ºC. Compared with placebo, paracetamol (acetaminophen) 1 g six times daily
for three days did not improve outcome [42]. However, a post-hoc subgroup
analysis of 661 patients with a baseline body temperature of 37 to 39ºC suggested
benefit for paracetamol.
●In a systematic review and meta-analysis of five small randomized controlled
trials with a total of 293 patients, there was no benefit for pharmacologic
temperature reduction for acute stroke [43]. All the trials enrolled patients within 24
hours of stroke onset, and the duration of treatment ranged from 24 hours to five
days. With addition of results from the PAIS trial, the updated meta-analysis found
no difference between active treatment and control for a favorable outcome (odds
ratio 1.1, 95% CI 0.9-1.3) [42].
Larger trials are needed to determine if pharmacologic temperature reduction improves
outcome from acute stroke, particularly for patients with temperature of ≥37ºC, though it
seems unlikely that acetaminophen will be effective by itself. In patients who are nil per
os (NPO), acetaminophen is now available in the United States as an intravenous
preparation.
Induced hypothermia is not currently recommended for patients with ischemic stroke,
outside of clinical trials [1].
Stroke unit care — Evidence suggests that patients with acute stroke have better
outcomes when admitted to a hospital unit that is specialized for the care of patients
with all types of acute stroke, including ischemic, intracerebral hemorrhage, and
subarachnoid hemorrhage [44-48]. The precise components of an acute stroke unit vary
between centers and countries, but generally include a hospital ward with dedicated
telemetry beds that is continuously staffed by a team of physicians, nurses and other
personnel who specialize in stroke care, emphasizing expertise in vascular neurology
and neurosurgery [49,50]. Additional components include prompt availability of
neuroimaging (eg, CT, MRI, various types of angiography, ultrasound, transcranial
Doppler) and cardiac imaging. Implementation of stroke protocols and disease-
performance measures may contribute to improved outcomes and decreased risk of
stroke-related complications, as shown in some reports [51,52].
Current national guidelines support stroke unit care, when available, for patients with
suspected acute stroke [1,53].
BLOOD PRESSURE MANAGEMENT The approach to blood pressure
management in acute ischemic stroke is inherently different from the approach in acute
hemorrhagic stroke. For this reason, a neuroimaging study with computed tomography
(CT) or magnetic resonance imaging (MRI) is critical to help guide blood pressure
therapy in patients with acute stroke. Likewise, there are important differences between
the blood pressure management in the acute and chronic phases of stroke.
The management of blood pressure in acute phase of stroke is reviewed in the sections
that follow. The management of blood pressure after the acute phase of stroke is
discussed separately. (See "Antihypertensive therapy for secondary stroke prevention".)
Blood pressure in acute ischemic stroke — The long-term benefit from
antihypertensive therapy does not mean that a reduction in blood pressure will be
beneficial during initial management of an acute ischemic stroke [54]. In patients with
ischemic stroke, the perfusion pressure distal to the obstructed vessel is low, and the
distal vessels are dilated. Because of impaired cerebral autoregulation (figure 2), blood
flow in these dilated vessels is thought to be dependent upon the systemic blood
pressure.
The arterial blood pressure is usually elevated in patients with an acute stroke. This
may be due to chronic hypertension, an acute sympathetic response, or other stroke-
mediated mechanisms [55]. In many cases, however, the acutely elevated blood
pressure is necessary to maintain brain perfusion in borderline ischemic areas [56].
The observation that the blood pressure frequently rises spontaneously following
cerebral ischemia is consistent with this protective hypothesis, although a stress
response to the acute event and to hospitalization may also contribute [57]. The
hypertensive effect is transient, as blood pressure falls by as much as 20/10 mmHg
within 10 days.
An analysis from the International Stroke Trial of 17,398 patients with an ischemic
stroke noted a U-shaped relationship between baseline systolic blood pressure and
outcomes [58]. Elevated systolic blood pressure was associated with an increased risk
of recurrent ischemic stroke (50 percent greater risk of recurrence with a systolic blood
pressure of >200 mmHg versus 130 mmHg), while low blood pressure (particularly <120
mmHg) was associated with an excess number of deaths from coronary heart disease.
A subsequent analysis of 1004 patients with acute ischemic stroke from Okinawa also
found a U-shaped relationship between admission blood pressure and death within 30
days after stroke onset [59]. The U-shaped relationship was shifted toward higher
pressure in patients who had previous hypertension compared with those who did not
have previous hypertension. This finding mirrors the shift seen in cerebral
autoregulation that occurs in longstanding hypertension (figure 2) [60].
Effect of lowering blood pressure — There are few data from randomized controlled
trials specifically designed to guide blood pressure management in the acute phase of
ischemic stroke (ie, the first 24 hours) when the ischemic penumbra may be at risk of
irreversible damage if cerebral blood flow is reduced by lowering the blood pressure [61].
The MAPAS trial found no clear benefit for blood pressure lowering within 12 hours of
acute ischemic stroke onset, but an adjusted analysis suggested that a goal systolic
blood pressure of 161 to 180 mmHg increased the odds of a good outcome compared
with higher or lower goal blood pressures [62]. The RIGHT-2 trial found that lowering
blood pressure within four hours of onset of suspected stroke did not improve functional
outcomes; the results are confounded by inclusion of patients with transient ischemic
attack (TIA), intracerebral hemorrhage, and stroke mimics [63]. Lowering the systemic
blood pressure in patients within 24 hours of acute ischemic stroke onset has been
associated with clinical deterioration in several observational studies [64-66].
Other large trials (eg, CATIS [67], SCAST [68], COSSACS [69], and ENOS [70])
enrolled patients as long as 30 to 48 hours after stroke onset, and are therefore less
informative regarding the impact of blood pressure treatment in the first hours of
ischemic stroke. In addition, many of these trials, including the meta-analyses discussed
below, enrolled patients with intracerebral hemorrhage, a group that might be expected
to benefit from early blood pressure lowering. Keeping these limitations in mind, some
of the randomized trial data suggest that initiating blood pressure reduction in acute
stroke or merely continuing prestroke blood pressure medications can be harmful:
●In a 2014 meta-analysis of 16 trials (including ENOS) of antihypertensive
medications that included over 19,000 patients with acute stroke, early blood
pressure reduction had no effect on functional outcome (odds ratio 1.0, 95% CI
0.93-1.07) [70]. Similarly, a 2015 meta-analysis of 13 randomized trials (also
including ENOS) and over 12,000 subjects found that blood pressure lowering
started within three days of ischemic stroke onset did not alter the risk of death or
dependency at three months or trial end point (relative risk, 1.04, 95% CI 0.96-
1.13) [71].
●A meta-analysis of individual patient data from COSSACS and ENOS trials found
that continuing versus stopping antihypertensive treatment had no effect on the
risk of death or dependency at final follow-up [72]. However, in a subgroup
analysis, patients who stopped antihypertensives within 12 hours of stroke onset
showed a nonsignificant trend towards less death or dependency. In the ENOS
trial itself, the group assigned to continuing blood pressure treatment had an
increased likelihood of hospital death or discharge to an institution, an increased
risk of death or disability (Barthel index <60) at 90 days, and significantly lower
cognition scores at 90 days compared with the group that stopped treatment, even
though there was no difference in functional outcome between the two groups [70].

These results are not definitive for the reasons noted above.

Blood pressure goals in ischemic stroke — Special considerations apply to blood

pressure control in patients with acute ischemic stroke who are eligible for intravenous
thrombolytic therapy. Before thrombolytic therapy is started, treatment is recommended
so that systolic blood pressure is ≤185 mmHg and diastolic blood pressure is ≤110
mmHg (table 6) [1]. The blood pressure should be stabilized and maintained at or below
180/105 mmHg for at least 24 hours after thrombolytic treatment. This issue is
discussed in detail separately. (See "Intravenous thrombolytic therapy for acute
ischemic stroke: Therapeutic use", section on 'Management of blood pressure'.)
For patients with ischemic stroke who are not treated with thrombolytic therapy, blood
pressure should not be treated acutely unless the hypertension is extreme (systolic
blood pressure >220 mmHg or diastolic blood pressure >120 mmHg), or the patient has
active ischemic coronary disease, heart failure, aortic dissection, hypertensive
encephalopathy, or pre-eclampsia/eclampsia [1,73]. When treatment is indicated,
cautious lowering of blood pressure by approximately 15 percent during the first 24
hours after stroke onset is suggested.
It is reasonable to start or restart antihypertensive medications during hospitalization for
patients with blood pressure >140/90 mmHg who are neurologically stable, unless
contraindicated [1]. This can be done as early as 24 to 48 hours after stroke onset for
most hospitalized patients, with the goal of gradually controlling hypertension within a
few days to a week [74]. Importantly, patients with extracranial or intracranial large
artery stenoses may require a slower reduction in blood pressure (eg, over 7 to 14 days
after ischemic stroke), as some degree of blood pressure elevation may be necessary
to maintain cerebral blood flow to ischemic brain regions. For this reason, we suggest
not restarting antihypertensive agents until after vascular imaging is completed and a
symptomatic large artery stenosis is excluded.
If acute antihypertensive therapy is needed, intravenous agents are generally used.
(See 'Choice of antihypertensive agent' below.)
Systemic hypotension and hypovolemia should be corrected to improve cerebral blood
flow and systemic organ function [1]. However, drug-induced hypertension is unproven
for the treatment of ischemic stroke.
Choice of antihypertensive agent — In the acute phase of stroke, there is no good
evidence to support the use of any specific antihypertensive agent to achieve
recommended blood pressure goals. Nevertheless, reversible and titratable intravenous
agents are best suited for precise blood pressure lowering. Consensus guidelines
suggest intravenous labetalol, nicardipine, and clevidipine as first-line antihypertensive
agents if pharmacologic therapy is necessary in the acute phase, since they allow rapid
and safe titration to the goal blood pressure (table 6) [1].
Intravenous nitroprusside should be considered second-line therapy since it carries
added theoretical risks of increasing intracranial pressure or affecting platelet function.
Medications likely to cause a prolonged or precipitous decline in blood pressure (eg,
rapid-acting formulations of nifedipine) should be avoided. In addition, their use is
associated with an increased risk of stroke, particularly in older adult patients [75].
Blood pressure in acute hemorrhagic stroke — In both intracerebral hemorrhage
(ICH) and subarachnoid hemorrhage (SAH), the approach to blood pressure
management must take into account the potential benefits (eg, reducing further bleeding)
and risks (eg, reducing cerebral perfusion) of blood pressure lowering.
Recommendations for blood pressure management in acute ICH and SAH are
discussed in detail separately. (See "Spontaneous intracerebral hemorrhage: Acute
treatment and prognosis", section on 'Blood pressure management' and "Aneurysmal
subarachnoid hemorrhage: Treatment and prognosis", section on 'Blood pressure
control'.)
ACUTE THERAPY
Ischemic stroke management — For eligible patients (table 2) with acute ischemic
stroke, intravenous alteplase is first-line therapy, provided that treatment is initiated
within 4.5 hours of symptom onset or the time last known to be well (ie, at neurologic
baseline). Because the benefit of alteplase is time dependent, it is critical to treat
patients as quickly as possible.
Mechanical thrombectomy (algorithm 1) is indicated for patients with acute ischemic
stroke due to a large artery occlusion in the anterior circulation who can be treated
within 24 hours of symptom onset or the time last known to be well at stroke centers
with appropriate expertise, regardless of whether they receive intravenous alteplase for
the same ischemic stroke event. The eligibility criteria and utility of thrombolytic therapy,
endovascular thrombectomy, and the treatment of patients not eligible for thrombolysis
are discussed separately. (See "Approach to reperfusion therapy for acute ischemic
stroke" and "Early antithrombotic treatment of acute ischemic stroke and transient
ischemic attack".)
In addition to intravenous thrombolysis with alteplase and endovascular thrombectomy,
a number of interventions for ischemic stroke are associated with either reduced
disability, complications, or stroke recurrence, including:
 ●Antithrombotic therapy with aspirin initiated within 48 hours of stroke onset
(see "Early antithrombotic treatment of acute ischemic stroke and transient
ischemic attack", section on 'Aspirin')
●Prophylaxis for deep venous thrombosis and pulmonary embolism
(see "Prevention and treatment of venous thromboembolism in patients with acute
stroke", section on 'Approach to VTE prevention')
●Antithrombotic therapy at discharge (see "Long-term antithrombotic therapy for
the secondary prevention of ischemic stroke" and "Atrial fibrillation in adults: Use
of oral anticoagulants")
●Lipid lowering with high intensity statin therapy (see "Overview of secondary
prevention of ischemic stroke", section on 'LDL-C lowering therapy')
●Blood pressure reduction after the acute phase of ischemic stroke has passed
(see "Antihypertensive therapy for secondary stroke prevention" and "Overview of
secondary prevention of ischemic stroke"); management of blood pressure in the
acute phase of ischemic stroke is discussed above (see 'Blood pressure
management' above)
●Behavioral and lifestyle changes including smoking cessation, exercise, weight
reduction for patients with obesity, and a Mediterranean style diet (see "Overview
of secondary prevention of ischemic stroke" and "Overview of smoking cessation
management in adults")
Appropriate and timely use of these therapies should be considered as soon as
ischemic stroke is recognized. Utilization of these interventions may be improved by the
use of standardized stroke care orders or critical pathways beginning with hospital
admission through discharge [1,76].
Full-dose anticoagulation is rarely indicated in the hyperacute phase of ischemic stroke,
although low-dose heparin anticoagulation is often used for prevention of venous
thromboembolism in patients with restricted mobility. (See "Prevention and treatment of
venous thromboembolism in patients with acute stroke".)
The main indication for oral anticoagulation after ischemic stroke is atrial fibrillation.
When indicated, oral anticoagulation can be started immediately for patients with a
transient ischemic attack, and soon after ischemic stroke onset for medically stable
patients with a small- or moderate-sized infarct and no bleeding complications or
uncontrolled hypertension. For patients with atrial fibrillation who have a large infarct,
symptomatic hemorrhagic transformation, or poorly controlled hypertension, withholding
oral anticoagulation for one to two weeks is generally recommended. (See "Early
antithrombotic treatment of acute ischemic stroke and transient ischemic attack",
section on 'Cardioembolic source'.)
●Statin therapy – For patients with acute ischemic stroke, we suggest starting or
continuing statin treatment as soon as oral medications can be used safely. There
is clear evidence that long-term intensive statin therapy is associated with a
reduced risk of recurrent ischemic stroke and cardiovascular events, as discussed
separately (see "Overview of secondary prevention of ischemic stroke", section on
'LDL-C lowering therapy'). The utility of statin therapy during the acute phase of
ischemic stroke is less well studied, but is supported by the following observations:
•A single-center randomized controlled trial of 89 patients who were already
treated with a statin and were assigned to continuation or cessation of statin
 therapy in the acute phase of ischemic stroke [77]. The rate of death or
dependency at three months was significantly lower with continuation of statin
treatment (39 versus 60 percent).
•An observational study, which evaluated over 12,000 subjects hospitalized
with ischemic stroke, found that statin use before and during hospitalization
was associated with improved outcome at hospital discharge and with
improved survival at one year [78,79]. Furthermore, initiation of statin treatment
early in hospitalization was associated with improved survival, while statin
discontinuation early in hospitalization, even for a short period, was associated
with decreased survival.
•An uncontrolled study of 448 patients reported that new or continued statin
treatment in the first 72 hours after acute ischemic stroke was associated with
improved early and late (one-year) survival [80].
•An observational study of 2072 patients who received intravenous
thrombolysis for acute ischemic stroke found that statin treatment started
within 72 hours of thrombolysis was associated with a favorable functional
outcome and a reduced risk of death at three months [81]. Of the 839 patients
treated with statins, 65 percent were statin naïve.
●SSRIs – For patients with hemiparesis but without depression after ischemic
stroke, evidence from a few small randomized controlled trials (including the
FLAME trial) suggested that early initiation of selective serotonin-reuptake
inhibitors (SSRIs) enhanced motor recovery and reduced dependency [82-84].
However, subsequent randomized controlled trials, including the FOCUS,
AFFINITY, and EFFECTS trials, which together enrolled over 5900 adult patients
with acute ischemic stroke or intracerebral hemorrhage, found no benefit in
functional outcome at six months for treatment with fluoxetine compared with
placebo [85-87]. Treatment with fluoxetine reduced the risk of developing
depression in FOCUS and EFFECTS but increased the risk of bone fractures in all
three trials, increased the risks of falls and epileptic seizures in AFFINITY, and
increased the risk of hyponatremia in EFFECTS.
Intracranial hemorrhage management — The treatment of patients with intracerebral
hemorrhage or subarachnoid hemorrhage is reviewed in detail elsewhere.
(See "Spontaneous intracerebral hemorrhage: Acute treatment and
prognosis" and "Aneurysmal subarachnoid hemorrhage: Treatment and
prognosis" and "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic
use", section on 'Management of symptomatic intracerebral hemorrhage'.)
Neuroprotective treatment — Numerous neuroprotective agents have shown
promising results in animal experiments. However, clinical trials have thus far failed to
confirm consistent benefit [88]. This failure may be due, at least in part, to limitations of
animal models of acute stroke and to shortcomings of clinical trials.
The search for effective neuroprotective treatment continues [88-93]. As an example, in
the ESCAPE-NA1 trial of over 1100 patients with acute stroke selected for mechanical
thrombectomy, the neuroprotectant nerinetide did not improve outcomes compared with
placebo [94]. Subgroup analysis suggested a possible benefit in patients who do not
receive alteplase, but further study is needed to confirm these findings.
PREVENTION OF COMPLICATIONS The prevention of medical complications
of stroke is an important goal of stroke management, and this aspect of care begins with
initial evaluation of the patient. Common acute and subacute medical problems
associated with stroke include:
●Myocardial infarction
●Heart failure
●Dysphagia
●Aspiration pneumonia
●Urinary tract infection
●Deep vein thrombosis
●Pulmonary embolism
●Dehydration
●Malnutrition
●Pressure sores
●Orthopedic complications and contractures
The prevention, impact, and management of these complications are discussed
separately. (See "Complications of stroke: An overview" and "Prevention and treatment
of venous thromboembolism in patients with acute stroke".)
Delirium, characterized by a disturbance of consciousness with decreased attention and
disorganized thinking, is another potential complication of stroke [95]. Findings from
systematic reviews and meta-analyses suggest that the rate of post-stroke delirium is
approximately 25 percent [96,97]. Patients with delirium have longer hospital stays and
higher inpatient and 12-month mortality rates [96]. Risk factors for developing post-
stroke delirium include preexisting cognitive decline, infection, and greater stroke
severity [98]. (See "Diagnosis of delirium and confusional states" and "Delirium and
acute confusional states: Prevention, treatment, and prognosis".)
SOCIETY GUIDELINE LINKS Links to society and government-sponsored
guidelines from selected countries and regions around the world are provided
separately. (See "Society guideline links: Stroke in adults".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces
are written in plain language, at the 5th to 6th grade reading level, and they answer the
four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read
materials. Beyond the Basics patient education pieces are longer, more sophisticated,
and more detailed. These articles are written at the 10th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you
to print or e-mail these topics to your patients. (You can also locate patient education
articles on a variety of subjects by searching on "patient info" and the keyword(s) of
interest.)

●Basics topics (see "Patient education: Stroke (The Basics)" and "Patient
education: Hemorrhagic stroke (The Basics)")
 ●Beyond the Basics topics (see "Patient education: Stroke symptoms and
diagnosis (Beyond the Basics)" and "Patient education: Ischemic stroke treatment
(Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The main goals in the initial phase of acute stroke management are to ensure
medical stability, to quickly reverse conditions that are contributing to the patient's
problem, to determine if patients with acute ischemic stroke are candidates for
reperfusion therapy, and to begin to uncover the pathophysiologic basis of the
neurologic symptoms. (See 'Initial assessment' above.)
●Important aspects of acute stroke evaluation and management include the
following:
•Assessing vital signs and ensuring stabilization of airway, breathing, and
circulation. (See 'Airway, breathing and circulation' above.)
•Obtaining a rapid but accurate history and examination to help distinguish
stroke mimics and other disorders in the differential diagnosis (table 1) of acute
stroke. (See 'History and physical' above and 'Neurologic evaluation' above.)
•Obtaining urgent brain imaging (with computed tomography [CT] or magnetic
resonance imaging [MRI]), neurovascular imaging (with CT angiography or
magnetic resonance angiography [MRA]) and other important laboratory
studies, including cardiac monitoring during the first 24 hours after the onset of
ischemic stroke. (See 'Immediate laboratory studies' above
and 'Neuroimaging' above and 'Cardiac studies' above.)
•Managing volume depletion and electrolyte disturbances. (See 'Fluids' above.)
•Checking serum glucose. Low serum glucose (<60 mg/dL [3.3 mmol/L])
should be corrected rapidly. It is reasonable to treat hyperglycemia if the
glucose level is >180 mg/dL (>10 mmol/L) with a goal of keeping serum
glucose levels within a range of 140 to 180 mg/dL (7.8 to 10 mmol/L).
•Assessing swallowing and preventing aspiration. (See 'Swallowing
assessment' above and "Complications of stroke: An overview", section on
'Dysphagia'.)
•Optimizing head of bed position. For patients with intracerebral hemorrhage,
subarachnoid hemorrhage, or ischemic stroke who are at risk for elevated
intracranial pressure, aspiration, cardiopulmonary decompensation, or oxygen
desaturation, we recommend keeping the head in neutral alignment with the
body and elevating the head of the bed to 30 degrees (Grade 1C). For patients
with stroke who are not at high risk for these complications, we suggest
keeping the head of the bed in the position that is most comfortable.
(See 'Head and body position' above.)
•Evaluating and treating the source of fever, if present; for patients with acute
stroke, we suggest maintaining normothermia for at least the first several days
after an acute stroke (Grade 2C). (See 'Fever' above.)
●The management of blood pressure in acute stroke depends on the type of
stroke. (See 'Blood pressure management' above.)
•For patients with acute ischemic stroke who will receive thrombolytic therapy,
antihypertensive treatment is recommended so that systolic blood pressure is
≤185 mmHg and diastolic blood pressure is ≤110 mmHg prior to treatment and
 <180/105 mmHg for the first 24 hours after treatment (table 6). This issue is
discussed in detail separately. (See "Intravenous thrombolytic therapy for
acute ischemic stroke: Therapeutic use", section on 'Management of blood
pressure'.)
•For patients with acute ischemic stroke who are not treated with thrombolytic
therapy, we suggest treating high blood pressure only if the hypertension is
extreme (systolic blood pressure >220 mmHg or diastolic blood pressure >120
mmHg), or if the patient has another clear indication (active ischemic coronary
disease, heart failure, aortic dissection, hypertensive encephalopathy, or pre-
eclampsia/eclampsia) (Grade 2C). When treatment is indicated, we suggest
cautious lowering of blood pressure by approximately 15 percent during the
first 24 hours after stroke onset (Grade 2C). (See 'Blood pressure goals in
ischemic stroke' above.)
•In both intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH),
the approach to blood pressure lowering must account for the potential
benefits (eg, reducing further bleeding) and risks (eg, reducing cerebral
perfusion). Recommendations for blood pressure management in acute ICH
and SAH are discussed in detail separately. (See 'Blood pressure in acute
hemorrhagic stroke' above and "Spontaneous intracerebral hemorrhage: Acute
treatment and prognosis", section on 'Blood pressure
management' and "Aneurysmal subarachnoid hemorrhage: Treatment and
prognosis", section on 'Blood pressure control'.)
●For eligible patients (table 2) with acute ischemic stroke,
intravenous alteplase therapy is first-line therapy, provided that treatment is
initiated within 4.5 hours of clearly defined symptom onset. Patients with acute
ischemic stroke due to a proximal large artery occlusion who can be treated within
24 hours of time last known to be at neurologic baseline should be evaluated for
treatment with mechanical thrombectomy (algorithm 1). The eligibility criteria and
utility of thrombolytic therapy, mechanical thrombectomy, and the treatment of
patients not eligible for thrombolysis are discussed separately. (See "Approach to
reperfusion therapy for acute ischemic stroke" and "Early antithrombotic treatment
of acute ischemic stroke and transient ischemic attack".)
●In addition to reperfusion therapy, a number of interventions for ischemic stroke
are associated with either reduced disability, complications, or stroke recurrence,
including (see 'Acute therapy' above):
•Antithrombotic therapy with aspirin initiated within 48 hours of stroke onset.
(See "Early antithrombotic treatment of acute ischemic stroke and transient
ischemic attack", section on 'Aspirin'.)
•Prophylaxis for deep venous thrombosis and pulmonary embolism.
(See "Prevention and treatment of venous thromboembolism in patients with
acute stroke", section on 'Approach to VTE prevention'.)
•For patients with acute ischemic stroke, we suggest starting or continuing
statin treatment as soon as oral medications can be used safely (Grade 2C).
(See 'Ischemic stroke management' above.)
Secondary prevention for specific causes of ischemic stroke
and transient ischemic attack
Author:
Natalia S Rost, MD, MPH
Section Editor:
Scott E Kasner, MD
Deputy Editor:
John F Dashe, MD, PhD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2021. | This topic last updated: Nov 18, 2021.
INTRODUCTION This topic will review the treatment of specific causes of transient
ischemic attack (TIA) and ischemic stroke where the potential cause has been identified,
emphasizing secondary prevention of recurrent cerebral ischemia and other vascular events. Risk
factor management, which is appropriate for all patients with ischemic stroke or TIA, is reviewed
in detail elsewhere. (See "Overview of secondary prevention of ischemic stroke".)
The initial assessment of patients with cerebral ischemia and acute therapy for ischemic stroke
are discussed separately. (See "Initial assessment and management of acute
stroke" and "Approach to reperfusion therapy for acute ischemic stroke" and "Early
antithrombotic treatment of acute ischemic stroke and transient ischemic attack".)
MEDICAL THERAPY Most patients with an ischemic stroke or TIA should be treated
with all available risk reduction strategies, including antithrombotic therapy (algorithm
1 and algorithm 2), blood pressure reduction, low-density lipoprotein lowering therapy, and
lifestyle modification. These strategies are reviewed in detail separately:
●Overview of secondary prevention of ischemic stroke
●Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack
●Long-term antithrombotic therapy for the secondary prevention of ischemic stroke
●Antihypertensive therapy for secondary stroke prevention
LARGE ARTERY DISEASE Options for the secondary prevention of ischemic stroke or
TIA caused by large artery disease include revascularization for symptomatic internal carotid
artery stenosis due to atherosclerosis, and multifactorial risk reduction including treatment with
antiplatelet agents, blood pressure control, and low-density lipoprotein cholesterol (LDL-C)
lowering therapy. The role of anticoagulation in this setting is quite limited. (See "Long-term
antithrombotic therapy for the secondary prevention of ischemic stroke".)

Some specific situations are discussed below for atheromatous carotid, vertebral, and intracranial
disease, and for nonatheromatous causes including carotid web, dissection, fibromuscular
dysplasia, and moyamoya.

Symptomatic carotid stenosis — Carotid endarterectomy is beneficial for patients with recently
symptomatic internal carotid artery atherosclerotic stenosis of 50 to 99 percent. This conclusion
is based upon a number of randomized, controlled trials that have demonstrated the efficacy of
endarterectomy in selected patients who have carotid atherosclerosis and symptoms such as a
TIA or a nondisabling stroke. This issue is discussed separately. (See "Management of
symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CEA'.)
Carotid artery stenting is another potential option for select patients with symptomatic internal
carotid artery atherosclerotic stenosis of 50 to 99 percent. Proponents of carotid stenting
emphasize its less invasive nature (since it can be performed with local anesthesia and sedation)
and the decreased likelihood of morbidity from coexisting coronary disease. Another group that
may benefit from stenting consists of those with a "hostile" neck who are at higher risk for
complications following standard carotid endarterectomy; included in this group are patients
with radiation-induced stenosis, previous neck exploration, or tracheostomy. Nevertheless,
carotid endarterectomy remains the preferred treatment for most patients with symptomatic
carotid atherosclerosis. (See "Overview of carotid artery stenting" and "Management of
symptomatic carotid atherosclerotic disease", section on 'Patients appropriate for CAS'.)
In addition to carotid revascularization, treatment with antiplatelet agents and management of
modifiable risk factors is important for preventing recurrent ischemic stroke in patients with
carotid artery disease. (See "Overview of secondary prevention of ischemic stroke".)
Carotid occlusion — Carotid artery occlusion may occur without clear symptoms, but it can be
associated with TIA and stroke. The subsequent yearly risk of a stroke ipsilateral to the occluded
carotid artery is 2 to 5 percent [1,2].
In most cases, medical management is the only practical option in the setting of complete carotid
occlusion. However, the optimal treatment remains undefined. Surgical revascularization is a
viable option only when residual flow can be demonstrated in the internal carotid artery (ie, near
occlusion), but efficacy is unproven. (See "Management of symptomatic carotid atherosclerotic
disease", section on 'Patients unlikely to benefit'.)
Historically, some experts used short-term (three to six months) anticoagulation for acute
symptomatic occlusion; the rationale for this approach is based on limited evidence that emboli
may form and propagate from the stump of the occluded artery after acute occlusion [3,4]. An
earlier randomized, controlled trial in patients with symptomatic carotid narrowing or occlusion
found that surgical treatment using extracranial to intracranial bypass failed to reduce the risk of
ischemic stroke [5], and the later Carotid Occlusion Surgery Study (COSS) trial in patients with
symptomatic carotid occlusion and hemodynamic cerebral ischemia also found no benefit for
extracranial to intracranial bypass surgery compared with medical therapy alone [6]. Data from
small retrospective studies suggest that recanalization can be achieved by stenting of extracranial
carotid artery occlusion [7,8], or by intra-arterial treatment combined with stenting [9], but
clinical benefit is uncertain.
Carotid web — Carotid web, considered a variant of fibromuscular dysplasia
(see 'Fibromuscular dysplasia' below), is a shelf-like projection of intimal fibrous tissue of the
internal carotid artery bulb that can be focal or multifocal [10]. It may appear as a filling defect
on computed tomographic angiography, magnetic resonance angiography, or conventional
contrast angiography (eg, digital subtraction angiography) [11,12].
Carotid web is rarely associated with severe stenosis. However, carotid web may alter
hemodynamic flow and increase the risk of platelet aggregation leading to thromboembolism
[13].
The optimal management of symptomatic carotid web is uncertain. The 2021 American Heart
Association/American Stroke Association guidelines recommend antiplatelet therapy for
secondary stroke prevention [14]. The guidelines also note that the risk of recurrent stroke with
symptomatic carotid web is high, and carotid stenting or endarterectomy may be considered to
prevent recurrent events.
Extracranial vertebral artery stenosis — In most cases, prevention of ischemic stroke and TIA
due to extracranial vertebral artery stenosis is managed by intensive medical treatment and
multifactorial risk reduction, including the use of antiplatelet agents (algorithm 1 and algorithm
2), antihypertensive drugs, and LDL-C lowering therapy [14]. In addition, angioplasty and
stenting is a treatment option [15-18], and surgical transposition of the vertebral artery to the
common carotid artery is another alternative for vertebral origin stenosis. However, efficacy for
these procedures is uncertain [14]. They are generally considered when maximal medical therapy
has failed to prevent embolism or low-flow ischemic events.
Intracranial large artery atherosclerosis — Atherosclerotic stenosis of the major intracranial
arteries (carotid siphon, middle cerebral artery, vertebral artery, and basilar artery) is an
important cause of ischemic stroke, particularly in Black, Asian, and Hispanic populations.
Patients with TIA or ischemic stroke attributed to intracranial atherosclerosis should receive
intensive medical management with antiplatelet therapy (algorithm 1 and algorithm 2) and strict
control of vascular risk factors, including the blood pressure control, LDL-C lowering therapy,
and physical activity and other lifestyle modification (eg, smoking cessation, weight control, salt
restriction, and a healthy diet). (See "Intracranial large artery atherosclerosis: Treatment and
prognosis", section on 'Secondary prevention'.)
Evidence from randomized controlled trials indicates that intensive medical management is
superior to stenting for patients with recently symptomatic high-grade intracranial large artery
stenosis [19]. (See "Intracranial large artery atherosclerosis: Treatment and prognosis", section
on 'Stenting'.)
Dissection — Beyond the hyperacute period, antithrombotic therapy with either anticoagulation
or antiplatelet drugs is accepted treatment for ischemic stroke and TIA caused by extracranial
artery dissection, although there is controversy regarding the choice between the two. In addition,
because of the presumed increased risk of subarachnoid hemorrhage, there is controversy
regarding the use of antithrombotic agents for ischemic symptoms in patients with either
intracranial dissection alone or intracranial extension of extracranial dissection. These issues are
reviewed in detail elsewhere. (See "Cerebral and cervical artery dissection: Treatment and
prognosis", section on 'Choosing between antiplatelet and anticoagulation therapy'.)
Endovascular methods or surgical repair also have been used to treat dissection, mainly for
patients who have recurrent ischemia despite antithrombotic therapy. (See "Cerebral and cervical
artery dissection: Treatment and prognosis", section on 'Recurrent ischemia'.)
Fibromuscular dysplasia — Fibromuscular dysplasia (FMD) is a noninflammatory,
nonatherosclerotic disorder that leads to arterial stenosis, occlusion, intraluminal thrombus,
aneurysm, dissection, and arterial tortuosity [20]. The most frequently involved arteries are the
renal and internal carotid arteries, followed by the vertebral, visceral, and external iliac arteries.
Disease presentation may vary widely, depending upon the arterial segment involved and the
severity of disease. TIA and ischemic stroke are potential manifestations of carotid or vertebral
artery FMD; hypertension is the most common presenting sign of renal artery FMD.
(See "Clinical manifestations and diagnosis of fibromuscular dysplasia".)
In patients with an ischemic stroke or TIA attributed to FMD, secondary prevention measures
include antiplatelet therapy, blood pressure control, and lifestyle modification [14]. For patients
with recurrent ischemic stroke or TIA attributed to carotid artery FMD, treatment using
angioplasty with or without stenting is an option.
Moyamoya — Moyamoya disease (MMD) is a unique cerebrovascular disorder characterized by
progressive large intracranial artery narrowing and the development of prominent small vessel
collaterals in patients who may have genetic susceptibilities but no underlying risk factors.
Moyamoya syndrome (MMS) refers to patients with moyamoya angiographic findings who also
have an associated medical condition. (See "Moyamoya disease: Etiology, clinical features, and
diagnosis", section on 'Classification and terminology'.)
Ischemic stroke and TIA affecting the anterior circulation are the most common clinical
presentations. Hemorrhagic complications of moyamoya, mainly intracerebral hemorrhage,
represent a significant clinical burden, particularly in adults. (See "Moyamoya disease: Etiology,
clinical features, and diagnosis", section on 'Clinical presentations'.)
Secondary stroke prevention for patients with symptomatic moyamoya is largely centered on
surgical revascularization techniques. Evidence regarding the benefit of antiplatelet agents is
limited and equivocal. In adults, hemorrhage may the predominant manifestation of moyamoya,
and anticoagulation is generally not indicated. (See "Moyamoya disease: Treatment and
prognosis", section on 'Secondary prevention'.)
For children and adults with asymptomatic or symptomatic ischemic MMD or MMS, some
experts use long-term therapy with aspirin or cilostazol. This also applies to patients who
undergo surgical revascularization.
SMALL ARTERY DISEASE Cerebral small artery disease, often referred to as small
vessel disease, may cause a TIA or lacunar infarction due to the occlusion of a small penetrating
branch of a large cerebral artery. (See "Lacunar infarcts".)
Early antiplatelet therapy is indicated for most patients with TIA or acute ischemic stroke due to
small artery disease who are not receiving oral anticoagulants, as shown in the algorithms
(algorithm 1 and algorithm 2). In the acute setting, most patients with a low-risk TIA or
moderate to major ischemic stroke are treated with aspirin alone; patients with a high-risk TIA or
minor ischemic stroke may benefit from dual antiplatelet therapy using aspirin
and clopidogrel for 21 days rather than aspirin alone. (See "Early antithrombotic treatment of
acute ischemic stroke and transient ischemic attack", section on 'Dual antiplatelet therapy'.)
Beyond the acute phase of stroke, long-term antiplatelet therapy for secondary stroke prevention
should be continued with either aspirin, clopidogrel, or the combination of aspirin-extended-
release dipyridamole. (See "Long-term antithrombotic therapy for the secondary prevention of
ischemic stroke".)
In addition to antiplatelet therapy, attention to hypertension, serum lipids, blood glucose, and
other modifiable risk factors is important for preventing lacunar strokes in patients with small
artery disease. (See "Overview of secondary prevention of ischemic stroke".)
CARDIOGENIC EMBOLISM Cerebral emboli from the heart and aorta behave the
same way as artery-to-artery emboli that cause TIAs and stroke. Cardiogenic embolism is
responsible for 14 to 30 percent of ischemic strokes [21]. In addition to atrial fibrillation, cardiac
sources of embolism for which anticoagulation therapy may be indicated include left ventricular
thrombus, cardiomyopathy, valvular disease, and congenital heart disease [14].
Minor potential sources of cardiogenic embolism include patent foramen ovale (PFO), left
ventricular regional wall motion abnormalities, severe mitral annular calcification, mitral valve
prolapse, mitral valve strands, and aortic valve disease (table 1) [22]. The risk of stroke
associated with these sources is low or uncertain, and except for PFO, the efficacy of and need
for specific treatment is undefined [23].
Atrial fibrillation — Atrial fibrillation is a major risk factor for ischemic stroke.
Anticoagulation with one of the direct oral anticoagulants
(DOACs; dabigatran, rivaroxaban, apixaban, or edoxaban) or warfarin is the most effective
treatment to reduce stroke risk [14]. This subject is reviewed in greater detail elsewhere.
(See "Stroke in patients with atrial fibrillation" and "Atrial fibrillation in adults: Use of oral
anticoagulants".)
For secondary stroke prevention, virtually all patients with atrial fibrillation who have a history
of stroke or TIA of cardioembolic origin should be treated with lifelong anticoagulation in the
absence of contraindications. (See "Stroke in patients with atrial fibrillation", section on 'Long-
term anticoagulation'.)
Placement of a left atrial appendage occlusion device may be an option for patients with
nonvalvular atrial fibrillation who have a contraindication to anticoagulation or strong preference
to avoid long-term anticoagulation. (See "Atrial fibrillation: Left atrial appendage occlusion".)
In rare cases when the patient is unwilling or unable to take anticoagulation despite careful
consideration of the advantages of oral anticoagulation, dual antiplatelet therapy is an alternative
to therapy with aspirin alone. This issue is discussed in detail separately. (See "Atrial fibrillation
in adults: Selection of candidates for anticoagulation", section on 'Alternatives to
anticoagulation'.)
Cardiac tumors — Cardiac tumors, mainly left-sided myxoma and fibroelastoma, are rare
causes of cardioembolic TIA or ischemic stroke. Surgical tumor resection via open heart surgery
is the main treatment option to prevent recurrent stroke [14]. (See "Cardiac tumors".)
Congenital heart disease — Patients with cyanotic congenital heart disease are at increased risk
for thromboembolism. The 2021 American Heart Association (AHA)/American Stroke
Association (ASA) guidelines state that it is reasonable to treat patients with cardioembolic
ischemic stroke or TIA attributed to congenital heart disease with warfarin anticoagulation [14].
(See "Medical management of cyanotic congenital heart disease in adults", section on
'Thromboembolism'.)
The Fontan procedure is a palliative operation that diverts systemic venous return to the lungs in
patients with an anatomic or functional single ventricle. For patients with Fontan circulation who
have a history of thromboembolism, warfarin anticoagulation is advised [14]. (See "Overview of
the management and prognosis of patients with Fontan circulation" and "Management of
complications in patients with Fontan circulation", section on 'Thrombosis'.)
Cardiomyopathy — For patients in sinus rhythm with prior ischemic stroke or TIA who have
either dilated cardiomyopathy (left ventricular ejection fraction ≤35 percent) or restrictive
cardiomyopathy, and without evidence of left atrial or left ventricular thrombus, the 2021
AHA/ASA guidelines note that the effectiveness of anticoagulation compared with antiplatelet
therapy is uncertain, and the choice should be individualized [14]. The role of antithrombotic
treatment for individuals with heart failure and prior thromboembolic events is reviewed in
greater detail elsewhere. (See "Antithrombotic therapy in patients with heart failure".)
Left ventricular thrombus — Patients with left ventricular thrombus in the specific setting of
an acute myocardial infarction have a significantly increased risk of embolic events. The 2021
American Heart Association/American Stroke Association guidelines state that patients with
ischemic stroke or TIA in the setting of a left ventricular mural thrombus should be treated
with warfarin (target international normalized ratio 2.5; range 2 to 3) for at least three months
[14]. Other experts consider using a DOAC rather than warfarin due to convenience in dosing
and more rapid achievement of therapeutic anticoagulation, so long as there is no specific
indication for warfarin (eg, prosthetic heart valve).
The issue of left ventricular thrombus and acute myocardial infarction is discussed in greater
detail separately. (See "Left ventricular thrombus after acute myocardial infarction".)
Patent foramen ovale — Patent foramen ovale (PFO) device closure is more effective than
medical therapy alone for select patients with a PFO-associated stroke (ie, a nonlacunar ischemic
stroke in the setting of a PFO with a right-to-left interatrial shunt and no other source of stroke
despite a comprehensive evaluation). Evaluation and treatment are summarized in the algorithm
(algorithm 3) and discussed in detail separately. (See "Treatment of patent foramen ovale (PFO)
for secondary stroke prevention".)
Valvular disease
●With atrial fibrillation – Patients with atrial fibrillation and valvular heart disease
should be treated with oral anticoagulation. The choice between warfarin and DOAC
therapy depends upon the type of underlying valvular disease; warfarin is generally
preferred for patients with atrial fibrillation and moderate to severe mitral stenosis or a
mechanical heart valve, while a DOAC may be preferred for patients with atrial fibrillation
and other types of valvular disease (eg, mild mitral stenosis, bioprosthetic valves, or native
aortic, pulmonary, or tricuspid valve disease) [14]. (See "Atrial fibrillation in adults: Use
of oral anticoagulants", section on 'Patients with valvular heart disease' and "Overview of
the management of mitral stenosis", section on 'Prevention of thromboembolism'.)
●Without atrial fibrillation – For patients in sinus rhythm with ischemic stroke or TIA
and native valvular disease or bioprosthetic heart valves, the 2021 AHA/ASA guidelines
recommend antiplatelet therapy [14]. This includes patients with mitral annular
calcification or mitral valve prolapse.
The 2021 AHA/ASA guidelines state that the role of oral anticoagulation has not been
adequately studied for patients who have rheumatic mitral valve disease without atrial
fibrillation and no other likely cause for ischemic stroke or TIA [14]. However, some
experts consider a prior embolic event in patients with moderate to severe mitral stenosis
as one of the indications for long-term oral anticoagulation with a vitamin K antagonist.
(See "Overview of the management of mitral stenosis", section on 'Prevention of
thromboembolism'.)
Note that transient atrial fibrillation and infective endocarditis should be considered as
potential causes when embolization occurs in patients with mitral stenosis who are in sinus
rhythm.
Mitral and aortic valvular disease is reviewed in greater detail elsewhere.
(See "Nonarrhythmic complications of mitral valve prolapse", section on 'Transient
ischemic attacks and cerebral vascular accidents' and "Clinical manifestations and
diagnosis of mitral annular calcification" and "Clinical manifestations and diagnosis of
aortic stenosis in adults", section on 'Embolic events'.)
●Mechanical heart valves – All mechanical heart valves require antithrombotic
prophylaxis [14,24]. Antithrombotic therapy for mechanical and bioprosthetic heart valves
is discussed in detail separately. (See "Antithrombotic therapy for mechanical heart
valves" and "Overview of the management of patients with prosthetic heart valves",
section on 'Antithrombotic therapy'.)
●Infective endocarditis – Infective endocarditis is an important cause of embolic stroke
and TIA for which anticoagulation is hazardous. Endocarditis must be excluded in any
patient with a TIA or stroke and other suggestive findings such as fever and a heart
murmur.
Treatment consists of antibiotic therapy for the infection. Early valve surgery is indicated
for patients with left-sided native valve infective endocarditis and one or more additional
 features, including symptoms or signs of heart failure, complicated infection, persistent
infection, and/or recurrent embolic events. (See "Clinical manifestations and evaluation of
adults with suspected left-sided native valve endocarditis" and "Antimicrobial therapy of
left-sided native valve endocarditis" and "Antithrombotic therapy in patients with infective
endocarditis".).
AORTIC ATHEROSCLEROSIS There are conflicting data regarding the stroke risk
associated with aortic atherosclerosis. However, most reports evaluating secondary stroke risk
have found that complex aortic atherosclerosis is a risk factor for recurrent stroke, especially for
aortic plaques ≥4 mm and mobile plaques. This issue is discussed separately. (See "Etiology,
classification, and epidemiology of stroke", section on 'Aortic atherosclerosis'.)
The optimal treatment for patients with stroke or TIA attributed to aortic disease is not clear; the
2021 American Heart Association/American Stroke Association (AHA/ASA) guidelines
recommend antiplatelet therapy (including short-term dual antiplatelet therapy for minor stroke)
and intensive lipid management to a low-density lipoprotein cholesterol target <70 mg/dL to
prevent recurrent stroke [14].
Medical therapy for secondary prevention of aortic atheromatous disease is discussed in greater
detail separately. (See "Thromboembolism from aortic plaque", section on 'Treatment'.)
The open-label ARCH trial was terminated prematurely due to slow recruitment and is therefore
inconclusive [25]. The ARCH trial enrolled 349 adults with ischemic stroke, TIA, or peripheral
embolism who had thoracic aortic plaque ≥4 mm and no other identified embolic source; patients
were randomly assigned to treatment with dual antiplatelet therapy (aspirin 75 to 150 mg daily in
combination with clopidogrel 75 mg daily) or warfarin (target international normalized ratio 2.5).
At a median follow-up of 3.4 years, the primary endpoint, a composite of cerebral infarction,
myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage, was
lower in the antiplatelet group compared with the warfarin group (7.6 versus 11.3 percent,
respectively), but the difference was not statistically significant (adjusted hazard ratio 0.76, 95%
CI 0.36-1.61).
SICKLE CELL DISEASE Stroke is a frequent complication of sickle cell disease (SCD),
and the risk of recurrent stroke is high. Stroke risk can be reduced with chronic transfusion
therapy. (See "Acute ischemic and hemorrhagic stroke in sickle cell disease" and "Prevention of
stroke (initial or recurrent) in sickle cell disease".)
For patients with SCD and ischemic stroke or TIA, the 2014 American Heart
Association/American Stroke Association (AHA/ASA) guidelines recommend regular blood
transfusions to reduce hemoglobin S to <30 percent of total hemoglobin [14]. In addition, the
guidelines note that treatment with hydroxyurea is reasonable if transfusion therapy is not
available or practical. General measures including traditional stroke risk factor identification and
management as well as the use of antiplatelet agents (for prior ischemic stroke) are also
reasonable.
The prevention of stroke in patients with SCD is discussed in greater detail separately.
(See "Prevention of stroke (initial or recurrent) in sickle cell disease".)
HYPERCOAGULABLE STATES
Antiphospholipid syndrome — The antiphospholipid syndrome (APS) is a hypercoagulable
state characterized by recurrent arterial or venous thromboembolism, or pregnancy loss, in
association with antibodies directed against plasma proteins that may be bound to anionic
phospholipids. The presence of such antibodies may be detected as lupus anticoagulants,
anticardiolipin antibodies, or anti-beta2 glycoprotein-I antibodies. (See "Diagnosis of
antiphospholipid syndrome".)
This disorder has been referred to as primary antiphospholipid syndrome when it occurs alone;
however, it can also be seen in association with systemic lupus erythematosus, other rheumatic
disorders, and autoimmune diseases. (See "Clinical manifestations of antiphospholipid
syndrome".)
Due to the high rate of recurrent thrombosis, long-term anticoagulation is the mainstay of
therapy for patients with thrombotic APS. However, for patients with arterial thromboembolism,
including ischemic stroke, data on the optimal therapeutic approach to prevent recurrent
thromboembolism are limited. While experts agree that anticoagulation
with warfarin (international normalized ratio range, 2 to 3) is the first-line therapy for patients
with APS and arterial thromboembolism, others suggest adding low-dose aspirin for selected
patients with arterial events who also have additional risk factors for atherosclerotic vascular
disease. Direct oral anticoagulants (DOACs) may be less effective than warfarin for thrombosis
prevention, particularly among patients with known or possible APL who are considered high
risk and/or have a history of arterial thrombosis. (See "Management of antiphospholipid
syndrome", section on 'Secondary thrombosis prevention'.)
Risk-benefit assessment is important in arterial thromboembolism, as some individuals may
reasonably choose to use another treatment approach. These issues are reviewed in detail
elsewhere. (See "Management of antiphospholipid syndrome", section on 'Secondary thrombosis
prevention'.)
Inherited thrombophilias — Inherited thrombophilias are hypercoagulable states that include a
number of disorders:
●Protein C deficiency
●Protein S deficiency
●Antithrombin III deficiency
●Activated protein C resistance
●Factor V Leiden as a cause of activated protein C resistance
●Prothrombin G20210A mutation
These conditions are thought to be rare causes of ischemic stroke in adults, but may be more
important causes of ischemic stroke in children. (See "Ischemic stroke in children and young
adults: Epidemiology, etiology, and risk factors", section on 'Hematologic'.)
The 2021 American Heart Association/American Stroke Association (AHA/ASA) guidelines
note that it is uncertain whether testing for these hematologic traits is beneficial in the context of
secondary stroke prevention [14]. Suspicion for hypercoagulable states as the cause of stroke
may be heightened in younger patients with cryptogenic stroke, a history or family history of
unprovoked thrombosis, prior spontaneous abortion, or concomitant systemic signs and
symptoms suggestive of hypercoagulability. The same guidelines note that for patients with
ischemic stroke or TIA of unknown source (despite a thorough diagnostic evaluation) who are
found to have an inherited thrombophilia, antiplatelet treatment is reasonable to reduce the risk
of recurrent stroke or TIA [14].
The evaluation and management of these conditions is discussed in greater detail separately.
(See "Antithrombin deficiency" and "Protein C deficiency" and "Protein S
deficiency" and "Factor V Leiden and activated protein C resistance" and "Prothrombin
G20210A" and "Overview of homocysteine" and "Cerebral venous thrombosis: Treatment and
prognosis".)
Cancer-related hypercoagulable state — Patients with cancer may be at increased risk for
stroke due to hypercoagulability and other potential mechanisms, including compression or
invasion of blood vessels, infections, paraneoplastic disorders, and complications of cancer
therapies [26,27]. (See "Pathogenesis of the hypercoagulable state associated with malignancy".)
For patients with TIA or ischemic stroke attributed to cancer hypercoagulability, optimal
treatment for secondary stroke prevention is unknown, and data are limited [27]. Empiric
treatment with low molecular weight heparin is often used despite the increased risk of bleeding
compared with antiplatelets [28]. In patients with venous thromboembolism (VTE) and cancer,
anticoagulant therapy is the cornerstone of treatment. However, compared with patients who do
not have cancer, anticoagulation in patients with cancer is complicated due to higher than usual
rates of recurrent VTE and bleeding while on anticoagulation as well as the impact of
comorbidities, procedures, and medications. (See "Anticoagulation therapy for venous
thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult
patients with malignancy".)
The 2021 AHA/ASA guidelines note only that in the setting of atrial fibrillation and cancer, it is
reasonable to consider anticoagulation with DOACs in preference to warfarin for stroke
prevention [14].
CRYPTOGENIC STROKE Cryptogenic stroke is variably defined and generally
designates the category of brain infarction that is not attributed to an established source of
cardioembolism, large artery atherosclerosis, or small artery disease. However, the term
cryptogenic stroke has been applied to patients with an incomplete diagnostic evaluation, a
complete but unrevealing evaluation, or an evaluation that identifies multiple potential causes of
stroke. (See "Cryptogenic stroke", section on 'Classification'.)
Embolic stroke of undetermined source (ESUS) is a subcategory of cryptogenic stroke defined as
a nonlacunar brain infarct without proximal arterial stenosis or cardioembolic sources; ESUS
requires a full standardized stroke evaluation to exclude other causes. While the less well-defined
term of cryptogenic stroke has been reported to account for about 25 to 40 percent of ischemic
strokes, the more specific term of ESUS consistently accounts for about 20 percent of ischemic
strokes. (See "Cryptogenic stroke", section on 'Embolic stroke of undetermined source'.)
For secondary prevention, most patients with a cryptogenic ischemic stroke or TIA should be
treated with blood pressure control, low-density lipoprotein cholesterol lowering therapy, and
lifestyle modification. Initial antiplatelet therapy is advised while awaiting the results of long-
term cardiac monitoring. For patients initially diagnosed with cryptogenic stroke who have atrial
fibrillation of any duration detected on long-term monitoring, even if detected remotely from the
incident stroke, anticoagulant therapy with warfarin or a direct oral anticoagulant is advised
rather than antiplatelet therapy. (See "Cryptogenic stroke", section on 'Secondary prevention'.)
SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines
from selected countries and regions around the world are provided separately. (See "Society
guideline links: Stroke in adults".)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written
in plain language, at the 5th to 6th grade reading level, and they answer the four or five key
questions a patient might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more detailed. These articles are written at
the 10th to 12th grade reading level and are best for patients who want in-depth information and
are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a variety
of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Stroke (The Basics)")

●Beyond the Basics topics (see "Patient education: Transient ischemic attack (Beyond the
Basics)" and "Patient education: Stroke symptoms and diagnosis (Beyond the
Basics)" and "Patient education: Ischemic stroke treatment (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Large artery disease – Secondary prevention for ischemic stroke or transient ischemic
attack (TIA) attributed to large artery disease may include the following measures:
•Symptomatic internal carotid stenosis – In addition to medical management,
revascularization, most often with carotid endarterectomy, is beneficial for patients
with recently symptomatic internal carotid artery atherosclerotic stenosis. In the setting
of complete carotid occlusion, medical management is the only practical option.
(See 'Symptomatic carotid stenosis' above.)
•Extracranial vertebral artery – In most cases, ischemic stroke and TIA due to
extracranial vertebral artery stenosis is managed by intensive medical treatment with
multifactorial risk reduction. (See 'Extracranial vertebral artery stenosis' above.)
•Intracranial atherosclerosis – Aggressive medical management is superior to
stenting for patients with recently symptomatic high-grade intracranial large artery
stenosis. (See 'Intracranial large artery atherosclerosis' above.)
•Arterial dissection – Antithrombotic therapy with either antiplatelet or anticoagulant
agents is used for the secondary prevention of ischemic stroke and TIA caused by
cervical arterial dissection. (See 'Dissection' above.)
●Small artery disease – Antiplatelet therapy and treatment of modifiable risk factors is
the mainstay for secondary stroke prevention in patients with lacunar stroke or TIA due to
small artery disease. (See 'Small artery disease' above.)
●Cardiogenic embolism – Virtually all patients with atrial fibrillation who have a history
of stroke or TIA should be treated with oral anticoagulation in the absence of
contraindications. (See 'Atrial fibrillation' above.)
Other cardiac sources of embolism for which anticoagulation is often indicated include:
•Left ventricular thrombus (see 'Left ventricular thrombus' above)
•Cardiomyopathy (see 'Cardiomyopathy' above)
•Prosthetic heart valves (see 'Valvular disease' above)
•Moderate to severe mitral stenosis, even in the absence of atrial fibrillation
(see 'Valvular disease' above)
•Congenital heart disease (see 'Congenital heart disease' above)
Patent foramen ovale (PFO) device closure is more effective than medical therapy alone
for select patients with a PFO-associated stroke. Evaluation and treatment are summarized
in the algorithm (algorithm 3) and discussed in detail separately. (See "Treatment of patent
foramen ovale (PFO) for secondary stroke prevention".)
 ●Aortic atherosclerosis – The optimal treatment for the prevention of ischemic stroke and
TIA attributed to aortic arch atherosclerosis is not clear. Medical management with
antiplatelet and low-density lipoprotein cholesterol lowering therapy is reasonable.
(See 'Aortic atherosclerosis' above.)
●Sickle cell disease – Stroke is a frequent complication of sickle cell disease, and the risk
of recurrent stroke is high. Stroke risk can be reduced with chronic transfusion therapy.
(See 'Sickle cell disease' above and "Prevention of stroke (initial or recurrent) in sickle cell
disease".)
●Hypercoagulable states – Anticoagulation with warfarin is the gold standard for patients
with antiphospholipid syndrome and arterial thromboembolism; some experts add low-
dose aspirin for selected patients with arterial events who also have additional risk factors
for atherosclerotic vascular disease.
With TIA or ischemic stroke attributed to cancer hypercoagulability, the optimal treatment
for secondary stroke prevention is unknown.
Inherited thrombophilias are thought to be rare causes of ischemic stroke in adults. For
patients with ischemic stroke or TIA of unknown source (despite a thorough diagnostic
evaluation) who are found to have an inherited thrombophilia, antiplatelet treatment is
reasonable. (See 'Hypercoagulable states' above.)

NIHSS — The NIHSS is both reliable and valid, and has become a standard stroke
impairment scale for use in both clinical trials and as part of clinical care in the United
States in many other countries [27-31]. As examples, the NIHSS score is part of the
assessment that helps determine whether a patient is a candidate for reperfusion
therapy with intravenous thrombolysis and/or mechanical thrombectomy
(see "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic
use" and "Mechanical thrombectomy for acute ischemic stroke"). In addition, the
baseline NIHSS score is predictive of long-term outcome after acute stroke, as noted
above. The NIHSS can also be assessed remotely and may be useful in telemedicine
programs [32].
The NIHSS measures neurologic impairment using a 15 item scale (table 7) [27]. A full
text version of the NIHSS is available online
at www.ninds.nih.gov/sites/default/files/NIH_Stroke_Scale.pdf, and a graphic version is
available at www.ninds.nih.gov/sites/default/files/NIH_Stroke_Scale_Booklet.pdf. An
NIHSS calculator (calculator 1) is best used by a certified NIHSS examiner in
conjunction with a copy of the full NIHSS. Both physician and nurse stroke providers
can be trained to use the scale with similar levels of accuracy [33]. Reliability can be
further improved through the use of standardized video training [34,35].
The NIHSS has been validated for retrospective use based upon information available
in the patient's medical record over a range of severities [36-39]. An important limitation
of the NIHSS is that it does not capture all stroke-related impairments, particularly with
infarction involving the vertebrobasilar circulation [40,41]. This is also true for modified,
shortened versions of the scale [42,43]
Modified NIHSS — The modified NIHSS (mNIHSS) is a shortened version of the
NIHSS that omits level of consciousness (item 1a), facial weakness (item 4), limb ataxia
(item 7), and dysarthria (item 10) from the original NIHSS and condenses the sensory
test (item 8) choices from three to two responses (table 8) [44]. In the original derivation
study and subsequent prospective validation, the validity and reliability of the mNIHSS
was nearly identical to the original NIHSS [42,44].
Pediatric NIHSS — The Pediatric National Institutes of Health Stroke Scale (PedNIHSS)
was developed by modifying the adult NIHSS so that examination items and testing
materials are age-appropriate (table 9 and figure 2 and figure 3 and figure 4) [45]. In a
multicenter, prospective cohort study of children with acute arterial ischemic stroke, the
PedNIHSS showed good interrater reliability when employed by trained pediatric
neurologists.

National Institutes of Health Stroke Scale (NIHSS)

Administer stroke scale items in the order listed. Record performance in each category after each subscale exam. Do not
go back and change scores. Follow directions provided for each exam technique. Scores should reflect what the patient
does, not what the clinician thinks the patient can do. The clinician should record answers while administering the exam
and work quickly. Except where indicated, the patient should not be coached (ie, repeated requests to patient to make a
special effort).

Instructions Scale definition Score

1a. Level of consciousness: The investigator 0 = Alert; keenly responsive.

must choose a response if a full evaluation is
prevented by such obstacles as an endotracheal
tube, language barrier, orotracheal
trauma/bandages. A 3 is scored only if the patient
makes no movement (other than reflexive
posturing) in response to noxious stimulation.
1 = Not alert; but arousable by minor stimulation to
obey, answer, or respond.
2 = Not alert; requires repeated stimulation to attend, or
_
is obtunded and requires strong or painful stimulation to
make movements (not stereotyped).
3 = Responds only with reflex motor or autonomic
effects or totally unresponsive, flaccid, and areflexic.

1b. Level of consciousness questions: The 0 = Answers both questions correctly.

patient is asked the month and his/her age. The 1 = Answers one question correctly.
answer must be correct - there is no partial credit 2 = Answers neither question correctly.
for being close. Aphasic and stuporous patients
who do not comprehend the questions will score
2. Patients unable to speak because of
_____
endotracheal intubation, orotracheal trauma,
severe dysarthria from any cause, language
barrier, or any other problem not secondary to
aphasia are given a 1. It is important that only the
initial answer be graded and that the examiner not
"help" the patient with verbal or non-verbal cues.
1c. Level of consciousness commands: The 0 = Performs both tasks correctly.
patient is asked to open and close the eyes and 1 = Performs one task correctly.
then to grip and release the non-paretic hand. 2 = Performs neither task correctly.
Substitute another one step command if the hands
cannot be used. Credit is given if an unequivocal
attempt is made but not completed due to
weakness. If the patient does not respond to _____
command, the task should be demonstrated to
him or her (pantomime), and the result scored (ie,
follows none, one or two commands). Patients
with trauma, amputation, or other physical
impediments should be given suitable one-step
commands. Only the first attempt is scored.

2. Best gaze: Only horizontal eye movements 0 = Normal.

will be tested. Voluntary or reflexive 1 = Partial gaze palsy; gaze is abnormal in one or both
(oculocephalic) eye movements will be scored, eyes, but forced deviation or total gaze paresis is not
but caloric testing is not done. If the patient has a present.
conjugate deviation of the eyes that can be 2 = Forced deviation, or total gaze paresis not
overcome by voluntary or reflexive activity, the overcome by the oculocephalic maneuver.
score will be 1. If a patient has an isolated
peripheral nerve paresis (cranial nerves III, IV or
VI), score a 1. Gaze is testable in all aphasic _____
patients. Patients with ocular trauma, bandages,
pre-existing blindness, or other disorder of visual
acuity or fields should be tested with reflexive
movements, and a choice made by the
investigator. Establishing eye contact and then
moving about the patient from side to side will
occasionally clarify the presence of a partial gaze
palsy.

3. Visual: Visual fields (upper and lower 0 = No visual loss.

quadrants) are tested by confrontation, using 1 = Partial hemianopia.
_____
finger counting or visual threat, as appropriate. 2 = Complete hemianopia.
Patients may be encouraged, but if they look at 3 = Bilateral hemianopia (blind including cortical
the side of the moving fingers appropriately, this
can be scored as normal. If there is unilateral
blindness or enucleation, visual fields in the
remaining eye are scored. Score 1 only if a clear-
cut asymmetry, including quadrantanopia, is
found. If patient is blind from any cause, score 3.
Double simultaneous stimulation is performed at
this point. If there is extinction, patient receives a
1, and the results are used to respond to item 11.
4. Facial palsy: Ask - or use pantomime to
encourage - the patient to show teeth or raise
eyebrows and close eyes. Score symmetry of
grimace in response to noxious stimuli in the
poorly responsive or non-comprehending patient.
If facial trauma/bandages, orotracheal tube, tape
or other physical barriers obscure the face, these
should be removed to the extent possible.
5. Motor arm: The limb is placed in the
appropriate position: extend the arms (palms
down) 90 degrees (if sitting) or 45 degrees (if
supine). Drift is scored if the arm falls before 10
seconds. The aphasic patient is encouraged using
urgency in the voice and pantomime, but not
noxious stimulation. Each limb is tested in turn,
beginning with the non-paretic arm. Only in the
case of amputation or joint fusion at the shoulder,
the examiner should record the score as
untestable (UN), and clearly write the
explanation for this choice.
6. Motor leg: The limb is placed in the
appropriate position: hold the leg at 30 degrees
(always tested supine). Drift is scored if the leg
blindness).
0 = Normal symmetrical movements.
1 = Minor paralysis (flattened nasolabial fold,
asymmetry on smiling).
2 = Partial paralysis (total or near-total paralysis of
_____
lower face).
3 = Complete paralysis of one or both sides (absence
of facial movement in the upper and lower face).
0 = No drift; limb holds 90 (or 45) degrees for full 10
seconds.
1 = Drift; limb holds 90 (or 45) degrees, but drifts
down before full 10 seconds; does not hit bed or other
support.
2 = Some effort against gravity; limb cannot get to or
maintain (if cued) 90 (or 45) degrees, drifts down to
_____
bed, but has some effort against gravity.
3 = No effort against gravity; limb falls.
4 = No movement.
UN = Amputation or joint fusion,
explain:________________
5a. Left arm
5b. Right arm
0 = No drift; leg holds 30-degree position for full 5
seconds. _____
1 = Drift; leg falls by the end of the 5-second period but
falls before 5 seconds. The aphasic patient is does not hit bed.
encouraged using urgency in the voice and 2 = Some effort against gravity; leg falls to bed by 5
pantomime, but not noxious stimulation. Each seconds, but has some effort against gravity.
limb is tested in turn, beginning with the non- 3 = No effort against gravity; leg falls to bed
paretic leg. Only in the case of amputation or immediately.
joint fusion at the hip, the examiner should record 4 = No movement.
the score as untestable (UN), and clearly write UN = Amputation or joint fusion,
the explanation for this choice. explain:________________
6a. Left leg
6b. Right leg

7. Limb ataxia: This item is aimed at finding 0 = Absent.

evidence of a unilateral cerebellar lesion. Test 1 = Present in one limb.
with eyes open. In case of visual defect, ensure 2 = Present in two limbs.
testing is done in intact visual field. The finger- UN = Amputation or joint fusion,
nose-finger and heel-shin tests are performed on explain:________________
both sides, and ataxia is scored only if present out
of proportion to weakness. Ataxia is absent in the _____
patient who cannot understand or is paralyzed.
Only in the case of amputation or joint fusion, the
examiner should record the score as untestable
(UN), and clearly write the explanation for this
choice. In case of blindness, test by having the
patient touch nose from extended arm position.

8. Sensory: Sensation or grimace to pinprick 0 = Normal; no sensory loss.

when tested, or withdrawal from noxious
stimulus in the obtunded or aphasic patient. Only
sensory loss attributed to stroke is scored as
abnormal and the examiner should test as many
body areas (arms [not hands], legs, trunk, face) as
needed to accurately check for hemisensory loss.
A score of 2, "severe or total sensory loss,"
should only be given when a severe or total loss
of sensation can be clearly demonstrated.
Stuporous and aphasic patients will, therefore,
1 = Mild-to-moderate sensory loss; patient feels
pinprick is less sharp or is dull on the affected side; or
there is a loss of superficial pain with pinprick, but
patient is aware of being touched.
2 = Severe to total sensory loss; patient is not aware of _____
being touched in the face, arm, and leg.
probably score 1 or 0. The patient with brainstem
stroke who has bilateral loss of sensation is
scored 2. If the patient does not respond and is
quadriplegic, score 2. Patients in a coma (item
1a=3) are automatically given a 2 on this item.
9. Best language: A great deal of information
about comprehension will be obtained during the
preceding sections of the examination. For this
scale item, the patient is asked to describe what is
happening in the attached picture, to name the
items on the attached naming sheet and to read
from the attached list of sentences.
Comprehension is judged from responses here, as
well as to all of the commands in the preceding
general neurological exam. If visual loss
interferes with the tests, ask the patient to identify
objects placed in the hand, repeat, and produce
speech. The intubated patient should be asked to
write. The patient in a coma (item 1a=3) will
automatically score 3 on this item. The examiner
must choose a score for the patient with stupor or
limited cooperation, but a score of 3 should be
used only if the patient is mute and follows no
one-step commands.
10. Dysarthria: If patient is thought to be
normal, an adequate sample of speech must be
obtained by asking patient to read or repeat words
from the attached list. If the patient has severe
aphasia, the clarity of articulation of spontaneous
speech can be rated. Only if the patient is
intubated or has other physical barriers to
producing speech, the examiner should record the
score as untestable (UN), and clearly write an
explanation for this choice. Do not tell the patient
0 = No aphasia; normal.
1 = Mild-to-moderate aphasia; some obvious loss of
fluency or facility of comprehension, without significant
limitation on ideas expressed or form of expression.
Reduction of speech and/or comprehension, however,
makes conversation about provided materials difficult
or impossible. For example, in conversation about
provided materials, examiner can identify picture or
naming card content from patient's response.
2 = Severe aphasia; all communication is through _____
fragmentary expression; great need for inference,
questioning, and guessing by the listener. Range of
information that can be exchanged is limited; listener
carries burden of communication. Examiner cannot
identify materials provided from patient response.
3 = Mute, global aphasia; no usable speech or auditory
comprehension.
0 = Normal.
1 = Mild-to-moderate dysarthria; patient slurs at least
some words and, at worst, can be understood with some
difficulty.
2 = Severe dysarthria; patient's speech is so slurred as
_____
to be unintelligible in the absence of or out of
proportion to any dysphasia, or is mute/anarthric.
UN = Intubated or other physical barrier,
explain:________________
why he or she is being tested.

11. Extinction and inattention (formerly 0 = No abnormality.

neglect): Sufficient information to identify 1 = Visual, tactile, auditory, spatial, or personal
neglect may be obtained during the prior testing. inattention or extinction to bilateral simultaneous
If the patient has a severe visual loss preventing stimulation in one of the sensory modalities.
visual double simultaneous stimulation, and the 2 = Profound hemi-inattention or extinction to more
cutaneous stimuli are normal, the score is normal. than one modality; does not recognize own hand or
_____
If the patient has aphasia but does appear to orients to only one side of space.
attend to both sides, the score is normal. The
presence of visual spatial neglect
or anosognosia may also be taken as evidence of
abnormality. Since the abnormality is scored only
if present, the item is never untestable.

_____
Adapted from: Goldstein LB, Samsa GP. Reliability of the National Institutes of Health Stroke Scale.
Extension to non-neurologists in the context of a clinical trial. Stroke 1997; 28:307.
Graphic 61698 Version 8.0
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