The ABC’s of Stroke Complications

W. David Freeman, M.D.,1 Steven B. Dawson, M.D.,1 and Kelly D. Flemming, M.D.2

ABSTRACT

Stroke is the third leading cause of death in the United States, with more
than 140,000 deaths per year. Complications related to stroke resulting in morbidity
and mortality are very common and may result from cerebral and extracerebral causes.
Cerebral causes include cerebral edema, hemorrhagic conversion of an ischemic
infarct, and progression of penumbra to infarction. Extracerebral complications

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include deep vein thrombosis and pulmonary embolism, urinary tract infection, and
aspiration. Many of these complications are largely preventable and often tracked as
‘‘quality metrics’’ in institutions with a stroke center designation. The focus of the
article is primarily on common poststroke complications, such as aspiration, DVT,
decubitus ulcers, seizures, and urinary catheter infections. Knowledge about potential
poststroke complications is critical to earlier diagnosis, proper preventive strategies,
and management.

KEYWORDS: Stroke complications, aspiration, deep vein thrombosis, pneumonia

Stroke-related death 1
and its complications2–26
(Fig. 1), can be conceptualized into 2 types: cerebral or
extracerebral (Table 1). Cerebral complications arise
intracranially and occur as part of the subsequent path-
ophysiology after the initial stroke, such as a massive
ischemic stroke leading to swelling, herniation, and
brain death. Extracerebral complications after stroke
are defined by the organ systems affected (e.g., endo-
crinologic, pulmonary, cardiac, gastrointestinal). This
classification of stroke complications is useful, holistic,
and helps provide a comprehensive approach in manag-
ing stroke patients.
Complications of stroke are largely preventable.
A simple mnemonic, the ABC’s, can help practitioners
remember and treat such complications (Table 2). The
prevention of these complications is important to re-
duce morbidity and mortality from stroke as well and
serve quality improvement goals.
CEREBRAL COMPLICATIONS OF STROKE
Cerebrovascular Pathophysiology
An overview of cerebral complications is provided in
Table 1. Ischemia causes brain injury, which manifests as
neurologic deficits. The type of neurologic deficit de-
pends on the area of brain affected. Neurons and glia are
strictly aerobic tissue, with the highest metabolic de-
mand of all tissues within the human body. The brain
takes at least 15% of the cardiac output, indicative of its
high metabolic demands for oxygen and glucose. Brain
tissue without oxygen and glucose quickly depletes intra-
cellular ATP and rapidly converts to converting glucose
to lactate, which produce 2 ATP, compared with up to
36 ATP from aerobic metabolism. Anaerobic conditions
are intolerable to brain tissue and quickly create an
intracellular acidosis, which triggers a cascade of events
that either lead to programmed cell death, if there are

1
Department of Neurology, Mayo Clinic, Jacksonville, Florida;
2
Department of Neurology, Mayo Clinic, Rochester, Minnesota.
Address for correspondence and reprint requests: W. David
Freeman, M.D., Mayo Clinic, Cannaday 2 East, Jacksonville, FL
32224 (e-mail: freeman.william1@mayo.edu).
Stroke; Guest Editor, Kelly D. Flemming, M.D.
Semin Neurol 2010;30:501–510. Copyright # 2010 by Thieme
Medical Publishers, Inc., 333 Seventh Avenue, New York, NY
10001, USA. Tel: +1(212) 584-4662.
DOI: http://dx.doi.org/10.1055/s-0030-1268863.
ISSN 0271-8235.
501
502 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER 5 2010
Figure 1 Complications after stroke. DVT, deep vein
thrombosis; UTI, urinary tract infection. (Modified from
Langhorne P. et al. Stroke 2000; 31:1223–1229).2
marginal energy/nutrient supply, or cell death in extreme
metabolic deficits. The region of the brain that receives
less than 10 mL/100 g/min of cerebral blood flow (CBF)
will infarct if this is not corrected in minutes. In ischemic
stroke, this area is termed the core region of infarction.
Brain tissue that receives more than 20 but less than
50 mL/100 g/min CBF is oligemic or reduced. Oligemic
brain tissue that surrounds the core region of ischemia is
termed penumbra (surrounds the core region of non-
viable tissue) and can only be tolerated for a finite period
before permanent cellular injury and death ensue.
At the onset of large-vessel ischemic stroke, such
as occlusion of the middle cerebral artery, there is a
region of core ischemia that becomes infarcted rapidly
within minutes, as well as an area called the penumbra,
which is potentially salvageable and amenable to throm-
bolysis (e.g., issue plasminogen activator [tPA]) and
reperfusion strategies. The most common complication
after infarction is the damage to the underlying paren-
chyma and the functional activity that area of the brain
controlled.
Secondary Pathophysiologic Mechanisms
After the initial ischemic area evolves, secondary path-
ophysiologic mechanisms may occur that result in
further deterioration of neurologic status. These in-
clude progression of the oligemic penumbra to infarc-
tion, hemorrhagic conversion of the ischemic infarct,
and the development of cerebral edema resulting in
increased intracranial pressure. In addition, recurrent
stroke and the development of seizures affect morbidity
and mortality.
Progression of Penumbra to Infarction
Secondary brain injury and mechanisms are also impor-
tant and a common cause of subsequent neurologic
deterioration after initial stroke. For example, a patient
with a middle cerebral artery occlusion with an area of
potentially viable penumbra has a variable amount of
time before the penumbra becomes completely in-
farcted or irreversible, similar to the core region of
infarction. Several other factors can lead to stroke
progression. The first is the ability of cerebrovascular
collaterals to maintain flow to the area of penumbra.
The second factor is time, which is of the essence, as
some patients have more robust collaterals. A third
factor is the degree of cerebral perfusion pressure (CPP)
which is derived from mean arterial pressure (MAP)
minus intracranial pressure (ICP). Many patients have
an acute hypertensive response in the setting of an acute
stroke. This can be thought of as a somewhat self-
protective reflex similar to the Cushing reflex. Hypo-
tension is injurious to ischemic stroke patients due to
this area of vulnerable normal brain tissue. Other
factors include blood rheology, hemoglobin, and oxy-
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gen delivery capacity of the blood, abnormal coagula-
tion, or thrombotic potential. Factors within the
vascular wall that contribute to vessel occlusion and
ischemic infarction include fatty material within pla-
ques causing platelet adhesion, subsequent red clot
formation, and in situ thrombotic occlusion.
Hemorrhagic Transformation
Conversion of an ischemic infarction into a hemorrha-
gic one, called hemorrhagic conversion, is due to the
breakdown of the blood–brain barrier (BBB) with
leakage of intravascular blood and its contents into
injured ischemic or infarcted brain tissue or infarcted
tissue. Subsequent continued bleeding can expand the
hemorrhage similar to a primary intraparenchymal
hemorrhage. Careful control of blood pressure after
acute stroke within stated guidelines3 (< 180 mm Hg
systolic after thrombolysis within the first 24 hours,
< 210 systolic without thrombolysis, or less than 160
after intracranial hemorrhage) is a primary means to
limit this complication as well as the avoidance of
unnecessary anticoagulants.
Mass Effect and Raised Intracranial Pressure
Mass effect with subsequent raised ICP is another form
of secondary brain injury (Fig. 2) that can result in
worsening of cerebral blood flow. One form of ischemic
stroke known to cause edema and significant mass effect
is that of the so-called malignant cerebral infarction.
This typically occurs in the setting of an occlusion of the
internal carotid artery or the middle cerebral artery. In
such cases, massive cerebral edema can occur, causing
herniation3 and subsequent brain death.
For patients with suspected raised ICP, place-
ment of an ICP monitor or ventriculostomy is required
for aggressive therapy. An osmotic agent, such as
 THE ABC’S OF STROKE COMPLICATIONS/FREEMAN ET AL 503

Table 1 Ischemic Stroke Complications

Cerebral Complications
Primary brain injury
Initial stroke: Neurologic and functional deficits, delirium
Recurrent stroke (9%)
Secondary brain injury
Stroke progression
Penumbra progression to infarction
Hemorrhagic conversion of ischemic infarct
Cerebral edema, mass effect, herniation, raised intracranial pressure
Hydrocephalus (communicating or noncommunicating)
Seizures 3%2 (higher in embolic strokes)
Stroke-specific complications
Neurologic breathing patterns (e.g., Cheyne-Stokes, cluster, apneustic, ataxic)
Autonomic dysfunction—acute hypertension, Cushing reflex
Depression/anxiety (12–16%2)
Pressure palsies (mononeuropathies) and critical illness myoneuropathy

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Pain—immobility, contractures, spasticity, or central pain syndrome
Extracerebral Complications
Head and neck
Angioedema after rtPA and/or ACEI/ARB38,39
Pulmonary
Aspiration without pneumonia, aspiration pneumonia (24%2), pneumonitis,
Acute lung injury, pulmonary edema (e.g., cardiac or neurogenic),
ARDS, pulmonary embolism
Endocrine
Sodium and water homeostasis disturbance (e.g., SIADH)
Cardiac
Neurocardiogenic injury (e.g., Tako Tsubo cardiomyopathy, troponin ‘leak’)
Myocardial infarction, cardiogenic shock, pulmonary edema
ECG changes: arrhythmias, ST and T wave changes on ECG, atrial fibrillation
Gastrointestinal
Cushing ulcer, gastrointestinal bleeding, ileus, malnutrition
Genitourinary
Urinary tract infection (24%2)
Limb
Deep vein thrombosis (2–3%2)
Contractures and adhesive capsulitis
Skin
Decubitus ulcers (21%2), infections
Adapted from Langhorne P., et al. Stroke 2000;31:1223–1229.2
ACEI, ACE inhibitor; ARB, angiotensin receptor blocking agent; ARDS, acute respiratory distress syndrome; ECG, electrocardiogram; rtPA,
recombinant tissue plasminogen activator; SIADH, syndrome of inappropriate antidiuretic hormone hypersecretion.

mannitol or hypertonic saline, can be given to reduce
ICP,3,18 but often is a temporizing measure. For patients
with symptomatic mass effect, consideration may be
given to hemicraniectomy.3,18 Medical and surgical
management of malignant cerebral edema and the role
of hemicraniectomy in acute cerebral infarction is be-
yond the scope of this review.3,18 It is, however, impor-
tant to remember that to prevent further ischemia, one
must maintain CPP. Cerebral perfusion pressure can be
calculated once ICP and MAP are obtained from mon-
itoring via the equation, CPP ¼ MAP – ICP. For most
patients with ischemic stroke, the CPP should be kept in
the range of 65 to 70 mm Hg or higher. Cerebral
perfusion pressure values greater than 130 may lead to
hyperemia, worsened cerebral edema, or hemorrhage.
Recurrent Stroke
Recurrent stroke occurs in
9% of patients after an
initial stroke within the first few weeks.2 (Fig. 1)
Identification of the underlying stroke mechanism
and targeting treatment remains the best way to reduce
504 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER 5 2010
Table 2 ‘‘ABC’s’’ of Stroke Management (American
Heart Association Guidelines)3,18
A–Airway/aspiration, cardiac monitor  24 hour all patients, O2
for hypoxic patients, intubation/mechanical ventilation for
compromised airway—Class I
B–Blood pressure control specific to stroke type—Class II.
Hypotension etiology should be evaluated and treated—Class I
C–CPP (measure and control ICP if elevated)—Class II
D–DVT prevention with compression devices—Class I, if no
active bleeding risk, then consider SQ UFH or LMWH-Class II
E–Early mobilization—Class I
F–Fever worked up & treated aggressively—Class I
G–Glucose > 140 – 185 mg/dL, use insulin; hypoglycemia
should be treated—Class I
CPP, cerebral perfusion pressure; DVT, deep vein thrombosis; ICP,
intracranial pressure; LMWH, low-molecular-weight heparin; SQ,
subcutaneous; UFH, unfractionated heparin.
subsequent stroke risk (e.g., atrial fibrillation, and
eventual anticoagulation).
Seizures
Seizures are common after stroke, occurring in 3% of
patients,18,23 particularly within the first 24 hours after
stroke, and are typically partial with or without secon-
dary generalization. A seizure may herald the onset of a
stroke due to reduced seizure threshold from cortical
excitation and ischemia. A seizure may also occur from
Figure 2 Mass effect and downward displacement of the
brainstem (herniation). Herniation not only displaces brain
tissue, but also causes vascular injury to brain tissue by
compressing perforating arteries and arterioles. (Permission
Mayo Foundation for Medical Education. All rights reserved).
an embolic event with transient ischemia and subsequent
reperfusion. Seizure, importantly, is no longer an abso-
lute exclusion for tPA.3 Approximately 1 to 2% of stroke
patients present with status epilepticus.24 Seizures cause
secondary neurologic deterioration after stroke by in-
creasing brain metabolic activity in vulnerable ischemic
brain tissue. Burneo et al found that patients with
seizures had a higher mortality at 30 days (36.2% vs
16.8%, p < 0.0001), at 1-year poststroke (48.6% vs
27.7%, p < 0.001), had a longer hospitalization, and
greater disability at discharge (p < 0.001).23 Risk factors
for seizure after stroke by multivariate analysis included
stroke severity, hemorrhagic stroke subtype, and the
presence of neglect on neurologic exam. The authors
concluded that seizures after stroke increased resources
utilization, hospital length of stay, and increased both
30-day and one-year mortality. Recurrent seizures de-
velop in 2% to 33% of poststroke patients, particularly of
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the embolic stroke type.3 Late seizures vary in incidence
from 3% to 67%, and appear higher in patients with
preexisting dementia.3 Treatment of seizure with anti-
epileptic agents is individualized to the patient and
recommended.3
EXTRACEREBRAL (SYSTEMIC)
COMPLICATIONS
Aspiration Pneumonia and Pneumonitis
Aspiration is common after stroke due to impaired
swallowing and protective reflexes that fail to prevent
material entering the trachea and lower airways. Aspira-
tion can be due to depressed level of consciousness with
frank (or silent) aspiration of gastrointestinal contents,
or may be due to dysphagia or impaired swallowing
function. Impaired swallowing and impairment of other
brainstem reflexes may lead to aspiration of normal
airway secretions that are typically swallowed on an
unconscious level. Such aspiration of gastrointestinal
contents or upper airway contents can lead to aspiration
pneumonia or pneumonitis.
One of the most crucial factors in preventing
aspiration pneumonia is screening for dysphagia at
stroke presentation. A patient failing a bedside screening
test25 should be made NPO (nothing by mouth) until a
suitable means of nutrition or liquid can be given to the
patient in a safe manner. Until that time, the patient can
be given intravenous (IV) fluids. Temporary placement
of nasogastric tubes can be considered. If the patient
cannot safely swallow material or maintain nutritional
goals by oral diet by hospital discharge, a percutaneous
gastrostomy tube is often considered.
Another strategy to prevent aspiration is intubat-
ing patients who are comatose and not protecting their
airway.3 This may reduce, but not completely eliminate,
aspiration risk. If there is clinical suspicion of aspiration,

Figure 3 Chest radiograph shows aspiration pneumonia in
the right lower lobe.
further evaluation is required. It is important to eval-
uate patients that may have aspirated at the time of the
stroke or subsequently by chest auscultation as well as a
chest radiograph. If there is evidence of an infiltrate
(Fig. 3), antibiotic treatment is recommended.3 Pa-
tients who aspirate, but do not develop a frank infiltrate
on chest radiograph, may still develop a transient
productive cough, a low-grade fever, and a self-limited
pneumonitis. In such patients, a full course of anti-
biotics may not be warranted (e.g., risks of C. difficile
colitis from antibiotics may outweigh the benefit).
However, stroke patients with cough and fever should
be observed closely for the development of pneumonia
clinically or on a subsequent chest radiograph. Anti-
biotics are recommended once an infiltrate or pneumo-
nia is detected. Patients with massive aspiration may
develop acute lung injury or acute adult respiratory
distress syndrome (ARDS) and require intubation and
mechanical ventilation, bronchoscopy, and bronchoal-
veolar lavage.
Acute Hypertensive Response
Blood pressure management is important in patients
with acute ischemic or hemorrhagic stroke. Patients
with chronic hypertension may require relatively higher
levels of MAP from both a systemic and brain perfusion
standpoint. Current guidelines recommend that emer-
gent antihypertensives should be withheld in patients
with acute ischemic stroke unless the blood pressure
exceeds 220/100 mm Hg or a thrombolytic agent (e.g.,
THE ABC’S OF STROKE COMPLICATIONS/FREEMAN ET AL 505
tPA) has been given.3 If a thrombolytic agent is admin-
istered, the blood pressure should be treated if greater
than 185/110 mm Hg. Severe uncontrolled hypertension
with a MAP higher than 130 or 150 mm Hg is felt to
increase the risk of intracranial hemorrhage after throm-
bolysis. The exact target of blood pressure has yet to be
established; however, a reasonable goal is lowering the
blood pressure by 15% to 25% if the blood pressure is
elevated over the first 24 hours.3 Short-acting antihy-
pertensive agents (e.g., labetalol, hydralazine) are typi-
cally used to prevent overshooting the target.3
Hypotension (e.g., systolic < 110 mm Hg or
MAP <70 in nonhypertensive patients or 10 mm Hg
or more points below a chronic hypertensive patient’s
baseline MAP in the setting of ischemic stroke is known
to be harmful.3 Acute hypotension should be immedi-
ately treated (e.g., fluid bolus if dehydrated or volume
depleted, or occasionally vasopressor agents) and causes
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of the hypotension investigated (e.g., myocardial infarc-
tion or injury, sepsis/bacteremia, vasovagal response,
etc).
Venous Thromboembolism (VTE)
Deep vein thrombosis (DVT) (Fig. 4) is a common
complication after stroke due to limb paresis and im-
mobility. Asymptomatic DVT has been reported in 18%
to 40% of stroke patients, typically in the affected paretic
limb.3,18 Clinically symptomatic DVT (limb pain, swel-
ling, and/or fever) may occur in 3% to 5% of stroke
patients.26–31 Deep vein thrombosis risk factors include
advancing age, paretic limb/immobility, dehydration,
and most importantly, stroke severity (i.e., NIH Stroke
Scale).3,26–28 Deep vein thrombosis may develop within
1 week of immobility, and the risk of DVT often persists
in patients in nursing homes after acute hospitaliza-
tion.26
Pulmonary embolism (PE) is the most feared
complication in patients harboring a DVT. Half of
patients with symptomatic PE die at presentation, thus
stressing the importance of prevention.
Aspirin alone is insufficient for DVT–PE pre-
vention,31 but provides a small benefit for secondary
ischemic stroke prevention.32 Several studies evaluated
the role of unfractionated heparin (UFH) in venous
thromboembolism (VTE) prevention. The IST
Trial33,34 was the largest UFH trial performed to date
with 19,435 stroke patients. The study allocated half of
the patients to unfractionated heparin (5000 or 12,500
IU subcutaneously BID twice daily) and half did not
receive heparin. In a factorial design, half of the patients
were also allocated to aspirin 300 mg daily and half to no
aspirin. Thus, 6 different treatment allocations were
possible. The primary endpoint was death by 14 days,
and secondary death or dependency at 6 months. The
rate of pulmonary embolism in those allocated to heparin
506 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER 5 2010

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Figure 4 Upper image: Deep vein thrombosis (DVT) with pulmonary embolism. Lower left: Sequential compressive device.
Lower right: Vena cava filters. (Permission Mayo Foundation for Medical Education. All rights reserved).

was 0.5% compared with
0.8% in those not allocated to
receive heparin. There was no significant difference in
the rate of PE in those allocated to aspirin versus those
that did not receive it. The rate of major hemorrhage
in the heparin group was 1.3% compared with 0.4% in
those not receiving heparin.
A meta-analysis of studies evaluating low-molec-
ular-weight heparin (LMWH) in acute ischemic stroke
confirmed a role for heparin in prevention of VTE.
Treatment with LMWH was associated with significant
reductions in DVT and PE; however, there was an
increase in major extracranial hemorrhage. The studies
included in this meta-analysis, however, were designed
mainly around the primary endpoint of stroke outcome
and reduction of recurrent stroke. Thus, VTE was a
secondary endpoint.

The PREVAIL (Prevention of Venous
Thromboembolism after Acute Ischemic Stroke) Trial28
was the largest trial comparing LMWH enoxaparin
40 mg subcutaneously daily against UFH 5000 IU every
12 hours in 1,762 nonambulatory ischemic stroke pa-
tients. The rates of symptomatic DVT between the
LMWH group and the UFH group were not signifi-
cantly different (p ¼ 0.18). However, the rates of asymp-
tomatic DVT detected by ultrasound were statistically
less prevalent in the low-molecular-heparin group versus
the unfractionated heparin group (p < 0.0001). The rate
of symptomatic ICH in each group was 1% (n ¼ 4
occurred on enoxaparin, 3 of whom died) compared
with n ¼ 6 on UFH, 4 of whom died, which was not
statistically significant. Higher initial NIH Stroke Scale
(e.g., > 14) predicted bleeding. Symptomatic extracra-
nial bleeding was 1% in enoxaparin group (2 fatal) and
0% in UFH.
Several unresolved questions remain regarding
venous thromboembolism prophylaxis in patients with
ischemic stroke. The optimum duration of VTE pro-
phylaxis remains unanswered as clinical trials are often
limited to less than 2 weeks, but risk often persists
beyond this period. It is also unclear if there is a superior
agent and at what dose: fixed dose versus weight based
LMWH, UFH 5000 twice daily, or UFH 5000 3 times
daily. In a Cochrane analysis by Sandercock et al com-
paring ischemic stroke patients treated with either enox-
aparin 40 mg daily or unfractionated heparin 5000 IU
TID, the rate of DVT PE was 19.7% in the enoxaparin
group compared with 33.4% in the UFH group.27
However, the rates of symptomatic DVT PE and intra-
cranial hemorrhage were not significantly different.27 At
present, consensus guidelines3 recommend either UFH
or LMWH for nonambulatory patients with stroke.
Although commonly used, data do not show
efficacy for reducing VTE with the use of thigh high
hose. The CLOTS 1 trial investigated this in 2,518
acute stroke (ischemic or hemorrhagic) patients.29 The
patients were randomized to routine care plus leg stock-
ings or routine care plus avoidance of stockings. Patients
were assessed by Doppler ultrasound of the legs at 7 to
10 days and again between 25 and 30 days. The primary
endpoint was symptomatic or asymptomatic DVT in the
popliteal or femoral veins. The results showed a 10% rate
of DVT in patients with stockings compared with 10.5%
without the stockings, which was a nonsignificant re-
duction in risk. The patients with stockings were more
likely to have skin breaks, ulcers, blisters, and skin
necrosis than did patients without the stockings. The
data do not support the use of stockings for DVT
prevention in stroke patients. Further, a small study
investigated the use of compression stockings in 97
immobile patients admitted to an acute stroke unit, 65
of whom were allocated to receive stockings and 32 of
whom were allocated to usual care without stockings.
THE ABC’S OF STROKE COMPLICATIONS/FREEMAN ET AL 507
Although the study reported a reduction in DVT in the
stockings group, the reduction was not significant.30
Pneumatic sequential compression devices (SCDs)
are best studied in postoperative patients and less well
studied in patients with stroke.31 SCDs can be used in
combination with UFH or LMWH for high-risk DVT
patients; however, there is no evidence to suggest added
benefit or harm. These devices used alone are best
reserved for patients who cannot receive anticoagulants.
Some patients may require an inferior vena cava
(IVC) filter (Fig. 4). According to the American Heart
Association guidelines,3,18 ischemic stroke patients who
cannot receive anticoagulants and have a confirmed
DVT should be considered for an IVC filter. It is
important to note that little data exists regarding the
long-term safety of IVC filters, the ability for the filter to
prevent small emboli, and the length of time the filter
should be left in place.3 Complications from IVC filters
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include partial or even complete occlusion of the IVC
filter leading to IVC obstruction.
Cardiac Complications after Stroke
Cardiac complications and electrocardiogram (ECG)
changes are common after stroke. One type of compli-
cation is neurocardiogenic injury. Neurocardiogenic in-
jury is defined as cardiac injury that results from a
primary neurologic insult such as a stroke. Neurocardio-
genic injury can cause ECG changes and even troponin
elevation. Pathologically this type of injury is felt to be
related to contraction band necrosis rather than coagu-
lation necrosis seen in coronary occlusion and myocardial
infarction (MI). Initially, it can be difficult to discrim-
inate between a stress-induced neurocardiogenic injury
from a true acute myocardial infarction (AMI) from
underlying coronary artery disease. However, neurocar-
diogenic injury, especially when severe, typically has a
‘‘left ventricular apical balloon pattern.’’ This is also
known as Tako Tsubo (named after the shape of an
‘‘octopus pot’’ due to its characteristic ventriculogram
and echocardiogram appearance), which has an anterior
and apical wall akinesis or hypokinesis. This is in con-
trast to a coronary distribution MI, which typically has
an ECG and echocardiogram appearance of dysfunction
in the vascular territory of the coronary vessel. The right
coronary artery distribution usually affects the right
lateral ventricle wall and base, whereas the left anterior
descending artery distribution is the anterior two-thirds
of the heart. Tako Tsubo cardiomyopathy after stroke
also typically improves in terms of the ejection fraction
on echocardiogram within a few weeks time compared
with a frank MI, which may leave permanently reduced
left ventricular ejection fraction. Serial troponins and
ECGs, as well as an echocardiogram and cardiology
evaluation, are useful in helping to distinguish between
these two entities and to help with management.
508 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER 5 2010
Figure 5 Stages of decubitus ulcers.
Stroke and coronary artery disease (CAD) are also
comorbidities.35,36 Stroke risk is highest within 3 months
of a MI.35,36 One third of stroke patients have CAD (or
silent CAD).35,36 Three percent of stroke patients die
from cardiac event in less than 90 days. In addition,
stroke may be the presenting sign of an MI in a small
percentage of patients (ventricular dysfunction). To
further complicate this issue, aphasic patients may not
complain of chest pain or may be diaphoretic and
tachycardic, which is nonspecific. Management of
MI after stroke typically includes starting or continuing
aspirin (if permitted from cerebrovascular standpoint) as
soon as possible. For patients who received tPA, aspirin
is withheld for 24 hours after tPA, then can be restarted
assuming there is no significant intracranial hemorrhage.
Supplemental oxygen and morphine are typically admin-
istered for MI, the latter agent for chest pain or angina to
reduce myocardial oxygen consumption. Intravenous
nitroglycerin or sublingual nitrates should be given if
blood pressure is elevated, but with caution in acute
stroke patients as these may cause hypotension, which
can make the stroke worse. Consultation with a cardiol-
ogist is advised when there is a concern for active
coronary ischemia and to help define an optimal blood
pressure and heart rate. For tachycardic patients, heart
rate control with b-blockers (IV metoprolol) can be
used, albeit cautiously to control rate with less effect
on blood pressure. If anemia is present (e.g., hematocrit
less than 30%), blood transfusion may reduce early
mortality in elderly patients with acute myocardial in-
farction.37 Finally, statin medications and subcutaneous
or IV heparin have been shown to reduce mortality after
MI, and may be used if safe from the cerebrovascular
standpoint.
Urinary Tract Infections
Urinary tract infections (UTIs) occur frequently in
patients with stroke. Patients with stroke may be limited
in describing symptoms, such as urinary frequency or
pain with urination, due to stroke-related disability
(aphasia, dysarthria, level of consciousness) or because
they have an indwelling catheter. Often, fever in iso-
lation is the manifestation that alerts clinicians to search
for a UTI. Risk factors for UTI include advancing age,
stroke severity, female sex, and use of urinary catheters.3
Bacteriuria is common in catheterized patients; thus, a
diagnosis of UTI in catheterized patients requires a
culture in addition to the urinalysis. Prevention is key
in stroke patients. Overuse of catheters is common. This
can be simply overcome by reviewing the daily need for a
urinary catheter, as well as other invasive lines, and
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discontinuing them at the first available opportunity.
Recent guidelines do not recommend prophylactic anti-
biotics to prevent urinary infection.3 Acidification of
urine with ascorbic acid may be helpful, in addition to
treating urinary tract infection with antibiotics when
present.
Decubitus Ulcers
Decubitus ulcers (Fig. 5) are an underrecognized prob-
lem in hospitalized patients with stroke. Decubitus
ulcers can lead to progressive skin erosion and potentially
even osteomyelitis. Risk factors for a decubitus ulcer
include immobility, poor nutrition, lack of turning,
urinary incontinence, and lack of wound care or proper
nursing. Strategies to minimize decubitus ulcer forma-
tion include daily nursing documentation about the
patient’s skin status, early recognition, and intervention
including bed turns every 2 hours, barrier creams and
cleaning, early mobilization by physical therapy, and
optimizing nutrition. When a decubitus ulcer is present,
consulting a wound care specialty nurse or implementing
the use of specialized mattresses can be helpful. For stage
IV wounds, a wound ‘‘VAC’’ and a consultation with a
plastic surgeon for a graft may be helpful. Hospital-
acquired decubitus ulcers are considered a quality metric
for many hospitals. In addition, the Center for Medicare
Services (CMS) does not reimburse wound care if the
patient develops decubiti while hospitalized due to the
potentially preventable nature of this complication.
SPECIAL CONSIDERATION—
ANGIOEDEMA AFTER TISSUE
PLASMINOGEN ACTIVATOR
Angioedema that forms after the use of IV-tPA can
cause life-threatening airway obstruction and respiratory
and cardiopulmonary arrest.38,39 The main risk factors

for the development of angioedema is exposure to ACE
inhibitors or similar drugs. The reported incidence is

5% of tPA-treated patients. Medical treatment in-
cludes oxygen, H1 and H2 blockade drugs, such as
famotidine and diphenhydramine, and steroids. Most
important is constant vigilance of the patient’s airway
and early intervention by a skilled airway provider, such
as an anesthesiologist or pulmonary critical care special-
ist. Patients who receive IV-tPA should be monitored in
the intensive care unit setting, and this is especially true
if angioedema develops.
CONCLUSION
Cerebral and extracerebral complications after ischemic
stroke are common, but many are preventable and
treatable. Awareness of these complications and vigi-
lance on the part of care providers can allow for early
recognition and treatment of these conditions. Creation
of specialized protocols and care maps to manage specific
stroke complications based on evidence-based guidelines
is suggested (Table 2).
REFERENCES
1. Rosamond W, Flegal K, Furie K, et al; American Heart
Association Statistics Committee and Stroke Statistics
Subcommittee. Heart disease and stroke statistics—2008
update: a report from the American Heart Association
Statistics Committee and Stroke Statistics Subcommittee.
Circulation 2010;122(1):e10
2. Langhorne P, Stott DJ, Robertson L, et al. Medical
complications after stroke: a multicenter study. Stroke 2000;
31(6):1223–1229
3. Adams HP Jr, del Zoppo G, Alberts MJ, et al; American
Heart Association; American Stroke Association Stroke
Council; Clinical Cardiology Council; Cardiovascular Radi-
ology and Intervention Council; Atherosclerotic Peripheral
Vascular Disease and Quality of Care Outcomes in Research
Interdisciplinary Working Groups. Guidelines for the early
management of adults with ischemic stroke: a guideline from
the American Heart Association/American Stroke Associa-
tion Stroke Council, Clinical Cardiology Council, Cardio-
vascular Radiology and Intervention Council, and the
Atherosclerotic Peripheral Vascular Disease and Quality of
Care Outcomes in Research Interdisciplinary Working
Groups: the American Academy of Neurology affirms the
value of this guideline as an educational tool for neurologists.
Stroke 2007;38(5):1655–1711
4. Davenport RJ, Dennis MS, Wellwood I, Warlow CP.
Complications after acute stroke. Stroke 1996;27(3):415–420
5. Kalra L, Yu G, Wilson K, Roots P. Medical complications
during stroke rehabilitation. Stroke 1995;26(6):990–994
6. Roth EJ, Lovell L, Harvey RL, Heinemann AW, Semik P,
Diaz S. Incidence of and risk factors for medical complications
during stroke rehabilitation. Stroke 2001;32(2):523–529
7. Dobkin BH. Neuromedical complications in stroke patients
transferred for rehabilitation before and after diagnostic
related groups. Neurorehabil Neural Repair 1987;1(1):3–7
THE ABC’S OF STROKE COMPLICATIONS/FREEMAN ET AL 509
8. Dromerick A, Reding M. Medical and neurological compli-
cations during inpatient stroke rehabilitation. Stroke 1994;
25(2):358–361
9. Johnston KC, Li JY, Lyden PD, et al; RANTTAS
Investigators. Medical and neurological complications of
ischemic stroke: experience from the RANTTAS trial. Stroke
1998;29(2):447–453
10. Weimar C, Roth MP, Zillessen G, et al; German Stroke
Date Bank Collaborators. Complications following acute
ischemic stroke. Eur Neurol 2002;48(3):133–140
11. Pinto AN, Melo TP, Lourenço ME, et al. Can a clinical
classification of stroke predict complications and treatments
during hospitalization? Cerebrovasc Dis 1998;8(4):204–209
12. Bae HJ, Yoon DS, Lee J, et al. In-hospital medical
complications and long-term mortality after ischemic stroke.
Stroke 2005;36(11):2441–2445
13. Oppenheimer S, Hachinski V. Complications of acute stroke.
Lancet 1992;339(8795):721–724
14. van der Worp HB, Kappelle LJ. Complications of acute
ischaemic stroke. Cerebrovasc Dis 1998;8(2):124–132
Downloaded by: World Health Organization ( WHO). Copyrighted material.
15. Ellekjaer H, Holmen J, Indredavik B, Terent A. Epidemi-
ology of stroke in Innherred, Norway, 1994 to 1996.
Incidence and 30-day case-fatality rate. Stroke 1997;28(11):
2180–2184
16. Lindgren I, Jönsson AC, Norrving B, Lindgren A. Shoulder
pain after stroke: a prospective population-based study.
Stroke 2007;38(2):343–348
17. Longstreth WT Jr, Bernick C, Fitzpatrick A, et al. Frequency
and predictors of stroke death in 5,888 participants in the
Cardiovascular Health Study. Neurology 2001;56(3):
368–375
18. Morgenstern LB, Hemphill JC III, Anderson C, et al;
American Heart Association Stroke Council and Council on
Cardiovascular Nursing. Guidelines for the management of
spontaneous intracerebral hemorrhage: a guideline for health-
care professionals from the American Heart Association/
American Stroke Association. Stroke 2010;41(9):2108–2129
19. Ivan CS, Seshadri S, Beiser A, et al. Dementia after stroke:
the Framingham Study. Stroke 2004;35(6):1264–1268
20. Auchus AP, Chen CP, Sodagar SN, Thong M, Sng EC.
Single stroke dementia: insights from 12 cases in Singapore.
J Neurol Sci 2002;203-204:85–89
21. Brott T, Broderick J, Kothari R, et al. Early hemorrhage
growth in patients with intracerebral hemorrhage. Stroke
1997;28(1):1–5
22. Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A.
Classification of cause of death after stroke in clinical
research. Stroke 2006;37(6):1521–1524
23. Burneo JG, Fang J, Saposnik G; Investigators of the Registry
of the Canadian Stroke Network. Impact of seizures on
morbidity and mortality after stroke: a Canadian multi-centre
cohort study. Eur J Neurol 2010;17(1):52–58
24. De Reuck J, Van Maele G. Status epilepticus in stroke
patients. Eur Neurol 2009;62(3):171–175
25. Singh S, Hamdy S. Dysphagia in stroke patients. Postgrad
Med J 2006;82(968):383–391
26. Bosson JL, Labarere J, Sevestre MA, et al. Deep vein
thrombosis in elderly patients hospitalized in subacute care
facilities: a multicenter cross-sectional study of risk factors,
prophylaxis, and prevalence. Arch Intern Med 2003;163(21):
2613–2618
27. Sandercock PA, Counsell C, Tseng MC. Low-molecular-
weight heparins or heparinoids versus standard unfractionated
510 SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER 5 2010
heparin for acute ischaemic stroke. Cochrane Database Syst
Rev 2008;(3):CD000119
28. Sherman DG, Albers GW, Bladin C, et al; PREVAIL
Investigators. The efficacy and safety of enoxaparin versus
unfractionated heparin for the prevention of venous
thromboembolism after acute ischaemic stroke (PREVAIL
Study): an open-label randomised comparison. Lancet 2007;
369(9570):1347–1355
29. Dennis M, Sandercock PA, Reid J, et al; CLOTS Trials
Collaboration. Effectiveness of thigh-length graduated
compression stockings to reduce the risk of deep vein
thrombosis after stroke (CLOTS trial 1): a multicentre,
randomised controlled trial. Lancet 2009;373(9679):
1958–1965
30. Muir KW, Watt A, Baxter G, Grosset DG, Lees KR.
Randomized trial of graded compression stockings for
prevention of deep-vein thrombosis after acute stroke. QJM
2000;93(6):359–364
31. Kamran SI, Downey D, Ruff RL. Pneumatic sequential
compression reduces the risk of deep vein thrombosis in
stroke patients. Neurology 1998;50(6):1683–1688
32. CAST (Chinese Acute Stroke Trial) Collaborative Group.
CAST: randomised placebo-controlled trial of early aspirin
use in 20,000 patients with acute ischaemic stroke. Lancet
1997;349(9066):1641–1649
33. International Stroke Trial Collaborative Group. The Interna-
tional Stroke Trial (IST): a randomised trial of aspirin,
subcutaneous heparin, both, or neither among 19435 patients
with acute ischaemic stroke. Lancet 1997;349(9065):
1569–1581
34. Kelly J, Lewis R. Heparin thromboprophylaxis after acute
stroke. Age Ageing 2001;30(1):89–90
35. Dexter DD Jr, Whisnant JP, Connolly DC, O’Fallon WM.
The association of stroke and coronary heart disease: a
population study. Mayo Clin Proc 1987;62(12):1077–1083
36. Tanne D, Goldbourt U, Zion M, Reicher-Reiss H,
Kaplinsky E, Behar S; The SPRINT Study Group.
Frequency and prognosis of stroke/TIA among 4808
survivors of acute myocardial infarction. Stroke 1993;24(10):
1490–1495
37. Wu WC, Rathore SS, Wang Y, Radford MJ, Krumholz
HM. Blood transfusion in elderly patients with acute
myocardial infarction. N Engl J Med 2001;345(17):
1230–1236
38. Hill MD, Lye T, Moss H, et al. Hemi-orolingual
Downloaded by: World Health Organization ( WHO). Copyrighted material.
angioedema and ACE inhibition after alteplase treatment
of stroke. Neurology 2003;60(9):1525–1527
39. Rafii MS, Koenig M, Ziai WC. Orolingual angioedema
associated with ACE inhibitor use after rtPA treatment of
acute stroke. Neurology 2005;65(12):1906