Neurocrit Care
DOI 10.1007/s12028-017-0449-9
Emergency Neurological Life Support: Acute Ischemic Stroke
Hartmut Gross1 • Noah Grose2,3
 Neurocritical Care Society 2017
Abstract Acute ischemic stroke is a neurological emer-
gency that can be treated with time-sensitive interventions,
including both intravenous thrombolysis and endovascular
approaches to thrombus removal. Extensive study has
demonstrated that rapid, protocolized, assessment and
treatment is essential to improving neurological outcome.
For this reason, acute ischemic stroke was chosen as an
emergency neurological life support protocol. The protocol
focuses on the first hour of medical care following the
acute onset of a neurological deficit.
Keywords Stroke
Ishcemic stroke

Emergency neurologic life support
Neurocritical care
Introduction
According to 2017 World Health Organization statistics,
cerebrovascular disease is the second cause of death
worldwide, with an estimated 6.3 million deaths per year—
coming a close second to ischemic heart diseases (8.7
million deaths per year) [1]. In the United States, approx-
imately 795,000 strokes occur annually, of which nearly
& Hartmut Gross
hgross@augusta.edu
Noah Grose
noah.grose@osumc.edu
1
Department of Emergency Medicine, Medical College of
Georgia at Augusta University, Augusta, GA, USA
2
Department of Neurology, The Ohio State University Wexner
Medical Center, Columbus, OH, USA
3
Adult Gerontological Acute Care Nurse Practitioner Program,
Mount Carmel College of Nursing, Columbus, OH, USA
25% are recurrent strokes [2]. Stroke is the 5th most
common cause of death, following cardiac disease, cancer,
chronic lower respiratory illness, and accidental injuries in
the U.S. Although there are many new advances in the
treatment of stroke, it is crucial that proper diagnosis and
management occur as soon as possible, since the later
therapies are instituted, the less likely the chance of suc-
cessful intervention.
The ENLS suggested algorithm for the initial manage-
ment of acute ischemic stroke is shown in Fig. 1.
Suggested items to complete within the first hour of eval-
uating a patient with acute ischemic stroke are shown in
Table 1.
Clinical Suspicion of Stroke
Acute stroke is suspected when a patient exhibits the
sudden onset of a focal neurological deficit (e.g. facial
weakness, arm/leg weakness, ataxia, aphasia, dysarthria,
visual field loss, gaze preference, sensory disturbances,
neglect, or other focal findings). In the absence of an
obvious seizure, the deficit can most likely be attributed to
stroke or transient ischemic attack (TIA). In countries that
treat stroke as an emergency, paramedical personnel are
typically the first to evaluate the patient in the home or at a
scene (Fig. 2). Patients with suspected acute stroke should
be triaged with the same priority as serious trauma or acute
myocardial infarction, regardless of the severity of deficit.
The standard treatments are to perform routine airway,
breathing, and circulation (ABC) assessments, administer
supplemental oxygen as needed, check blood/capillary
glucose, perform a validated stroke severity scale exami-
nation [e.g. Cincinnati Prehospital Stroke Scale (CPSS),
Las Angeles Prehospital Stroke Screen (LAPSS),
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Fig. 1 ENLS acute ischemic stroke protocol

Table 1 Acute ischemic stroke checklist for the first hour

h Activate stroke code system (if available)
h Vital signs
h Supplemental oxygen to maintain saturation >94%
h Determine time of onset/last known well
h Determine NIHSS score
h CT or other vascular imaging study
h Medication list*
h IV access–18 g peripheral IV (for advanced imaging)
h Labs: capillary glucose, CBC with platelets, PT/INR, PTT, and beta-HCG for women of child-bearing age
h EKG
* When asking about medications, be sure to ask specifically about anticoagulants: e.g. warfarin, heparin, low molecular weight heparin
(enoxaparin, dalteparin, tinzaparin), target-specific anticoagulants (e.g. dabigatran, apixaban, edoxaban, and rivaroxaban), and when medication
was last taken/administered

Prehospital Acute Stroke Severity (PASS), Field Assess-
ment Stroke Triage–Emergency Destination (FAST–ED),
Rapid Artery Occlusion Evaluation (RACE), Los Angeles
Motor Scale (LAMS)], IV access should be obtained and
the time of symptom onset (or least known well time)
should be established. Pre-hospital notification should be
completed and the patient should be transported to the
closest appropriate certified stroke facility (see Table 2)
[3].
Patients may have a stroke while in the hospital, at
rehabilitation centers, nursing homes or may present
directly to an emergency department (ED) triage. Nurses or
Advanced Practice Providers (APPs, including both
advanced practice nurses and physician’s assistants) may
be the first health care provider to have contact with the
patient in these circumstances, so it is important for them to
recognize and respond quickly and appropriately. In cases
of uncertainty whether or not a patient is having a stroke

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Fig. 2 Clinical suspicion of stroke algorithm: this algorithm assumes
the patient is outside of the hospital when stroke occurs. Based on the
results of brain imaging, the patient can be triaged to one of the three
ENLS protocols (bottom)
and whether or not to activate a stroke team, the simple
mantra, ‘‘If in doubt, call it out,’’ may be helpful.
Prehospital systems should call ahead to the receiving
hospital, and patients should preferentially be transported
to a certified stroke center. Immediately on arrival to an
ED, patients should be screened for stability, undergo rapid
clinical stroke assessment (‘‘at the door’’), then be taken
directly for rapid imaging, with non-contrast computed
tomography (CT). Non-invasive computed tomography
angiography (CTA) should be obtained as quickly as pos-
sible to expedite the identification of large vessel
intracranial occlusion. These are often completed in
succession, but should not delay the administration of IV
alteplase [4]. Some centers use abbreviated/accelerated
MRI/MRA studies instead of CT.
Utilization of telestroke networks (hub-and-spoke) has
helped to solve the shortage of neurologists in rural areas
and has demonstrated high rates of safe administration of
IV alteplase while decreasing time to initiate IV alteplase
[5–7]. Hemorrhage and mortality rates and functional
outcomes are comparable to randomized trials of patients
treated live at study sites. Many regional arrangements
have been made for ‘‘telestroke’’ consultation in order to
expedite the administration of thrombolytic therapy in the
‘‘drip-and-ship’’ model followed by transfer to a higher
level certified stroke center if necessary or possible. If
patients are eligible for IV alteplase, it should be admin-
istered prior to transport. Transport of patients from spoke
to hub (originating to destination site) may involve air
medical transport.
As shown in Fig. 2, imaging is essential to confirm the
correct diagnosis and exclude intracranial hemorrhage.
Treatment should then proceed according to one of three
ENLS protocols (shaded): Subarachnoid Hemorrhage,
Intracranial Hemorrhage, or Acute Ischemic Stroke. If the
CT is free of hemorrhage or mass effect, then a presump-
tive ischemic stroke or TIA is present.
When confronted with a patient whose focal neurolog-
ical symptoms have begun within the preceding few hours,
it should be assumed that the patient will eventually be
diagnosed with stroke. Most TIAs are brief, typically
lasting less than 20 min before completely resolving.
Therefore, if the patient is still manifesting physical signs
of a stroke in the ED, those signs likely indicate a stroke.
In some centers, patients may be screened for clinical
stability immediately upon arrival (‘‘at the door’’), then
taken directly to CT based on clinical symptoms suspicious
for an acute stroke. However, there are a number of stroke
mimics including seizure, hypoglycemia, sepsis, fever,
migraines, and Bell’s palsy. It is not uncommon for
patients with stroke mimics to be treated with alteplase;
mimics should be ruled out as best possible in the narrow
time window, but if inadvertently treated with throm-
bolytics, the risk of harm is very small. Bottom line: if the
patient is manifesting physical signs of a stroke in the ED
and falls within American Heart Association/American
Stroke Association (AHA/ASA) recommendations, then IV
alteplase should be offered/administered.
Each of the following elements should be addressed in
rapid protocolized succession.
Time of Onset
One of the chief criteria used to select patients for acute
stroke interventions is the patient’s time of stroke onset or
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Table 2 Prehospital standard assessment and treatment
h Perform history and physical exam
h Determine time patient was last known well (LKW)
h ABCs (routine airway, breathing, and circulation assessments)
h Administer supplemental oxygen as needed
h Check blood/capillary glucose
h Perform a stroke severity scale examination
h Obtain intravenous (IV) access
h Obtain blood tubes vials for evaluation at the receiving stroke center (optional)
h Transport the patient to the closest appropriate certified stroke center
h Activate pre-hospital notification
h To decrease door to imaging time, strongly consider a brief doorway assessment in arrival to the ED and take the patient to brain imaging
on the EMS gurney
last known well (LKW). Acute stroke treatment is time
sensitive and delays can lead to a lower likelihood of a
good outcome and an increased risk of intracranial hem-
orrhage. The time the patient was last known to be without
neurological deficits must be established from the patient
or a bystander. If the patient went to bed and awoke with
the stroke symptoms, the time of onset is considered to be
when the patient went to bed. It is always worthwhile to
ask the patient or family member about getting up during
the night to go to the bathroom as the information may
allow changing the LKW time to a more recent time, which
may place the patient back into a treatable time window.
It is worth noting that ‘‘wake-up strokes’’ are an area of
key research. Some centers are studying and treating these
patients under research protocols using advanced imaging
techniques to determine which patients have salvageable
tissue and the risk of complications for different treatment
modalities [8–10]. This will no doubt soon be an area of
new diagnostic and treatment protocols and there are
already ongoing studies such as the Endovascular Therapy
Following Imaging Evaluation for Ischemic Stroke 3
(DEFUSE 3) trial. The Trevo and Medical Management
Versus Medical Management Alone in Wake Up and Late
Presenting Strokes (DAWN) trial was recently completed
and preliminary results suggest benefit of endovascular
intervention for a cohort identified with persistent infarct/
perfusion mismatch.
Vital Signs
Pulse oximetry should guide supplemental oxygen to
achieve an oxygen saturation C94%. Hyperoxia may be
detrimental in stroke, so there is no need for high flow
oxygen for patients with adequate oxygenation [3].
Blood pressure (BP) must be obtained. Low BP is
uncommon in acute stroke and may indicate exacerbation
of symptoms of a previous stroke due to poor perfusion of
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previously injured tissue. Blood pressures in excess of
220/120 mmHg should be lowered, regardless of the ulti-
mate diagnosis. There are consensus suggestions of
allowing permissive hypertension up to 220/120 mmHg for
acute stroke patients who are not candidates for alteplase,
including those who have failed attempts to lower BP to
allow alteplase eligibility [4].
If the patient is a potential alteplase candidate, inter-
ventions to control BP should be initiated immediately.
The target BP for IV alteplase candidates is less than
185/110 mmHg, and once alteplase is initiated, BP must be
maintained below 180/105 mmHg for 24 h after adminis-
tration of alteplase to limit the risk of intracranial
hemorrhage [4]. A strategy of careful blood pressure low-
ering should be employed while being mindful of not
dropping the blood pressure too much once the patient is at
goal. Short-acting intravenous agents such as labetalol,
nicardipine, clevidipine, or hydralazine are preferred (see
Table 3) to achieve a BP < 185/110 mmHg.
Hypertension is common in the setting of ischemic
stroke. Titratable IV antihypertensive agents like labetalol,
hydralazine and nicardipine are the recommended agents of
choice, in the treatment of hypertension in the acute set-
ting. Clevidipine has been used as an alternative agent for
blood pressure control in the acute stroke setting.
If the patient’s BP proves refractory to the above med-
ications, the patient is considered to be high risk for ICH
and should not be treated with alteplase. However, efforts
to reduce BP below 220/120 mmHg should be continued.
Permissive hypertension (allowing BP to naturally rise) is
allowed for TIA, as it is for non-alteplase treated patients,
up to 220/120 mmHg. This elevated blood pressure may be
gradually lowered over the next 24–48 h.
Neurocrit Care

Table 3 IV Antihypertensive agents used to lower BP to attain alteplase eligibility

Labetalol
10–20 mg IV bolus over 1–2 min; may repeat every 10 min
Consider doubling dose (i.e., 20, 40, 80 mg) to a maximum total dose of 300 mg, followed by a maintenance infusion (0.5–8 mg/min)
The importance of the maintenance infusion should not be underestimated or dismissed. If a bolus was required to lower the blood pressure,
then the BP should be assumed to climb again as soon as the bolus wears off, potentially placing the patient in danger of ICH due to the
uncontrolled BP. Start an infusion if labetalol boluses successfully lower the BP. If the patient is no longer deemed a candidate for alteplase
and permissive hypertension is being planned, then the infusion may be discontinued, provided the BP does not rise above 220/120 mmHg
Hydralazine
10–20 mg IV q 4–6 h
Nicardipine
Begin with 5 mg/h IV infusion
Titrate by 2.5 mg/h at 5–15 min intervals to a maximum total dose of 15 mg/h to achieve goal BP. Be prepared to lower the dose once target
BP has been reached
Clevidipine
Begin with 1–2 mg/h IV infusion
Double medication dose every 90 s until BP goal is neared, then increase in smaller increments until desired BP goal is reached
Maximum dose is 32 mg/h

Laboratory Examination a doorway assessment by the clinician and simultaneous

An adequate laboratory examination includes capillary
blood glucose (CBG), complete blood count (CBC) with
platelets, chemistries, prothrombin time/partial thrombo-
plastin time (PT/PTT), international normalized ratio
(INR), and beta-human chorionic gonadotrophin (HCG) for
women of child bearing age. At a minimum, a capillary
blood glucose (finger-stick) should be performed prior to
alteplase administration, since it can be completed quickly
to rule out hypoglycemia as a stroke mimic.
In selected patients who are taking direct thrombin
inhibitors or direct factor Xa inhibitors, it may be prudent
to check a thrombin time (TT), and/or ecarin clotting time
(ECT), or chromogenic antiXa activity assays, respec-
tively. However, if a patient is deemed a candidate for
tissue plasminogen activator (alteplase) and there is no
reason to suspect abnormal laboratory test results, alteplase
should be administered without waiting for these labora-
tory values to prevent further delay [4]. If patients
coagulation and platelet count results are abnormal
(INR > 1.7 or PT is abnormally elevated, platelet count
<100,000 mm3) then alteplase should be discontinued
(2013 AHA/ASA guidelines).
Imaging
There should be a goal of completing a head CT scan or
MRI within 25 min of the patient’s arrival. CTA of the
head and neck should be completed when possible with this
initial CT. Chest X-ray is no longer routinely recom-
mended during the acute phase of the workup [4]. With
EMS pre-hospital notification of a potential stroke patient,
patient registration can facilitate rapid patient transport to
imaging.
Activate Stroke Team
If available, the stroke code system should be activated.
The acute stroke team should evaluate the patient <15 min
of the patient entering the ED. Again, prehospital notifi-
cation by EMS and paging the stroke team can expedite
patient assessment on arrival and in CT, thereby decreasing
time to determine alteplase candidacy.
NIHSS
The National Institutes of Health Stroke Scale (NIHSS) is a
standardized method for examiners to reproducibly and
quantifiably assess a patient’s stroke symptoms. This is the
preferred scoring system and may be used by a variety of
non-neurological medical providers [4]. Scores range from
zero (no deficit) to 42.
The scale has some limitations especially in scoring
brainstem strokes. In the 2007 AHA/ASA guidelines, an
NIHSS of 4 was a threshold to treat an acute ischemic
stroke with alteplase, but now, a low score is not an
absolute contraindication and potential risks should be
weighed against anticipated benefits. While the NIHSS
helps to standardize the exam, a better tool to determine
whether or not to recommend alteplase is to determine if
the symptoms are disabling to the patient. In mild strokes,
asking the patients directly if their symptoms are disabling
or hindering them will often make the decision process
easy. It is notable that in a large 2011 study of patients

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Table 4 Risk of intracranial hemorrhage with IV alteplase treatment
[12]
NIHSS score Risk of intracranial hemorrhage (%)
0–10 2–3
11–20 4–5
>20 17
deemed ‘‘too good to treat,’’ 28% could not be discharged
home and another 28% could not walk independently at
discharge [11]. Clinicians should carefully consider, and
document, the individual patient’s relative risks, potential
benefit and premorbid status when evaluating a patient for
treatment with alteplase.
Health care providers wishing to learn how to perform
the NIHSS and receive free certification can find these
resources online through the American Stroke Association
and the National Stroke Association.
The NIHSS score may also be used as a guideline to
predict risk of intracerebral hemorrhage in patients who are
given alteplase, as shown in Table 4. However, despite this
escalating risk of hemorrhage, patients in all NIHSS strata
benefit from alteplase.
Intravenous Fluids
Patients presenting with acute stroke are typically hypo- or
euvolemic. Hypovolemia can worsen ischemic injury as a
result of impaired perfusion to brain tissue. Hypervolemia
may exacerbate ischemic brain edema and increase stress
on the myocardium. Euvolemia is desirable in the acute
stroke setting and most stroke patients should receive
maintenance isotonic intravenous fluids in the form of
normal saline. Hypotonic and dextrose including fluids
should be avoided. The utilization of plasma volume
expanders has not demonstrated benefit.
Onset <3 h
Alteplase is a thrombolytic medication and is the only
tissue plasminogen activator approved for treatment of
acute stroke in the U.S. If the time from stroke system
onset is less than 3 h, it should be confirmed that there are
no contraindications for IV alteplase (Table 5). One rela-
tive contraindication is ‘‘clearing neurological deficit.’’
Some patients will clear to near or full recovery without
alteplase, while others may improve somewhat from a
severe stroke but then fail to clear further. If a patient has
plateaued or still has significant stroke symptoms and no
other contraindication, treatment with alteplase should
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proceed as it would otherwise. Also some patients will
present with stuttering symptoms. If symptoms completely
resolve, clinicians should reset the clock to start a new
alteplase candidacy window; if there are still symptoms—
however mild—the time of onset remains unchanged.
Patients with stuttering symptoms tend to be high risk for
extending their vascular occlusions. Be aware that some
patients will have pressure dependent lesions and lowering
of BP may actually exacerbate their symptoms; conversely,
allowing their BP to rise above their threshold will improve
their deficit.
In 2015, the new Food and Drug Administration (FDA)
guidelines for Alteplase use were released. Many restric-
tions were removed or relaxed. Table 6 compares the
AHA/ASA 2013 and the 2015 FDA guidelines. Many
clinicians practice using a hybrid of the two guidelines. It is
important to recognize that the majority of experience with
alteplase administration over the past 20 years has utilized
treatment algorithms consistent with the AHA/ASA
guidelines.
Common reasons to avoid administering intravenous
(IV) alteplase are time (duration from first symptom
>4.5 h), recent surgery, current bleeding at a non-com-
pressible site, as well as large area of cerebral infarction
that is already apparent as low density on the initial brain
CT or MRI study (>1/3 of the middle cerebral artery
(MCA) territory).
Patients with major neurological deficits have a high risk
of poor outcome, regardless of whether or not alteplase is
administered. In these cases, realistic expectations and
risks associated with either choice should be discussed with
the patient’s family members, and a joint decision should
be made. While a glucose level greater than 400 mg/dL is
not a contraindication, it should be noted that high glucose
may be a stroke mimic, can be associated with worse
outcome, and may increase the risk of intracranial hem-
orrhage. Similarly, the presence of fever should prompt a
reconsideration of the diagnosis. For example, a simple
urinary tract infection can bring back old, subclinical
stroke symptoms and, once corrected, these stroke-like
symptoms may resolve.
Onset Between 3 and 4.5 h
In the U.S., alteplase has not yet been approved by the FDA
for use between 3 and 4.5 h, though it has been approved in
Europe and Canada. However, alteplase use in this time-
frame has been endorsed by the AHA/ASA4 and is widely
used in the U.S.
The inclusion criteria are similar to those of onset <3 h
(discussed above), but are modified as noted in Table 7.
Neurocrit Care

Table 5 Eligibility and absolute and relative contraindications for use of IV alteplase (AHA/ASA 2013 guidelines) [4]
Eligibility
Diagnosis of ischemic stroke causing measurable neurological deficit. Neurological signs should not be minor and isolated. Neurological
signs should not be clearing spontaneously
Onset less than 3 h before initiating alteplase
Patient is at least 18 years old (see section on special considerations: pediatric stroke)
Absolute exclusion criteria if positive
No major head trauma or prior stroke in the previous 3 months
Symptoms of stroke should not be suggestive of subarachnoid hemorrhage
No arterial puncture at a non-compressible site or lumbar puncture in the previous 7 days
No history of previous intracranial hemorrhage
No history of intracranial neoplasm, aneurysm, or arteriovenous malformation
No intracranial or intraspinal surgery in the previous 3 months
Blood pressure not elevated (systolic <185 mmHg and diastolic <110 mmHg)
No evidence of active bleeding or acute trauma (fracture) on examination
Platelet count <100,000 mm3
If receiving heparin in previous 48 h, aPTT must be in normal range
Not taking an oral anticoagulant or, if anticoagulant being taken, INR < 1.7 or PT > 15 s
No dabigatran, apixaban, or rivaroxaban use for chronic anticoagulation for conditions such as atrial fibrillation. There is still little
information on assessing influence or levels of these medications in patients with acute stroke. There are suggestions to check an activated
thromboplastin time (aPTT), INR, platelet count, thromboplastin time (TT), ecarin clotting time (ECT) and anti factor 10a level (if
available). Without normalized special tests (as listed), use of alteplase is NOT recommended in patients with recent use (within 48 h) of
these products
Blood glucose concentration <50 mg/dL (2.7 mmol/L)
CT does not show a multilobar infarction (hypodensity >1/3 cerebral hemisphere)
Relative exclusion criteria if positive—use caution if recommending alteplase if one or more are positive
Stroke symptoms are rapidly improving or only minor
Pregnancy
Seizure with postictal residual neurological impairments
Major surgery or major trauma in the previous 14 days
Gastrointestinal or urinary tract hemorrhage in the previous 21 days
Myocardial infarction in the previous 3 months
Some additional considerations
Caution should be exercised in treating a patient with major deficits
Caution using alteplase in patients treated with low molecular weight heparin in the past 24 h
Patient or family members understand the potential risks and benefits from treatment. No written consent is required but the conversation
should be documented in the clinical notes. Do not delay IV therapy if a surrogate is not readily available as this can lead to worse outcomes
Alteplase is not FDA approved for treatment of patients under the age of 18. However, alteplase has been used off-label in selected pediatric
patients with strokes, following careful counseling of parents and using identical eligibility and contraindication criteria to those used in
adults. (See special considerations: pediatric stroke below)

Patient is an IV Alteplase Candidate: IV Alteplase
Administration
After placing two peripheral IV lines, actual body weight is
ideally used rather than estimated body weight. If weight
estimation must be done, then two experienced health care
providers should agree on the weight to be used for cal-
culation. Alteplase is dosed at 0.9 mg/kg and should be
mixed by swirling (rather than shaking), with the total dose
not to exceed 90 mg.
The initial 10% of the total alteplase dose is given by
bolus over 1 min, then the remainder is infused over 1 h.
As alteplase is dispensed in 50 and 100 mg bottles, excess
alteplase should be withdrawn from the vial and discarded
to avoid accidental infusion of the excess. A 100-ml bag of
saline should be administered after the 1 h infusion to flush
the IV line to ensure that the entire dose is administered.
This flush should be run at the same rate as the infusion to
avoid a terminal alteplase bolus.
During the hospital admission or transfer period, there
should be continued observation for complications of

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Table 6 Comparison of AHA/ASA acute stroke management guidelines (2013) and 2015 FDA prescribing information for alteplase treatment
of acute ischemic stroke [13] (adapted)
Criterion AHA/ASA acute stroke guideline Alteplase Feb 2015 FDA approved product information

Prior stroke Exclusion: prior stroke within 3 months Removed entirely

Seizure at onset Relative exclusion: seizure at onset with postictal Removed entirely
neurological impairments
Bleeding diathesis/ Exclusion: Bleeding diathesis remains a contraindication, but all laboratory
OACs Platelet count <100,000/mm values and specific examples removed
Heparin received within 48 h, resulting in
abnormally elevated aPTT
Current use of anticoagulant with INR > 1.7 or
PT > 15 s
Current use of direct thrombin inhibitors or direct
factor Xa inhibitors with elevated sensitive
laboratory tests
ICH Exclusion: history of previous ICH Contraindication removed
Warning added for recent ICH
BP Exclusion: elevated BP (systolic >185 mm Hg or Contraindication: current severe uncontrolled hypertension
diastolic >110 mm Hg) remains, specific BP values removed. Warning for BP > 175/
110 mm Hg remains for all alteplase indications
Blood glucose Exclusion: blood glucose <50 mg/dL Removed entirely
Severe stroke Not listed Removed entirely
Mild stroke Relative exclusion: only minor or rapidly improving Removed entirely
stroke symptoms (clearing spontaneously)
Neuroimaging Exclusion: CT demonstrates multilobar infarction Removed entirely
findings (hypodensity >1/3 cerebral hemisphere)
Subarachnoid Exclusion: symptoms suggest SAH Contraindication: SAH
hemorrhage
Use in specific populations
Pregnancy Relative exclusion No change
Nursing mothers Not listed Unknown risk
Children Inclusion: C18 y of age Pediatric use not established
Elderly Not listed Warning added: age >77 year was one of several interrelated
baseline characteristics associated with an increased risk of ICH;
efficacy results suggest a reduced but still favorable clinical
outcome
Gastrointestinal or Warning: gastrointestinal or genitourinary bleeding Warning: gastrointestinal or genitourinary bleeding
genitourinary within the past 21 days
bleeding

Table 7 Additional inclusions to IV alteplase use between 3 and
4.5 h [14]
Meet all criteria of <3 h since onset of stroke
Age < 80 years
No anticoagulant use, regardless of INR
NIHSS B 25
No combined history of prior stroke and diabetes
alteplase, including airway obstruction due to angioedema
(consider rapid intubation), hemorrhage (stop alteplase),
and sudden deterioration in mental status. Additionally,
blood pressure may rise and require intervention to mitigate
the risk of intracranial hemorrhage. Guidelines require that
a patient be checked (BP and neurological assessment)
every 15 min for the first 2 h after starting alteplase, then
every 30 min for the next 6 h, then hourly for the next 16 h.
While the half-life of alteplase is approximately 5 min,
and only 20% of the medication is still present and active at
10 min after completion of the infusion, prothrombin and
activated partial thromboplastin times are prolonged and
fibrinogen levels are decreased for 24 h or more. A sudden
decline in neurological status during or following alteplase
administration may be due to an intracranial hemorrhage
[16]. Intracranial bleeds following IV alteplase carry a 50%
or greater mortality rate. This is often accompanied by a
marked rise in BP; however, a marked rise or fall in BP

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alone may signal an ICH. In these cases, the following
steps should be immediately taken:
• Stop alteplase infusion
• Vital signs every 15 min (neurological assessment for
signs of increased intracranial pressure). Assess GCS/
pupil response. Treat blood pressure and use non-
invasive interventions to lower ICP (raise head of bed,
neck midline) [15].
• Obtain a head CT scan STAT
• Notify the neurosurgeon on call; if a neurosurgeon is not
available, begin the process of transferring the patient to
a facility with neurosurgical capability once CT scan
results are available
• STAT labs: PT, PTT, platelets, fibrinogen, type and
cross 2–4 unit PRBCs
• Give the following:
• 6–8 units of IV cryoprecipitate
The 200–250 mg of fibrinogen contained in each bag
of cryoprecipitate and will increase the plasma
fibrinogen level by about 6–8 mg/dL in a 70-kg adult.
A fibrinogen level should be measured at 30–60 min
after completion of the transfusion to determine if
additional doses are needed. Ten bags of cryoprecip-
itate are usually given if the fibrinogen level is
between 50 and100 mg/dL and 20 bags are given if it
is less than 50 mg/dL. The therapeutic goal is to keep
the plasma fibrinogen level above 100 mg/dL. Circu-
lating half-life of fibrinogen is 3–5 days.
• 1 bag of single donor platelets or 6–8 bags of random
donor platelets may also be transfused
Onset Between 0 and 6 h: Endovascular Treatment
If the patient has a large vessel occlusion (LVO)—e.g.,
proximal (M1) middle cerebral artery (MCA), intracranial
internal carotid artery (ICA), basilar or vertebral artery—or
suspected LVO and the patient is within 6 h of LKW,
mechanical thrombectomy treatment should be considered.
If the patient is a candidate for intravenous alteplase, it
should be administered expeditiously, regardless of
endovascular procedure candidacy. Previously, intra-arte-
rial (IA) thrombolysis was considered to be an option;
[17, 18] however, alteplase had no FDA recommendation
for intraarterial use and is no longer recommended as
isolated therapy. Several 2015 randomized trials of
thrombectomy in acute, LVO ischemic stroke have shown
marked clinical efficacy and reduction in mortality
[19–23]. Patients with distal occlusions—e.g., M2, M3,
anterior cerebral arteries, posterior cerebral arteries, ver-
tebral or basilar artery have uncertain benefits.
Patients with a high NIHSS will often have a LVO. LVO
can be confirmed by seeing a hyper-dense sign (i.e., clot
within the vessel) on non-contrast CT, but this sign is
insensitive. CTA or MRA are more diagnostic, as is con-
ventional angiography. It is prudent to contact the
neurointerventional physician on call, if one is available. If
the treating hospital does not have this capability, rapid
transfer to a comprehensive stroke center (CSC) is rec-
ommended. If the patient is suspected to have a LVO
transfer to a CSC should not be delayed; these patients can
deteriorate quickly and a delay in transfer could limit
capability of potential endovascular intervention. Some
hospitals use CTA and/or CTP or MRI/MRA techniques to
select appropriate patients referred for endovascular inter-
vention; there is no standard for these practices. Sites
performing multimodal CT imaging should be able to
expeditiously perform a high-quality study and have the
capacity to transfer the patient to a CSC in such a timely
manner that the assessment is relevant to endovascular
decision making.
Exclusions for IA thrombolysis or embolectomy include
absence of a large vessel occlusion on CTA or MRA, or
large area of infarction already present on the brain
imaging study. Many providers use an ASPECT score of
greater than 6 to proceed with intervention [24]. Others
will use additional MRI, MRA, and DWMRI. Additionally,
some interventionists may opt to extend the time window
based on these studies and/or with posterior circulation
strokes. Table 8 summarizes the AHA/ASA recommenda-
tions for endovascular intervention.
An area of intense investigation is trying to determine
the ideal destination for patients in the field with suspected
LVO. Various rapid assessment tools are being trialed to
help EMS best decide which patient may have a LVO.
Based on patient location, and distances and direction of
local Primary Stroke Centers (PSC) and regional CSC,
work is being done to try to determine which patients
should travel a short distance further to a CSC versus going
a shorter distance to a PSC to initiate IV alteplase and then
be transferred out. Unless there are compelling mitigating
circumstances, it is recommended by AHA/ASA that EMS
not bypass the closest facility to go to the higher-level
facility if such a diversion would add 15–20 min to the
transport time. These recommendations predate the most
recent data demonstrating the value of endovascular
intervention in selected patients. When there are several
PSCs and CSCs with roughly equal distances for transport,
AHA/ASA generally recommends transportation to the
highest-level facility [3]. Ground versus helicopter trans-
port factors into this as well, especially when the closest
PSC is in the opposite direction of the CSC. Prearranged
transfer agreements will no doubt be important when rec-
ommendations are released.
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Table 8 Recommendations for endovascular intervention [24]

Patients eligible for intravenous alteplase should receive intravenous alteplase even if endovascular treatments are being considered
Patients should receive endovascular therapy with a stent retriever if they meet all the following criteria:
(a) prestroke mRS score 0–1,
(b) acute ischemic stroke receiving intravenous alteplase within 4.5 h of onset
according to guidelines from professional medical societies,
(c) causative occlusion of the internal carotid artery or proximal MCA (M1),
(d) age C18 years, (note: there is no upper age limit),
(e) NIHSS score of C6,
(f) ASPECTS of C6, and
(g) treatment can be initiated (groin puncture) within 6 h of symptom onset
As with intravenous alteplase, reduced time from symptom onset to reperfusion with endovascular therapies is highly associated with better
clinical outcomes
When treatment is initiated beyond 6 h from symptom onset, the effectiveness of endovascular therapy is uncertain for patients with acute
ischemic stroke who havecausative occlusion of the internal carotid artery or proximal MCA (M1)
In carefully selected patients with anterior circulation occlusion who have contraindications to intravenous alteplase, endovascular therapy
with stent retrievers completed within 6 h of stroke onset is reasonable
Although the benefits are uncertain, use of endovascular therapy with stent retrievers may be reasonable for carefully selected patients with
acute ischemic stroke in whom treatment can be initiated (groin puncture) within 6 h of symptom onset and who have causative occlusion of
the M2 or M3 portion of the MCAs, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries
Endovascular therapy with stent retrievers may be reasonable for some patients <18 years of age with acute ischemic stroke who have
demonstrated large vessel occlusion in whom treatment can be initiated (groin puncture) within 6 h of symptom onset, but the benefits are
not established in this age group
Observing patients after intravenous alteplase to assess for clinical response before pursuing endovascular therapy is not required to achieve
beneficial outcomes and is not recommended
Endovascular therapy with stent retrievers is recommended over intra-arterial fibrinolysis as first-line therapy
It might be reasonable to favor conscious sedation over general anesthesia during endovascular therapy for acute ischemic stroke. However,
the ultimate selection of anesthetic technique during endovascular therapy for acute ischemic stroke should be individualized based on
patient risk factors, tolerance of the procedure, and other clinical characteristics

Table 9 Sample acute stroke admission orders

Neuro check every 15 min for 2 h, then every 30 min for 6 h, then hourly
Supplemental oxygen to keep O2 saturation >94%
BP check every 15 min for 2 h, then every 30 min for 6 h, then every hour for 16 h
Keep BP after alteplase treatment <180/105 mmHg (note: this is lower than pre-treatment values); if no alteplase
given, keep BP < 220/120 mmHg
Bedside swallow test (30 mL water PO) before anything else PO

Hospital Admission or Transfer and increased risk of intracranial hemorrhage following

Assuming there are no complications of alteplase or
endovascular therapy, Table 9 lists the orders that should
be considered while waiting for the patient to be admitted.
Note this sample is based on 2013 AHA/ASA guidelines.
Additional admission orders must address glucose,
volume status, body temperature, and catheters:
• Keep glucose 140–180 mg/dL; consider insulin drip if
the blood glucose is persistently >200 mg/dL or the
patient is known to have insulin-dependent diabetes
mellitus. Hyperglycemia is proven to worsen outcomes
ischemic strokes.
• Administer IV fluids, preferably isotonic saline, at
1.5 ml/kg/h initially, with a goal of euvolemia
• Continue telemetry/bedside cardiac monitoring princi-
pally to detect intermittent atrial fibrillation, and should
continue for at least 72 h after admission.
• Treat fever sources with appropriate antibiotics or
therapies while preventing fever with antipyretics. While
occasionally used in post cardiac arrest situations as a
neuroprotective maneuver, hypothermia has not been
sufficiently studied to recommend at present. The
presence of fever should prompt a investigation of the
cause of the fever.

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• If alteplase was administered, avoid indwelling urinary
catheter, nasogastric tubes, and intraarterial catheters for
4 h, and do not give anticoagulant/antiplatelet therapy
for 24 h. Urinary catheters should in general be avoided
unless absolutely needed.
• In a 2017 study, position of the HOB was not found to
make any difference in out come of the stroke injury
[25]. Elevation of the HOB is still recommended for
decreasing risk of aspiration. Additionally, many
patients are more comfortable with the HOB elevated.
• Patients should be NPO until evaluated for swallowing
difficulties, by a bedside RN evaluation or a speech
therapist [26].
Special Considerations: Pediatric Stroke
While not as common as adults, pediatric stroke occurs in
1.6–13/100,000 children each year [27–29] with select
populations, such as children under 1 year of age, children
with sickle cell disease or cardiac disorders, having a
higher incidence. Challenges in identifying stroke within
the pediatric population include at times different presen-
tation than adults and broad differential diagnoses.
Pediatric stroke may often present with seizures, particu-
larly within the younger pediatric population. Headache,
and other diffuse, non-localizing signs may also be part of
the presenting symptoms. Additionally, other diagnoses,
such as migraine, may be equally or even more likely in
children presenting with an acute neurologic change [30].
Imaging, particularly with magnetic resonance imaging, is
crucial for establishing the diagnosis. The Pediatric NIHSS
(PedNIHSS), similar to the adult NIHSS, is a validated,
age-appropriate tool for quantifying neurologic deficits in
pediatric stroke [31].
Despite its lack of approval for children under 18 years
of age, there are several case reports of alteplase use in
pediatric ischemic stroke cases in the literature. A recent
multi enter trial to examine safety and efficacy of alteplase
in children 2–18 was unfortunately closed early due to
insufficient enrollment [32]. This study highlights the
challenge of confirming a diagnosis of stroke in children
within 4.5 h of symptom onset. There are several case
reports and series of children <18 years old undergoing
endovascular treatment for LVO documenting high rates of
recanalization and favorable outcomes; however, there are
no randomized trials [24]. While individual physicians may
continue to offer thrombolysis therapy with appropriate
parental informed consent, one should be careful to apply
similar strict inclusion and exclusion safety criteria as used
in adults. Regardless of age or antithrombotic treatment,
similar neuroprotective strategies should be employed for
pediatric stroke as described above for adult stroke. Such
strategies include avoiding fever and maintaining normo-
glycemia, euvolemia and adequate blood pressure.
There are currently no guidelines recommendations
regarding use of alteplase in patients with stroke due to
sickle cell disease. Prevention by transfusing selected
children with low hemoglobin levels periodically decreased
the incidence of stroke from 10 to 1% in the STOP trial [33].
Current standard therapy for sickle cell patients with acute
stroke includes optimal hydration, blood exchange trans-
fusion, and correction of hypoxia and hypotension. Safety
and efficacy of intravenous alteplase and endovascular
interventions in this population is not established.
TIA
The diagnosis of TIA is based on the new onset of focal
neurological symptoms and signs that are explainable by a
vascular disease (e.g., arterial occlusion of a single or
group of arteries adequately explain the patient’s signs and
symptoms), and these signs and symptoms resolve within
24 h (most TIAs resolve in a much shorter period of time).
However, up to one-third of TIAs have demonstrable
injury on MRI [34]. These cases are now classified as stroke.
Despite evidence of tissue injury, it is unlikely that emer-
gency reperfusion therapy should be attempted, since all
symptoms have resolved. Approximately 50% of patients
with a TIA will have CT findings of a prior ischemic stroke
even though this may have been clinically silent.
TIAs present a conundrum as there clearly was an event
and the patient is at some risk for a recurrence. There are
several tools that may help provide guidance assessing the
risk of recurrence or outright stroke at different time
intervals. Each has limitations and one must assess patient
compliance, available resources in one’s practice environ-
ment as a decision is made with the patient and family for
the best disposition and follow-up. The ABCD2 score is
commonly used and is presented below.
Table 10 Calculate ABCD2 score [35]
ABCD2 score Points
Age > 60 years (add 1 point) 1
BP C 140/90 mmHg at initial evaluation (add 1 point) 1
Clinical features of the TIA
Speech disturbance without weakness, or 1
Unilateral weakness 2
Duration of symptoms
10–59 min, or 1
>60 min 2
Diabetes mellitus in patient’s history 1
Add all of the points for the total ABCD2 score (0–7). Table 11 lists
the estimated percent risk of a stroke occurring within various time
ranges
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Table 11 Percent risk of stroke following TIA with various ABCD2 scores [35]
Total risk Score 2 day 7 day 90 day

Low 0–3 1.0 1.2 3.1

Moderate 4–5 4.1 5.9 9.8
High 6–7 8.1 12 18

Table 12 Acute ischemic

stroke communication regarding
assessment and referral
h Age
h Airways status
h Time of symptom onset
h NIHSS
h CT/CTA or MRI/MRA results
h Alteplase administration (initiation and completion time) or contraindication(s) to alteplase
h Endovascular intervention(s) if applicable

ABCD2 Score • Initiate high-intensity statin (atorvastatin 40–80 mg/day

or rosuvastatin 20–40 mg or equivalent). Consider
The ABCD2 score is an ordinal scale that provides risk moderate intensity statins (atorvastatin 10–20 mg, rosu-
prediction of subsequent stroke following a TIA. Like vastatin 5–10 mg, simvastatin 20–40 mg, pravastatin
other scales it is not perfect, but can help stratify risk to 40–80 mg) in patients >75 years old [37].
some degree. Table 10 demonstrates how to calculate this
If ECG or rhythm strip shows atrial fibrillation, consider
score.
starting anticoagulation (oral anticoagulant or low molec-
Based on this risk stratification, some physicians choose
ular weight heparin) or ASA; calculate CHADS2 or
to admit high-risk patients and discharge those at low-risk.
CHA2DS2-VASc [38], and HAS-BLED [39], scores to
There is controversy regarding admission of moderate-risk
help guide long term therapy. In these cases, referral to a
patients, and this decision follows local practices
vascular neurologist or cardiologist is appropriate.
(Table 11).

Low-Risk TIA High-Risk TIA

For low-risk patients (ABCD2 scores 0–3), an out-patient
workup in the 1–2 days following score calculation may be
most appropriate. Alternately, observation or admission may
be an option. In either case, stroke risk can be decreased by
rapid institution of the following regimen: [36]
• Begin an antithrombotic agent (ASA 81 mg/day, clopi-
dogrel 75 mg/day, or ASA 25 mg/extended release
dipyridamole 200 mg twice daily)
• Perform carotid imaging: ultrasound, CTA, or MRA
• Consider transthoracic echocardiography; if bilateral
infarcts are present on CT or there is high suspicion of
cardiac embolic source, and transthoracic echo is
normal, obtain transesophageal echocardiograph (TEE)
• Consider 30-day ambulatory cardiac monitor to detect
intermittent atrial fibrillation (cryptogenic A-fib). This
should be strongly considered if the workup shows no
other etiology for cause of stroke or TIA.
• Encourage smoking cessation
For patients with higher risk TIAs (ABCD2 scores >3),
hospital admission is advisable. Permissive hypertension is
encouraged (not to exceed 220/120 mmHg), and blood
pressure limits should be gradually lowered over 24–48 h.
Medical–Legal Considerations
Administration of alteplase carries inherent risk of bleeding
complications, which can be lethal. Therefore, patients
must be properly screened for inclusion and exclusion
criteria. Patients and families must be counseled quickly,
but properly about the risks and benefits of alteplase ther-
apy. The following points should be kept in mind:
• Far more lawsuits have been filed for failure to offer
thrombolytic treatment, than for bleeding complications
arising from alteplase treatment [40, 41].
• For acute stroke patients meeting guidelines for throm-
bolytic therapy who are unable to consent for themselves
and have no family to consent for them, the treating

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physician should not delay treatment to find a surrogate
to give permission for treatment.
• Written/signed consent for administering alteplase is not
necessary. The consenting conversation, however,
should be documented in the medical record.
• If a patient is not being offered thrombolytic therapy, there
should be clear communication with the patient/family
why alteplase is contraindicated. This conversation should
be documented in the medical record.
Communication
When communicating to an accepting or referring physi-
cian about this patient, consider including the key elements
listed in Table 12.
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