ARTICLES
Delayed Recognition of Initial Stroke in Children: Need
for Increased Awareness
CONTRIBUTORS: Jayasri Srinivasan, MBBS, FRACP,a,b Steven P.
Miller, MDCM, MAS, FRCPC,b,c Thanh G. Phan, MBBS, FRACP,d and
Mark T. Mackay, MBBS, FRACPa
aDepartment of Pediatric Neurology, Royal Childrens Hospital,
Melbourne, Australia; Departments of bPediatric Neurology and
cPediatrics, British Columbia Childrens Hospital, Vancouver,
Canada; and dDepartment of Neurosciences, Monash Medical
Centre, Melbourne, Australia
KEY WORDS
stroke, cerebrovascular disease, cerebral vascular accident
ABBREVIATIONS
AISarterial ischemic stroke
CT computed tomographic
ICDInternational Classication of Diseases
IQRinterquartile range
www.pediatrics.org/cgi/doi/10.1542/peds.2008-3544
doi:10.1542/peds.2008-3544
Accepted for publication Mar 13, 2009
Address correspondence to Mark T. Mackay, MBBS, FRACP,
Department of Paediatric Neurology, Childrens Neuroscience
Centre, Royal Childrens Hospital, Melbourne, Australia 3052.
E-mail: mark.mackay@rch.org.au
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2009 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no nancial relationships relevant to this article to disclose.
PEDIATRICS Volume 124, Number 2, August 2009
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WHATS KNOWN ON THIS SUBJECT: Pediatric AIS, like AIS in
adults, is associated with high morbidity and mortality rates.
Unlike that in adults, however, pediatric stroke often is
unrecognized, for a variety of reasons.
WHAT THIS STUDY ADDS: This study quanties the time to
diagnosis of pediatric stroke and aims to highlight the factors
that perpetuate delay, namely, the lack of awareness of
physicians regarding pediatric stroke. This is in contrast to many
previous studies.
abstract
OBJECTIVE: The goal was to identify the delays involved in diagnosing
pediatric arterial ischemic stroke (AIS), a major cause of morbidity and
death in children.
METHODS: Neonates (28 days of age) and children with a rst pre-
sentation of radiologically conrmed AIS between June 1993 and Jan-
uary 2006 were identied retrospectively. The time to diagnosis of AIS
(ie, time from clinical onset to radiologic conrmation) was calculated,
and factors inuencing stroke diagnosis were reviewed.
RESULTS: A total of 107 patients (19 neonates and 88 children) with a
diagnosis of AIS were identied. The median time to AIS diagnosis was
87.9 hours for neonates, signicantly longer than 24.8 hours for chil-
dren (P .0002). Sixty-nine percent of the children with AIS demon-
strated a likely cardioembolic cause, and 51 (58%) of the 88 children
were inpatients at the time of stroke. The inpatients were seen by a
physician more quickly (P .01) and received a diagnosis of AIS
sooner (P .01). Seventy-six (86%) of the 88 children had a focal
neurologic decit when rst seen by a physician. Physicians docu-
mented a diagnosis/differential diagnosis for 44 (50%) of 88 children,
and they documented a suspicion of AIS for only 23 (26%) of 88 children.
The presence of seizures or focal signs was not associated with a
quicker time to stroke conrmation.
CONCLUSIONS: The considerable delays in the diagnosis of pediat-
ric AIS are most likely related to the lack of awareness of stroke
among medical staff members, despite risk factors and focal signs
at presentation. Pediatrics 2009;124:e227e234
e227
Stroke is a major cause of morbidity
and death in children. Long-term neu-
rologic decits occur in 50% to 85% of
infants and children after arterial isch-
emic stroke (AIS).1 Limited awareness
regarding pediatric stroke among phy-
sicians and in the community is a ma-
jor issue. For adults, advertising cam-
paigns (eg, Time Is Brain Lost) and
education of primary care physicians
have led to signicant decreases in the
time to presentation.2 One study re-
corded a mean time of 34.5 hours from
clinical onset to presentation to any
health care professional for children,
and studies have demonstrated long
delays to neuroimaging.3,4 For chil-
dren, stroke symptoms are attributed
frequently to stroke-mimickers such
as migraine, encephalitis, tumors, and
postictal Todd paralysis, which can ac-
count for up to one fth of cases pre-
senting with stroke-like symptoms.5,6
Recent pediatric studies suggested
that factors such as delays in seeking
medical attention and mode of onset
were predictive of the delayed diagno-
sis of stroke and of the underlying
cause.7,8
Various consensus guidelines have
highlighted the importance of improv-
ing time to stroke diagnosis.911 Before
assessment of acute thrombolysis in
the pediatric population, the factors
causing delays in stroke diagnosis
must be identied and addressed. The
aims of this study were to determine
the time between clinical onset and
diagnosis of AIS in a tertiary Austra-
lian pediatric hospital and to identify
factors that inuenced the time to
diagnosis.
METHODS
We identied retrospectively all chil-
dren 0 to 18 years of age who were
diagnosed as having a rst episode of
AIS during a 12.5-year period, from
June 1, 1993, to January 30, 2006, at the
Royal Childrens Hospital (Melbourne,
e228 SRINIVASAN et al
TABLE 1 ICD Revisions 9 and 10 Codes Used
ICD Diagnosis
Code
433.1 Occlusion and stenosis of carotid artery
433.11 Occlusion and stenosis of carotid artery with cerebral infarction
434.0 Cerebral thrombosis
434.00 Cerebral thrombosis without mention of cerebral infarction
434.01 Cerebral thrombosis with cerebral infarction
434.10 Cerebral embolism without mention of cerebral infarction
434.11 Cerebral embolism with cerebral infarction
434.9 Cerebral artery occlusion, unspecied
434.90 Cerebral artery occlusion, unspecied, without cerebral infarction
434.91 Cerebral artery occlusion, unspecied, with cerebral infarction
437.5 Moyamoya disease
437.9 Cerebrovascular disease, unspecied
438 Late effects of cerebrovascular disease
G08 Intracranial and intraspinal phlebitis and thrombophlebitis
G93.2 Benign intracranial hypertension
I63.0 Cerebral infarction attributable to thrombosis of precerebral arteries
I63.2 Cerebral infarction attributable to occlusion of precerebral arteries, not otherwise specied
I63.3 Cerebral infarction attributable to thrombosis of cerebral arteries
I63.4 Cerebral infarction attributable to embolism of cerebral arteries
I63.5 Cerebral infarction attributable to occlusion of cerebral arteries, not otherwise specied
I63.6 Cerebral infarction attributable to cerebral venous thrombosis, nonpyogenic
I63.8 Other cerebral infarction
I63.9 Cerebral infarction, unspecied
I64 Stroke, not specied as hemorrhage or infarction
I65.2 Occlusion and stenosis of carotid artery
I66.0 Occlusion and stenosis of middle cerebral artery
I66.1 Occlusion and stenosis of anterior cerebral artery
I66.2 Occlusion and stenosis of posterior cerebral artery
I66.8 Occlusion and stenosis of other cerebral artery
I66.9 Occlusion and stenosis of unspecied cerebral artery
I67.5 Moyamoya disease
I67.8 Other specied cerebrovascular diseases
I67.9 Cerebrovascular disease, unspecied
I69.3 Sequelae of cerebral infarction
I69.4 Sequelae of stroke, not specied as hemorrhage or infarction
Australia). The Royal Childrens Hospi- parenchymal infarction on neuroimag-
tal is a tertiary pediatric referral cen- ing scans. Inclusion criteria included a
ter for the states of Victoria and Tas- rst presentation of AIS in patients
mania that treats 280 000 children from the newborn period (dened as
each year. This study was approved by 28 days of age) up to 18 years of age,
the ethics committee. with radiologic conrmation of AIS. Pa-
Cases were ascertained by using Inter- tients with the following conditions
national Classication of Diseases were excluded: sinovenous thrombo-
(ICD) revisions 9 and 10 codes applied sis and hemorrhagic stroke subtypes,
to discharge diagnoses (Table 1), on systemic vasculitides, birth before 36
the basis of standardized methods rec- weeks of gestation, other non-AIS dis-
ommended by the International Pediat- orders associated with focal decits,
ric Stroke Study. These cases were and recurrent strokes. Subjects who
cross-referenced with the institutions did not have documentation of the
hematology database and stroke reg- times of clinical onset and neuroimag-
istry (which commenced in 2002) to ing were excluded.
ensure that no patients were missed. Medical records were reviewed retro-
AIS was dened as (1) an acute neuro- spectively by Dr Srinivasan, and data
logic decit lasting 24 hours and (2) on the pathways to stroke diagnosis
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were collected. Prehospital times re-
corded included the time of clinical on-
set and the time to the Royal Childrens
Hospital or another medical center.
Whether the child presented to the ter-
tiary center directly or indirectly
(through a family physician or periph-
eral hospital) also was ascertained.
Posthospital times recorded in-
cluded the time of physician assess-
ment, the time of initial imaging, and
the time of neuroimaging conrming
AIS. The time of neuroimaging conrm-
ing AIS was obtained from a time
stamp recorded at the time of the pro-
cedure and might not have been equiv-
alent to the time of initial neuroimag-
ing, if a diagnosis of AIS was not made
immediately after the rst imaging
study (for example, if the initial study
was a computed tomographic [CT]
study that did not reveal the AIS).
The time of clinical onset was deter-
mined in a number of ways. The pre-
ferred method was to use the exact
time of clinical onset (such as 9:00 AM),
as documented in the medical chart by
physicians or nurses. In the absence
of such information, the clinical onset
was extrapolated from other docu-
mented information. For example,
if the physicians documented that
hemiparesis began 2 hours ago at
11:00 AM, then stroke onset was esti-
mated at 9:00 AM. If the symptoms were
present at awakening, then the last
time the patient was seen in normal
condition was used. For the sedated
population and for certain ICU pa-
tients, the time of clinical onset was
determined from the detailed regular
neurologic observations performed by
ICU nursing staff members, which
yielded a time of clinical onset within
15 minutes. In cases with discrepan-
cies between the physicians and
nurses, the order of preference was
as follows: earliest precise time
documented, neurologic observations
charted by nurses, and information ex-
PEDIATRICS Volume 124, Number 2, August 2009
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trapolated from other documented
data as described above. The following
information also was collected: age at
time of diagnosis, presence of localiz-
ing signs, seizures at presentation,
risk factors, documented differential
diagnoses (including suspicion of AIS),
and neuroimaging modality.
Focal neurologic decits included fo-
cal neurologic signs and focal sei-
zures. A focal sign was dened as a
motor (hemiplegia, monoplegia, or
ataxia), sensory (paresthesia or dyses-
thesia), visual (visual eld decit or
eye deviation), or speech (dysarthria
or dysphasia) decit. Stroke subtypes
were classied into 8 categories by us-
ing the Pediatric Stroke Classication,
a preliminary modication of the Trial
of ORG 10172 in Acute Stroke Treat-
ment system, that is, sickle cell dis-
ease, cardioembolic stroke, moya-
moya syndrome, cervical arterial
dissection, stenoocclusive arteriopa-
thy, other determined cause, multiple
probable/possible causes, and unde-
termined cause.12
The associations between variables
were analyzed by using Stata 9.2
(Stata, College Station, TX), with the
2-sample rank-sum (Mann-Whitney)
test and Kruskal-Wallis test where ap-
propriate. P values of .05 were con-
sidered statistically signicant.
RESULTS
Study Group
During this 12.5-year period, 375 pa-
tients had 1 of the listed ICD codes
(Fig 1). A total of 107 patients, including
19 neonates and 88 children, met the
inclusion criteria. Most patients
(70%) had a precise time of clinical
onset documented.
The overall median age at the time of
diagnosis was 20 months (interquar-
tile range [IQR]: 62 days to 112
months), and the male/female ratio
was 1.27:1. The median age at the time
ARTICLES
of diagnosis for children was 36
months (IQR: 6 118 months). The me-
dian age at the time of diagnosis for
neonates was 6 days (IQR: 312 days).
There were no signicant differences
between the excluded and included
populations with respect to gender or
age. Sixty percent of the study subjects
were inpatients at the time of stroke
onset. The remaining 40% were not in-
patients at the time of AIS onset, with
13% presenting directly to the Royal
Childrens Hospital emergency depart-
ment after clinical onset and 27% pre-
senting through a peripheral center.
Children (Nonneonatal Population)
Times to AIS Conrmation
A median time of 24.8 hours (IQR: 10.2
67.0 hours) from clinical onset to ra-
diologic conrmation of AIS was noted
for the population of children (Tables 2
and 3). For inpatients, the median time
was 21.3 hours (IQR: 5.8 54.1 hours);
for outpatients, the median time was
27.4 hours (IQR: 18.9 74.6 hours; P
.001).
Six (6.8%) of 88 patients were diag-
nosed as having AIS within 3 hours (Ta-
ble 2); all were inpatients with cardio-
embolic risk factors (Table 3). Five
patients had structural heart disease.
Five of the 6 children had focal signs.
Five of the 6 children also had radio-
logic evidence of hemorrhagic conver-
sion or involvement of more than one
third of the middle cerebral artery ter-
ritory on initial imaging scans. Fifty
percent of all 88 children with AIS did
not have their stroke radiologically
conrmed until 24 hours after clini-
cal onset.
Times to Seeing a Physician and
Initial Imaging
The time of rst physician assessment
was documented for 37 (42%) of the 88
children, and the median time from
clinical onset to the rst evaluation by
a physician in this group was 1 hour
e229
 Nonneurologic (died at age 5 mo
375 neonates and children

as result of cardiac failure)

identified

Neurologic (increased ICP)

Neurologic (increased ICP)

Neurologic (increased ICP)

Cause of Death
179 patients excluded as not
having had AIS
66 patients excluded as not first

Not applicable

Not applicable
presentation of AIS
130 neonates and children with
first presentation of AIS
identified

Mild motor

Mild motor
Discharge
23 patients excluded as having

Status at

decit

decit
inadequate documentation of

Death
Death

Death

Death
timing

Total of 107 patients:

19 neonates

Heparin and then

Heparin and then

Heparin and then

88 children

Treatment

warfarin

warfarin
clexane
None
None

None
19 neonates 88 children

More Than One

Third of MCA
Territory
Yes
Yes

Yes

Yes

Yes
No
FIGURE 1
Patients included in study.

Hemorrhagic
Conversion

ECMO indicates extracorporeal membrane oxygenation; ACA, anterior cerebral artery; MCA, middle cerebral artery; ICP, intracranial pressure.
Yes
Yes

Yes

Yes
TABLE 2 Distribution of Times From Clinical included seizures, central nervous

No

Onset to Conrmation of AIS
Diagnosis (N 88)
Time
No
system infections, sepsis, tumors, in-
n (%)
creased intracranial pressure, and,

Unilateral MCA and ACA

Both left MCA and right
less commonly, migraines, musculo-

external watershed
Stroke Topography
Within 3 h 6 (6.8)
3 to 6 h 9 (10.2) skeletal conditions, and electrolyte

Unilateral MCA

Unilateral MCA

Unilateral MCA

Unilateral MCA
6 to 9 h 5 (5.7) disturbances. The small number of cli-
9 to 24 h 24 (27.3)
24 h 44 (50.0)
nicians who documented a suspicion
of AIS precluded analysis of whether
suspicion of AIS inuenced the time to
Neurologic

neuroimaging.
Decits
Focal

(IQR: 0 4.5 hours). Of all children, 75%

Yes

Yes

Yes

Yes

Yes
No

were seen by a physician within 3

Presence of Focal Signs or Focal
hours. For inpatients, the median time
Seizures
TABLE 3 Data for Children Meeting Time Criteria for Thrombolysis

Hypoplastic left heart syndrome,

Hypoplastic left heart syndrome,

after Norwood procedure and

to physician assessment was 20 min-

Tricuspid atresia, after cardiac
ECMO (for charcoal aspiration)
Dilated cardiomyopathy, ECMO

Complex cyanotic congenital

utes (IQR: 0 180 minutes); for outpa- At the time of the rst physician as-
sessment, 76 (86%) of 88 patients
after catheterization
Risk Factors

tients, the median time was 120 min-

utes (IQR: 57 408 minutes; P .003) had a focal sign (Table 4). The major-
catheterization

heart disease

(Table 2). The time to initial imaging ity of focal signs were motor decits
except for the neonates, for whom
ECMO

was 11.4 hours (IQR: 4.6 25.5 hours)

for inpatients and 9.6 hours (IQR: 4.5 focal seizures predominated. The
20.6 hours) for outpatients (P .05). presence of a focal sign was associ-
Age at AIS

ated with increased suspicion of AIS

100 mo
17 mo

2 mo

33 mo

59 mo
Onset

31 d

Initial Suspicion of AIS (P .02), with physicians suspecting

A suspected diagnosis or differential AIS for 23 (30%) of the 76 children
diagnosis was documented by the rst with focal decits, compared with no
Conrmation
of AIS, h
Time to

physician to see the patient for 44 suspicion of AIS for the 12 children
1.65
2.17

2.20

2.45

2.97

3.00

(50%) of the 88 patients. Physicians without focal decits. However, the

documented suspicion of AIS for only presence of a focal sign was not as-
23 (26%) of the 88 children. Other sociated with a shorter time to
Patient

D
B

C
A

documented differential diagnoses stroke conrmation.

e230 SRINIVASAN et al
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 ARTICLES

TABLE 4 Types of Focal Neurologic Decits in TABLE 5 Etiologic Subtypes in Childhood Population, on the Basis of Modied Trial of ORG 10172 in
Childhood Population (N 76) Acute Stroke Treatment Classication
Focal Neurologic Decit n Classication n (%)
Motor alone 30 Total Inpatient at Time Noninpatient at Time
Motor with other features of AIS (N 51) of AIS (N 37)
Seizures 2
Cardioembolic stroke 40 (45.4) 35 (68.6) 5 (13.5)
Speech decit 9
Dissection 2 (2.3) 0 (0) 2 (5.4)
Visual decit 8
Stenoocclusive arteriopathy 8 (9.1) 1 (2) 7 (18.9)
Sensory decit 1
Other determined cause 12 (13.6) 3 (5.9) 9 (24.3)
2 of above 5
Possible/probable risk factor 20 (22.7) 12 (23.5) 8 (21.6)
Focal seizures alone 4
No identiable risk factors 6 (6.8) 0 (0) 6 (16.2)
Focal seizures and visual decit 6
Total 88 51 37
Sensory (visual and/or other sensory) 11
No patients who met the inclusion criteria were identied within the categories of sickle cell disease or moyamoya
Motor decit indicates focal weakness or uncoordination;
syndrome. Cardioembolic causes include congenital heart disease, cardiac surgery, extracorporeal membrane oxygen-
speech decit, dysphasia or aphasia; visual decit, visual
ation, and endocarditis. Other determined causes include bromuscular dysplasia, primary angiitis of the central nervous
eld decit or eye deviation.
system, radiation-related angiopathy, transtentorial herniation, chronic illnesses, and trauma. Possible/probable risk
factors include migraine, central nervous system infection, sepsis, postprocedural status, and thrombophilia.

There were no signicant associations
between seizures at presentation and
suspicion of AIS or between seizures at
presentation and time to conrmation.
None of the cases reviewed in our ret-
rospective study had documentation
detailing cognitive decits in children
with acute stroke.
Risk Factors for AIS
By using the Pediatric Stroke Classi-
cation system, detailed stroke causes
for the 88 nonneonates were catego-
rized (Table 5). The 19 neonates were
excluded from this analysis. Two of the
8 Pediatric Stroke Classication cate-
gories, namely, moyamoya syndrome
and sickle cell disease, were not rep-
resented among the children.
Admission Status at Time of Stroke
Almost 58% of our children (n 51)
were inpatients at the time of AIS (Ta-
ble 6). All inpatients with AIS had iden-
tiable risk factors, compared with
84% of the outpatients. Almost 69% of
inpatient strokes resulted from a likely
cardioembolic mechanism secondary
to previously recognized cardiac risk
factors, including structural cardiac
defects, previous cardiac surgery
and/or cardiac catheterization, or
treatment with an extracorporeal cir-
culation device (eg, extracorporeal
membrane oxygenation treatment).
TABLE 6 Relationship of AIS to Age and Admission Status
Time to diagnosis, median (IQR), h
Neonate (n 19)
Nonneonate (n 88)
Time to AIS conrmation, median (IQR), h
Inpatient (n 51)
Noninpatient (n 37)
Time to rst physician assessment, median (IQR), min
Inpatient (n 37)
Noninpatient (n 26)
Imaging
The proportions of children who un-
derwent brain MRI, brain CT imaging,
or ultrasonography as initial imaging
were 88.9%, 94.9%, and 30%, respec-
tively. MRI and CT scanning were per-
formed as initial imaging primarily in
the older population, with more ultra-
sound studies in the neonatal popula-
tion. Initial imaging yielded negative
results despite AIS for 62 of 74 children
who underwent CT imaging and 3 of 6
children who underwent ultrasonog-
raphy. MRI, when used as the initial im-
aging modality, conrmed all strokes
in 8 children.
Neonatal Population
The median time to conrmation of AIS
for the neonates was 87.9 hours (IQR:
53.4 166.4 hours), which was signi-
cantly longer than the time for the chil-
dren, for whom the median time to AIS
conrmation was 24.8 hours (IQR:
Time P
87.9 (53.4166.4) .0002
24.8 (10.267)
21.3 (5.854.1) .001
27.4 (18.974.6)
20 (0180) .003
120 (57408)
10.2 67.0 hours; P .0002). There was
signicantly less documentation of AIS
suspicion in the medical records of ne-
onates (P .04), and seizures were
more common at presentation for ne-
onates, compared with children (P
.0001). Anterior circulation AIS pre-
dominated for both age groups (68%
for neonates and 63% for children).
DISCUSSION
Children
There is signicant delay in the diagno-
sis of stroke in children, with a median
time of almost 25 hours from clinical
onset to radiologic conrmation of AIS.
Gabis et al3 demonstrated a large pre-
hospital delay (mean time: 28.5 hours)
contributing to the overall delay in
stroke diagnosis (mean time: 35.7
hours). In contrast, our study showed
that the median time from clinical on-
set to assessment by a physician was 1

PEDIATRICS Volume 124, Number 2, August 2009 e231

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hour, with three fourths of the children
being seen by a physician within 3
hours after clinical onset. These nd-
ings are similar to those of a recent
study from the United Kingdom, which
found that three fourths of children
were seen by a physician within 6
hours.4 Although prehospital delay
was demonstrated recently to be pre-
dictive of delayed AIS diagnosis,7 our
ndings suggest that the delay in diag-
nosis is more likely posthospital delay,
largely related to the lack of aware-
ness of stroke among medical staff
members.
Eighty-six percent of our children had
1 focal sign at the time of presenta-
tion, but one third of our patients had
nonmotor (ie, nonhemiplegic) presen-
tations. One half of the physicians doc-
umented a differential diagnosis, and
even fewer included stroke in the list of
possibilities.
Our ndings suggest that pediatric
stroke is an underrecognized problem
within the medical community, despite
the signicant associated long-term
disability and the fact that more than
one half of children have residual func-
tional decits.1 Furthermore, almost
58% of our older subjects were inpa-
tients at the time of their AIS, and al-
most 69% had known cardiac risk fac-
tors for stroke. This is important
because cardiac disease is the most
common, previously recognized risk
factor.1315 Children with cardiac dis-
ease represent the one group that
could potentially be targeted with pri-
mary prevention strategies.
Although they met the theoretical
3-hour criterion for intravenous throm-
bolysis, 5 of 6 children in our series
who presented within 3 hours
would not have been eligible for intra-
venous thrombolysis because of exten-
sive infarction or the presence of
hemorrhagic conversion.16,17 Cranial
ultrasonography and CT scanning are
not as sensitive as MRI of the brain
e232 SRINIVASAN et al
when used as the initial imaging mo-
dality to diagnose AIS; our study
showed that the stroke diagnosis was
missed for 3 of 6 children who initially
underwent ultrasonography and 62 of
74 children who initially underwent CT
scanning. This is similar to the results
of a United Kingdom study in which AIS
was not detected on CT scans in 47% of
cases.4
Stroke-mimickers, such as hemiplegic
migraine or Todd paresis, can cause
delay in AIS diagnosis.5 Emergency ra-
diologic conrmation of acute infarc-
tion and arterial occlusion will un-
doubtedly be essential requirements
in the rst pilot safety trials of throm-
bolysis in childhood stroke.18
Hyperacute therapies have not been
approved for children, and physicians
may feel less urgency to perform rapid
imaging. If such therapies were to be
shown to be effective for children, then
the time to diagnosis would likely de-
crease as clinicians and radiologists
prioritize neuroimaging studies.
Neonates
Pediatric stroke registry data suggest
that 25% to 30% of all cases occur in
neonates and almost 50% in children
1 year of age.13 Not surprisingly, di-
agnosis took longer for neonates with
AIS than for the childhood population.
This is because localizing signs often
are absent, which makes stroke on-
set difcult to determine accurately
for neonates. Focal seizures can pre-
dominate over motor decits. Stroke
should be suspected for any neonate
presenting with seizures, lethargy,
or apnea, the latter 2 features being
seen in neonatal stroke in the setting
of encephalopathy.19
Study Population and Limitations
Our study had a larger study popula-
tion, compared with previous stud-
ies.3,4 We dened our time of stroke di-
agnosis as the time of neuroimaging
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conrming stroke. Our study was per-
formed in a tertiary center where
there is close collaboration between
pediatric neurologists and radiolo-
gists, which makes use of the time of
neuroimaging a more-reliable ap-
proach to assess the time of stroke di-
agnosis in our population. The results
were not reviewed independently, and
the timing of negative studies was not
analyzed, because positive imaging re-
sults represented an inclusion crite-
rion. All scans were evaluated by at-
tending radiologists who were familiar
with neuroimaging. When assessment
is performed with a suspicion of AIS,
the radiologists interpretation of the
neuroimaging scans at the Royal Chil-
drens Hospital is conveyed immedi-
ately to the referring doctor.
Other studies dened the time of AIS
diagnosis to be the time the diagnosis
was entered in the medical chart.4 We
chose radiologic conrmation be-
cause a suspected diagnosis or differ-
ential diagnosis was documented by
the rst physician to see the patient
for only 50% of our population and a
suspicion of AIS was documented for
only 26% of children. A limitation of our
denition for determining the time to
stroke diagnosis is that radiologic con-
rmation may not equal clinical conr-
mation; however, because there often
are delays or omissions in medical
documentation, we think that the time
to radiologic diagnosis is most likely to
represent the true time to AIS diagno-
sis in our population.
A limitation of this study is possible as-
certainment bias, given the retrospec-
tive design and limitations in ICD codes
for diagnosing stroke. Almost 50% of
the cases in our initial population were
miscoded with ICD codes and did not
represent AIS. However, all of the eligi-
ble stroke cases seen in our tertiary
center were included in this study.
Other limitations include our study
population being composed of patients
 ARTICLES

from a large tertiary pediatric hospi- have contraindications to hyperacute CONCLUSIONS

tal, which houses a major cardiac unit.
Therefore, cardioembolic stroke is
more frequent in our population than
in other studies, and the results are
not entirely applicable to the general
population. However, we would have
anticipated that such a high-risk popu-
lation would have a shorter time to
stroke diagnosis than that in a gen-
eral, community-based center. The fact
that only 17% of our patients were neo-
nates reects the fact that we are not
colocated with an obstetric unit and
most neonatal cases are treated at
other centers. In addition, sickle cell
disease is uncommon in the Australian
pediatric population, and patients with
moyamoya syndrome might have been
excluded for reasons such as previous
AIS.
Patient-related factors inuencing the
time to diagnosis include the possible
need for a general anesthetic for imag-
ing for young children, and comorbidi-
ties such as cardiac disease and criti-
cal illness may mean that children are
too ill to be transported to the scanner.
In addition, admission to an ICU, and
thus the need for sedation, may mask
focal signs. Many inpatients may
therapy, leading to delayed imaging
because clinicians think that imag-
ing results are unlikely to change
management.
The delays associated with AIS are at-
tributable to both decreased aware-
ness in the medical community and
problems with access to neuroimag-
ing, including those associated with
patient comorbidities precluding ur-
gent scanning. The lack of available
treatment options for the pediatric
stroke population is the likely reason
for delayed imaging for children, be-
cause similar ndings have been ob-
served for adult stroke patients.20 Cur-
rent practice is the likely culprit in
perpetuating delays, and this factor
needs to be addressed. Although
thrombolysis is an important factor,
there are other measures for address-
ing delays in diagnosis that can
change long-term outcomes. Mea-
sures that have been shown to im-
prove outcomes in adults include
control of fever and hypertension,
maintenance of normal oxygenation,
normalization of serum glucose levels,
and early access to rehabilitation.11
It is hoped that progress will de-
crease the time lag to stroke diagno-
sis through better understanding of
risk factors in the pediatric popula-
tion.21 The American College of Chest
Physicians has stated, the infre-
quency of stroke in children results
in delayed recognition and an inabil-
ity to intervene early with medica-
tions that may reduce subsequent
neurologic decits.9 Clearly, there
are delays in childhood stroke diag-
nosis that must be addressed with
increased awareness among medi-
cal professionals, particularly for
high-risk groups such as children
with cardiac disease. Ideally, devel-
opment of hospital-based pediatric
stroke services will improve early di-
agnosis of stroke, to allow children
the benets of acute medical inter-
ventions that have been shown to
improve outcomes in the adult
population.
ACKNOWLEDGMENTS
We thank Drs James H. Lee and Manali
Chitre for their valuable contributions
in editing the manuscript.

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e234 SRINIVASAN et al
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Delayed Recognition of Initial Stroke in Children: Need for Increased Awareness
Jayasri Srinivasan, Steven P. Miller, Thanh G. Phan and Mark T. Mackay
Pediatrics 2009;124;e227; originally published online July 20, 2009;
DOI: 10.1542/peds.2008-3544
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2009 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Delayed Recognition of Initial Stroke in Children: Need for Increased Awareness
Jayasri Srinivasan, Steven P. Miller, Thanh G. Phan and Mark T. Mackay
Pediatrics 2009;124;e227; originally published online July 20, 2009;
DOI: 10.1542/peds.2008-3544

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/124/2/e227.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2009 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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