Pediatric Neurology 56 (2016) 8e17

Contents lists available at ScienceDirect

Pediatric Neurology
journal homepage: www.elsevier.com/locate/pnu

Topical Review

Guidelines for Urgent Management of Stroke in Children

Michael J. Rivkin MD a, b, c, d, *, Timothy J. Bernard MD, MSCS e, f,
Michael M. Dowling MD, PhD, MSCS g, h, i, Catherine Amlie-Lefond MD j, k
a

Department of Neurology, Boston Childrens Hospital, Boston, Massachusetts

Department of Psychiatry, Boston Childrens Hospital, Boston, Massachusetts
c
Department of Radiology, Boston Childrens Hospital, Boston, Massachusetts
d
Department of Neurology, Harvard Medical School, Boston, Massachusetts
e
Department of Pediatrics, Hemophilia and Thrombosis Center, Aurora, Colorado
f
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado
g
Division of Pediatric Neurology, University of Texas Southwestern Medical Center Dallas, Dallas, Texas
h
Department of Pediatrics, University of Texas Southwestern Medical Center Dallas, Dallas, Texas
i
Department of Neurology, University of Texas Southwestern Medical Center Dallas, Dallas, Texas
j
Department of Neurology, Seattle Childrens Hospital, Seattle, Washington
k
Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington
b

abstract
Stroke in children carries lasting morbidity. Once recognized, it is important to evaluate and treat children with
acute stroke efciently and accurately. All children should receive neuroprotective measures. It is reasonable to
consider treatment with advanced thrombolytic and endovascular agents. Delivery of such care requires purposeful institutional planning and organization in pediatric acute care centers. Primary stroke centers established
for adults provide an example of the multidisciplinary approach that can be applied to the evaluation and
treatment of children who present with acute stroke. The organizational infrastructure of these centers can be
employed and adapted for treatment of children with acute stroke. It is likely that care for children with acute
stroke can best be delivered by regional pediatric primary stroke centers dedicated to the care of children with
pediatric stroke.
Keywords: stroke, pediatric, emergency department, stroke center

Pediatr Neurol 2016; 56: 8-17

2016 Published by Elsevier Inc.

Although both children and adults can experience

strokes that affect very similar vascular territories in brain
and share similar features on neuroimaging, the course of
clinical management of the patient in each age group can
vary considerably. An adult who suddenly develops typical
symptoms of a stroke such as hemiparesis, aphasia, ataxia,
or hemianopsia comes to medical attention quickly, often is
assessed in the eld and in hospital by teams with special
training in the evaluation and care of adults with stroke, and

Article History:
Received July 26, 2015; Accepted in nal form January 18, 2016
* Communications should be addressed to: Dr. Rivkin; Department of
Neurology; Boston Childrens Hospital; Fegan 11; 300 Longwood
Avenue; Boston, MA 02115.
E-mail address: michael.rivkin@childrens.harvard.edu
0887-8994/$ e see front matter 2016 Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.pediatrneurol.2016.01.016

is treated in a medical center designated as a primary stroke

center. Children with stroke, in contradistinction to adults,
encounter delay in their delivery to medical attention. Once
in a medical setting, the acute neurological decit often is
not recognized, and stroke as etiology of presenting signs
and symptoms is often not considered. Consequently, children who have stroke encounter considerable delay before
acquisition of diagnostic imaging. Examination of the
diagnostic process for children in the emergency department and on the inpatient service who have had stroke
revealed considerable diagnostic delay due to failure to
include stroke in the differential diagnosis.1-3
We will examine the development of adult primary acute
stroke centers. Next, features that compel the development
of multidisciplinary acute stroke programs for children will
be presented. Subsequently, a method for construction of a

M.J. Rivkin et al. / Pediatric Neurology 56 (2016) 8e17

pediatric stroke center and components of care for children

with acute arterial stroke will be considered. Finally, these
features will be illustrated through presentation of an actual
patient with acute arterial stroke who was treated successfully with tissue plasminogen activator (tPA).
The rst decade of the twenty-rst century brought
transformation in acute stroke care for adults, and more
than half of all adults access to care at a primary stroke
center.4 Indeed, an adult with acute stroke may be evaluated and treated in the eld by an emergency medical team
especially trained in the care of patients with acute stroke.
Communication between the eld team and the hospitalbased primary stroke center medical team will facilitate
the arrangement of emergency room, neuroradiological,
pharmacologic, or interventional services even before the
patient arrives to the hospital (analogous to primary coronary intervention in acute myocardial infarction).
Children with acute stroke should be diagnosed within
4.5 hours following symptom onset so that thrombolytic
treatment5,6 or thrombectomy might be administered.7
Administration of tPA facilitates degradation of brin in
thrombus and can lead to early recanalization of an artery
occluded by thrombus. Although the use of tPA treatment
for adults with acute stroke is established, experience with
its use in children remains limited. Questions remain
regarding its use in patients younger than two years, at
times greater than 4.5 hours from stroke onset, and in those
at either extreme of clinical severity.
Studies in adults have revealed that despite an increased
risk of fatal intracranial hemorrhage during the rst few
days after treatment, tPA signicantly improves the likelihood of a favorable outcome when administered within
4.5 hours of stroke onset in appropriately selected patients.
Moreover, it appears that earlier treatment correlates with
better outcome.8 Potential adverse effects of tPA include
idiosyncratic nausea, vomiting, bradycardia, fever, allergic
response, cardiac arrhythmia, and hypotension (in up to
10%).9 Life-threatening nonidiosyncratic side effects consist
of hemorrhage in gastrointestinal (5% of patients), genitourinary (4%), or central nervous system (6.4%). Symptomatic
intracranial hemorrhage, in particular, remains a concern
following administration of tPA in patients. The Alberta
Stroke Program Early CT Scoring (ASPECTS) scheme has
proved accurate and useful in identifying stroke size in the
middle cerebral artery (MCA) territory on head computed
tomography (CT) and in the estimation of the likelihood of
occurrence of symptomatic intracranial hemorrhage
following treatment with tPA.5,10 Magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) specifically are even more sensitive than CT in the detection of
acute stroke.11 However, as found with head CT, the size of
DWI abnormality was found to correlate directly with the
likelihood of symptomatic intracranial hemorrhage
following tPA therapy.12
Recent developments in endovascular therapy of adults
with stroke have reverberated across the eld of pediatric stroke. The Multicenter Randomized CLinical trial of
Endovascular treatment for Acute stroke in the Netherlands
(MR CLEAN) multicenter study of endovascular therapy
administered to adults with proximal large cerebral artery
occlusion many of whom had already been treated with
intravenous tPA demonstrated not only more rapid arterial

recanalization but also superior outcome compared with

standard medical therapy.13 These results were conrmed in
both Endovascular Treatment for Small Core and Anterior
Circulation Proximal Occlusion with Emphasis on Minimizing
CT to Recanalization Times (ESCAPE) as well as Solitaire with
the Intention for Thrombectomy as Primary Endovascular
Treatment (SWIFT PRIME) studies.9,14 The exciting results
from these studies have revealed endovascular therapy and
thrombectomy to be rst-line treatments for acute stroke in
adults with large cerebral vessel occlusion. Although exciting
for adults with stroke, the role of this therapeutic procedure in
children with acute stroke is not yet clear.
In adults, the benet of treatment by a medical team
organized and trained in the care of patients with acute
stroke extends beyond the use of intravenous tPA or
endovascular therapy. Patients treated in primary stroke
centers follow an improved clinical course compared with
those treated by clinicians not organized into stroke teams.
Lower mortality rate, readmission rate, and complication
rate and shorter length of in-patient stays have been
observed in patients treated at adult primary stroke centers.15-17 These features argue strongly for a similar
approach to care of children with acute stroke.
Reason to emulate the adult experience of acute stroke care in
children

Stroke, although regarded by many to be rare in children,

is not. Both prevention of mortality and attenuation of
morbidity constitute potent reasons to optimize the ability
to recognize and to treat rapidly children with stroke.
Cerebrovascular disease represents one of the ten most
common causes of mortality in patients ranging in age from
ve through 24 years.18 Although stroke occurs with a frequency 175 to 200/100,000 among adults, stroke occurs
in children older than one month as frequently as 13/
100,000 per year.19 The stroke incidence is higher in neonates (25 to 40/100,000 births) and is highest among premature infants (up to 100/100,000 births).
The morbidity in children following arterial stroke is
considerable. As many as 50% of neonates and 65% of children older than 1 month sustain lasting motor decits as a
consequence of stroke. Furthermore, up to 60% of children
who have had neonatal stroke demonstrate cognitive decits, especially those of executive function and language.
Similarly, half of children who have stroke at greater than age
one month have been found to have cognitive decits.20-24
The mortality rate for children with stroke is one third
that found in adults with either ischemic or hemorrhagic
stroke. Consequently, a much higher proportion of children
than adults carry the consequences of their cerebral injury
for decades.25-28 The cost for care of children who have had
a stroke at either in the neonatal or at an older age appears
to be both high and sustained.27 Consequently, the aggregate cost for care of a patient with stroke is likely greater for
a child than for an adult.29
Organization for a primary pediatric stroke center: Just little
adult centers?

The morbidity and mortality associated with cerebrovascular disease argues convincingly for mobilization of

10

M.J. Rivkin et al. / Pediatric Neurology 56 (2016) 8e17

resources to evaluate and treat children with stroke as early

as possible. The establishment of primary stroke centers
across the United States has resulted in multidisciplinary
teams and facilities trained in and adept at providing hyperacute care for adults with stroke that includes intravenous thrombolytic and endovascular thrombectomy for
patients with acute stroke.9,30 Recently, pediatric centers
participating in the landmark Thrombolysis in Pediatric
Stroke (TIPS) study organized systematically to gain
competence in the response to and assessment of children
presenting with acute stroke for treatment with tPA.7,31,32
As a group and in the course of preparation for study
participation the 23 centers developed pediatric stroke
teams able to respond immediately to patients around the
clock, built pediatric stroke emergency department and
intensive care unit (ICU) ordersets, and arranged for both
acute pediatric stroke MRI evaluation as well as anesthesiologist support for imaging at any time of day or night.32
Remarkably, in the process of preparation for urgent evaluation and treatment of children with acute arterial
ischemic stroke, these centers fullled most criteria that
adult centers meet to attain designation as a primary stroke
center for treatment of adults with stroke.32 In so doing,
these pediatric centers have moved the eld forward to
dene the safety guidelines for use of tPA as therapy for
children who present with acute arterial stroke.7
Currently, the total dose of tPA considered appropriate
for administration to children who present within 4.5 hours
of stroke onset and who qualify for treatment is the same as
the dose used in adults, 0.9 mg/kg, with the rst 10% given
as a bolus. The developmental trajectory of the brinolytic
system during childhood is well documented and raises the
possibility that the most effective dose of tPA for children
may be higher than 0.9 mg/kg.33
Stroke team organization and patient screening constitute important initial steps in an algorithm for assessment of
children with acute stroke. By denition, the pediatric acute
stroke team is a multidisciplinary group that can respond
quickly and work well together. Close cooperation with the
ICU team is important because patients who receive
thrombolytic or endovascular treatment will be transferred
to the ICU immediately following therapy. Consequently,
planning, preparation, and practice using mock code routines are all essential for successful deployment of the team
when a patient actually presents. The acute stroke team at
Boston Childrens Hospital comprises the cerebrovascular
disorders and stroke neurology attending physician, cerebrovascular disorders and stroke fellow, neurology on-call
resident, neuroradiologist, medical-surgical ICU fellow,
central pharmacist, and on-call anesthesiologist (Fig 1). The
team is activated by pager through a hospital central
communication center and is available around the clock.
Team members converge to assess the patient rapidly at the
point of care. Most patients are located in the emergency
department at the time of presentation. However, children
with symptoms of acute stroke can present in the pediatric
ICU, surgical recovery room, or in-patient hospital ward.
Children two years or older who present with sudden
symptom onset of unilateral weakness or sensory decit,
acute vision loss or diplopia, sudden onset aphasia, or difculty walking and who have been symptomatic for less than
ve hours are considered ideal candidates for screening by

the team for thrombolytic treatment. In addition, because

seizure constitutes a very common presenting sign of acute
stroke in children, any child with rst-time seizure and focal
ndings on neurological examination is also urgently evaluated for acute stroke.34 Each patient is examined quickly for
assignment of a pediatric National Institutes of Health Stroke
Scale (NIHSS) score and conveyed to the MRI suite for evaluation by a hyperacute stroke evaluation, which consists of
axial
DWI,
uid-attenuated
inversion
recovery,
susceptibility-weighted imaging, and time-of-ight magnetic resonance angiography of head and neck acquisitions.
Imaging is read immediately and shared with the clinical
team responsible for the patient. If MRI is not immediately
available, cranial computed tomography with CT angiography can be substituted. In either instance, the absence of
intracranial hemorrhage and other excluding features, evidence of early ischemic brain injury, and presence of arterial
obstruction in a vessel subserving the region of parenchymal
ischemia have been prerequisites for use of tPA (Fig 2).7
As discussed earlier, several trials of endovascular
treatment and thrombectomy have established efcacy of
this therapy in adults presenting with acute stroke due to
occlusion of large cerebral arteries. These developments
have generated considerable interest in the eld of pediatric
stroke regarding use of this treatment in children. The role
of this therapeutic procedure in children with acute stroke
is not yet clear. However, given the establishment of pediatric acute stroke centers through TIPS, it is anticipated that
this question will be addressed soon.
Several neuroprotective measures can be taken irrespective of whether a pediatric patient qualies for
thrombolytic treatment with tPA. Maintenance of normoglycemia has been identied as a therapeutic objective in
the care of patients with acute stroke. Study of both animal
models and humans has demonstrated that hyperglycemia
is detrimental following brain ischemia affecting vasoregulatory, thrombotic, and inammatory pathways.35 Hyperthermia following stroke correlates with the presence of
an elevated white blood cell count, antibiotic use, and high
NIHSS score and has been associated with worsened
outcome in patients with stroke.36 Blood pressure targets
during treatment for acute arterial ischemic stroke have
received considerable attention in adults. Initially, studies
suggested that elevations of systolic, diastolic, and mean
arterial pressure in acute stroke correlated with either
mortality or increased morbidity.37,38 Subsequent, placebocontrolled study demonstrated no difference in outcome
between patients treated with placebo or antihypertensive
medicine after acute stroke. Moreover, high blood pressure
often normalized within 24 hours in most cases.39-42
Blood pressure management during treatment for acute
stroke has received scant attention in children. Brush43
conducted a retrospective review of blood pressure after
acute stroke in children and found that hypertension
occurred on at least one occasion in over 60%. Although 12month and in-hospital mortality were higher among children who had hypertension following acute stroke, there
was no relationship found between hypertension and
vascular territory, etiology, or neurological disability.43 Adil
and colleagues44 demonstrated that systemic hypertension
in children with ischemic stroke was associated with
increased length of hospitalization and increased mortality.

M.J. Rivkin et al. / Pediatric Neurology 56 (2016) 8e17

11

Acute Stroke Guideline: INITIAL APPROACH

1. Any child with potential stroke
Including all BCH ED and children from outside BCH
via Critical Care Transport Team (BCH or other)

2. Stroke Screening Questions

I.
Is there a focal neurological deficit?
a. Unilateral weakness or sensory change
b. Vision loss or double vision
c. Speech difficulty
d. Dizziness or trouble walking
II.
Did the problem begin or get worse suddenly?
III.
Has the problem been present for less than 5 hours?
(When was the child last seen well?)

4a. ED or responsible service supports ABCs

(consider ICU STAT on wards),
starts IV x 2 if not already in place,
draws stat INR, PTT, type and screen, CBC,
PLTs, fibrinogen, glucose, electrolytes

Stroke Stat team:

Stroke Fellow/Attending
ED Neurology resident
Neuroradiologist
ED Pharmacist
[MSICU Fellow, Intensive
Care Neurology resident,
Anesthesia (FYI Only)]
See Acute Stroke Team
Activation Plan

3. Child
meets all acute
stroke criteria (I-III)

No

Yes/
Not sure

Consider urgent
consult to
Neurology and
urgent MR while
considering other
diagnoses and
initiating
neuroprotective
care

4. Call Stroke Stat

IMMEDIATELY
Via Comm Center (x5-2170)
ALL HOURS
o

5. Possible stroke confirmed

by ED neurology resident in
consultation with stroke attending
Pediatric NIHSS performed

No

Initial Supportive Rx:

NPO, head of bed flat
Normotension: target SBP is between
50th and 90th %ile for age, treat low BP
with NS +/- pressors, treat significant
HTN with labetalol to lower by ~25%
over 24 hours (more quickly if tPA
candidate, see page 2)
Normovolemia: Isotonic fluid (ie, 0.9%
NaCl) at maintenance with bolus prn
Normoglycemia: For age >2, no
glucose in IV fluids unless
hypoglycemic; for age <2, use glucosecontaining fluids, eg: D50.9%NaCl
Normal O2, CO2 and pH
Normothermia: treat patient w/ T>37o
with acetaminophen
Seizure control: AED ASAP with any
suspected seizure activity

Yes

6. Neurology resident or ED/ward

staff request emergent MRI (page
neuroradiology attending on call)

7. Prepare patient for transport to MRI with

appropriate equipment and personnel

Go to
PAGE 2

If patient on the ward,

transfer to MSICU

FIGURE 1.
First steps of algorithm for assessment and care of children who present to Boston Childrens Hospital (BCH) with signs and symptoms of acute arterial
ischemic stroke. AED, antiepileptic drug; BP, blood pressure; CBC, complete blood count; ED, emergency department; HTN, hypertension; ICU, intensive care
unit; INR, international normalized ratio; IV, intravenous; MRI, magnetic resonance imaging; MSICU, medical-surgical ICU; NIHSS, National Institutes of
Health Stroke Scale; NPO, nothing by mouth; PLT, platelet; PTT, partial thromboplastin time; tPA, tissue plasminogen activator. (The color version of this
gure is available in the online edition.)

12

M.J. Rivkin et al. / Pediatric Neurology 56 (2016) 8e17

2. Acute Stroke Guideline: MRI and tPA CANDIDACY

Axial DWI, FLAIR, SWI, TOF

MRA COW

See
PAGE 3 for
ALTERNATIVE
workflow if MRI
unavailable

1. Perform stroke hyperacute MRI protocol

Optional: perfusion weighted

imaging sequence
Transport patient
back to ED or MSICU

Consider other diagnostic tests (eg:

cerebral angiography) and/or IA tPA
or other endovascular therapy

Admit patient and provide

No

neuroprotective and supportive

acute stroke treatment per
stroke/ICU service

Stroke Stat team:

Stroke Attending
ED Neurology resident
Neuroradiologist
ED Pharmacist
[Anesthesia, MSICU Fellow,
Intensive Care Neurology
resident (FYI Only) ]

2. MRI free of
hemorrhage & early infarct
present w/ evidence of vascular
occlusion

See Acute Stroke Team

Activation Plan

Yes
Yes

Time from onset + estimated time to

arrival > 4.5 hrs, or age < 2 years, or
resolving deficit, or tPA
contraindication**

Time from onset + estimated time to

arrival < 4.5 hours, and age > 2,
and persistent deficit, and no tPA
contraindication**
Yes

**tPA contraindications:
HISTORY
> 4.5 hrs from last seen well
Patients in whom time of symptom onset is unknown
Stroke, major head trauma or intracranial surgery in the last 3 months
History of prior intracranial hemorrhage, known AVM or aneurysm
Major surgery or parenchymal biopsy within 10 days
GI or GU bleeding within 21 days
Patient with neoplasm/malignancy or within one month of completion
of treatment for cancer.
Patients with underlying significant bleeding disorder. Patients with
mild platelet dysfunction , mild von Willebrand disease or other mild
bleeding disorders are not excluded.
Previously dx d primary angiitis of the central nervous system or
secondary arteritis.
PATIENT FACTORS
Patient who would decline a blood transfusion if indicated.
Clinical presentation c/w acute myocardial infarction or post MI
pericarditis that requires evaluation by cardiology before treatment
Arterial puncture at noncompressible site or lumbar puncture w/in last
7 days. Patients who have had cardiac cath via a compressible artery
are NOT excluded.
ETIOLOGY
Stroke due to SBE, sickle cell disease, meningitis, embolism (bone
marrow, air or fat), or moyamoya disease.
EXAM
Persistent systolic blood pressure > 15% above the 95th percentile
for age while sitting or supine
Mild deficit (PedNIHSS <6) at start of tPA infusion
Severe deficit suggesting very large territory stroke pre-tPA
PedNIHSS >25, regardless of infarct volume seen on neuroimaging
IMAGING
Symptoms suggestive of SAH even if CT or MRI of head are normal
CT with hypodensity/sulcal effacement >33% of MCA territory or
ASPECTS 7
Intracranial cervicocephalic arterial dissection.
LAB DATA
Glucose <50 mg/dL (2.78 mmol/L) or >400 mg/dL (22 mmol/L)
Bleeding diathesis including Platelets <100,000, PT >15 sec (INR
>1.4) or elevated PTT > upper limits of the normal range.

tPA CANDIDATE

4. Stroke team member calls ED pharmacist (x51894) with

request to prepare tPA infusion and places order in CHAMPS
using ED Stroke Orderset and STAT designation

5. DWI shows infarct and

MRA confirms
arterial occlusion

No

Admit patient and provide

neuroprotective and supportive
acute stroke treatment per
stroke/ICU service

Yes
6. Stroke neurologist confirms
final intention to treat using
IV tPA and notifies ED pharmacist
(x51894); admit patient to MSICU

Go to
PAGE 4

FIGURE 2.
Boston Childrens Hospital algorithm for evaluation and care of children who present with signs and symptoms of acute arterial ischemic stroke: magnetic
resonance imaging (MRI) acquisition and steps for determination of eligibility for treatment with tissue plasminogen activator (tPA). ASPECTS, Alberta Stroke
Program Early CT Scoring; AVM, arteriovenous malformation; COW, Circle of Willis; CHAMPS, Childrens Hospital Applications Maximizing Patient Safety; CT,
computed tomography; DWI, diffusion-weighted imaging; ED, emergency department; FLAIR, uid-attenuated inversion recovery; GI, gastrointestinal; GU,
genitourinary; IA, intra-arterial; ICU, intensive care unit; INR, international normalized ratio; IV, intravenous; MCA, middle cerebral artery; MI, myocardial
infarction; MRA, magnetic resonance angiography; MSICU, medical-surgical ICU; PedNIHSS, pediatric National Institutes of Health Stroke Scale; PT, prothrombin
time; PTT, partial thromboplastin time; SAH, subarachnoid hemorrhage; SBE, subacute bacterial endocarditis; SWI, susceptibility-weighted imaging; TOF, timeof-ight. (The color version of this gure is available in the online edition.)

M.J. Rivkin et al. / Pediatric Neurology 56 (2016) 8e17

13

IV tPA TREATMENT PROTOCOL

IV tPA CANDIDATE
< 4.5 hrs from onset, age >2 years, persistent focal
deficit, no contraindications, BOTH proven infarct
AND arterial occlusion on MR or CT/CTA
Yes
ED Pharmacy prepares tPA infusion with stat release
to ED or MSICU.
Bolus dose: 10% of total dose IV over 5 min
Infusion dose: remaining 90% IV over 1 hour
Total dose: 0.9 mg/kg IV
Nurse/MD double checks dose with pharmacy

Maintain cardiorespiratory and BP monitoring. If agebased tPA parameters acceptable (see green box to
right) begin tPA infusion as soon as available
(in ED or en route to MSICU).
Note: dedicated IV for tPA required to proceed.

Systolic BP should be maintained

between 50th %ile for age and 15%
above 95th %ile for age (see below)
Treat to lower BP if > 15% above
95th %ile for age for more than 1 hr.
OR
If > 20% above 95th %ile for age at
any time
SEE CHART BELOW

Systolic Blood Pressure Parameters - Female

Age

50%

95%

>15%
above
95%

>20%
above
95%

1 4 years

90

111

128

133

5 years

94

113

130

136

6 10 years

96

121

139

145

11 18 years

105

131

151

157

>18 years

110

140

161

168

Labetalol 0.2 mg/kg IV

push over 2-3 min, repeat q15
minutes prn; consider nicardipine
drip, 1 mcg/kg/min, titrate to
desired BP
Use with caution in patients with
asthma or underlying cardiac
disease

Systolic Blood Pressure Parameters - Male

Age

50%

95%

>15%
above
95%

>20%
above
95%

1 4 years

90

112

129

134

5 years

95

113

130

136

6 10 years

96

121

139

145

11 18 years

105

140

161

168

>18 years

110

140

161

168

Updated 5/27/14
FIGURE 3.
Boston Childrens Hospital algorithm for evaluation and care of children who present with signs and symptoms of acute arterial ischemic stroke: intravenous
(IV) tissue plasminogen activator (tPA) treatment and blood pressure (BP) management. CT, computed tomography; CTA, CT angiography; ED, emergency
department; MR, magnetic resonance; MSICU, medical-surgical intensive care unit. (The color version of this gure is available in the online edition.)

14

M.J. Rivkin et al. / Pediatric Neurology 56 (2016) 8e17

Currently, the best approach to blood pressure management

in children with acute stroke has yet to be dened. At our
center, blood pressure is treated when it exceeds 15% above
the 95th percentile for sex, age, and height for greater than
an hour or anytime the blood pressure exceeds 20% above
the 95th percentile (Fig 3, example from Boston Childrens
Hospital).
As mentioned earlier, seizure can be a presenting sign of
acute stroke in a child and is associated with increased risk of
subsequent epilepsy.34,45 Seizure should be treated with
anticonvulsant therapy. Repeated seizure and status epilepticus should be aggressively treated and effectively suppressed. Continuous electroencephalography monitoring
should be considered to evaluate for subclinical seizure.34
Finally, decompressive hemicraniectomy (DCH) can be
performed to afford relief from increased intracranial
pressure in patients with acute stroke accompanied by an
extreme amount of cerebral edema. This surgical procedure
can mitigate fatal herniation syndromes and diminish
additional pressure-related ischemic injury found in malignant MCA syndromes. The malignant MCA syndrome as
dened in adults with acute stroke is dened as involvement of >50% of the MCA territory by cranial CT or >145 mL
of MCA volume on DWI by acute infarction accompanied
clinically by a depressed level of consciousness. In this
circumstance a DCH can be both life-saving and associated

with a good outcome. Notably, among adults DCH has been

associated with better outcomes especially when performed in younger patients and earlier in the course of
acute stroke.46-49
Among children with acute stroke, 26 patients treated
with DCH as part of their treatment for stroke have been
reported in the literature. Strokes involved right or left MCA
territories. The time to DCH from presentation with symptoms ranged widely, from two to 291 hours. Although
quantitative measures of neurological outcome were not
provided, neurological decits were generally described as
mild to moderate.50,51 At our centers, DCH has been
employed effectively in children who present with large
MCA territory stroke and who demonstrate declining
mental status as well as cerebral edema early in their clinical course (Fig 4, example of patient treated with DCH at
Boston Childrens Hospital).
An illustrative patient for treatment of acute arterial stroke

A 16-year-old male developed halting speech and rightsided weakness while at home with his family making
dinner. He was immediately brought to the Boston Childrens Hospital Emergency Department at which he arrived
45 minutes after symptom onset. In the Emergency
Department a right hemiparesis and expressive aphasia

FIGURE 4.
Example of decompressive hemicraniectomy in pediatric stroke. A 17-year-old male presented with sudden onset of left hemiparesis and hemianopia.
Magnetic resonance imaging showed diffusion-weighted signal abnormality to indicate ischemic injury involving much greater than 33% of the middle
cerebral artery territory on the right (A, B, arrows). Large size of infarct in the middle cerebral artery territory, declining mental state, and evidence of early
cerebral edema led to diagnosis of acute right middle cerebral artery stroke with malignant middle cerebral artery syndrome. Decompressive hemicraniectomy was performed, which accommodated the right hemispheric cerebral edema and expansion. Note extent of decompressive hemicraniectomy
(C, D); see arrowheads and its accommodation of increasingly edematous right hemisphere. ADC, apparent diffusion coefcient; DWI, diffusion-weighted
imaging; FLAIR, uid-attenuated inversion recovery; T2W, T2 weighted. (The color version of this gure is available in the online edition.)

M.J. Rivkin et al. / Pediatric Neurology 56 (2016) 8e17

were documented on examination and a Stroke Stat was

called. Assessment by the Stroke Stat Team produced a
pediatric NIHSS score of 7. He was taken for MRI that began
1.5 hours after onset of symptoms. The MRI revealed an area
of restricted diffusion in the left postcentral gyrus

15

consistent with an acute infarct (see Fig 5). Arterial spin

label perfusion-weighted imaging demonstrated hypoperfusion corresponding to the area of restricted diffusion
and extending beyond it (Fig 5). The magnetic resonance
arteriography revealed abrupt focal change in the caliber of

FIGURE 5.
Magnetic resonance imaging of a male who presented with aphasia and right-sided weakness. (A, B) Consecutive uid-attenuated inversion recovery
(FLAIR) (left) and diffusion-weighted imaging (DWI)-trace (right) images showing diffusion restriction (see arrows) with no clear increased signal in FLAIR
images in left postcentral gyrus indicative of early stroke. Arterial spin label perfusion-weighted imaging (ASL PWI) (C) shows region of asymmetrically
darker signal in the left hemisphere including and extending beyond the postcentral gyrus indicating regional hypoperfusion (arrows). (E) Magnetic
resonance arteriography (MRA) shows ow signal loss in arterial branch from M2 portion of the middle cerebral artery on left (arrow). (F) Susceptibilityweighted image (SWI) showing small round area of susceptibility signal in region corresponding to ow signal loss in MRA (E, see arrow) indicating middle
cerebral artery M2 branch occlusion by thrombus. (D) ASL PWI following treatment with intravenous tissue plasminogen activator that shows resolution of
hypoperfusion seen in ASL PWI (C) before treatment with intravenous tissue plasminogen activator.

16

M.J. Rivkin et al. / Pediatric Neurology 56 (2016) 8e17

an M2 branch of the left MCA within the Sylvian ssure that

corresponded to a small focus of susceptibility on
susceptibility-weighted imaging51 (Fig 5). Other intracranial and extracranial arteries demonstrated normal ow
signal. The patient met all standard adult inclusion and
exclusion criteria for intravenous tPA therapy, including
blood pressure parameters, laboratory studies, and lack of
intracranial hemorrhage on head imaging. Intravenous tPA
was infused 3.5 hours after onset of symptoms using a dose
of 0.9 mg/kg, with 10% of the total dose given over
5 minutes and the remaining 90% given over one hour.
During the infusion the patients pediatric NIHSS score
improved from 7 to 3. Follow-up MRI imaging obtained
24 hours later revealed no evidence of intracranial hemorrhage and resolution of hypoperfusion signal on arterial
spin label perfusion-weighted imaging (Fig 5). The patient
continued to improve and was discharged two days later
with a pediatric NIHSS score of 1.

11.

12.

13.

14.

15.

16.

17.

Conclusion
18.

Stroke in children carries lasting and often life-long

morbidity. Although the possibility of acute stroke can be
overlooked, if recognized it is reasonable to consider
treatment with advanced thrombolytic and endovascular
agents. All children should receive neuroprotective measures. Such care requires purposeful institutional planning
and organization in pediatric acute care centers. Primary
stroke centers established for adults provide an example of
the multidisciplinary approach that can be applied to the
evaluation and treatment of patients who present with
acute stroke. The organizational infrastructure of these
centers can be employed and adapted for treatment of
children with acute stroke. It is likely that care for children
beset by acute stroke can best be delivered by regional
pediatric primary stroke centers dedicated to the care of
children with pediatric stroke.

19.

20.

21.

22.

23.

24.

25.

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