Escolar Documentos
Profissional Documentos
Cultura Documentos
Canada; and dDepartment of Neurosciences, Monash Medical WHAT THIS STUDY ADDS: This study quanties the time to
Centre, Melbourne, Australia diagnosis of pediatric stroke and aims to highlight the factors
KEY WORDS that perpetuate delay, namely, the lack of awareness of
stroke, cerebrovascular disease, cerebral vascular accident physicians regarding pediatric stroke. This is in contrast to many
ABBREVIATIONS previous studies.
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
abstract
OBJECTIVE: The goal was to identify the delays involved in diagnosing
Accepted for publication Mar 13, 2009
pediatric arterial ischemic stroke (AIS), a major cause of morbidity and
Address correspondence to Mark T. Mackay, MBBS, FRACP,
Department of Paediatric Neurology, Childrens Neuroscience
death in children.
Centre, Royal Childrens Hospital, Melbourne, Australia 3052. METHODS: Neonates (28 days of age) and children with a rst pre-
E-mail: mark.mackay@rch.org.au sentation of radiologically conrmed AIS between June 1993 and Jan-
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). uary 2006 were identied retrospectively. The time to diagnosis of AIS
Copyright 2009 by the American Academy of Pediatrics (ie, time from clinical onset to radiologic conrmation) was calculated,
FINANCIAL DISCLOSURE: The authors have indicated they have and factors inuencing stroke diagnosis were reviewed.
no nancial relationships relevant to this article to disclose.
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
infants and children after arterial isch- 433.1 Occlusion and stenosis of carotid artery
433.11 Occlusion and stenosis of carotid artery with cerebral infarction
emic stroke (AIS).1 Limited awareness 434.0 Cerebral thrombosis
regarding pediatric stroke among phy- 434.00 Cerebral thrombosis without mention of cerebral infarction
sicians and in the community is a ma- 434.01 Cerebral thrombosis with cerebral infarction
434.10 Cerebral embolism without mention of cerebral infarction
jor issue. For adults, advertising cam- 434.11 Cerebral embolism with cerebral infarction
paigns (eg, Time Is Brain Lost) and 434.9 Cerebral artery occlusion, unspecied
education of primary care physicians 434.90 Cerebral artery occlusion, unspecied, without cerebral infarction
434.91 Cerebral artery occlusion, unspecied, with cerebral infarction
have led to signicant decreases in the 437.5 Moyamoya disease
time to presentation.2 One study re- 437.9 Cerebrovascular disease, unspecied
corded a mean time of 34.5 hours from 438 Late effects of cerebrovascular disease
G08 Intracranial and intraspinal phlebitis and thrombophlebitis
clinical onset to presentation to any G93.2 Benign intracranial hypertension
health care professional for children, I63.0 Cerebral infarction attributable to thrombosis of precerebral arteries
and studies have demonstrated long I63.2 Cerebral infarction attributable to occlusion of precerebral arteries, not otherwise specied
I63.3 Cerebral infarction attributable to thrombosis of cerebral arteries
delays to neuroimaging.3,4 For chil- I63.4 Cerebral infarction attributable to embolism of cerebral arteries
dren, stroke symptoms are attributed I63.5 Cerebral infarction attributable to occlusion of cerebral arteries, not otherwise specied
frequently to stroke-mimickers such I63.6 Cerebral infarction attributable to cerebral venous thrombosis, nonpyogenic
I63.8 Other cerebral infarction
as migraine, encephalitis, tumors, and
I63.9 Cerebral infarction, unspecied
postictal Todd paralysis, which can ac- I64 Stroke, not specied as hemorrhage or infarction
count for up to one fth of cases pre- I65.2 Occlusion and stenosis of carotid artery
senting with stroke-like symptoms.5,6 I66.0 Occlusion and stenosis of middle cerebral artery
I66.1 Occlusion and stenosis of anterior cerebral artery
Recent pediatric studies suggested I66.2 Occlusion and stenosis of posterior cerebral artery
that factors such as delays in seeking I66.8 Occlusion and stenosis of other cerebral artery
medical attention and mode of onset I66.9 Occlusion and stenosis of unspecied cerebral artery
I67.5 Moyamoya disease
were predictive of the delayed diagno- I67.8 Other specied cerebrovascular diseases
sis of stroke and of the underlying I67.9 Cerebrovascular disease, unspecied
cause.7,8 I69.3 Sequelae of cerebral infarction
I69.4 Sequelae of stroke, not specied as hemorrhage or infarction
Various consensus guidelines have
highlighted the importance of improv-
ing time to stroke diagnosis.911 Before Australia). The Royal Childrens Hospi- parenchymal infarction on neuroimag-
assessment of acute thrombolysis in tal is a tertiary pediatric referral cen- ing scans. Inclusion criteria included a
the pediatric population, the factors ter for the states of Victoria and Tas- rst presentation of AIS in patients
causing delays in stroke diagnosis mania that treats 280 000 children from the newborn period (dened as
must be identied and addressed. The each year. This study was approved by 28 days of age) up to 18 years of age,
aims of this study were to determine the ethics committee. with radiologic conrmation of AIS. Pa-
the time between clinical onset and Cases were ascertained by using Inter- tients with the following conditions
diagnosis of AIS in a tertiary Austra- national Classication of Diseases were excluded: sinovenous thrombo-
lian pediatric hospital and to identify (ICD) revisions 9 and 10 codes applied sis and hemorrhagic stroke subtypes,
factors that inuenced the time to to discharge diagnoses (Table 1), on systemic vasculitides, birth before 36
diagnosis. the basis of standardized methods rec- weeks of gestation, other non-AIS dis-
ommended by the International Pediat- orders associated with focal decits,
METHODS ric Stroke Study. These cases were and recurrent strokes. Subjects who
We identied retrospectively all chil- cross-referenced with the institutions did not have documentation of the
dren 0 to 18 years of age who were hematology database and stroke reg- times of clinical onset and neuroimag-
diagnosed as having a rst episode of istry (which commenced in 2002) to ing were excluded.
AIS during a 12.5-year period, from ensure that no patients were missed. Medical records were reviewed retro-
June 1, 1993, to January 30, 2006, at the AIS was dened as (1) an acute neuro- spectively by Dr Srinivasan, and data
Royal Childrens Hospital (Melbourne, logic decit lasting 24 hours and (2) on the pathways to stroke diagnosis
e228 SRINIVASAN et al
Downloaded from by guest on May 22, 2017
ARTICLES
were collected. Prehospital times re- trapolated from other documented of diagnosis for children was 36
corded included the time of clinical on- data as described above. The following months (IQR: 6 118 months). The me-
set and the time to the Royal Childrens information also was collected: age at dian age at the time of diagnosis for
Hospital or another medical center. time of diagnosis, presence of localiz- neonates was 6 days (IQR: 312 days).
Whether the child presented to the ter- ing signs, seizures at presentation, There were no signicant differences
tiary center directly or indirectly risk factors, documented differential between the excluded and included
(through a family physician or periph- diagnoses (including suspicion of AIS), populations with respect to gender or
eral hospital) also was ascertained. and neuroimaging modality. age. Sixty percent of the study subjects
Posthospital times recorded in- Focal neurologic decits included fo- were inpatients at the time of stroke
cluded the time of physician assess- cal neurologic signs and focal sei- onset. The remaining 40% were not in-
ment, the time of initial imaging, and zures. A focal sign was dened as a patients at the time of AIS onset, with
the time of neuroimaging conrming motor (hemiplegia, monoplegia, or 13% presenting directly to the Royal
AIS. The time of neuroimaging conrm- ataxia), sensory (paresthesia or dyses- Childrens Hospital emergency depart-
ing AIS was obtained from a time thesia), visual (visual eld decit or ment after clinical onset and 27% pre-
stamp recorded at the time of the pro- senting through a peripheral center.
eye deviation), or speech (dysarthria
cedure and might not have been equiv- or dysphasia) decit. Stroke subtypes
alent to the time of initial neuroimag- Children (Nonneonatal Population)
were classied into 8 categories by us-
ing, if a diagnosis of AIS was not made ing the Pediatric Stroke Classication, Times to AIS Conrmation
immediately after the rst imaging a preliminary modication of the Trial A median time of 24.8 hours (IQR: 10.2
study (for example, if the initial study of ORG 10172 in Acute Stroke Treat- 67.0 hours) from clinical onset to ra-
was a computed tomographic [CT] ment system, that is, sickle cell dis- diologic conrmation of AIS was noted
study that did not reveal the AIS). ease, cardioembolic stroke, moya- for the population of children (Tables 2
The time of clinical onset was deter- moya syndrome, cervical arterial and 3). For inpatients, the median time
mined in a number of ways. The pre- dissection, stenoocclusive arteriopa- was 21.3 hours (IQR: 5.8 54.1 hours);
ferred method was to use the exact thy, other determined cause, multiple for outpatients, the median time was
time of clinical onset (such as 9:00 AM), probable/possible causes, and unde- 27.4 hours (IQR: 18.9 74.6 hours; P
as documented in the medical chart by termined cause.12 .001).
physicians or nurses. In the absence The associations between variables Six (6.8%) of 88 patients were diag-
of such information, the clinical onset were analyzed by using Stata 9.2 nosed as having AIS within 3 hours (Ta-
was extrapolated from other docu- (Stata, College Station, TX), with the ble 2); all were inpatients with cardio-
mented information. For example, 2-sample rank-sum (Mann-Whitney) embolic risk factors (Table 3). Five
if the physicians documented that test and Kruskal-Wallis test where ap- patients had structural heart disease.
hemiparesis began 2 hours ago at propriate. P values of .05 were con- Five of the 6 children had focal signs.
11:00 AM, then stroke onset was esti- sidered statistically signicant. Five of the 6 children also had radio-
mated at 9:00 AM. If the symptoms were logic evidence of hemorrhagic conver-
present at awakening, then the last RESULTS sion or involvement of more than one
time the patient was seen in normal third of the middle cerebral artery ter-
Study Group
condition was used. For the sedated ritory on initial imaging scans. Fifty
population and for certain ICU pa- During this 12.5-year period, 375 pa- percent of all 88 children with AIS did
tients, the time of clinical onset was tients had 1 of the listed ICD codes not have their stroke radiologically
determined from the detailed regular (Fig 1). A total of 107 patients, including conrmed until 24 hours after clini-
neurologic observations performed by 19 neonates and 88 children, met the cal onset.
ICU nursing staff members, which inclusion criteria. Most patients
yielded a time of clinical onset within (70%) had a precise time of clinical Times to Seeing a Physician and
15 minutes. In cases with discrepan- onset documented. Initial Imaging
cies between the physicians and The overall median age at the time of The time of rst physician assessment
nurses, the order of preference was diagnosis was 20 months (interquar- was documented for 37 (42%) of the 88
as follows: earliest precise time tile range [IQR]: 62 days to 112 children, and the median time from
documented, neurologic observations months), and the male/female ratio clinical onset to the rst evaluation by
charted by nurses, and information ex- was 1.27:1. The median age at the time a physician in this group was 1 hour
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
Treatment
warfarin
warfarin
clexane
None
None
None
19 neonates 88 children
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
No
Onset to Conrmation of AIS
Diagnosis (N 88)
system infections, sepsis, tumors, in-
Time n (%)
creased intracranial pressure, and,
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
Yes
Yes
Yes
Yes
No
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
heart disease
(Table 2). The time to initial imaging ity of focal signs were motor decits
except for the neonates, for whom
ECMO
2 mo
33 mo
59 mo
Onset
31 d
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
D
B
C
A
e230 SRINIVASAN et al
Downloaded from by guest on May 22, 2017
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 TABLE 6 Relationship of AIS to Age and Admission Status
between seizures at presentation and Time P
suspicion of AIS or between seizures at Time to diagnosis, median (IQR), h
presentation and time to conrmation. Neonate (n 19) 87.9 (53.4166.4) .0002
Nonneonate (n 88) 24.8 (10.267)
None of the cases reviewed in our ret- Time to AIS conrmation, median (IQR), h
rospective study had documentation Inpatient (n 51) 21.3 (5.854.1) .001
detailing cognitive decits in children Noninpatient (n 37) 27.4 (18.974.6)
Time to rst physician assessment, median (IQR), min
with acute stroke. Inpatient (n 37) 20 (0180) .003
Noninpatient (n 26) 120 (57408)
Risk Factors for AIS
By using the Pediatric Stroke Classi-
cation system, detailed stroke causes Imaging 10.2 67.0 hours; P .0002). There was
for the 88 nonneonates were catego- signicantly less documentation of AIS
The proportions of children who un-
rized (Table 5). The 19 neonates were suspicion in the medical records of ne-
derwent brain MRI, brain CT imaging,
excluded from this analysis. Two of the onates (P .04), and seizures were
or ultrasonography as initial imaging
8 Pediatric Stroke Classication cate- more common at presentation for ne-
were 88.9%, 94.9%, and 30%, respec-
gories, namely, moyamoya syndrome onates, compared with children (P
tively. MRI and CT scanning were per-
and sickle cell disease, were not rep- .0001). Anterior circulation AIS pre-
formed as initial imaging primarily in
resented among the children. dominated for both age groups (68%
the older population, with more ultra-
sound studies in the neonatal popula- for neonates and 63% for children).
Admission Status at Time of Stroke
tion. Initial imaging yielded negative
Almost 58% of our children (n 51) results despite AIS for 62 of 74 children DISCUSSION
were inpatients at the time of AIS (Ta- who underwent CT imaging and 3 of 6
ble 6). All inpatients with AIS had iden- Children
children who underwent ultrasonog-
tiable risk factors, compared with raphy. MRI, when used as the initial im- There is signicant delay in the diagno-
84% of the outpatients. Almost 69% of aging modality, conrmed all strokes sis of stroke in children, with a median
inpatient strokes resulted from a likely in 8 children. time of almost 25 hours from clinical
cardioembolic mechanism secondary onset to radiologic conrmation of AIS.
to previously recognized cardiac risk Neonatal Population Gabis et al3 demonstrated a large pre-
factors, including structural cardiac The median time to conrmation of AIS hospital delay (mean time: 28.5 hours)
defects, previous cardiac surgery for the neonates was 87.9 hours (IQR: contributing to the overall delay in
and/or cardiac catheterization, or 53.4 166.4 hours), which was signi- stroke diagnosis (mean time: 35.7
treatment with an extracorporeal cir- cantly longer than the time for the chil- hours). In contrast, our study showed
culation device (eg, extracorporeal dren, for whom the median time to AIS that the median time from clinical on-
membrane oxygenation treatment). conrmation was 24.8 hours (IQR: set to assessment by a physician was 1
e232 SRINIVASAN et al
Downloaded from by guest on May 22, 2017
ARTICLES
REFERENCES
1. Ganesan V, Hogan A, Shack N, Gordon A, Isaacs E, Kirkham FJ. Outcome after ischemic stroke in
childhood. Dev Med Child Neurol. 2000;42(7):455 461
2. Saver JL. Time is brain: quantied. Stroke. 2006;37(1):263266
3. Gabis LV, Yangala R, Lenn NJ. Time lag to diagnosis of stroke in children. Pediatrics. 2002;110(5):
924 928
4. McGlennan C, Ganesan V. Delays in investigation and management of acute arterial ischaemic
stroke in children. Dev Med Child Neurol. 2008;50(7):537540
5. Shellhaas RA, Smith SE, OTool E, Licht DJ, Ichord RN. Mimics of childhood stroke: characteristics
of a prospective cohort. Pediatrics. 2006;118(2):704 709
6. Braun KP, Kappelle LJ, Kirkham FJ, Deveber G. Diagnostic pitfalls in pediatric ischemic stroke. Dev
Med Child Neurol. 2006;48(12):985990
7. Rafay MF, Pontigon AM, Chiang J, et al. Delay to diagnosis in acute pediatric arterial ischemic
stroke. Stroke. 2009;40(1):58 64
8. Braun KP, Rafay MF, Uiterwaal CS, Pontigon AM, DeVeber G. Mode of onset predicts etiological
diagnosis of arterial ischemic stroke in children. Stroke. 2007;38(2):298 302
9. Monagle P, Chan A, Massicotte P, Chalmers E, Michelson AD. Antithrombotic therapy in children:
the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3
suppl):645S 687S
10. Royal College of Physicians, Paediatric Stroke Working Group. Stroke in Childhood: Clinical Guide-
lines for Diagnosis, Management and Rehabilitation. London, England: Royal College of Physicians;
e234 SRINIVASAN et al
Downloaded from by guest on May 22, 2017
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
Updated Information & including high resolution figures, can be found at:
Services /content/124/2/e227.full.html
References This article cites 20 articles, 9 of which can be accessed free
at:
/content/124/2/e227.full.html#ref-list-1
Citations This article has been cited by 12 HighWire-hosted articles:
/content/124/2/e227.full.html#related-urls
Subspecialty Collections This article, along with others on similar topics, appears in
the following collection(s):
Neurology
/cgi/collection/neurology_sub
Permissions & Licensing Information about reproducing this article in parts (figures,
tables) or in its entirety can be found online at:
/site/misc/Permissions.xhtml
Reprints Information about ordering reprints can be found online:
/site/misc/reprints.xhtml
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