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Pediatric stroke in the emergency department

Abstract Strokes are more commonly seen in adults but also occur in the pediatric population. Similar to adult strokes, pediatric strokes are considered medical emergencies and require prompt diagnosis and treatment to maximize favorable outcomes. Unfortunately, the diagnosis of stroke in children is often delayed, commonly because of parental delay or failure to consider stroke in the differential diagnosis. Children, especially young children, often present differently than adults. Much of the treatment for pediatric strokes has been adapted from adult guidelines but the optimal treatment has not been clearly defined. In this article, we review pediatric strokes and the most recent recommendations for treatment.

of perinatal strokes are AIS although CSVT and hemorrhagic strokes can occur. Agrawal et al identified a prevalence of perinatal AIS of 29 per 100,000 live births. This increased to 37 per 100,000 live births when perinatal hemorrhagic strokes were included. 2 Fullerton et al identified an incidence of first-time childhood stroke of 2.3 per 100,000 children (1.2 with AIS and 1.1 with hemorrhagic stroke). When further divided into age subgroups, infants (>30 days but <1 year of age) had the highest annual stroke rates including AIS and hemorrhagic strokes. Late teens (15 to 19 years of age) had the second highest annual stroke rates. When hemorrhagic strokes were further divided into intracerebral hemorrhage and subarachnoid hemorrhage, late teens actually had the highest rate of subarachnoid hemorrhage. Boys had a higher risk of strokes than girls. Black children had greater than twice the risk of stroke compared to white children. After patients with sickle cell disease were excluded, black children still had a 61% increased risk. Asian children had a similar risk to white children and Hispanic children had a lower risk. 3 There is frequently a delay in the diagnosis of stroke in pediatric patients with multiple studies showing a median time from onset of symptoms to diagnosis of AIS of >20 hours. [4][5][6] A neurologic deficit in young children may be subtle and parents may delay seeking care. Additionally, stroke is often misdiagnosed or not initially considered in the differential diagnosis. Rafay et al found that stroke was suspected by the initial physician in only 38% of patients who were ultimately diagnosed with AIS. 4 Strokes in children, as in adults, are a medical emergency and should be treated rapidly to maximize favorable outcomes.
There is a paucity of data regarding morbidity and mortality because of delays in treating strokes in children. However, the adult literature has shown that earlier thrombolytic treatment for AIS is associated with decreased in-hospital mortality as well as decreased disability. 7,8 In an effort to improve the treatment of pediatric strokes, pediatric centers have emulated adult stroke centers and have developed acute stroke protocols. 9,10 In one study, the development of a stroke alert protocol decreased the median time to diagnosis by over one half for children who presented to the emergency department with acute neurologic deficits. 9

PERINATAL STROKES
We discuss perinatal strokes separately because they often present differently than childhood strokes and are poorly understood.

Arteriopathies
Arteriopathies account for the majority of childhood AIS. Patients with an arteriopathy have a 5-fold increased risk of recurrent stroke compared to patients with an idiopathic AIS. 15 Arteriopathies include focal cerebral arteriopathies, arterial dissection, moyamoya, and vasculitides.
Focal cerebral arteriopathies (FCA) are unifocal and unilateral irregularities of the large intracranial arteries. FCA is further divided into FCA-d, or dissection type, which refers to intracranial arterial dissection, and FCA-i, or inflammation type, which refers to FCA that is presumed to be inflammatory. 16 In cases of FCA-i, it is thought that an infectious process leads to local vascular inflammation, which then leads to thrombus formation and stroke. Recent upper respiratory infection is a positive predictor of having an FCA-i, suggesting that infection could promote a proinflammatory or procoagulant effect. 17,18 Infection with varicella zoster virus, in particular, has been labeled postvaricella arteriopathy and has been shown to increase the risk of stroke for 6 months following infection. 19 Extracranial arterial dissection is another important cause of AIS.
Over half of patients with arterial dissection experience concurrent or recent trauma but a significant percentage occur spontaneously. Connective tissue and genetic disorders can also predispose to dissection. 20 Moyamoya ("puff of smoke" in Japanese) disease is caused by stenosis of the internal carotid arteries at the base of the brain along with the development of collateral vessels, which give the appearance of a puff of smoke. Lee  defects, Ebstein anomaly, arrhythmias, and cardiomyopathy secondary to myocarditis. 22 Additionally, patients who undergo cardiac catheterization or cardiac surgery are at an increased risk. 23,24 Patients who require ventricular assist devices are also at an increased risk of AIS although hemorrhagic strokes can occur. 25,26

Sickle cell disease
One disease that deserves special attention is sickle cell disease.
Patients with sickle cell disease are at risk for developing a vasculopathy, typically of the internal carotid and middle cerebral arteries, which places them at an increased risk for stroke, especially AIS. The development of screening with transcranial Doppler (TCD) to identify elevated cerebral blood flow has led to chronic red blood cell transfusion therapy and a significantly decreased risk of stroke. In a study evaluating the incidence of stroke since instituting TCD screening and chronic transfusion therapy, 2.1% of patients still had AIS. A significant number of these patients had abnormal TCD velocities and the majority had a lack of appropriate TCD screening or insufficient chronic transfusion therapy. 27

Cerebral sinus venous thrombosis
CSVT is a rare but important cause of pediatric stroke. Thrombosis leads to elevated venous pressure, which can lead to secondary ischemia and infarction. Hemorrhagic transformation can also occur.
In one study, the incidence of CSVT was 0.67 cases per 100,000 pediatric patients with 43% neonates and 54% < 1 year of age. The majority of patients had a risk factor but they were different depending on the age. For neonates, the majority had a perinatal complication such as hypoxic encephalopathy. In preschool children, head and neck infections such as otitis media, sinusitis, and mastoiditis were significant risk factors. Dehydration was an important risk factor in all ages. Prothrombotic states have also been associated with CSVT. 28   Migraines are the most common stroke mimic. Mackay et al found that 28% of pediatric patients with stroke symptoms were diagnosed with migraines. 42 In a study comparing pediatric AIS patients to migraine patients, children with migraines were significantly older than those with AIS with a median age of 13 years for migraine patients and 5 years for AIS patients. Sudden symptom onset was more frequent in AIS patients whereas symptoms occurred more gradually in migraine patients. Visual and sensory disturbances were more frequent in migraine patients as were vomiting and resolution of neurologic deficits before emergency department assessment. 43

DIAGNOSTIC STUDIES
Urgent neuroimaging is essential for rapid diagnosis and timely intervention. MRI of the brain is the preferred initial study and could iden-

Sensory
For children too young or otherwise uncooperative for reporting gradations of sensory loss, observe for any behavioral response to pin prick, and score it according to same scoring scheme as a "normal" response, "mildly diminished," or "severely diminished" response 0 = Normal; no sensory loss 1 = Mild to moderate sensory loss; patient feels pinprick is less sharp or is dull on the affected side; or there is a loss of superficial pain with pinprick but patient is aware he/she is being touched 2 = Severe to total sensory loss; patient is not aware of being touched in the face, arm, and leg 9. Best language For children 2-6 years or older children with premorbid language disability, item scored based on observations of language comprehension and speech during preceding examination 0 = No aphasia, normal 1 = Mild to moderate aphasia 2 = Severe aphasia 3 = Mute, global aphasia; no usable speech of auditory comprehension. 10. Dysarthria 0 = Normal 1 = Mild to moderate; patient slurs at least some words and, at worst, can be understood with some difficulty 2 = Severe; patient's speech is so slurred as to be unintelligible or is mute/anarthric 9 = Intubated or other physical barrier (Continues)

TA B L E 3 (Continued)
Examination Score 11. Extinction and inattention 0 = No abnormality 1 = Visual, tactile, auditory, spatial, or personal inattention or extinction to bilateral simultaneous stimulation in 1 of the sensory modalities 2 = Profound hemi-inattention to more than 1 modality. Does not recognize own hand or orients to only 1 side of space F I G U R E 1 Imaging and labs for suspected pediatric stroke. 44,46,47 Imaging adapted from the International Paediatric Stroke Study Neuroimaging Consortium. 44 MRI, magnetic resonance imaging; DWI, diffusion weighted imaging; ADC, apparent diffusion coefficient; GRE, gradient echo; SWI, susceptibility weighted imaging; CT, computed tomography; MRA, magnetic resonance angiography; CTA, computed tomography angiogram; CBC w/diff, complete blood count with differential; BUN, blood urea nitrogen; Cr, creatinine; PT/INR, prothrombin time/international normalized ratio; PTT, partial thromboplastin time; Retic, reticulocyte if the administration of thrombolytics is being considered. Many centers have developed rapid or abbreviated brain MRI protocols, which can be completed in a shorter time than conventional MRIs. This allows for more rapid diagnosis and may allow for MRIs to be performed in pediatric patients who would otherwise require sedation. These protocols typically include diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps to diagnose ischemic stroke as well as gradient echo (GRE) sequences or susceptibility-weighted imaging (SWI) to detect hemorrhage. 44 The International Paediatric Stroke Study Neuroimaging Consortium devised an imaging protocol for children aged 29 days to 18 years with suspected stroke (Figure 1). Christy et al looked at children who were admitted with acute AIS. Children received either a computed tomography (CT) head, a full MRI, an abbreviated MRI consisting of T-2-weighted fast spin-echo images + DWI sequence, or a combination of CT and MRI. This was a small study but the abbreviated MRI protocol was 100% sensitive for detecting AIS. The abbreviated MRI protocol did miss a small petechial hemorrhage on one patient. However, their abbreviated protocol did not include GRE or SWI sequences, which are more sensitive at detecting hemorrhage. 45 If there are contraindications to MRI, MRI is not readily available, or the patient is unstable or uncooperative, then non-contrast head CT should be performed along with CT angiogram (CTA) of the head and neck. If the CT studies are not diagnostic, an MRI would still need to be performed because of the poor sensitivity of CT for pediatric AIS. In one series, CT diagnosed AIS in only 53% of cases. 4 If CTA or MRA are not diagnostic in a patient with a strong suspicion of arteriopathy, conventional catheter angiogram may be required. 44 In addition to imaging, standard laboratory studies are typically ordered (Figure 1). 46,47 Other tests should be ordered based on the patient's presentation.

TREATMENT
Initial treatment always consists of the ABCs (airway, breathing, and circulation

Arterial ischemic stroke
There are limited data on the effects of hypertension, fever, and glucose control in pediatric AIS patients but it is reasonable to follow the adult stroke guidelines. It is unclear whether hypertension after stroke leads to higher mortality or morbidity. In one study of pediatric patients with AIS, hypertension was associated with increased mortality and increased length of stay. 49

Sickle cell disease
Exchange transfusion is the treatment of choice for sickle cell disease patients with AIS with a goal of decreasing the percentage of hemoglobin S to <30%. If the patient's initial hemoglobin is <10 g/dL, a simple blood transfusion can be started but the hemoglobin should not go above 11 g/dL to avoid hyperviscosity or volume overload.
Exchange transfusion will still be necessary in order to decrease the percentage of hemoglobin S to the goal of <30%. If the patient's initial hemoglobin is already >10 g/dL, exchange transfusion should be the initial treatment. 13,47 Hulbert et al found that children with sickle cell disease with a stroke who received only a simple transfusion had a 50-fold greater incidence of recurrent stroke compared with those who received exchange transfusion. 57 Additionally, oxygen should be given to keep oxygen saturation >95%. If febrile, antipyretics and empiric intravenous antibiotics should be given. 13,47

OUTCOMES
A recent study, using data from the International Pediatric Stroke Study registry, looked at the outcomes of pediatric patients with AIS at discharge and at 2 years following the stroke. Death occurred before hospital discharge in 1.5% of neonates and 3.3% of non-neonates. At 2 years, the majority of patients had a normal outcome and 24.7% had moderate or severe neurological impairment. Neonates had the best outcomes both at discharge and at 2 years. However, there was a small increase in the number of neonates with impairment at 2 years because of deficits that emerged during the rapid development of the first 2 years of life. When patients were further divided into age subgroups, there was a U-shaped curve in outcomes at 2 years with neonates faring the best followed by patients aged 15-18 years.
Patients aged 1 month to 1 year had the worst outcomes. 58

SUMMARY
Strokes also occur in the pediatric population and actually occur most commonly in the perinatal period. Although many pediatric stroke patients will present similarly to adults, the emergency physician must also consider the possibility of stroke in pediatric patients who present with seizures or altered mental status, especially in younger patients.