Acute Childhood Arterial Ischemic and Hemorrhagic Stroke in the Emergency Department

PEDIATRICS/ORIGINAL RESEARCH

Acute Childhood Arterial Ischemic and Hemorrhagic Stroke in the Emergency Department Adriana Yock-Corrales, MD, Mark T. Mackay, MBBS, FRACP, Ian Mosley, PhD, MBus, RN, Wirginia Maixner, MBBS, Franz E. Babl, MD, MPH, FRACP, FAAP From the Emergency Department, Royal Children’s Hospital Melbourne, Victoria, Australia (Yock-Corrales, Babl); Murdoch Children’s Research Institute, Melbourne, Victoria, Australia (Mackay, Babl, Mosley); Department of Neurology, Royal Children’s Hospital, Melbourne, Victoria, Australia (Mackay); University of Melbourne, Melbourne, Victoria, Australia (Mackay, Babl, Maixner); Monash University, Melbourne, Victoria, Australia (Mosley); National Stroke Research Institute, Melbourne, Victoria, Australia (Mosley); Department of Neurosurgery, Royal Children’s Hospital, Melbourne, Victoria, Australia (Maixner).

Study objective: Little is known about the presenting features of acute ischemic and hemorrhagic stroke in children presenting to the emergency department (ED). Yet, initial clinical assessment is a key step in the management pathway of stroke. We describe the presentation in the ED of children with confirmed acute ischemic and hemorrhagic stroke subtypes. Methods: We conducted a retrospective descriptive case series of consecutive patients aged 1 month to younger than 18 years and presenting to a single-center tertiary ED with radiologically confirmed acute ischemic stroke or hemorrhagic stroke during a 5-year period. Patients were identified by medical record search with International Classification of Diseases, 10th Revision codes for hemorrhagic stroke and through the hospital stroke registry for acute ischemic stroke. Signs, symptoms, and initial management were described. Results: Fifty patients with acute ischemic stroke and 31 with hemorrhagic stroke were identified. Mean age was 8.7 years (SD 5.2), and 51% were male. Fifty-six percent were previously healthy. Median time from onset of symptoms to ED presentation was 21 hours (interquartile range 6 to 48 hours) for acute ischemic stroke and 12 hours (interquartile range 4 to 72 hours) for hemorrhagic stroke. Acute ischemic stroke presented with symptoms of focal limb weakness (64%; 95% confidence interval [CI] 49% to 77%), facial weakness (60%; 95% CI 45% to 73%), and speech disturbance (46%; 95% CI 31% to 60%). Few patients with acute ischemic stroke presented with vomiting and altered mental status. Most patients with acute ischemic stroke had a Glasgow Coma Scale (GCS) score of 14 or greater (86%; 95% CI 73% to 94%) and presented with at least 1 focal neurologic sign (88%; 95% CI 73% to 98%). Hemorrhagic stroke presented with headache (73%; 95% CI 54% to 87%), vomiting (58%; 95% CI 40% to 75%), and altered mental status (48%; 95% CI 30% to 67%). GCS score in hemorrhagic stroke was less than 14 in 38% and less than 8 in 19% (95% CI 7% to 37%). Less than one third of patients had focal limb weakness, facial weakness, or slurred speech. Nineteen percent of patients with hemorrhagic stroke were intubated in the ED and admitted to the ICU. None of the acute ischemic stroke patients were intubated in the ED, and 4% were admitted to the ICU. Conclusion: Diagnosis of stroke in children with acute ischemic stroke and hemorrhagic stroke was delayed. Acute ischemic stroke presented mainly with focal findings; hemorrhagic stroke, with headache, vomiting, and mental status change. [Ann Emerg Med. 2011;58:156-163.] Please see page 157 for the Editor’s Capsule Summary of this article. Provide feedback on this article at the journal’s Web site, www.annemergmed.com. A podcast for this article is available at www.annemergmed.com. 0196-0644/$-see front matter Copyright © 2010 by the American College of Emergency Physicians. doi:10.1016/j.annemergmed.2010.10.013

INTRODUCTION The licensing of acute thrombolytic agents such as tissue plasminogen activator has transformed the approach to adult stroke care from prevention and rehabilitation to include acute and hyperacute, time-critical protocols for the emergency 156 Annals of Emergency Medicine

treatment of stroke.1 The recent European Cooperative Acute Stroke Study (ECASS) III study demonstrated improved outcome when used up to 4.5 hours from symptom onset.2 Stroke is now managed as a medical emergency.3-5 In adults, advertising campaigns such as “Time is Brain Lost”6 and Volume , .  : August 

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Editor’s Capsule Summary

What is already known on this topic Pediatric stroke is uncommon and can be difficult to diagnose. What question this study addressed This 5-year retrospective case series describes the presenting features of acute ischemic and hemorrhagic stroke in 81 children at one tertiary care pediatric emergency department. What this study adds to our knowledge Children with acute ischemic stroke presented mainly with focal findings (limb or facial weakness, slurred speech), whereas children with hemorrhagic stroke had headache, vomiting, and mental status change. Compared with adults, children presented late and had longer wait times for imaging. How this is relevant to clinical practice Practitioners should consider hemorrhagic stroke in the differential diagnosis of altered mental status or headache and vomiting in children and acute ischemic stroke in the presence of focal neurologic findings.

education of primary care physicians have led to a significant decrease in the time to treatment.7 Strategies to improve recognition and management of stroke are urgently required for the pediatric population as well. Importance Delays, which are a key factor affecting the performance of acute stroke interventions,8 have been documented in 4 recent retrospective pediatric studies of ischemic stroke from the United States, Canada, United Kingdom, and Australia.9-12 These delays are likely due a number of issues, including limited knowledge about stroke and lack of awareness about signs and symptoms in the community and among physicians9; stroke symptoms in children are frequently attributed to other problems such as migraine, encephalitis, tumors or Todd’s paralysis. In adults presenting with “brain attacks” (defined as apparently focal brain dysfunction of apparently abrupt onset), the use of clinical recognition tools by paramedics and emergency physicians has been shown to improve diagnostic accuracy in adults and to differentiate stroke from stroke mimics.13 Stroke symptoms in adults are well defined, and the probability of stroke in patients with brain attacks is high, accounting for 69% of cases in a recent study.14 In contrast, the presenting signs and symptoms of pediatric stroke have not been Volume , .  : August 

Pediatric Ischemic Versus Hemorrhagic Stroke fully defined; there is a lower a priori probability of stroke in children with brain attacks, and its differentiation from nonstroke disorders remains to be clarified. In particular, stroke studies in children have focused on acute ischemic stroke,9-12,14 yet children also present with hemorrhagic stroke.15 To our knowledge, there are currently no studies assessing the differences in presentation between arterial ischemic stroke and hemorrhagic stroke. This distinction will be a crucial element for the creation of a brain attack pathway and stroke recognition tools in children. Goals of This Investigation Our main goal was to determine the clinical characteristics of radiologically confirmed pediatric stroke on presentation to the emergency department (ED) of a tertiary hospital; specifically, to describe the major arterial ischemic and hemorrhagic stroke subtypes in children. We sought to also describe the results of different modes of neuroimaging used to diagnose these patients.

MATERIALS AND METHODS Study Design This was a retrospective, single-center case series of consecutive presentations of children with strokes to the ED of the Royal Children’s Hospital, Melbourne, Victoria, Australia, during a 5-year period between January 2003 and December 2008. Setting Royal Children’s Hospital is the tertiary pediatric referral center for the state of Victoria. Annual ED census is 67,000 and hospital census is 280,000 patients. The hospital ethics committee approved the study. Selection of Participants We included stroke patients aged 1 month to younger than 18 years who were admitted through our ED. We sought to focus on the presenting features of patients assessed in our ED regardless of whether they had been treated in another ED previously. Case identification for acute ischemic stroke was based on the Royal Children’s Hospital stroke registry, which commenced in 2002 and is the registry for the Royal Children’s Hospital, capturing all cases of acute ischemic stroke; and for hemorrhagic stroke, on a search of the hospital information system of discharge diagnoses with relevant International Classification of Diseases, 10th Revision (ICD-10) codes (ICD-10 codes 431 [intracerebral hemorrhage] and 432.9 [unspecified intracranial hemorrhage]). Patients were entered into the stroke registry after neurology consultations complemented by monthly searches of the hospital information system. Registry patients are not blinded. Patients identified were crossreferenced with a separate ED electronic hospital admission database to ensure that no patients were missed. We excluded stroke patients who did not present to the study ED (eg, direct admission to ICU or ward from another Annals of Emergency Medicine 157

Pediatric Ischemic Versus Hemorrhagic Stroke inpatient setting) but included patients transferred from another ED directly to our ED. Patients with neonatal stroke, traumatic brain hemorrhage, and cerebral sinovenous thrombosis were excluded from this study. We did not exclude patients who sustained an ischemic stroke after neck trauma with subsequent arterial dissection. Patients with incomplete medical records were also excluded. Acute ischemic stroke was defined as acute neurologic deficits lasting more than 24 hours and caused by cerebral ischemia, with neuroimaging showing parenchymal infarction, conforming to known arterial territories and corresponding to the clinical presentation.16 Transient ischemic attack was defined as a transient episode of neurologic dysfunction caused by focal brain ischemia in children with abnormal cerebrovascular imaging but without neuroimaging showing parenchymal infarction. Acute ischemic stroke and transient ischemic attack were combined for the purpose of analysis. Hemorrhagic stroke was defined as an acute neurologic deficit lasting more than 24 hours, with neuroimaging showing intracranial hemorrhage not associated with ischemic infarction. ED triage urgency was assessed with the national Australian Triage Scale.17 Patients with Australian Triage Scale categories 1, 2, 3, 4, and 5 are to be treated immediately, within 10, 30, 60, and 120 minutes, respectively. A pediatric modification of the Trial of Org 10172 in Acute Stroke Therapy (TOAST) classification system was used to define stroke subtypes, which include sickle cell disease, cardiac embolism, cervical arterial dissection, moyamoya disease, stenoocclusive cerebral arteriopathy, other determined cause, multiple probable/possible causes, and undetermined cause. All patients with undetermined cause had normal investigations, including cerebrovascular imaging, echocardiogram, and prothrombotic studies.18 Time from onset of symptoms to presentation was defined as the time when the parents or caregiver first became aware that the patient had symptoms to the time of triage in the ED at Royal Children’s Hospital.19 Data Collection and Processing Two researchers (A.Y.-C., F.E.B.) used a structured piloted standardized abstraction form to collect the data. The form was completed after a review of the medical charts. Data were abstracted from electronic ED records, written ED documents by ED and consulting neurology and neurosurgery staff, admission and progress notes, and laboratory and radiology reports. Data collected included demographics, age, medical history relevant for stroke, timing of onset of symptoms, presenting symptoms and signs in ischemic and hemorrhagic stroke, type of imaging, investigations, and interventions. Presenting signs and symptoms were extracted according to the first ED notes and the first neurologist’s or neurosurgeon’s notes. Clinical variables were predefined and selected on the basis of symptoms or signs that were found to be useful in discriminating stroke from stroke mimics in previous adult studies.14,16,20,21 If these variables could not be extracted from 158 Annals of Emergency Medicine

Yock-Corrales et al the medical records, they were recorded as missing. Portions of the data were abstracted by 2 investigators and entered twice. The abstractors, 2 emergency physicians (A.Y.-C. and F.E.B.), were unblinded to the purpose of the study. Disputes in terms of conflicting descriptions of signs and symptoms or final diagnosis were adjudicated by a child neurologist (M.T.M.). Interrater reliability was not formally assessed. Primary Data Analysis The differences between acute ischemic stroke and hemorrhagic stroke groups were assessed descriptively. Dichotomous variables are presented as percentages and 95% confidence intervals (CIs). Continuous variables are presented as mean and SD (normal distribution) or median and interquartile range (IQR) (non-normal distribution). For clinical findings, the denominator was variable, reflecting data not recorded or unable to be assessed (in patients with low Glasgow Coma Scale [GCS] score/intubation). Analysis was performed with Stata (version 10.0; StataCorp, College Station, TX).

RESULTS Search by ICD-10 codes and of the Royal Children’s Hospital stroke registry identified 88 relevant patients during the 5-year study period. A total of 81 patients were included in the study, 47 patients with acute ischemic stroke, 3 with transient ischemic attacks, and 31 with hemorrhagic stroke (Table 1). Cerebrovascular imaging abnormalities in the 3 children with transient ischemic attacks included Moyamoya syndrome, unilateral steno-occlusive vasculopathy, and vertebral artery dissection. Seven patients were excluded: 5 had incomplete documentation and 2 were transferred directly from other hospitals to inpatient neurology, neurosurgery, or ICU. Patients ranged in age from 4 months to 17 years, with a mean age of 7 years (SD 5.1) for acute ischemic stroke and 11 years (SD 4.2) for hemorrhagic stroke. Sixty percent (95% CI 49% to 71%) of patients arrived by ambulance and 32% (95% CI 22% to 43%) arrived by private car. High triage categories 1 and 2 were assigned to 58% (95% CI 39% to 75%) of hemorrhagic stroke patients and to 26% (95% CI 14% to 40%) of acute ischemic stroke patients. Forty-eight percent of patients with acute ischemic stroke (95% CI 33% to 62%) had pertinent medical history, as did 25% of patients with hemorrhagic stroke (95% CI 19% to 54%) (Table 1). Median time from onset of symptoms to the ED presentation was 21 hours (IQR 6 to 48 hours) for acute ischemic stroke and 12 hours (IQR 4 to 72 hours) for hemorrhagic stroke. Table 2 shows presenting complaints and neurologic examination findings. Most patients (82%; 95% CI 72% to 90%) in both groups presented with sudden onset of symptoms. Acute ischemic stroke presented with symptoms of focal limb weakness in 64% (95% CI 49% to 77%) of patients, facial weakness in 60% (95% CI 45% to 73%), speech disturbance in 46% (95% CI 31% to 60%), and limb incoordination/ataxia in 26% (95% CI 14% to 40%). Few patients with acute ischemic stroke presented with vomiting and altered mental status. Volume , .  : August 

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Table 1. Demographic characteristics of children with acute ischemic stroke and hemorrhagic stroke. Total, Nⴝ81 Variable Age, y, mean Age ⬍2 y Male sex Triage category* 1⫹2 3⫹4⫹5 Mode of arrival Arrival by ambulance From home Interhospital transfer Private car Public transport Other Medical history Healthy Migraine/headache Head/neck trauma † Previous stroke Family history of stroke Chickenpox Sickle cell disease Cardiac disease Others

n

%

AIS, Nⴝ50

HS, Nⴝ31

95% CI

N

%

95% CI

n

%

95% CI

8.7 10 41

12 50

SD 5.3 6–21 39–62

7.0 9 25

18 50

SD 5.1 8–31 35–64

11.4 1 16

3.2 52

SD 4.2 0–16 33–70

31 50

38 61

27–49 50–72

13 37

26 74

14–40 60–85

18 13

58 42

39–75 24–61

49 23 26 26 1 5

60 28 32 32 1.2 6

49–71 18–39 22–43 22–43 0–6 2–13

27 10 18 19 — 4

54 20 36 38 — 8

39–68 10–33 23–51 24–53 — 2–19

22 13 8 7 1 1

71 42 26 22 3.2 3.2

52–85 24–71 11–44 9–41 0–16 0–16

46 8 7 3 3 3 2 2 7

57 10 9 3.7 3.7 3.7 2.4 2.4 9

45–68 4–18 3–17 0–10 0–10 0–10 0–8 0–8 3–17

26 7 5 3 — 2 2 1 4

52 14 10 6 — 4 4 2 8

37–66 6–26 3–22 1–16 — 0–13 0–13 0–10 2–19

20 1 2 — 3 1 — 1 3

64 3.2 6.5 — 10 3.2 — 3.2 10

45–80 0–16 0–21 — 2–25 0–16 — 0–16 2–25

AIS, Acute ischemic stroke; HS, hemorrhagic stroke. *Triage categories: Australian Triage Scale.17 Patients with Australian Triage Scale category 1, 2, 3, 4, and 5 are to be treated immediately, within 10, 30, 60, and 120 minutes, respectively. † Included patients with moyamoya syndrome.

Hemorrhagic stroke presented with headache (73%; 95% CI 54% to 87%), vomiting (58%; 95% CI 40% to 75%), and altered mental status (48%; 95% CI 30% to 67%). Symptoms of focal weakness were present in only 35% (95% CI 19% to 54%) of patients; few presented with speech disturbances or limb incoordination/ataxia. On examination, most patients with acute ischemic stroke had a GCS score greater than 14 (86%; 95% CI 73% to 94%). No patients had a GCS score of 8 or less. Patients with acute ischemic stroke showed signs of facial weakness (70%; 95% CI 55% to 82%), limb weakness (62%; 95% CI 47% to 75%), and slurred speech (32%; 95% CI 19% to 47%). Most patients with acute ischemic stroke (88%; 95% CI 73% to 98%) presented with at least 1 focal neurologic sign (limb weakness, face asymmetry, slurred speech, visual defect or eye movement abnormality, ataxia, or focal numbness). GCS score in hemorrhagic stroke was less than 14 in 38% of patients and less than 8 in 19% (95% CI 7% to 37%). Less than one third of patients had focal limb weakness, facial weakness, or slurred speech. Table 3 shows neuroimaging, ED management, and subsequent medical and surgical interventions. Diagnoses of acute ischemic stroke and hemorrhagic stroke were confirmed with cranial computed tomography (CT) or magnetic resonance imaging (MRI). In the acute ischemic stroke group, 36 (72%; 95% CI 57% to 83%) received a CT Volume , .  : August 

scan as the initial imaging modality; it was nondiagnostic in 16 (44%) patients. Nineteen children had CTs before arrival at Royal Children’s Hospital, and 17 were performed at Royal Children’s Hospital within a median of 4 hours 20 minutes (IQR 3 to 5.3 hours) from arrival in the ED. MRI was performed for 47 (94%; 95% CI 83% to 98%) children with acute ischemic stroke as the first imaging modality in 14 children and after CT in 33 children. MRI confirmed stroke diagnosis in all cases. In 3 patients, MRI was not performed because 2 children had known moyamoya disease and the third patient had a pacemaker for central hypoventilation syndrome, which precluded imaging. In the hemorrhagic stroke group, 30 (96%; 95% CI 83% to 99%) patients had a noncontrast CT; 13 scans were performed before the patients’ arrival at Royal Children’s Hospital and 17 in the Royal Children’s Hospital ED within a median of 2 hours 26 minutes (IQR 1 to 4.1 hours) from arrival in the ED. CTs were diagnostic for hemorrhagic stroke in all patients. One patient had an external, diagnostic MRI; therefore, no CT was performed. As shown in Table 3, most patients ultimately also had an MRI performed for neurosurgical assessment and management. Six of 31 patients with hemorrhagic stroke were intubated in the ED (19%; 95% CI 7% to 37%) and admitted to the ICU (19%; 95% CI 7% to 37%). Ultimately, 45% (95% CI 27% to 63%) of hemorrhagic stroke patients required surgical Annals of Emergency Medicine 159

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Table 2. Clinical features between acute ischemic and hemorrhagic stroke in children. Total Variable Time to presentation ⬍6 h Well week before Sudden onset Woke from sleep Improvement since onset Worsening symptoms Focal limb weakness Facial weakness Limb incoordination/ataxia Speech disturbances Visual disturbances Focal numbness Vomiting Headache Altered mental status Seizure Fever No lateralizing symptoms Neurologic examination Glasgow Coma Scale score ⱖ14 9–13 ⱕ8 Limb weakness Facial asymmetry Could walk Slurred speech Visual defect/eye movement abnormality Sensory loss Ataxia No neurologic signs

AIS

HS

n

N*

% (95% CI)

n

N*

% (95% CI)

n

N*

% (95% CI)

30 75 67 18 13 47 43 41 15 27 14 5 27 44 24 15 6 38

81 81 81 81 81 81 81 81 81 80 78 80 81 77 81 81 80 81

37 (26–48) 92 (85–97) 82 (72–90) 22 (13–32) 16 (8–25) 58 (46–69) 53 (41–64) 50 (39–62) 18 (10–28) 33 (23–45) 18 (10–28) 6 (2–14) 33 (23–44) 57 (45–68) 29 (20–41) 18 (10–28) 7 (2–15) 47 (35–58)

15 44 41 11 9 27 32 30 13 23 7 4 9 22 9 8 5 18

50 50 50 50 50 50 50 50 50 50 48 50 50 47 50 50 49 50

30 (18–44) 88 (75–95) 82 (68–91) 22 (11–36) 18 (8–31) 54 (39–68) 64 (49–77) 60 (45–73) 26 (14–40) 46 (31–60) 14 (6–27) 8 (2–19) 18 (8–31) 46 (32–62) 18 (8–31) 16 (7–29) 10 (3–22) 36 (23–51)

15 31 26 7 4 20 11 11 2 4 7 1 18 22 15 7 1 20

31 31 31 31 31 31 31 31 31 30 30 30 31 30 31 31 31 31

48 (30–67) — 83 (66–94) 22 (9–41) 13 (3–30) 64 (45–80) 35 (19–54) 35 (19–54) 6 (0–21) 13 (3–30) 23 (9–42) 3 (0–17) 58 (40–75) 73 (54–87) 48 (30–67) 22 (9–41) 3 (0–17) 64 (45–80)

62 13 6 39 43 53 17 14 13 6 21

81 81 81 75 75 72 72 70 75 75 75

76 (65–85) 16 (8–25) 7 (2–15) 52 (40–63) 57 (45–68) 73 (62–83) 23 (14–35) 20 (11–32) 17 (9–28) 8 (3–16) 28 (18–39)

43 7 — 31 35 37 15 8 12 5 6

50 50 50 50 50 47 47 45 50 50 50

86 (73–94) 14 (5–26) — 62 (47–75) 70 (55–82) 78 (64–89) 32 (19–47) 17 (8–32) 24 (13–38) 10 (3–22) 12 (2–27)

19 6 6 8 8 16 2 6 1 1 15

31 31 31 25 25 25 25 25 25 24 25

61 (42–78) 19 (7–37) 19 (7–37) 32 (14–53) 32 (14–53) 64 (42–82) 8 (0–26) 24 (9–45) 4 (0–21) 4 (0–20) 60 (38–79)

*Denominator variable reflecting data not recorded or unable to be assessed (in patients with low GCS score/intubation).

Table 3. Interventions in children with acute ischemic and hemorrhagic stroke. AIS, Nⴝ50 Variable Intubation Admitted to ICU CT scan in ED MRI ⬍24 h MRI ⬎24 h

HS, Nⴝ31

n

%

95% CI

n

%

95% CI

— 2 36 37 10

— 4 72 74 20

— 0–13 57–83 59–83 10–33

6 6 30 14 8

19 19 96 45 25

7–37 7–37 83–99 27–64 11–44

CT, Computed tomography; MRI, magnetic resonance imagining.

“undetermined” type per the Paediatric Stroke Classification18 had negative prothrombotic test, cerebrovascular imaging, and echocardiogram results. The one patient classified as “possible cause” had a positive prothrombotic test result (anticardiolipin antibody) but otherwise no evidence of a connective tissue disorder. In the patients with acute ischemic stroke, the anterior circulation was affected in the majority of children, 68% (95% CI 53% to 80%). In the hemorrhagic stroke group, the majority, 48% (95% CI 30% to 67%), had arteriovenous malformations as the cause for the hemorrhage (Table 5).

LIMITATIONS intervention for intracranial bleeding. None of the acute ischemic stroke patients were intubated in the ED, and 2 of 50 were admitted to the ICU. Ninety-two percent of acute ischemic stroke patients received medical management in the form of anticoagulant or antiplatelet therapy (Table 4). In acute ischemic stroke, steno-occlusive arteriopathy was the most common cause of stroke in 36% (95% CI 23% to 50%) of children (Table 5). All 18 patients categorized as 160 Annals of Emergency Medicine

Ideally, this study would have prospectively identified and analyzed all patients presenting to the ED with acute neurologic deficit or change in mental status to determine the relevance of the presence or absence of signs and symptoms in determining the likelihood of stroke and its subtypes. The current study is also limited by the retrospective extraction of data from the charts, which may lead to erroneous measures of the frequency of signs and symptoms. Conflicting notes in the charts may lead to Volume , .  : August 

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Table 4. Treatment of children with acute ischemic and hemorrhagic stroke. AIS, Nⴝ50 Variable Medical treatment Anticoagulation* Unfractionated heparin LMWH Aspirin Warfarin Antiepileptic drugs Steroids Antihypertensive medication Surgical treatment* Resection of AVM⫹EVD Decompressive craniotomy Excision AVM Insertion EVD Balloon embolization Neck surgery Both surgical and medical None

HS, Nⴝ31

n

%

95% CI

n

46

92

80 to 97

15

48

29 14 28 1 5 4 —

58 28 56 2 10 8 —

43–72 16–42 41–70 0–10 3–21 2–19 —

1 1 1 — 10 4 2

3.2 3.2 3.2 — 32 12 6.4

0–16 0–16 0–16 — 16–51 3–29 5–33

1 — —

2 — —

0–10 — —

14 4 5

45 12 16

27–64 3–29 5–33

— — — 1 —

— — — 2

— — — 0–10

3 1 1 — 10

9.6 3.2 3.2 — 32

3

6

1–16

%

7

22

95% CI 30 to 66

2–25 0–16 0–16 16–51 9–41

LMWH, Low-molecular-weight heparin; AVM, arteriovenous malformation; EVD, external ventricular drain. *Some of the patients received more than 1 treatment.

Table 5. Causes of arterial ischemic stroke and hemorrhagic stroke in children.* n AIS, Nⴝ50 Circulation Completed anterior Completed posterior Anterior and posterior TIA anterior (2) TIA posterior (1) Pediatric stroke classification* Steno-occlusive arteriopathy Undetermined Moyamoya syndrome Arterial dissection Cardioembolic Possible cause HS, Nⴝ31 Causes of HS AVM Subarachnoid hemorrhage Vertebral artery dissection Cavernous venous malformation Undetermined

%

95% CI

34 12 1 3

68 24 2 6

53–80 13–38 0–10 0–16

18 18 7 5 1 1

36 36 14 10 2 2

23–50 23–50 5–26 3–22 0–10 0–10

15 4 2 2 8

48 12 6.4 6.4 25

30–67 3–30 0–21 0–21 11–44

TIA, Transient ischemic attack. *Pediatric stroke classification subtypes.18

further errors, although we focused on the first emergency physician and the first neurologist or neurosurgeon notes. Because of the retrospective methodology, we cannot rule out that notes were written or added to after neuroimaging Volume , .  : August 

results were known. Signs and symptoms in stroke patients may also evolve and change. In addition, acute ischemic stroke patients were identified in a prospective registry and hemorrhagic stroke patients were identified by a retrospective ICD-10 search, which may have been incomplete. Efforts were made to minimize this error by cross-searching the records with the electronic administrative system in the ED. Finally, the data were from a tertiary pediatric referral hospital; therefore, results may not be generalizable to the pediatric population as a whole.

DISCUSSION To our knowledge, this is the first study to describe presenting features of both acute arterial ischemic and hemorrhagic stroke in childhood. The key findings of this study are that symptoms and signs of pediatric acute ischemic stroke and hemorrhagic stroke are different and that CT imaging has limited sensitivity in detecting acute ischemic stroke. Management requirements in the acute care setting differ for acute ischemic stroke and hemorrhagic stroke in terms of the need for tracheal intubation and intensive care admission. This study has confirmed that focal weakness and speech disturbance are common presenting symptoms and that face and limb weakness are common presenting signs in pediatric acute ischemic stroke. Similar findings have been reported in previous pediatric studies, but less detail was provided because the studies were more focused on describing reasons for delayed diagnosis rather than the constellation of presenting symptoms and signs.9,10,12,22 Seizures were present in just 16% of patients with acute ischemic stroke. This proportion is well below the level previously reported (⬎50%).23,24 The clinical variables selected for this study were based on those found to be useful in discriminating stroke from stroke mimics in adult studies because little is known about the presentation of pediatric stroke. Our study suggests that pediatric acute ischemic stroke has presenting features similar to those of adult acute ischemic stroke. More than half of our patients presented with symptoms of acute-onset limb weakness or speech disturbance, and less than one quarter presented with symptoms of focal numbness or visual disturbance, both findings similar to those of adult studies of acute ischemic stroke.14,21 The lower incidence of visual defect and numbness may in part be due to the difficulty in assessing children, particularly young children. Hemorrhagic stroke accounts for approximately half of stroke in childhood.15 In our study, 38% of children presented with hemorrhagic stroke. The majority were previously healthy, in contrast to nontraumatic adult hemorrhagic stroke, in which hypertension is a major risk factor.25,26 There is little published on the clinical presentation of pediatric hemorrhagic stroke. Symptoms described include headache, vomiting, decreased level of consciousness, and seizures,26-29 similar to symptoms reported in adults.27 All children in our study who had a GCS score less than 9 also had a diagnosis of hemorrhagic stroke, and half did not have focal neurologic signs. A recent study of Annals of Emergency Medicine 161

Pediatric Ischemic Versus Hemorrhagic Stroke pediatric hemorrhagic stroke found that age younger than 1 year and male sex were predictors of poor outcome at 30 days. In contrast, presenting signs and symptoms, such as headache, emesis, seizures, focal deficits, altered mental status, and GCS score less than 9, were not significant predictors of poor outcome.15 To our knowledge, there are no published data describing delays to diagnosis of pediatric hemorrhagic stroke. In this study, time to diagnosis was shorter for hemorrhagic stroke than acute ischemic stroke, even though children were less likely to present with focal signs, which may be partly explained by the fact that many hemorrhagic stroke patients presented with a severely altered conscious state. Two thirds of hemorrhagic stroke patients arrived by ambulance, and the majority had high (Australian Triage Scale score 1 or 2) triage categories on arrival, which would prompt rapid ED assessment. We suspect that rapid assessment and diagnosis may be associated with increased awareness among emergency staff that vomiting, headache, and altered conscious state are indicators of serious intracranial pathology, warranting urgent neuroimaging. All our patients had a neuroimaging test confirming stroke diagnosis. In the hemorrhagic stroke group, median time from triage assessment to neuroimaging was 2 hours 26 minutes. In contrast, median time from triage assessment to CT imaging for acute ischemic stroke was 4 hours 20 minutes; to MRI, 15 hours. The more rapid imaging in hemorrhagic stroke may be explained by the higher triage category and higher suspicion of serious intracranial pathology. CT identified all cases of hemorrhagic stroke but identified only about half the cases of acute ischemic stroke, which is consistent with a recent study reporting limited diagnostic utility of CT in children with acute ischemic stroke9 and suggests that urgent MRI is the best imaging modality for detection of acute ischemic stroke. Unfortunately, this is a major time-limiting step because of limited access to urgent MRI and the need for sedation or general anesthesia in children younger than 5 years. Recommendations about anticoagulant and antithrombolytic therapy in adult acute ischemic stroke are based on strong evidence from randomized controlled trails.30,31 In contrast, there is a paucity of data for children, and the variable treatment of our patients reflects the fact that recommendations on acute interventions and secondary prevention treatments are only at an expert consensus level and not based on clinical trials.32,33 Current evidence is not such that extrapolation of adult therapies to pediatric ischemic strokes should be advocated. A multicenter study to establish safe and appropriate tissue plasminogen activator dosing in the pediatric population is planned in the near future.34 Acute thrombolysis was not administered to any of our patients with acute ischemic stroke. An important obstacle to thrombolytic treatment in children is the delay to stroke diagnosis, as set out in recent retrospective pediatric studies.9-12 Out-of-hospital factors, including parent’s help-seeking action (ie, not bringing their children directly to the ED), 162 Annals of Emergency Medicine

Yock-Corrales et al nonambulance transport, and nonabrupt onset of symptoms, contributed to delayed stroke diagnosis in the Canadian and US studies.10,11 Inhospital factors, including lack of awareness among physicians, also contributed to delayed stroke diagnosis in the Australian and UK studies.9 Best practice for the emergency treatment of acute stroke patients includes rapid recognition and response to warnings signs in the community, rapid ambulance transport with hospital notification, and rapid diagnosis and treatment in the hospital.35 As highlighted in consensus guidelines, there is an urgent need for more rapid identification of stroke symptoms in children in the out-ofhospital setting and on arrival in the ED. There are currently no validated pediatric stroke recognition tools for use by emergency physicians or paramedics. In this study of stroke patients presenting to the ED, we found that the presenting symptoms and signs of acute ischemic stroke in childhood are similar to those of acute ischemic stroke in adults with sudden-onset focal findings. Pediatric hemorrhagic stroke differs from acute ischemic stroke in particular in lower GCS scores and fewer focal symptoms and signs. CT is still considered to be the modality of choice in the emergency setting to detect the presence of hemorrhage acutely after the onset of symptoms, but MRI may be the more appropriate first-line neuroimaging modality to confirm the diagnosis of acute ischemic stroke. This data set will inform the development of brain attack protocols in the ED and modification of adult stroke recognition tools. The development of a brain attack clinical pathway may improve identification of stroke patients and allow differentiation of stroke from other acute neurologic conditions. It may also aid rapid triage, medical assessment, and neuroimaging, potentially increasing the feasibility of thrombolytic therapy for ischemic stroke and rapid neurosurgical intervention in children for hemorrhagic stroke. Supervising editor: Kathy N. Shaw, MD, MSCE Author contributions: AY-C was responsible for data analysis. AY-C and FEB were responsible for drafting of the article. AY-C, MM, IM, and FEB were responsible for study design. AY-C, MM, and WM were responsible for data collection. MM and FEB were responsible for funding. MM, IM, WM, and FEB were responsible for draft review. FEB was responsible for ethics application. FEB takes responsibility for the paper as a whole. Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). Grant support from the National Stroke Foundation, Melbourne, Australia, and the Murdoch Children’s Research Institute, Melbourne, Australia. Publication dates: Received for publication May 12, 2010. Revisions received July 19, 2010, and September 27, 2010. Accepted for publication October 25, 2010. Available online February 18, 2011. Volume , .  : August 

Yock-Corrales et al Address for correspondence: Franz E. Babl, MD, MPH, FRACP, FAAP, Emergency Department, Royal Children’s Hospital, Melbourne, Victoria, Australia; 61-3-9345-6153, fax 61-3-9345-6006; E-mail [email protected].

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