Pediatric stroke: Risk factors and diagnostic challenges

February 1, 2015

Recent data indicate that the incidence of stroke in the pediatric population is much higher than previously estimated, and the explanation may be multifactorial, including more accurate methods of ascertainment as well as increased recognition because of greater awareness and advances in imaging.

Recent data indicate that the incidence of stroke in the pediatric population is much higher than previously estimated, and the explanation may be multifactorial, including more accurate methods of ascertainment as well as increased recognition because of greater awareness and advances in imaging.1,2 However, pediatric stroke is still uncommon, with an incidence rate calculated at between 2 and 13 per 100,000 person-years.3

Despite its low incidence, stroke represents a leading cause of mortality among children and is associated with significant costs and morbidity. Stroke ranks among the top 10 causes of death in children4 and carries an average cost exceeding $80,000 for acute care.5 Moreover, children who have suffered a stroke continue to accrue higher healthcare costs than their unaffected counterparts. Up to 25% of untreated children will have a recurrence, and two-thirds suffer long-term cognitive, behavioral, and functional deficits accompanied by socioeconomic burdens.1,6

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Although awareness about pediatric stroke seems to be growing, for a variety of reasons, the diagnosis is often delayed or even missed.7-10 Index of suspicion among families and healthcare providers may be low because of the relative infrequency of stroke in children and because the risk factors for stroke and its presenting features are different in children than in adults. In addition, there is a broader differential diagnosis for the presenting signs of pediatric stroke, and it may be mistaken for stroke mimickers, of which there are many. However, in 1 study of 143 patients seen by the stroke consult team at a tertiary center, only 21% of the children had stroke mimics.11 Timely diagnosis also may be limited by access to appropriate neuroimaging, and the impetus for rapid diagnosis may be lessened by the lack of established hyperacute therapies.

Understanding of the presenting features, etiology, and risk factors of pediatric stroke can help practicing physicians recognize children who may have suffered a stroke and thereby enable prompt and proper diagnostic evaluation. This information also should allow targeted education for families/caregivers of high-risk children about the warning signs and the urgency of seeking medical care. Finally, understanding the risk factors can guide an appropriately thorough history and examination of the patient who has suffered a stroke so that predisposing issues are identified. The latter information may allow for interventions that can reduce the risk of recurrence and also may have prognostic significance for determining recurrence risk and timing.12

 

 

Clinical features

This article focuses on “childhood stroke,” which encompasses children aged 1 month to 18 years. The risk of stroke is highest in children aged younger than 1 year, and particularly during the perinatal period.13

According to different definitions, perinatal stroke describes events occurring from 20 to 28 weeks’ gestation through 7 to 28 days after birth. Perinatal strokes are mostly arterial ischemic events,3 but cerebral venous sinus thrombosis (CVST) occurs more often in neonates than in children of any other age group.14 Perinatal stroke often presents with recurrent focal seizures. Other signs include apnea, poor feeding, and lethargy. However, up to 40% of perinatal stroke patients may have no symptoms.15 Thus, suspicion for a problem may not arise until the child is older and begins to show a tendency to favor one side of the body or develop other motor signs or developmental or learning delays.

Clinical manifestations of childhood stroke vary depending on stroke type and the individual’s age. However, certain signs and symptoms should raise an index of suspicion that a stroke has occurred (Table 1).16

 

ARTERIAL ISCHEMIC STROKE

Manifestations of childhood arterial ischemic stroke (AIS) may be minimal and transient, but typically include seizures, headache, vomiting, and hemiparesis with or without facial palsy.12,17 Dysphasia, ataxia, dysarthria, and visual deficits may be present depending on the area of ischemic involvement. Neonates and infants who have experienced an AIS are particularly likely to develop seizures, altered mental status, and apnea. Irritability, lethargy, and poor feeding also may be observed; focal neurologic deficits may be less noticeable for developmental reasons.18,19 Although seizures are also a common feature in older children with AIS, they may develop hours to even days after the stroke rather than as an immediate manifestation.17

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Certain features provide diagnostic clues. For example, sudden-onset “thunderclap” headache or severe pain affecting the neck, shoulder, or occipital region may indicate cervical artery dissection. When the neurological symptoms have a more insidious rather than abrupt onset and exhibit a progressive, fluttering, or recurrent course, the AIS may have an arteriopathic origin.20 Children with a headache accompanied by neurological deficits may not be concerned by the latter when the cause is AIS whereas children experiencing hemiplegic migraine tend to be frightened by any functional loss.17

 

HEMORRHAGIC STROKE

Presenting signs of pediatric hemorrhagic stroke also vary by age. Abrupt onset is characteristic, but the signs may be subtle and nonspecific in infants, depending on the site of the hemorrhage and its size.3,18 Older children in particular may present with headache, vomiting, and rapid decline of neurological function along with focal neurologic signs. Altered mental status and seizures often are seen in children aged younger than 6 years.18

 

CEREBRAL VENOUS SINUS THROMBOSIS

Signs of CVST include seizures, increased intracranial pressure, and headache.3 It also may be associated with hydrocephalus; subdural effusion or hematoma; subarachnoid or intracranial hemorrhage; or infarction.

 

 

Etiology and risk factors

The list of causes and risk factors for childhood stroke is long and varies depending on stroke type and the child’s age. Importantly, children often have more than 1 risk factor that compounds their risk for stroke or stroke recurrence.

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Cerebral arteriopathies, vasculopathies, and cardiac disease (congenital and acquired) represent the leading risk factors/causes for AIS in children. Others include a variety of hematologic disorders and coagulopathies, infection, metabolic disorders, iron deficiency, trauma, medications, and migraine (Table 2).1,12,17 Of note, significant infection, such as meningitis and sepsis as well as varicella, has long been recognized as a risk factor for stroke. However, stroke also has been reported in children with more minor infections.17

Hemorrhagic strokes in children include spontaneous intracerebral hemorrhage and nontraumatic subarachnoid hemorrhage. Cerebral vascular abnormalities (arteriovenous malformation, cavernous malformation, and aneurysms) are the leading causes for these events, accounting for between 40% and 90% of pediatric hemorrhagic strokes.12 Other less common causes include hematologic or clotting disorders (sickle cell disease, thrombocytopenia, hemophilia, von Willebrand disease, coagulopathy secondary to hepatic dysfunction or vitamin K deficiency) and hypertension. However, in various studies, childhood intracerebral hemorrhage was idiopathic in up to 23% of cases.12
 

 

Neuroimaging diagnosis

Table 3 summarizes the role of the various neuroimaging modalities for suspected pediatric stroke.18

The most sensitive technique for diagnosing AIS is diffusion-weighted magnetic resonance imaging (MRI) of the brain, which also affords an accurate determination of the area of the infarct and differentiates acute from chronic lesions, and which has a role in diagnosing some common stroke mimics in children.12,17,18 However, there are challenges to obtaining MRI. Image acquisition requires the patient to hold still for a long time, and so sedation or anesthesia may be necessary in younger children. In addition, some children may be too ill to undergo the imaging.

There is more likely to be emergency access to computed tomography (CT), which also has the benefit of not requiring sedation. In addition, CT is considered the preferred technique for detecting hemorrhage. However, MRI can also detect hemorrhage with the appropriate techniques added to the standard imaging protocol, and CT has low sensitivity for detecting acute AIS. In 1 study including 74 children, CT missed the diagnosis of AIS in 84% of cases while AIS was confirmed by MRI in all the children.8

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In addition to MRI, the diagnostic evaluation of pediatric patients with suspected AIS or hemorrhagic stroke should include vascular imaging of the brain and neck vessels. Magnetic resonance angiography (MRA) is considered first-line for AIS; magnetic resonance venography (MRV) should be performed if venous infarction or CVST is suspected; and MRI, MRA, and MRV should be done when possible in children with hemorrhagic stroke.12

Since acute hemorrhage can occlude detection of brain arteriovenous malformations, repeat vascular imaging should be considered after any parenchymal hematoma has reabsorbed in cases where the initial studies are negative or inconclusive.12

Computed tomography angiography and CT venography also can be used to detect vascular abnormalities. Relative to the MR techniques, the CT imaging is more readily available; can be completed quickly, thus obviating the need for sedation; and may provide better visualization of vascular structures.21 However, factors offsetting those advantages include exposure to ionizing radiation and iodinated contrast agents as well as the practical difficulties associated with delivery of contrast agents.12 Nevertheless, CT may be preferred if patients are unstable or when acute intracranial hemorrhage seems likely, and it becomes the only option if the child has any contraindications to MRI (eg, presence of cochlear implants, cardiac pacemakers).18

Cranial ultrasound has a role in infants whose anterior fontanel is not yet closed, but it is even less sensitive than CT for detecting AIS.

Catheter (conventional) angiography represents the most accurate imaging modality for assessing cerebral vasculature, but it is an invasive procedure that usually requires general anesthesia in children. The risks of complications are particularly high in children aged younger than 1 year, and it is not often used.3 However, there are certain situations in which conventional angiography may be considered (Table 3).18

Additional diagnostic evaluations

The diagnostic workup of pediatric stroke patients also aims to identify underlying etiologies. In children with AIS, workup should include electrocardiogram to determine the cardiac rhythm and Holter or telemetry monitoring when arrhythmia is suspected.12,17 Echocardiography also should be performed to identify structural or functional abnormalities.17

A basic laboratory evaluation of childhood AIS comprises assessment of thrombosis, inflammation, and autoimmune disease markers along with a blood lipid profile, and it should include a complete blood count, erythrocyte sedimentation rate, C-reactive protein, fasting lipid profile, antinuclear antibody levels, and a basic thrombophilia screen.12 A toxicology screen, looking for cocaine, heroin, or sympathomimetic drug use, and pregnancy testing in girls of childbearing potential should also be considered.12,17

In children with hemorrhagic stroke, laboratory testing to identify risk factors for bleeding should include platelet count, basic clotting studies, and activated partial thromboplastin time.12

In all cases, additional testing is guided by medical history and clinical presentation.
 

Conclusion

Despite its prominence as a cause of morbidity and mortality among children, pediatric stroke is an underrecognized problem. Limited awareness in the community and among healthcare professionals results in delays in diagnosis that may affect patient outcomes. Community pediatricians can play an important part in ensuring children receive prompt and proper care by refreshing their knowledge of the risk factors and presenting features of stroke in children.

 

REFERENCES

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2. Agrawal N, Johnston SC, Wu YW, Sidney S, Fullerton HJ. Imaging data reveal a higher pediatric stroke incidence than prior US estimates. Stroke. 2009;40(11):3415-3421.

3. Roach ES, Golomb MR, Adams R, et al; American Heart Association Stroke Council; Council on Cardiovascular Disease in the Young. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke. 2008;39(9):2644-2691. Erratum in: Stroke. 2009;40(1):e8-e10.

4. National Vital Statistics System, National Center for Health Statistics, Centers for Disease Control and Prevention (CDC). 10 leading causes of death by age group, United States-2012. CDC website. http://www.cdc.gov/injury/wisqars/pdf/leading_causes_of_death_by_age_group_2012-a.pdf. Accessed January 23, 2015.  

5. Gardner MA, Hills NK, Sidney S, Johnston SC, Fullerton HJ. The 5-year direct medical cost of neonatal and childhood stroke in a population-based cohort. Neurology. 2010;74(5):372-378.

6. Jones BP, Ganesan V, Saunders DE, Chong WK. Imaging in childhood arterial ischaemic stroke. Neuroradiology. 2010;52(6):577-589.

7. Martin C, von Elm E, El-Koussy M, Boltshauser E, Steinlin M; Swiss Neuropediatric Stroke Registry study group. Delayed diagnosis of acute ischemic stroke in children-a registry-based study in Switzerland. Swiss Med Wkly. 2011;141:w13281.

8. Srinivasan J, Miller SP, Phan TG, Mackay MT. Delayed recognition of initial stroke in children: need for increased awareness. Pediatrics. 2009;124(2):e227-e234.

9. Rafay MF, Pontigon AM, Chiang J, et al. Delay to diagnosis in acute pediatric arterial ischemic stroke. Stroke. 2009;40(1):58-64.

10. Gabis LV, Yangala R, Lenn NJ. Time lag to diagnosis of stroke in children. Pediatrics. 2002;110(5):924-928.

11. Shellhaas RA, Smith SE, O'Tool E, Licht DJ, Ichord RN. Mimics of childhood stroke: characteristics of a prospective cohort. Pediatrics. 2006;118(2):704-709.

12. Jordan LC, Hillis AE. Challenges in the diagnosis and treatment of pediatric stroke. Nat Rev Neurol. 2011;7(4):199-208.

13. Children’s Hemiplegia and Stroke Association. Pediatric stroke. Available at http://www.chasa.org/medical/pediatric-stroke/. Accessed January 23, 2015.

14. deVeber G, Andrew M, Adams C, et al; Canadian Pediatric Ischemic Stroke Study Group. Cerebral sinovenous thrombosis in children. N Engl J Med. 2001;345(6): 417-423.

15. Basu AP. Early intervention after perinatal stroke: opportunities and challenges. Dev Med Child Neurol. 2014;56(6):516-521.

16. International Alliance for Pediatric Stroke. Strokes can happen at any age. Available at: http://www.iapediatricstroke.org/infographic.pdf. Accessed January 23, 2015.

17. Steinlin M. A clinical approach to arterial ischemic childhood stroke: increasing knowledge over the last decade. Neuropediatrics. 2012;43(1):1-9.

18. Freundlich CL, Cervantes-Arslanian AM, Dorfman DH. Pediatric stroke. Emerg Med Clin N Am. 2012;30(3):805-828.

19. Kirton A, Armstrong-Wells J, Chang T, et al; International Pediatric Stroke Study Investigators. Symptomatic neonatal arterial ischemic stroke: the International Pediatric Stroke Study. Pediatrics. 2011;128(6):e1402-e1410.

20. 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.

21. Truwit CL. CT angiography versus MR angiography in the evaluation of acute neurovascular disease. Radiology. 2007;245(2):362-366.

Ms Krader has 30 years of experience as a medical writer. She has worked as both a hospital pharmacist and a clinical researcher/writer for the pharmaceutical industry and is presently a freelance writer in Deerfield, Illinois. She has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.