Sroke continuum 2014

Evaluation and
Management of Acute
Ischemic Stroke
Pooja Khatri, MD, MSc
ABSTRACT
Purpose of Review: This review provides an overview of emergent evaluation of the
stroke patient with an emphasis on practical issues regarding ischemic stroke treatment.
Recent Findings: The IV recombinant tissue-type plasminogen activator (rtPA)
treatment window has been expanded from 3 to 4.5 hours from symptom onset.
The evidence for better outcomes with more rapid initiation of reperfusion therapies is
very strong. Adjunctive endovascular therapy has not been shown to benefit all
patients with moderate or severe strokes, and investigations are underway to identify
subgroups that may benefit from this approach. Endovascular therapy should be
considered for patients who are ineligible for IV rtPA and can begin treatment within
6 hours of stroke onset.
Summary: Effective emergent evaluation of a stroke patient requires well-organized
systems that maximize speed of assessment and administration of appropriate
therapies, including IV rtPA and endovascular therapies.
Continuum (Minneap Minn) 2014;20(2):283–295.
INTRODUCTION
This article provides a practical over-
view regarding the emergent evalua-
tion of a patient with acute ischemic
stroke, including the decision to
administer acute reperfusion therapy
and other acute supportive care.
It should be noted that ‘‘acute re-
perfusion therapy’’ refers to treat-
ment aimed at emergently restoring
blood flow in the acutely occluded
cerebral artery, and may consist of IV
thrombolysis and/or specific endovas-
cular interventions such as intra-
arterial thrombolysis or mechanical
embolectomy.
This discussion is framed around
the most recent American Heart
Association/American Stroke Associ-
ation guidelines, which serve as use-
ful and comprehensive references to
the reader.1
EMERGENT EVALUATION OF
THE POTENTIAL ACUTE
REPERFUSION CANDIDATE
Rapid evaluation and treatment is
critical for the best outcomes. This
has been shown both in the setting of
IV thrombolysis (IV recombinant
tissue-type plasminogen activator
[rtPA]) and endovascular therapy.
With IV rtPA, the number needed to
treat to prevent one death or signifi-
cant disability is 8 when treating
within 3 hours of symptom onset,
and 14 when treating from 3 to 4.5
hours.2,3
Figure 1-1 demonstrates the
odds of good outcome with IV rtPA
treatment among subjects pooled
from major trials to date.4
It has also
been demonstrated that every 30-
minute delay in acute reperfusion
leads to a 10% relative reduction in
the likelihood of a good outcome.5
Address correspondence
to Dr Pooja Khatri, Department
of Neurology, University of
Cincinnati, 260 Stetson Street,
ML 0525, Cincinnati, OH
45267-0525,
pooja.khatri@uc.edu.
Relationship Disclosure:
Dr Khatri has received
research grants from the
NIH and research support
from Penumbra Inc and
Genentech, Inc.
Unlabeled Use of
Products/Investigational
Use Disclosure:
Dr Khatri discusses the use of
IV tissue plasminogen activator
for minor stroke and of
endovascular therapy for stroke
treatment, neither of which are
approved by the US Food and
Drug Administration.
* 2014, American Academy
of Neurology.
283Continuum (Minneap Minn) 2014;20(2):283–295 www.ContinuumJournal.com
Review Article
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

A patient should receive IV rtPA
within 1 hour of arrival to an emergency
department (and sooner is better) with
the following goals.6
& Emergency department physician
sees patient within 10 minutes
of arrival
& Stroke consultant is notified
within 15 minutes of arrival
& CT scan is completed within
25 minutes of arrival
& CT is interpreted within 45
minutes of arrival
Strategies likely to increase the
speed of treatment include early
stroke-team notification (preferably be-
fore or concurrent with CT scan per-
formance); storage of rtPA in the
emergency department; recognition
that glucose level is the only necessary
laboratory result if no clinical suspicion
for bleeding diathesis is present; and
mixing of IV rtPA (1:1 ratio with sterile
water or normal saline) early.
DECISION TO ADMINISTER
ACUTE REPERFUSION THERAPY
The following information is needed
from the emergency department upon
initial consultation to guide clinical
decision making.
& Time that patient was last known
to be well
& Any significant medical history
& A brief neurologic examination
(ideally the NIH Stroke Scale [NIHSS])
& Glucose level (finger stick) and any
other significant laboratory results
& Current blood pressure
& Results of acute brain imaging,
typically CT scan, when available
Each of these points and their role
in decision making are described in
subsequent sections.
Time
The patient’s ‘‘last known well’’ time
determines potential treatment options.
KEY POINTS
h Rapid evaluation and
treatment are critical for
the best outcomes.
h A patient should receive
IV recombinant
tissue-type plasminogen
activator within 1 hour
of arrival to an
emergency department
(and sooner is better).
FIGURE 1-1 Odds of good outcome based on stroke onset to treatment time. Pooled
analysis of European Cooperative Acute Stroke Study (ECASS), Alteplase
Thrombolysis for Acute Noninterventional Therapy in Ischaemic Stroke
(ATLANTIS), National Institute of Neurological Disorders and Stroke (NINDS), and
Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) subjects demonstrates that
later onset to treatment times lead to lower odds of a treatment effect of IV rtPA
compared with placebo. Treatment beyond 270 minutes appears to have no benefit.
Reprinted with permission from Lees KR, et al, Lancet.
4
B 2010 Elsevier. www.sciencedirect.com/science/
article/pii/S0140673610604916.
284 www.ContinuumJournal.com April 2014
Acute Stroke

It is important to distinguish the time
last known well from the time that the
stroke deficits were first discovered, as
demonstrated by Case 1-1.
IV thrombolysis, specifically using
rtPA, should be considered for patients
for whom it can be administered within
4.5 hours of onset. IV rtPA (at the dose
of 0.9 mg/kg, maximum dose 90 mg,
with 10% given as an initial bolus) has
been shown to improve clinical out-
comes for patients within 3 hours of
onset by two randomized trials (jointly
referred to as the National Institutes of
Neurological Disorders and Stroke
[NINDS] tPA Stroke Study),2
and within
3 to 4.5 hours by one randomized trial
(European Cooperative Acute Stroke
Study III).3
Specifically, within 3 hours
of onset, despite a 6% increased risk of
symptomatic intracranial hemorrhage,
the overall absolute benefit of treatment
is a 13% lower rate of significant dis-
ability (defined as a modified Rankin
Scale of 0 or 1). This benefit is estimated
to be as high as 33% for any improve-
ment in the spectrum of independence
to severe disability or death; Figure 1-27
illustrates potential treatment effects.8
Several community cohorts,9
pooled
analyses of other IV rtPA trials,4
and the
3-hour subgroup of the Third Interna-
tional Stroke Trial (IST-3) provide
further supportive evidence.10
Of note,
KEY POINT
h IV thrombolysis,
specifically using
recombinant tissue-type
plasminogen activator,
should be considered
for patients for whom it
can be administered
within 4.5 hours of
onset of stroke deficits.
Case 1-1
A 78-year-old woman with a history of diabetes mellitus presented to the
emergency department with acute left-sided weakness at 4:00 PM. Her
husband had called 9-1-1 immediately upon identifying her symptoms at
3:30 PM. Emergency medical services (EMS) had promptly evaluated the
patient and brought her to the stroke-ready emergency department.
En route, EMS had prenotified the hospital, where a CT scan was
performed upon the patient’s arrival. The CT scan showed minimal early
ischemic changes and no intracranial hemorrhage. The patient’s
finger-stick glucose level was 95 mg/dL, and her examination revealed left
hemiplegia and anosognosia. Her husband reported that her only
medication was metformin and she had no recent surgeries or prior history
of intracranial hemorrhage. However, upon further discussion regarding
the time of onset with the stroke clinician, it became clear that, while the
patient’s symptoms were discovered at 3:30 PM, her husband had last seen
her well before he left for work at 9:00 AM. The patient reported feeling
fine until her husband came home. Her cell phone was checked, and she
had not spoken to anyone that day. Her neighbor was called by the husband,
and the patient had not been witnessed to be well by anyone else since
9:00 AM. Thus, it was 7 hours from last known well at this point, and IV
recombinant tissue-type plasminogen activator (rtPA) was not administered.
Comment. In this case, if the patient had not had anosognosia, it may
have been appropriate to identify the last known well time based on the
patient’s own history. However, given her lack of appreciation for her
deficit, her report could not be trusted. A normal CT scan has not been
demonstrated to identify patients who might benefit from IV rtPA
regardless of time from last known well. However, an active and promising
area of investigation is to develop imaging markers that can identify
patients who will benefit from IV rtPA treatment based on physiologic
time. Had it not been for the unknown and potentially greater than
4.5-hour time of onset, the patient in this case would have been eligible
for IV rtPA.

the US Food and Drug Administration
has only approved the 3-hour time
window for IV rtPA, whereas clinical
guidelines recommend treatment up
to 4.5 hours based on the current
evidence.1
It should also be noted that
no other lytic agent, such as reteplase
or tenecteplase, has been demonstrated
as an effective treatment for acute
ischemic stroke.
Endovascular therapy for IV re-
combinant tissue-type plasminogen
activatorYineligible patients. For pa-
tients ineligible for IV rtPA (because
of, for example, time of onset,
coagulopathy, or recent surgery) who
have significant stroke deficits (typically,
an NIHSS score of 8 or higher),
endovascular therapy should be consid-
ered if treatment can be initiated within
6 hours (Case 1-2). Indirect evidence,
including the Prolyse in Acute Cerebral
Thromboembolism (PROACT) II trial
of recombinant prourokinase and the
Middle Cerebral Artery Embolism Local
Fibrinolytic Intervention Trial (MELT)
of urokinase,11Y13
suggests that intra-
arterial rtPA initiated within 6 hours of
onset will lead to better clinical out-
comes than supportive care alone (ie,
no reperfusion therapy). More recent
evidence suggests that endovascular
devices open major arterial occlusions
more effectively, leading to their fre-
quent clinical use in this setting; spe-
cifically, the most recent generation of
mechanical embolectomy devices, in-
cluding the Penumbra Aspiration Sys-
tem, the Solitaire Stent Retriever, and
the TREVO2 Stent Retriever, report
revascularization rates exceeding
80%.14Y16
Comparable safety and effi-
cacy between IV rtPA within 3 hours
versus endovascular therapy within 6
hours in the SYNTHESIS trial also sup-
ports the approach for IV rtPAYineligible
patients who present early.17
Case series
data also suggest reasonable safety for
the use of intra-arterial thrombolysis in
the nonneurosurgical postoperative set-
ting.18
Devices available in the United
States are shown in Figure 1-4.
The role of imaging selection to
identify patients beyond 6 hours from
onset who will benefit from acute
reperfusion therapies remains to be
determined. A phase 2b study, the
Mechanical Retrieval and Recanalization
of Stroke Clots Using Embolectomy
(MR RESCUE) trial, tested the penum-
bral hypothesis.19
A favorable CT-based
or magnetic resonanceYbased penum-
bral selection pattern was defined as a
KEY POINT
h For patients ineligible
for IV recombinant
activator who have
significant stroke
deficits (typically, an NIH
Stroke Scale score of 8
or greater), endovascular
therapy should be
considered if treatment
can be initiated within
6 hours.
FIGURE 1-2 Changes in final outcome as a result of intravenous
recombinant tissue-type plasminogen activator
(IV rtPA) treatment within 3 hours of onset.
Reprinted from Saver JL, Medscape.
7
emedicine.
medscape.com/article/1160840-overview.
Acute Stroke

Case 1-2
A 65-year-old woman who was postoperative from coronary artery bypass graft surgery was found to have
right-sided weakness and confusion in the postoperative anesthesia care unit (PACU) upon regaining consciousness
from general anesthesia at 3:00 PM. She was last known to be neurologically normal at 12:00 PM. The on-call
neurologist, who was immediately activated by the PACU nurse, identified a left middle cerebral artery
syndrome with global aphasia and right hemiparesis (NIH Stroke Scale score of 20). Given the recent surgery,
she deemed the patient to be ineligible for IV recombinant tissue-type plasminogen activator (rtPA), and
alerted the neurointerventional team regarding a potential endovascular case while transporting the patient to
the CT scanner. The CT scan revealed no intracranial hemorrhage, no early ischemic changes, and a hyperdense
left middle cerebral artery; the patient was briskly taken directly from the CT scanner to the neuroangiography
suite. Groin stick was performed at 4 hours after her last time seen normal, and a left proximal middle cerebral
artery thrombus was evacuated by mechanical embolectomy at 4.5 hours with complete angiographic reperfusion
observed on finalangiogram, asdemonstrated inFigure 1-3. Upon reexamination after the procedure, the patient
had regained strength on her right side and her aphasia (now primarily expressive) was improved. Follow-up CT
scan showed a small branch middle cerebral artery infarct.
Comment. Given the recent surgery, IV rtPA could not be safely administered in this patient. In this case,
emergent endovascular treatment was a consideration. Rapid time to angiographic reperfusion likely
contributed to the improved clinical outcome seen after the procedure. Of note, despite the observation of
complete angiographic reperfusion, some infarct burden remained. This may have been due to a distal
embolus or brain tissue that was irreversibly infarcted by the time angiographic reperfusion was achieved.
FIGURE 1-3 Example of middle cerebral artery (MCA) infarction with hyperdense left middle cerebral artery on baseline CT
scan (A). Proximal MCA (M1) occlusion on pretreatment digital subtraction angiogram in coronal (B) and
sagittal (C) planes, mechanical extraction of intact thrombus (D), and complete angiographic reperfusion in
coronal (E), and sagittal (F) planes.
Courtesy of Aaron Grossman, MD, PhD, and Todd Abruzzo, MD, University of Cincinnati Medical Center.

predicted infarct core comprising 70%
or more of ‘‘at-risk’’ tissue as identified
by a complex voxel-by-voxel algorithm,
and incorporating baseline NIHSS score
for the CT-based cases as well. Patients
for whom endovascular treatment could
be initiated within 8 hours of symptom
onset were randomized to mechanical
embolectomy versus supportive care,
and stratified by the presence of penum-
bra. The presence of penumbra did not
discriminate between subjects who would
differentially benefit from mechanical em-
bolectomy, but did predict better clinical
outcomes among those with penumbra
regardless of treatment arm. Evidence for
newer definitions of penumbra, and its
use beyond 8 hours from onset, are
limited to nonrandomized cohort studies
of treated patients only.20,21
These single-
arm trials are unable to discriminate
between a predictor of treatment effect
and a marker of better clinical outcome
regardless of treatment. This is an active
area of investigation, and several planned
and ongoing randomized trials will likely
inform this discussion in the future.22
Medical History
In addition to eligibility based on time
from onset, acute reperfusion treat-
ment options are further determined
by eliciting key medical history.
IV rtPA exclusion criteria and relative
contraindications are listed in Box 1-1.1
A consensus definition of deficits that
should typically be considered disabling
(regardless of total NIHSS score) is
shown in Table 1-1.
Based on limited evidence, poten-
tial eligibility for endovascular therapy
in IV rtPAYineligible patients might
include age younger than 85 years,
NIHSS greater than or equal to 8, and
treatment within 6 hours of onset.1,10,11
Brief Examination and NIHSS
The examination helps the clinician
determine that the patient is indeed
having a stroke and gauge its severity.
The NIHSS score, in particular, is a useful
way to describe and follow the patient’s
examination (Appendix A). All clinicians
who care for stroke patients in the
acute setting should be NIHSS certified
KEY POINTS
h Rapidly improving
deficits should not be
considered a
contraindication unless
the remaining deficit
is minor.
h Additional exclusion
criteria for IV
plasminogen activator
within the 3- to
4.5-hour time window
include a history of
stroke and diabetes
mellitus, NIH Stroke
Scale score greater than
25, age greater than
80 years, and warfarin
use (regardless of
international normalized
ratio value).
h All clinicians who care
for stroke patients in the
acute setting should be
NIH Stroke Scale
certified.
FIGURE 1-4 Devices cleared by the US Food and Drug Administration for acute stroke clot removal: A, Merci Retriever; B, Solitaire
stent retriever; C, Penumbra aspiration system; and D, TREVO2 stent retriever.
Panel A courtesy of Concentric Medical, Inc; Panel B courtesy of Covidien; Panel C courtesy of Penumbra, Inc; Panel D courtesy of Stryker.
Acute Stroke

BOX 1-1 IV rtPA Exclusion and Relative Contraindication Criteria
Key IV rtPA Exclusion Criteria
& Stroke or significant head trauma within 3 months
& Major surgery or serious trauma within 14 days
& Gastrointestinal or urinary hemorrhage within 21 days
& Arterial puncture at a noncompressible site within 7 days
& History of intracranial hemorrhage
& Intracranial neoplasm, arteriovenous malformation, or aneurysm
) Some experts consider treating patients with remotely secured or unruptured aneurysms
& Symptoms of subarachnoid hemorrhage
& Active internal bleeding
& Pretreatment blood pressure with systolic 9185 mm Hg or diastolic 9110 mm Hg
& Clear and large hypodensity on CT scan
& Current bleeding diathesis including
) International normalized ratio (INR) 91.7
) Heparin within 48 hours resulting in abnormal partial thromboplastin time (PTT)
) Platelets G100,000/mm3
) Direct thrombin inhibitor (eg, dabigatran) or factor Xa inhibitor (eg, rivaroxaban, apixaban)
use within 48 hours
h Optimal laboratory testing thresholds for safe IV recombinant tissue-type plasminogen
activator (rtPA) use in this setting remain to be determined and are an area of active
investigation.
& Serum glucose G50
) If persistent symptoms after correction, or infarct is verified/supported by imaging, most experts
would consider IV rtPA treatment.
Relative Contraindications for IV rtPA1
& Minor deficit
) Rapidly improving deficits should not be considered a contraindication unless the remaining
deficit is minor.23
) A common definition of minor deficits is an NIH Stroke Scale (NIHSS) score e5 and not clearly
disabling.
) A consensus definition of deficits that should typically be considered disabling (regardless of total
NIHSS score) is shown in Table 1-1.
& Myocardial infarction in the past 3 months
) Some experienced centers treat this as a contraindication only if the myocardial infarction is
subacute and transmural, or other signs suggest a high risk of hemopericardium, such as clinical
or ECG evidence of pericarditis.
) Concurrent acute myocardial infarction may benefit from IV rtPA as well and should be
considered in consultation with a cardiologist; however, only lower stroke dosing of 0.9 mg/kg
(not higher cardiac dosing of approximately 1.1 mg/kg) should be used in this setting.
& Seizure at presentation
) If stroke is verified by imaging, IV rtPA treatment should be considered. However, the severity of
concurrent stroke must be judged in the context of ictal/postictal presentation.
& Pregnancy
) Must weigh risks and benefits in the individual circumstances.
Continued on next page

(http://nihss-english.trainingcampus.
net/uas/modules/trees/windex.aspx).
However, emergency physicians are
not always NIHSS trained, and a de-
scriptive examination can be used
to estimate the NIHSS score and
thereby the severity of the stroke in that
circumstance.
Treating a stroke mimic, such as
a complicated migraine or seizure,
with IV rtPA is inevitable sometimes.
Fortunately, the risk of intracranial
hemorrhage when treating a stroke
mimic with IV rtPA inadvertently is
extremely low (less than 1%) based on
case series of tPA-treated stroke
mimics and the cardiology literature.24
Therefore, time to treatment should
not be lost with ancillary testing such
as MRI or CT angiography if stroke
seems likely but not definitive.
The role of adjunctive endovascular
treatment for severe IV rtPAYtreated
ischemic strokes remains to be deter-
mined. The only randomized trial of
the combined IV rtPA/endovascular
approach to date, the Interventional
Management of Stroke (IMS) III trial,
did not demonstrate its superiority
over IV rtPA alone among subjects of
18 to 83 years of age with severe
strokes (NIHSS score of 8 or higher),
although safety parameters were
comparable.25
The trial results also
suggested that the clinical benefit of
successful flow restoration may be lost
beyond 7 hours from stroke onset in
the average patient. It has been hy-
pothesized that subgroups of patients
may benefit from endovascular therapy,
such as those with the most severe
deficits (eg, an NIHSS score greater than
KEY POINTS
h The risk of intracranial
hemorrhage when
treating a stroke mimic
with IV recombinant
activator inadvertently
is extremely low (less
than 1%).
h The combined IV/
endovascular approach
in all patients with an
NIH Stroke Scale score
of 8 or greater is not
superior to IV
alone despite
comparable safety.
BOX 1-1 IV rtPA Exclusion and Relative Contraindication Criteria (continued)
Additional Exclusion Criteria for IV rtPA Within the 3- to 4.5-Hour Time Window1
& History of stroke AND diabetes mellitus
& NIHSS score 925
& Age 980 years old
& On warfarin (regardless of INR value)
TABLE 1-1 Proposed Operational Definition of Disabling Deficitsa,b
The following typically should be considered disabling deficits:
Complete hemianopsia (Q2 on NIH Stroke Scale [NIHSS] question 3), or
Severe aphasia (Q2 on NIHSS question 9), or
Visual or sensory extinction (Q1 on NIHSS question 11), or
Any weakness limiting sustained effort against gravity (Q2 on NIHSS
question 6 or 7),
Any deficits that lead to a total NIHSS 95, or
Any remaining deficit considered potentially disabling in the view of the
patient and the treating practitioner. Clinical judgment is required.
a
Reprinted with permission from Re-examining Acute Eligibility for Thrombolysis (TREAT) Task
Force, Stroke.23
stroke.ahajournals.org/content/44/9/2500.abstract.
b
All neurologic deficits present at the time of the treatment decision should be considered in
the context of individual risk and benefit, as well as the patient’s baseline functional status.
Acute Stroke

20), patients with demonstrated large
proximal arterial occlusions (such as
internalcarotid artery terminusocclusions
or occlusions that are greater than 8 mm
in length), and those whose occlusions
are recanalized more rapidly or effectively.
Several randomized trials of more selec-
tive patient subgroups are now underway.
Glucose and Other Laboratory
Results
Testing for serum glucose level is
necessary before the IV rtPA treatment
decision.1
This should take minimal
time when performed by finger stick
and is often done by EMS en route.
This test allows the clinician to exclude
stroke mimics of hypoglycemia or
hyperglycemia. If the hypoglycemic
patient’s symptoms resolve after glu-
cose administration, then IV rtPA may
not be indicated. Hyperglycemia can
present with choreiform movements
that can be mistaken for stroke symp-
toms. Experts generally believe that
neither hypoglycemia nor hyperglyce-
mia should preclude IV rtPA treatment
if the deficits are believed to be caused
by concurrent ischemia.
Other laboratory results should be so-
licited if available, but they are not ne-
cessary. In particular, INR, PTT, and
platelet count will help determine IV rtPA
eligibility. However, IV rtPA administration
should not be delayed for any laboratory
result other than finger-stick glucose
level unless a clinical suspicion for an
abnormality exists. Fewer than three in
1000 patients will have unsuspected
thrombocytopenia,26
and fewer than four
in 1000 patients will have an unsus-
pected INR greater than 1.7.27
Blood Pressure
Blood pressure is generally maintained
relatively high after acute ischemic
stroke. In the setting of cerebral ischemia,
a loss of cerebral autoregulation occurs
such that systemic blood pressures
directly affect cerebral perfusion pres-
sure. In this setting, increased systemic
blood pressure will improve blood flow
to the cerebral infarct, often via collateral
blood vessels, and thereby may reduce
the extent of irreversible ischemia.
The upper limits of blood pressure
control are dictated by the decision of
whether to administer acute reperfu-
sion therapy. The blood pressure
must be less than 185 mm Hg systolic
and 110 mm Hg diastolic for IV rtPA
eligibility, and must be maintained
below 180/105 mm Hg during and
after IV rtPA administration. Gentle
blood pressure reduction can usually
be achieved with labetalol 10 mg IV. If
this dose is not enough, then it might
be doubled. If no response occurs, a
nicardipine infusion (5 mg per hour
IV, titrate up by 2.5 mg per hour every
5 to 15 minutes, maximum 15 mg per
hour) may be needed and typically
achieves the blood pressure goals. If
nicardipine is not available, or contra-
indications exist for this or labetalol,
another consideration is IV enalaprilat
3.25 mg to 6.5 mg.
Acute Brain Imaging
Imaging of the brain parenchyma serves
the primary role of ruling out intracranial
hemorrhage, including intracerebral,
subarachnoid, and epidural/subdural lo-
cations. At most centers, a noncontrast
CT scan is the most rapid modality
available, although some centers may
use limited MRI (specifically consisting
of diffusion-weighted imaging [DWI],
either susceptibility-weighted [SW] im-
aging or gradient echo [GRE] se-
quences, and fluid-attenuated inversion
recovery [FLAIR] sequences) if rapidly
available. Rarely, an acute CT scan will
reveal a large and clear hypodensity that
will lead to questioning the time of
onset of the stroke and the possibility
of an undiagnosed subacute stroke,
both of which would contraindicate IV
KEY POINT
h One should not delay IV
administration for any
laboratory result other
than finger-stick glucose
level unless a clinical
suspicion for an
abnormality exists.

rtPA. Subtle changes may also be seen
on CT scan, such as loss of gray-white
differentiation or sulcal effacement, to
support the diagnosis of ischemic
stroke. While subtle ischemic changes
on CT scan are not contraindications to
acute reperfusion therapy, they do
portend worse outcomes compared
with those with lesser acute ischemic
changes on CT scan.28
Advanced imaging, specifically head
and neck vascular imaging with CT
angiography or magnetic resonance
angiography, can be valuable in plan-
ning the approach to endovascular
therapy if indicated, determining the
etiology of stroke for secondary pre-
vention (eg, carotid endarterectomy),
or obtaining supportive evidence for
an ischemic stroke diagnosis. Using
this as a first-line imaging approach for
all ‘‘rule-out stroke patients’’ in an
emergency department is likely to be
inappropriate, given the additional
radiation exposure to a diverse group
of patients. In settings where an expert
physician triages stroke patients, CT
angiography or magnetic resonance
angiography may be useful in selected
cases (ie, IV rtPAYineligible patients who
arrive in the emergency department
early) to identify symptomatic occlu-
sions amenable to acute endovascular
therapy while the neurointerventional
team is being mobilized. In all cases,
advanced neuroimaging should not de-
lay the administration of IV rtPA.
To date, there is no known role for
other forms of advanced imaging,
such as perfusion studies with CT
perfusion or magnetic resonance
perfusion-weighted imaging, to select
patients for acute reperfusion thera-
pies. In particular, no data have
supported the utility of identifying
penumbra (ie, brain at risk for infarc-
tion without reperfusion) for IV rtPA
decisions, as the majority of these
patients will have penumbra within
4.5 hours, and the role of penumbral
imaging for selecting patients for acute
reperfusion treatment beyond 4.5 hours
remains to be determined (as discussed
earlier in this review).
POSTREPERFUSION THERAPY
CARE
Standard post-tPA management for the
first 24 hours includes the following:
& admission to a step-down or
intensive care unit
& maintenance of nothing-by-mouth
(NPO) status until dysphagia
screening is performed to avoid
aspiration pneumonia
& administration of isotonic IV fluids
(not dextrose containing because
of risk of hyperglycemia)
& blood pressure and neurologic
monitoring every 15 minutes for
2 hours, then every 30 minutes
for 6 hours, then every hour for
16 hours after treatment
& aggressive blood pressure treatment
if systolic blood pressure is greater
than 180 mm Hg or diastolic blood
pressure is greater than 105 mm Hg
& emergent CT scan of the brain if
neurologic decline, acute increase
in blood pressure, nausea, vomiting,
or new headache is present to rule
out hemorrhagic transformation
& repeat brain imaging at 24 hours
to assess for asymptomatic
hemorrhage and to allow initiation
of antiplatelet therapy
OTHER ACUTE ISCHEMIC
STROKE MANAGEMENT
CONSIDERATIONS
Blood Pressure in Patients With
No Reperfusion Therapies
Data are very limited to dictate the
optimal blood pressure in this set-
ting. Experts generally recommend
permissive hypertension if tolerated
KEY POINTS
h Subtle ischemic changes
on CT scan are not
contraindications to
acute reperfusion
therapy.
h Standard postYtissue
management for the
first 24 hours includes
aggressive blood pressure
treatment if systolic blood
pressure is greater than
180 mm Hg or diastolic
blood pressure is greater
than 105 mm Hg.
Acute Stroke

(up to 220/120 mm Hg) in the non-
reperfusion therapy setting and con-
sideration of lowering blood pressure
by 15% over the first 24 hours.1
Less commonly, blood pressure
may be low in the acute setting, and
stroke deficits may improve with raising
the pressure. Most experts will attempt
IV fluid boluses to raise blood pressure
in the setting of relative hypotension
and see if stroke symptoms improve
with this intervention. If the stroke
deficits appear to be pressure depen-
dent, more aggressive blood pressure
support with pressors may be consid-
ered. Evidence for the role of pressors
in the acute stroke setting is limited,
however.
Glucose in the Acute Setting
Hyperglycemia (greater than 140 mg/dL)
during the first 24 hours after stroke is a
poor prognostic indicator. Whether acute
correction will lead to better clinical out-
comes after stroke is unknown. Current
recommendations are to treat hyper-
glycemia to achieve a level lower than
180 mg/dL, and stricter glucose control
is under study in a major randomized
clinical trial.1
Antithrombotic Therapy in the
Acute Setting
Aspirin should be initiated within 48
hours in all patients and is typically
initiated in the emergency department
if no acute reperfusion therapy is
administered. If IV rtPA or acute
endovascular therapy is administered,
aspirin is initiated at approximately 24
hours and only after confirmation of no
hemorrhagic transformation on the
24-hour CT scan. Early aspirin treat-
ment leads to a 1% absolute reduction
of stroke over the next 2 weeks.29,30
Recent evidence from a randomized
trial in China of TIA and minor stroke
patients who were not treated with IV
tPA has suggested that short-term
combined aspirin and clopidogrel admin-
istration may better prevent early stroke
recurrence in minor strokes or TIAs, and
further randomized study is currently
underway in the United States.31
It is well established that acute
anticoagulation (including unfractionated
and low-molecular-weight heparin)
does not improve clinical outcomes
after acute ischemic stroke compared
with antiplatelet therapy in unselected
patients. There may be a role for acute
anticoagulation in specific circum-
stances in which early stroke recurrence
risk is high, but clinical data are lacking.
SUMMARY
In summary, effective emergent evalua-
tion of a stroke patient requires well-
organized systems that maximize speed
of assessment and administration of
appropriate therapies. This article pro-
vides a practical overview of this pro-
cess, and the reader is referred to the
American Heart Association/American
Stroke Association clinical guidelines
for more detailed discussions. When
these systems cannot appropriately be
implemented at a given hospital, it is
imperative that triage and bypass plans
be implemented to maximize clinical
outcomes after stroke.
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h Experts generally
recommend permissive
hypertension if tolerated
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in the nonreperfusion
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h Current recommendations
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h Short-term combined
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