S3
STROKE AND NEURODEGENERATIVE DISORDERS
Stroke and Neurodegenerative Disorders. 1. Acute Stroke
Evaluation, Management, Risks, Prevention, and Prognosis
Bryan J. O’Neill, MD, Carolyn C. Geis, MD, Ross A. Bogey, DO, Alex Moroz, MD, Phillip R. Bryant, DO
ABSTRACT. O’Neill BJ, Geis CC, Bogey RA, Moroz A,
Bryant PR. Stroke and neurodegenerative disorders. 1. Acute
stroke evaluation, management, risks, prevention, and prog-
nosis. Arch Phys Med Rehabil 2004;85(3 Suppl 1):S3-10.
This self-directed learning module highlights recent devel-
opments in the acute care of stroke patients, prediction of
outcome after stroke, evaluation of risk factors, secondary
prevention of stroke, and the evaluation of the young adult with
stroke. It is part of the study guide on stroke and neurodegen-
erative disorders in the Self-Directed Physiatric Education Pro-
gram for practitioners and trainees in physical medicine and
rehabilitation. This article contains sections on the acute eval-
uation and management of the stroke patient, prediction of
functional outcome after stroke, and secondary prevention of
stroke. Special emphasis is given to the evaluation of the young
adult with stroke.
Overall Article Objectives: (a) To summarize the acute
evaluation and management of stroke, particularly in the young
stroke patient; and (b) to review the risk factors for stroke and
secondary prevention measures.
Key Words: Preventive medicine; Rehabilitation; Stroke;
Treatment outcome.
© 2004 by the American Academy of Physical Medicine and
Rehabilitation
1.1 Educational Activity: A 68-year-old woman presents
to the emergency department with aphasia and right
hemiparesis 2 hours prior to arrival. Discuss the ini-
tial evaluation process, the role of acute imaging and
laboratory studies, and options for treatment.
CUTE STROKE MANAGEMENT is initiated prior to
A hospital arrival. To be eligible for thrombolytic therapy,
the patient must arrive in the emergency department (ED)
within 2.5 hours of the onset of stroke symptoms. To improve
the acute care of stroke patients, a “chain of recovery” was
developed.1 The chain has 5 components: identification of the
stroke patient through improved public awareness, dispatch of
911 (telephone) emergency personnel to ensure immediate
triage and dispatch of appropriate emergency medical service
(EMS) personnel, response and transport by EMS personnel,
alerting of the ED to mobilize stroke care providers, and
From the Department of Rehabilitation Medicine, Thomas Jefferson University,
Philadelphia, PA (O’Neill); Neuroscience Center, Halifax Medical Center, Daytona
Beach, FL (Geis); Department of Physical Medicine and Rehabilitation, Rehabilita-
tion Institute of Chicago, Chicago, IL (Bogey); Department of Rehabilitation Medi-
cine, New York University School of Medicine, Rusk Institute of Rehabilitation
Medicine, New York, NY (Moroz); and Division of Physical Medicine and Rehabil-
itation, University of Utah School of Medicine, Salt Lake City, UT (Bryant).
No commercial party having a direct financial interest in the results of the research
supporting this article has or will confer a benefit upon the authors(s) or upon any
organization with which the author(s) is/are associated.
Reprint requests to Bryan J. O’Neill, MD, Dept of Rehab Med, Thomas Jefferson
Univ, 25 S 9th St, Philadelphia, PA, 19107, e-mail: bryan.oneill@jefferson.edu.
0003-9993/04/8503-8926$0.00/0
doi:10.1053/j.apmr.2003.11.013
diagnosis and treatment of reversible or unstable conditions
before ED arrival.1
When the acute stroke patient arrives at the hospital, he/she
is triaged to a high acuity area. Vital signs are assessed,
intravenous access is obtained, cardiac monitoring is initiated,
pulse oximetry is measured, and blood glucose is confirmed.
An accurate and focused history establishing the time of onset
and surrounding events such as trauma, seizure, and migraine
headaches is completed. Risk factors for stroke are identified.
The physical examination includes head and neck evaluation
for trauma and bruits, cardiac examination for arrhythmias or
murmur, pulse examination for asymmetry to check for aortic
dissection, and a focused neurologic examination.2 The Na-
tional Institutes of Health Stroke Scale (NIHSS) is the basis of
this neurologic examination.3 Complete blood count with plate-
lets, electrolytes, renal and hepatic function, coagulation test-
ing, blood glucose, electrocardiogram, cardiac enzymes, and
chest radiograph are among the ancillary tests recommended to
evaluate for coexisting conditions that strokes can mimic.2,4
Emergent, noncontrast computed tomography (CT) is the most
frequently used initial imaging study done primarily to evaluate
for intracranial hemorrhage and possible nonvascular causes of
focal neurologic lesions, such as a tumor.4,5
Intravenous thrombolysis with recombinant tissue-type plas-
minogen activator (rtPA) was approved by the US Food and
Drug Administration (FDA) in 1996, based on the results of the
National Institute of Neurological Disorders and Stroke
(NINDS) rtPA Stroke Study.4 The NINDS study showed fa-
vorable outcomes in patients treated with intravenous rtPA
versus placebo within 3 hours of symptom onset.6 Outcome
measurements included the NIHSS, modified Rankin scale,
Barthel Index, and Glasgow Outcome Scale. Similarly, the
European Cooperative Acute Stroke Study7 (ECASS) and
ECASS–II8 compared intravenous rtPA and placebo. These
trials, which allowed treatment up to 6 hours after symptom
onset, did not find intravenous rtPA to be superior to placebo.
Subsequent analyses9 of these trials showed favorable out-
comes in those patients who were treated within 3 hours. Clark
et al10 tested rtPA use up to 5 hours after stroke onset. This
study did not support the use of intravenous rtPA beyond 3
hours after stroke onset. This group’s second study11 treated
patients up to 6 hours after stroke onset and again found no
benefit. Recent guidelines from the Stroke Council of the
American Stroke Association (ASA) strongly recommend in-
travenous rtPA at 0.9mg/kg, with a maximum dose of 90mg in
carefully selected patients within 3 hours of ischemic stroke
onset. Table 1 shows characteristics of patients with ischemic
stroke who should be considered for intravenous rtPA.
Anticoagulant therapy is not recommended within 24 hours
after intravenous rtPA administration.4 Further, the American
Heart Association (AHA), the American Academy of Neurol-
ogy, and the ASA Council recommended that routine antico-
agulation not be instituted for patients with acute ischemic
stroke who receive intravenous rtPA. They also recommended
that urgent anticoagulation not be given to patients with mod-
erate to severe stroke because of the significant risk of intra-
cranial bleeding complications.12
Arch Phys Med Rehabil Vol 85, Suppl 1, March 2004
S4 STROKE MANAGEMENT, O’Neill
Table 1: Characteristics of Patients With Ischemic Stroke Who
Should be Considered for rtPA Treatment
Stroke symptoms
● Measurable neurologic deficit diagnosed as ischemic stroke
● No spontaneous resolution of neurologic signs
● Neurologic signs should not be minor or isolated (caution
should be used in treating patients with major neurologic
deficits)
● Stroke symptoms should not be consistent with subarachnoid
hemorrhage
● Symptom onset less than 3 hours before start of treatment
Past medical and surgical history
● Lifetime: no history of previous intracranial hemorrhage
● 3 months: no head trauma, previous stroke, or myocardial
infarction
● 21 days: no gastrointestinal or urinary tract hemorrhage
● 14 days: no major surgery
● 7 days: no arterial puncture in a noncompressible area
Examination
● Blood pressure: systolic, ⬍185mmHg; diastolic, ⬍110mmHg
● No acute trauma, including fracture
● No evidence of active bleeding
● No seizure with postictal neurologic impairments
Studies
● INR ⱕ1.5 if taking an anticoagulant
● PTT normal if heparin has been received within the past 48
hours
● Platelet count ⱖ100,000mm3
● Blood glucose ⱖ50mg/dL
● CT shows absence of multilobar infarction (hypodensity ⬎1⁄3
cerebral hemisphere)
Social
● The patient or family understand the possible risks and
benefits from treatment
Abbreviations: INR, international normalized ratio; PTT, partial
thromboplastin time.
Intra-arterial thrombolytic therapy, although not FDA ap-
proved, may be an option for patients up to 6 hours after onset
of stroke symptoms that arise from large vessel occlusions of
the middle cerebral artery4,13,14 (MCA). Further research is
ongoing.
Numerous neuroprotective agents have shown promise in
animal studies, but none has been effective in humans.15-17
Treatment with growth factors and stem cells is currently under
investigation.18
1.2 Educational Activity: A 65-year-old man sustains a
hemorrhagic left hemisphere stroke resulting in
global aphasia, dense right hemiplegia, and bladder
incontinence. Compare this patient’s rehabilitation
potential with a 65-year-old man presenting with a
lacunar stroke with dysarthria and mild left hemipa-
resis.
Jorgensen et al19 studied 1000 stroke patients and found that
patients with intracerebral hemorrhage (ICH) were more likely
to have higher stroke severity and poorer outcome. After con-
trolling for severity of impairment, however, they found no
difference between ischemic and hemorrhagic strokes in terms
of mortality, time course of neurologic recovery, neurologic
outcome, time course of activities of daily living (ADL) recov-
ery, and functional outcome. They concluded that the higher
mortality rates and likelihood of poor outcome were related
exclusively to severity of stroke. In an acute rehabilitation
Arch Phys Med Rehabil Vol 85, Suppl 1, March 2004
setting, Ween et al20 found that patients with intracranial hem-
orrhage improved more than patients with ischemic stroke but
did so more slowly. The persons with hemorrhagic strokes in
this study were less impaired on admission, possibly because of
rehabilitation admission bias. This difference in stroke severity
accounts for the recovery rate difference between these 2
studies.
The mortality rate of stroke in the United States has declined
steadily since the 1950s. This is likely the result of better acute
management and better control of the modifiable risk factors,
especially hypertension, which has received increased attention
over the last several decades.21 More recently, this decline in
mortality may have leveled off.22 The mortality rate from all
strokes in the first 30 days ranges from 17% to 34%. The rate
in hemorrhagic strokes, however, has been reported as high as
48%.21 A recent study by Rosamond et al23 found that 30-day
mortality was 7.6% in patients with ischemic strokes and
37.5% in patients with hemorrhagic strokes. They found that
mortality from hemorrhagic strokes was 4.5 times higher than
that for ischemic strokes. The prognosis for the patient with
intracranial hemorrhage is largely dependent on the size of the
hemorrhage and the patient’s general functional status as mea-
sured by the Glasgow Coma Scale score.24 Early neurologic
deterioration occurs in about one third of patients and is asso-
ciated with large hemorrhage volume (⬎45mL), rebleeding,
and midline shift. Thirty-day mortality rate approaches 50% in
this group.24 Other than in intracerebellar hemorrhage, which
responds well to surgical decompression, there is no consensus
on the best treatment for intracranial hemorrhage.25
Numerous studies have attempted to identify the predictors
of favorable or unfavorable outcome in stroke patients. Over 50
determinants have been proposed as predictors of stroke out-
come. Variation in outcome measures (survival, disposition,
functional status) and study design make comparison of these
studies difficult.26-29 Kwakkel et al27 recently performed a
critical review of the literature and found the following vari-
ables to be valid predictors of functional recovery during
rehabilitation: age, previous stroke, urinary incontinence, un-
consciousness at onset, disorientation in time and place, sever-
ity of paralysis, sitting balance, admission ADL score, level of
social support, and cerebral metabolic rate outside the infarct
area in hypertensive patients determined by positron emission
tomography (PET) scan. The most reliable and consistent pre-
dictor of functional outcome during rehabilitation is the pa-
tient’s functional ability at admission.20,26,30 An admission
FIM™ instrument score of 60 or greater is associated with a
higher likelihood of functional improvement.20 Other factors
that may predict functional outcome are listed in table
2.20,21,26-31 In the clinical situation, it is difficult to apply any of
these factors to an individual patient, yet physicians are often
asked to predict a patient’s rehabilitation potential and ultimate
functional outcome. Persistent urinary or fecal incontinence
and the presence of a social support system would likely be key
determinants in ultimate discharge destination.31
Prognosis for recovery after lacunar strokes is generally
favorable, because language and cognition are usually pre-
served in these strokes. Samuelsson et al32 found that 82% of
patients with first ever lacunar infarction had no or minimal
motor impairment at 1 month and 81% were independent with
ADLs. Initial motor impairment and degree of white matter
disease were the strongest predictors of a poor functional
outcome in this group. Lacunar infarcts result from occlusion
of the deep penetrating branches of the large cerebral arteries,
most commonly the middle cerebral, the posterior cerebral,
basilar, and less commonly the anterior cerebral and vertebral
arteries. The most common sites of lacunar infarcts are the
 STROKE MANAGEMENT, O’Neill
Table 2: Possible Predictors of Functional Outcome After
Stroke20,21,26-31
Age
Severity of stroke or paralysis
Prior stroke
Persistent urinary incontinence
Bowel incontinence
Visuospatial deficits
Unilateral hemineglect
Coma at onset
Poor cognitive function
Multiple neurologic deficits
Impaired sitting balance
Poor social supports
Limitations in ADLs
Depression
Severe aphasia
Severe comorbid medical conditions
Cerebral metabolic rate (PET scan)
putamen, caudate, pons, internal capsule, thalamus, and the
convolutional white matter. Lacunar infarctions are associated
with hypertension about 90% of the time. There are at least 20
well-described lacunar syndromes, the most common of which
are pure sensory stroke, pure motor hemiparesis, clumsy hand–
dysarthria, and ataxic hemiparesis (table 3).33 A recent mag-
netic resonance imaging (MRI) study looking at diffusion and
perfusion-weighted images challenges the notion that lacunar
syndromes can be reliably diagnosed clinically. Gerraty et al34
found that, in 13 of 19 patients with presumed lacunar syn-
dromes, a larger artery embolism was determined to be the
cause. This may be important in determining the appropriate
diagnostic investigation and eventual treatment options for
secondary prevention.
1.3 Clinical Activity: Your patient with lacunar infarct
was taking aspirin and smoking 2 packs of cigarettes
a day before his stroke. The family requests that you
make recommendations to prevent further strokes.
Secondary prevention of stroke is an important aspect of
rehabilitation management. Approximately 7% of all patients
with a history of transient ischemic attack (TIA) or stroke will
have a recurrent event each year.35 Only 40% of patients with
a first stroke will survive 5 years. The early deaths are attrib-
utable to the initial stroke, but the later deaths are primarily
from recurrent stroke or other cardiovascular events.36-39 The
risk of recurrent stroke and the fatality rate clearly increase
with an increasing number of risk factors.40
Stroke and coronary artery disease (CAD) share many of the
same modifiable risk factors. These potentially modifiable risk
factors for stroke include hypertension, elevated cholesterol
level, diabetes, smoking, obesity, carotid artery stenosis, and
low levels of physical activity. Additionally, antiplatelet ther-
apy, carotid endarterectomy, and anticoagulation may be ben-
eficial in secondary prevention for certain groups of patients.41
The careful identification and reduction of these factors may
greatly reduce the risk of recurrent stroke, progressive disabil-
ity, and death. Educating the patient and family about how to
reduce risk and modify lifestyle should be integrated into the
patient’s comprehensive stroke rehabilitation program.
Hypertension is a major independent risk factor for stroke
and it is present in approximately 30% to 35% of the adult
population. Several large trials have shown the benefit of
S5
antihypertensive treatment in the primary prevention of stroke,
with an overall relative risk reduction of 35% to 45%.41-44 Of
stroke survivors, about two thirds will have hypertension.
There is strong evidence that reducing blood pressure in these
patients reduces risk of recurrent stroke.45 The much-awaited
and recently published Perindopril Protection Against Recur-
rent Stroke Study reinforced this finding46 but was criticized by
some for its design.47 It seems prudent, therefore, that until a
specific agent is proven superior, one should consider potential
adverse effects and costs when deciding on a specific antihy-
pertensive agent. The ideal blood pressure goal is not clear.
Current AHA guidelines for primary prevention of cardiovas-
cular disease (CVD) and stroke suggest a target blood pressure
of less than 140/90 in otherwise healthy patients, 130/85 in
patients with renal disease or heart failure, and 130/80 in
patients with diabetes.48 Until studies show differently, these
can be used as guidelines in the poststroke patient as well.
However, overly aggressive blood pressure management in the
initial poststroke phase should be avoided because it may lead
to worsening of neurologic status or symptomatic orthostasis,
which can interfere with early mobilization and rehabilitation.
There is an approximate 1.5- to 2-fold increase in the relative
risk of stroke among smokers versus nonsmokers.44 The risk is
even higher with heavy smoking (ⱖ2 packs/d), particularly if
associated with hypertension. The increased risk associated
with smoking returns to baseline in light smokers or near
baseline in heavy smokers within 5 years of cessation and
appears to be independent of age.49 Physicians should develop
a tailored plan of intervention to aid each patient in smoking
cessation.50 This may involve nicotine replacement (gum,
patch, inhaler) or the use of buproprion hydrochloride to reduce
the craving for cigarettes, when not contraindicated. Psycho-
logic support, counseling, and smoking cessation classes may
be beneficial as well. Coordinating with the patient’s primary
care physician and the enlisting the patient’s family support is
essential to ensure long-term success.
Hyperlipidemia is a clear risk factor for CAD but has re-
cently been linked to increased risk of CVD as well. Data from
multiple trials and meta-analyses suggest that statin drugs
lower the primary risk of stroke by 24% to 25%.41,44 There are
no published, randomized trials of lipid-lowering drugs therapy
in secondary prevention of stroke. The National Cholesterol
Education Program guidelines suggest that patients with stroke
or TIA have a coronary heart disease risk profile equivalent to
those with known CAD. The recommended goal of lipid man-
agement in this high-risk patient group is a low-density li-
poprotein cholesterol (LDL-C) of less than 100mg/dL.51 This
goal may be accomplished through dietary management or
medication therapy. The recommendation of the AHA Stroke
Council is that patients with known coronary heart disease and
Table 3: Most Common Lacunar Syndromes
Syndrome Lesion Location
Pure sensory stroke Thalamus
Pure motor stroke Posterior limb internal capsule
Basis pontis
Cerebral peduncle
Clumsy hand–dysarthria Anterior limb internal capsule
Pons
Ataxia hemiparesis Corona radiata
Internal capsule
Pons
Cerebellum
Arch Phys Med Rehabil Vol 85, Suppl 1, March 2004
S6 STROKE MANAGEMENT, O’Neill
elevated LDL-C levels should be considered for treatment with
a statin.44 The statin drugs likely mediate cardiac and cerebro-
vascular protection through both lipid and nonlipid mecha-
nisms.52
Persons with diabetes mellitus face an approximate 2-fold
higher risk of ischemic stroke. They are also more likely to
have other major risk factors for stroke including hypertension
and hyperlipidemia. Tight blood pressure control in diabetes
has been shown to reduce stroke risk beyond that attributable to
antihypertensive effects alone.41,53 Tight glycemic control does
not reduce the risk of stroke but may reduce microvascular
complications, such as nephropathy, retinopathy, and periph-
eral neuropathy.44
Antiplatelet therapy, unless contraindicated, is recom-
mended for all patients who have experienced noncardioem-
bolic stroke or TIA to reduce the risk of recurrent stroke and
other vascular events.54 The medications in this class include
aspirin, clopidogrel, ticlopidine, and dipyridamole. The Anti-
platelet Trialists’ Collaboration55 performed a meta-analysis of
287 randomized trials in high-risk patients (peripheral vascular,
CAD, CVD) and found that, as a group, antiplatelet agents
reduced the risk of nonfatal stroke by about 25%. Similar risk
reduction was found in patients with prior stroke or TIA. There
was a small increased risk of hemorrhagic stroke, but this was
outweighed by a reduction in risk of ischemic stroke. Other
meta-analyses56,57 found a uniform stroke risk reduction of
13% to 15% with antiplatelet agents compared with placebo
across a wide range of doses.
Aspirin irreversibly inhibits cyclooxygenase and thereby
inhibits platelet aggregation. It is rapidly absorbed and has
antiplatelet effects within 1 hour. Aspirin is appealing because
of its low cost, ease of administration, and perceived safety
profile. The risk of gastrointestinal (GI) hemorrhage is as high
as 2% to 3% in multiple trials and may rise with increasing
doses.58 In meta-analyses, no difference was found between
high-dose (500 –1500mg/d) and medium-dose (75–325mg/d)
aspirin therapy. Given the lack of evidence for increased effi-
cacy at higher doses and the potential for greater side effects,
most experts recommend low- to medium-dose therapy (50 –
325mg/d) for secondary stroke prevention.59 For patients with
cerebrovascular events occurring while taking aspirin, switch-
ing to an alternative antiplatelet agent or adding a second agent
may be considered, but this treatment has not yet been ade-
quately studied.
Ticlopidine and clopidogrel are thienopyridines that inhibit
adenosine diphosphate–induced fibrinogen binding to platelets,
a necessary step in the platelet aggregation process. Both drugs
have shown effectiveness in prevention of secondary stroke
compared with placebo. In a study60 directly comparing ticlo-
pidine with aspirin, the former was found to be about 20%
more effective in reducing stroke. The incidence of severe GI
side effects is less than with aspirin, but rash and diarrhea are
common. Ticlopidine is associated with a 1% incidence of
severe neutropenia and a rare but significant incidence of
thrombotic thrombocytopenic purpura.54,60 These side effects
and ticlopidine’s need for close monitoring of blood counts
limit its effective clinical use.
In the CAPRIE trial, clopidogrel was found to be slightly
more effective than aspirin in preventing secondary stroke
(relative risk reduction, 8%)61 in the subgroup of patients with
stroke as the qualifying condition. The side-effect profile is
comparable to aspirin with no increase in incidence of neutro-
penia and therefore no need for frequent blood count monitor-
ing. The subgroup of patients that would benefit from these
agents instead of aspirin is not yet clear. Clopidogrel is a
Arch Phys Med Rehabil Vol 85, Suppl 1, March 2004
reasonable alternative for patients who cannot tolerate aspirin
because of allergy or GI side effects.
Dipyridamole, although not effective alone, may confer ad-
ditional benefit when added to aspirin therapy. Although find-
ings by the Antiplatelet Trialists Collaboration did not support
this treatment, 1 randomized trial62 supported the addition of
long-acting dipyridamole to reduce the risk of death in patients
after stroke. These results may be clarified with the completion
of the European/Australian Stroke Prevention in Reversible
Ischaemia Trial, which compared aspirin, warfarin, and aspirin
plus dipyridamole in patients with prior stroke or TIA.63
Warfarin is highly effective in both primary and secondary
prevention of stroke in patients with atrial fibrillation. The risk
of stroke in patients with atrial fibrillation without valvular
abnormalities is 5% per year. The risk is even higher in patients
with atrial fibrillation and concomitant valvular abnormalities.
In patients with prior stroke and atrial fibrillation, warfarin is
uniformly recommended.59 In patients with atrial fibrillation
alone, most stroke prevention guidelines suggest that patients
be stratified according to other risk factors, which include
advanced age, systolic hypertension, a history of hypertension,
impaired left ventricular function, and diabetes mellitus.44,59
Anticoagulation with warfarin is recommended for persons
at high risk, and aspirin is usually recommended for those at
low risk or those who cannot be safely anticoagulated. Long-
term oral anticoagulation reduces the risk of thromboembolic
stroke by 68% in those with high-risk features.44,64
Carotid endarterectomy is currently recommended for symp-
tomatic patients with severe (70%–99%) carotid stenosis with
a relative risk reduction of 48%.41,65 Early surgery can be safely
performed in patients who have nondisabling stroke. Results
from the North American Symptomatic Carotid Endarterec-
tomy Trial66 indicate that surgery in patients with symptomatic
moderate stenosis (50%– 69%) yields only a moderate reduc-
tion in stroke risk, with a risk reduction of 27%. The results are
applicable only if the surgical complication rate is less than
6%. Patients with less than 50% stenosis did not benefit from
surgery.66
The impacts of obesity, physical inactivity, and poor diet on
risk of secondary stroke have not been well studied. Regular
exercise tailored to accommodate an individual’s impairments,
weight reduction, and a well-balanced diet are recommended as
part of a healthy lifestyle that helps to reduce the comorbid
conditions that may lead to stroke.44 Alcohol as a risk factor for
ischemic stroke is controversial, but likely dose dependent: low
doses may be protective, whereas higher doses increase risk of
a hemorrhagic stroke.44 Sleep apnea has recently been impli-
cated as a risk factor for stroke.67 Proposed mechanisms in-
clude decreased cerebral perfusion and increased coagulability
during sleep-disordered breathing. Diurnal hypertension may
also play a role. The application of positive pressure breathing
may reduce the risk of hypertension and stroke.67
Elevated homocysteine levels have been associated with
increased risk of stroke. Secondary prevention trials are under-
way. Because folic acid together with vitamin B6 and B12
reduce plasma levels of homocysteine with no significant side
effects,68 it may be reasonable to use folate and B vitamin
supplements in stroke patients with elevated homocysteine
levels.
1.4 Educational Activity: A 16-year-old woman who is 6
months pregnant with no history of trauma, presents
with aphasia and right hemiparesis. Discuss her dif-
ferential diagnosis and treatment.
The acute onset of aphasia and right hemiparesis suggests of
a left MCA ischemic stroke or left hemisphere hemorrhage. An
 STROKE MANAGEMENT, O’Neill
initial CT scan should distinguish between an ischemic stroke
and a hemorrhagic stroke associated with aneurysm rupture or
arteriovenous malformation (AVM). It would also rule out less
likely causes for this focal neurologic deficit, such as mass
effect from tumor. The fetal exposure to radiation from a single
CT scan of the head is limited and can be further minimized by
the use of a shield. Practice guidelines69 suggest that the
decision to order imaging studies be based on neurologic
indication, despite pregnancy.
Stroke in the young adult is a well recognized, yet uncom-
mon, entity. According to the National Survey of Stroke, 3.7%
of all strokes occurred in patients under 45 years of age.70
Others71 have found as high as 8.5% of strokes occurring in the
young adult population. The age of 15 has been proposed to
separate childhood from young adult stroke because those in
the 15- to 18-year-old group share more similarities in stroke
etiology with the 18- to 45-year-old group than with the under-
15 age group.72
Hemorrhagic strokes account for at least one third of all
strokes in young adults compared with one fifth among all
stroke survivors.30 In 1 series, of 113 young stroke victims,
41% were from ICH, 17% from subarachnoid hemorrhage, and
42% from cerebral infarct.71 Ruptured aneurysms or AVMs are
responsible for most of the hemorrhagic strokes in this age
group. MRI and magnetic resonance angiography (MRA) have
emerged as useful tools for detecting these underlying struc-
tural abnormalities. Initial management of the patient with ICH
is beyond the scope of this article and the reader is referred to
the AHA Stroke Council guidelines25 for further information.
The causes of ischemic stroke in the young adult are more
diverse than in the elderly and require a more extensive inves-
tigation to find an underlying cause. This investigation may
involve procedures such as cerebral angiography, cardiac eval-
uation including transesophageal echocardiography, testing for
coagulopathies, and evaluation for collagen vascular diseases.
Despite thorough investigation, the etiology of stroke remains
undetermined in as many as 20% of young adults. Cardioem-
bolic stroke, atherosclerotic stroke, and stroke from nontrau-
matic arterial dissection are the 3 most frequent of this type of
stroke: together they account for 42% to 64% of all ischemic
strokes in the young adult71-78 (see table 4 for causes of stroke
in young adults). Cardioembolic stroke is the most common
subtype of ischemic stroke in young adults. Mitral valve prolapse,
as an isolated finding, is no longer thought to be a cause of stroke
in young adults. Transesophageal echocardiography is more sen-
sitive than traditional echocardiography in identifying potential
cardiac sources in a patient with an embolic event.69
Nontraumatic dissection of the carotid or vertebral artery is
an underrecognized cause for stroke in the young adult. It
should be considered in young patients who lack risk factors
for stroke and in those who experience sudden head or neck
pain with the onset of their neurologic signs. In addition,
dissection of the carotid artery may produce a Horner syn-
drome or lower cranial nerve palsies. Vertebral artery dissec-
tion may cause nausea, vertigo, disequilibrium, and occipital
headache. It is associated with connective tissue disorders such
as Marfan syndrome, Ehlers-Danlos syndrome, and fibromus-
cular dysplasia. MRI or MRA of the head and neck is useful to
screen for arterial dissection. Conventional angiography may
be done if the diagnosis is unclear and there is a strong
suspicion of arterial dissection. Anticoagulation is usually rec-
ommended until there is evidence of clot resolution on MRA.74
Hypercoagulable states are responsible for 6% to 15% of
ischemic strokes in young adults.71-78 Most strokes of this type
are associated with acquired antiphospholipid antibody syn-
drome. The inherited deficiencies of proteins C, S, and anti-
S7
Table 4: Causes of Stroke in Young Adults
Ischemic Stroke Hemorrhagic Stroke
Cardioembolic Aneurysm
Atrial fibrillation AVM
Patent foramen ovale Hypertension
Prosthetic heart valve Tumor
Rheumatic heart disease Coagulation disorder
Cardiomyopathy Moyamoya disease
MI with left ventricular thrombus Eclampsia
Infective endocarditis
Atherosclerotic occlusive disease
Arterial dissection
Hematologic
Oral contraceptives/pregnancy
Antiphospholipid antibodies
Proteins C, S, or antithrombin III
deficiency
Lupus anticoagulant
Factor V Leiden gene mutation
Vasculitis/connective tissue disorder
Migraine
Drug abuse
Abbreviation: MI, myocardial infarction.
thrombin III, as well as the Factor V Leiden gene mutation, are
less likely causes of stroke. Oral anticoagulation should be
considered in these individuals, unless contraindicated.
Drug abuse, especially cocaine, is a major cause of stroke in
the young adult. Heroin, marijuana, and amphetamines have
also been implicated. Less common causes of ischemic stroke
in the young adult include migraine syndrome, oral contracep-
tive use, and vasculitis. Although pregnancy is frequently listed
as a risk factor for stroke in young adults, population-based
studies to support this belief are lacking. Estimates for stroke
incidence from US population-based studies range from 3.8 to
29.1 strokes per 100,000 deliveries.79,80 Kittner et al,81 in a
large population-based study, found that the risks of both
cerebral infarction and ICH are increased in the postpartum
period but not significantly during the pregnancy itself. Kittner
suggests that the high relative risk of stroke in the postpartum
period may be related to the blood volume changes or rapid
hormonal changes after delivery.
Eclampsia accounts for the largest number of nonhemor-
rhagic, pregnancy-related strokes (47%). Other causes include
vertebral artery dissection, cerebral angiopathy, inherited pro-
tein S deficiency, and disseminated intravascular coagulation
associated with amniotic fluid embolism. Hemorrhagic strokes
are most likely caused by eclampsia (44%) or ruptured vascular
malformations (37%); the cause is not clearly determined in
19%.82 Others79,81 have confirmed the importance of eclampsia
and pregnancy-associated hypertension as significant risk fac-
tors for both ischemic and hemorrhagic strokes. Eclampsia can
cause a global encephalopathic syndrome with headaches, vi-
sual disturbances, impairments of consciousness, seizures, and
focal neurologic deficits as a consequence of severe hyperten-
sion and cerebral edema. It may be accompanied by vaso-
spasm, hemorrhage, and disseminated intravascular coagula-
tion.83 Neurologic outcome in patients with eclampsia is
generally favorable in the absence of the latter conditions.
Cesarean delivery is an important risk factor for both stroke
and intracranial venous thrombosis.79,84 Amniotic fluid embo-
lism is a rare cause of stroke and occurs most commonly at the
time of delivery. Choriocarcinoma is another rare pregnancy-
Arch Phys Med Rehabil Vol 85, Suppl 1, March 2004
S8 STROKE MANAGEMENT, O’Neill
specific cause of stroke. Any of the known causes for stroke in
the young may also occur during pregnancy. Treatment of
peripartum stroke is directed at the underlying etiology. If
anticoagulation is indicated, standard unfractionated heparin or
low–molecular-weight heparin are the preferred drugs because
they do not cross the placenta barrier. Warfarin is associated
with developmental anomalies and is contraindicated during
the first trimester.73 It is associated with hemorrhage in late
pregnancy and, if used during the middle and third trimester,
should be discontinued for the last several weeks before deliv-
ery.
Outcome for patients who suffer an ischemic infarct during
pregnancy is generally favorable, and death is rare. Intraparen-
chymal hemorrhage associated with eclampsia, however, car-
ries a high mortality rate and poor prognosis.79,82,85,86 Lamy et
al87 studied young women with a history of ischemic stroke and
found a low risk of recurrence associated with subsequent
pregnancies. The postpartum period was associated with in-
creased risk of recurrent stroke, most notably among those with
an identifiable cause for the initial stroke. Pregnancy outcome,
however, was similar to that expected in the general popula-
tion. Lamy concluded that previous stroke is not a contraindi-
cation to subsequent pregnancy.
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