Challenges in the diagnosis and treatment of pediatric stroke

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Stroke in children is rarely due to traditional stroke risk factors such as hypertension and diabetes. Rather, stroke in this patient group typically results from the simultaneous occurrence of multiple stroke risk factors, the presence of which necessitates a thorough evaluation to determine the cause of this disorder. Several challenges exist in the care of children with stroke. Of note, recognition of pediatric stroke onset by parents and caregivers is often delayed, highlighting the need for increased awareness of and education regarding this condition. Moreover, various neurological conditions resemble stroke in pediatric patients and a definite diagnosis of this disorder requires MRI; adding to the diagnostic challenge, young children may need to be sedated to undergo acute MRI. Perhaps the most significant challenge is the need for clinical research studies focusing on pediatric stroke treatment, so as to allow evidence-based treatment decision-making. A final challenge is the standardization of outcome assessment after stroke for a wide range of ages and developmental levels. In this Review, we examine recent findings and diagnostic issues pertaining to both arterial ischemic stroke and hemorrhagic stroke in children.

Key Points

  • Common risk factors for pediatric arterial ischemic stroke include cerebral arteriopathies, congenital or acquired cardiac disease, and sickle cell disease

  • Cerebral vascular abnormalities are the most common causes of hemorrhagic stroke in children

  • A combination of multiple, seemingly minor risk factors may lead to stroke in childhood

  • Delayed recognition of stroke in children by families and health-care providers is a significant issue for both medical care and clinical trials

  • Clinical trials of treatment strategies—particularly trials of antithrombotic medications (aspirin versus anticoagulants) and rehabilitation methods—are needed for pediatric stroke

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Figure 1: Arteriopathy in pediatric stroke.
Figure 2: Acute hemorrhagic stroke and susceptibility-weighted imaging.
Figure 3: Idiopathic moyamoya disease.
Figure 4: Acute arterial ischemic stroke with diffusion–perfusion mismatch.


  1. 1

    Kaatsch, P., Rickert, C. H., Kühl, J., Schüz, J. & Michaelis, J. Population-based epidemiologic data on brain tumors in German children. Cancer 92, 3155–3164 (2001).

  2. 2

    Lynch, J. K., Hirtz, D. G., DeVeber, G. & Nelson, K. B. Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics 109, 116–123 (2002).

  3. 3

    Giroud, M. et al. Stroke in children under 16 years of age. Clinical and etiological difference with adults. Acta Neurol. Scand. 96, 401–406 (1997).

  4. 4

    Chung, B. & Wong, V. Pediatric stroke among Hong Kong Chinese subjects. Pediatrics 114, e206–e212 (2004).

  5. 5

    Agrawal, N., Johnston, S. C., Wu, Y. W., Sidney, S. & Fullerton, H. J. Imaging data reveal a higher pediatric stroke incidence than prior US estimates. Stroke 40, 3415–3421 (2009).

  6. 6

    Rafay, M. F. et al. Delay to diagnosis in acute pediatric arterial ischemic stroke. Stroke 40, 58–64 (2009).

  7. 7

    Srinivasan, J., Miller, S. P., Phan, T. G. & Mackay, M. T. Delayed recognition of initial stroke in children: need for increased awareness. Pediatrics 124, e227–e234 (2009).

  8. 8

    Dlamini, N., Billinghurst, L. & Kirkham, F. J. Cerebral venous sinus (sinovenous) thrombosis in children. Neurosurg. Clin. N. Am. 21, 511–527 (2010).

  9. 9

    Amlie-Lefond, C. et al. Predictors of cerebral arteriopathy in children with arterial ischemic stroke: results of the International Pediatric Stroke Study. Circulation 119, 1417–1423 (2009).

  10. 10

    Ganesan, V., Prengler, M., McShane, M. A., Wade, A. M. & Kirkham, F. J. Investigation of risk factors in children with arterial ischemic stroke. Ann. Neurol. 53, 167–173 (2003).

  11. 11

    Beslow, L. A. et al. Predictors of outcome in childhood intracerebral hemorrhage: a prospective consecutive cohort study. Stroke 41, 313–318 (2010).

  12. 12

    Fullerton, H. J., Wu, Y. W., Sidney, S. & Johnston, S. C. Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging. Pediatrics 119, 495–501 (2007).

  13. 13

    Sträter, R. et al. Genetic risk factors of thrombophilia in ischaemic childhood stroke of cardiac origin. A prospective ESPED survey. Eur. J. Pediatr. 158 (Suppl. 3), S122–S125 (1999).

  14. 14

    Nowak-Gottl, U. et al. Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. Blood 94, 3678–3682 (1999).

  15. 15

    Sebire, G., Meyer, L. & Chabrier, S. Varicella as a risk factor for cerebral infarction in childhood: a case–control study. Ann. Neurol. 45, 679–680 (1999).

  16. 16

    Hills, N. K., Johnston, S. C., Sidney, S. & Fullerton, H. J. Minor infection predisposes to arterial ischemic stroke in children [abstract 72]. Stroke 40, e124 (2009).

  17. 17

    Lanthier, S., Carmant, L., David, M., Larbrisseau, A. & de Veber, G. Stroke in children: the coexistence of multiple risk factors predicts poor outcome. Neurology 54, 371–378 (2000).

  18. 18

    Kleinman, J. T., Gailloud, P. & Jordan, L. C. Recovery from spatial neglect and hemiplegia in a child despite a large anterior circulation stroke and Wallerian degeneration. J. Child Neurol. 25, 500–503 (2010).

  19. 19

    Al-Jarallah, A., Al-Rifai, M. T., Riela, A. R. & Roach, E. S. Nontraumatic brain hemorrhage in children: etiology and presentation. J. Child Neurol. 15, 284–289 (2000).

  20. 20

    Jordan, L. C., Johnston, S. C., Wu, Y. W., Sidney, S. & Fullerton, H. J. The importance of cerebral aneurysms in childhood hemorrhagic stroke: a population-based study. Stroke 40, 400–405 (2009).

  21. 21

    Jordan, L. C., Kleinman, J. T. & Hillis, A. E. Intracerebral hemorrhage volume predicts poor neurologic outcome in children. Stroke 40, 1666–1671 (2009).

  22. 22

    Meyer-Heim, A. D. & Boltshauser, E. Spontaneous intracranial haemorrhage in children: aetiology, presentation and outcome. Brain Dev. 25, 416–421 (2003).

  23. 23

    Gabis, L. V., Yangala, R. & Lenn, N. J. Time lag to diagnosis of stroke in children. Pediatrics 110, 924–928 (2002).

  24. 24

    Shellhaas, R. A., Smith, S. E., O'Tool, E., Licht, D. J. & Ichord, R. N. Mimics of childhood stroke: characteristics of a prospective cohort. Pediatrics 118, 704–709 (2006).

  25. 25

    Bowen, B. C. MR angiography versus CT angiography in the evaluation of neurovascular disease. Radiology 245, 357–360 (2007).

  26. 26

    Truwit, C. L. CT angiography versus MR angiography in the evaluation of acute neurovascular disease. Radiology 245, 362–366 (2007).

  27. 27

    Chappell, E. T., Moure, F. C. & Good, M. C. Comparison of computed tomographic angiography with digital subtraction angiography in the diagnosis of cerebral aneurysms: a meta-analysis. Neurosurgery 52, 624–631 (2003).

  28. 28

    Kidwell, C. S. et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. JAMA 292, 1823–1830 (2004).

  29. 29

    Roach, E. S. et al. 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 39, 2644–2691 (2008).

  30. 30

    Dowling, M. M. & Ikemba, C. M. Intracardiac shunting and stroke in children: a systematic review. J. Child Neurol. 26, 72–82 (2011).

  31. 31

    Beslow, L. A. & Jordan, L. C. Pediatric stroke: the importance of cerebral arteriopathy and vascular malformations. Childs Nerv. Syst. 26, 1263–1273 (2010).

  32. 32

    Kenet, G. et al. Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation 121, 1838–1847 (2010).

  33. 33

    Pepe, G. et al. Prevalence of factor V leiden mutation in non-European populations. Thromb. Haemost. 77, 329–331 (1997).

  34. 34

    Hessner, M. J. et al. Prevalence of prothrombin G20210A, factor V G1691A (Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T in seven different populations determined by multiplex allele-specific PCR. Thromb. Haemost. 81, 733–738 (1999).

  35. 35

    Varga, E. A., Sturm, A. C., Misita, C. P. & Moll, S. Cardiology patient pages. Homocysteine and MTHFR mutations: relation to thrombosis and coronary artery disease. Circulation 111, e289–e293 (2005).

  36. 36

    Great Ormond Street Hospital for Children NHS Trust. Stroke and Neurovascular Disorders, Investigation and Management [online], (2011).

  37. 37

    Monagle, P. et al. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133, 887S–968S (2008).

  38. 38

    DeVeber, G. & Kirkham, F. Guidelines for the treatment and prevention of stroke in children. Lancet Neurol. 7, 983–985 (2008).

  39. 39

    Eleftheriou, D. & Ganesan, V. Controversies in childhood arterial ischemic stroke and cerebral venous sinus thrombosis. Expert Rev. Cardiovasc. Ther. 7, 853–861 (2009).

  40. 40

    Broderick, J. P. et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 30, 905–915 (1999).

  41. 41

    Weir, C. J., Murray, G. D., Dyker, A. G. & Lees, K. R. Is hyperglycaemia an independent predictor of poor outcome after acute stroke? Results of a long-term follow up study. BMJ 314, 1303–1306 (1997).

  42. 42

    Jordan, L. C. & Hillis, A. E. Hemorrhagic stroke in children. Pediatr. Neurol. 36, 73–80 (2007).

  43. 43

    Messé, S. R. et al. Prophylactic antiepileptic drug use is associated with poor outcome following ICH. Neurocrit. Care 11, 38–44 (2009).

  44. 44

    Naidech, A. M. et al. Anticonvulsant use and outcomes after intracerebral hemorrhage. Stroke 40, 3810–3815 (2009).

  45. 45

    Abend, N. S. et al. Impact of continuous EEG monitoring on clinical management in critically ill children. Neurocrit Care doi:10.1007/s12028-010-9380-z.

  46. 46

    Poungvarin, N. et al. Effects of dexamethasone in primary supratentorial intracerebral hemorrhage. N. Engl. J. Med. 316, 1229–1233 (1987).

  47. 47

    Tellez, H. & Bauer, R. B. Dexamethasone as treatment in cerebrovascular disease. 1. A controlled study in intracerebral hemorrhage. Stroke 4, 541–546 (1973).

  48. 48

    Passero, S., Ciacci, G. & Ulivelli, M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology 61, 1351–1356 (2003).

  49. 49

    Adams, R. J. et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N. Engl. J. Med. 339, 5–11 (1998).

  50. 50

    Adams, R. J. et al. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N. Engl. J. Med. 353, 2769–2778 (2005).

  51. 51

    Enninful-Eghan, H., Moore, R. H., Ichord, R., Smith-Whitley, K. & Kwiatkowski, J. L. Transcranial Doppler ultrasonography and prophylactic transfusion program is effective in preventing overt stroke in children with sickle cell disease. J. Pediatr. 157, 479–484 (2010).

  52. 52

    Hulbert, M. L. et al. Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia. J. Pediatr. 149, 710–712 (2006).

  53. 53

    Scott, R. M. et al. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J. Neurosurg. 100, 142–149 (2004).

  54. 54

    Goldenberg, N. A. et al. Antithrombotic treatments, outcomes, and prognostic factors in acute childhood-onset arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol. 8, 1120–1127 (2009).

  55. 55

    DeVeber, G. In pursuit of evidence-based treatments for paediatric stroke: the UK and Chest guidelines. Lancet Neurol. 4, 432–436 (2005).

  56. 56

    [No authors listed] Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N. Engl. J. Med. 333, 1581–1587 (1995).

  57. 57

    Monagle, P., Chan, A., Massicotte, P., Chalmers, E. & Michelson, A. D. Antithrombotic therapy in children: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126, 645S–687S (2004).

  58. 58

    Amlie-Lefond, C. et al. Use of alteplase in childhood arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol. 8, 530–536 (2009).

  59. 59

    Amlie-Lefond, C. et al. Thrombolysis in acute childhood stroke: design and challenges of the thrombolysis in pediatric stroke clinical trial. Neuroepidemiology 32, 279–286 (2009).

  60. 60

    Ruf, B. et al. Early decompressive craniectomy and duraplasty for refractory intracranial hypertension in children: results of a pilot study. Crit. Care 7, R133–R138 (2003).

  61. 61

    Robertson, S. C., Lennarson, P., Hasan, D. M. & Traynelis, V. C. Clinical course and surgical management of massive cerebral infarction. Neurosurgery 55, 55–61 (2004).

  62. 62

    Vahedi, K. et al. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials. Lancet Neurol. 6, 215–222 (2007).

  63. 63

    Smith, S. E. et al. Outcome following decompressive craniectomy for malignant middle cerebral artery infarction in children. Dev. Med. Child Neurol. 53, 29–33 (2011).

  64. 64

    Mendelow, A. D. et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet 365, 387–397 (2005).

  65. 65

    Rabinstein, A. A., Atkinson, J. L. & Wijdicks, E. F. Emergency craniotomy in patients worsening due to expanded cerebral hematoma: to what purpose? Neurology 58, 1367–1372 (2002).

  66. 66

    Ganesan, V., Prengler, M., Wade, A. & Kirkham, F. J. Clinical and radiological recurrence after childhood arterial ischemic stroke. Circulation 114, 2170–2177 (2006).

  67. 67

    De Schryver, E. L., Kappelle, L. J., Jennekens-Schinkel, A. & Boudewyn Peters, A. C. Prognosis of ischemic stroke in childhood: a long-term follow-up study. Dev. Med. Child Neurol. 42, 313–318 (2000).

  68. 68

    Russell, M. O. et al. Effect of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease. Blood 63, 162–169 (1984).

  69. 69

    Chabrier, S., Husson, B., Lasjaunias, P., Landrieu, P. & Tardieu, M. Stroke in childhood: outcome and recurrence risk by mechanism in 59 patients. J. Child Neurol. 15, 290–294 (2000).

  70. 70

    Hogan, A. M., Kirkham, F. J. & Isaacs, E. B. Intelligence after stroke in childhood: review of the literature and suggestions for future research. J. Child Neurol. 15, 325–332 (2000).

  71. 71

    Ganesan, V. et al. Outcome after ischaemic stroke in childhood. Dev. Med. Child Neurol. 42, 455–461 (2000).

  72. 72

    Yang, J. S., Park, Y. D. & Hartlage, P. L. Seizures associated with stroke in childhood. Pediatr. Neurol. 12, 136–138 (1995).

  73. 73

    deVeber, G. A., MacGregor, D., Curtis, R. & Mayank, S. Neurologic outcome in survivors of childhood arterial ischemic stroke and sinovenous thrombosis. J. Child Neurol. 15, 316–324 (2000).

  74. 74

    Everts, R. et al. Cognitive functioning, behavior, and quality of life after stroke in childhood. Child. Neuropsychol. 14, 323–338 (2008).

  75. 75

    Westmacott, R., Askalan, R., MacGregor, D., Anderson, P. & Deveber, G. Cognitive outcome following unilateral arterial ischaemic stroke in childhood: effects of age at stroke and lesion location. Dev. Med. Child Neurol. 52, 386–393 (2010).

  76. 76

    Fullerton, H. J., Wu, Y. W., Sidney, S. & Johnston, S. C. Recurrent hemorrhagic stroke in children: a population-based cohort study. Stroke 38, 2658–2662 (2007).

  77. 77

    Beslow, L. A. et al. ABC/XYZ estimates intracerebral hemorrhage volume as a percent of total brain volume in children. Stroke 41, 691–694 (2010).

  78. 78

    Kleinman, J. T., Hillis, A. E. & Jordan, L. C. ABC/2: estimating ICH volume, total brain volume, and predicting outcome in children. Dev. Med. Child Neurol. doi:10.1111/j.1469–87492010.03798.x.

  79. 79

    Wolf, S. L. et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. JAMA 296, 2095–2104 (2006).

  80. 80

    Wolf, S. L. et al. Retention of upper limb function in stroke survivors who have received constraint-induced movement therapy: the EXCITE randomised trial. Lancet Neurol. 7, 33–40 (2008).

  81. 81

    Boyd, R. et al. INCITE: A randomised trial comparing constraint induced movement therapy and bimanual training in children with congenital hemiplegia. BMC Neurol. 10, 4 (2010).

  82. 82

    Aarts, P. B., Jongerius, P. H., Geerdink, Y. A., van Limbeek, J. & Geurts, A. C. Effectiveness of modified constraint-induced movement therapy in children with unilateral spastic cerebral palsy: a randomized controlled trial. Neurorehabil. Neural Repair 24, 509–518 (2010).

  83. 83

    Deluca, S. C., Echols, K., Law, C. R. & Ramey, S. L. Intensive pediatric constraint-induced therapy for children with cerebral palsy: randomized, controlled, crossover trial. J. Child Neurol. 21, 931–938 (2006).

  84. 84

    Hoare, B. J. et al. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy (UPDATE). Cochrane Database of Systematic Reviews, Issue 1. Art. No.: CD003469. doi:10.1002/14651858.CD003469.pub4 (2010).

  85. 85

    Fehlings, D., Rang, M., Glazier, J. & Steele, C. Botulinum toxin type A injections in the spastic upper extremity of children with hemiplegia: child characteristics that predict a positive outcome. Eur. J. Neurol. 8 (Suppl. 5), 145–149 (2001).

  86. 86

    Kirton, A. et al. Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke: a randomised trial. Lancet Neurol. 7, 507–513 (2008).

  87. 87

    Schlaug, G., Renga, V. & Nair, D. Transcranial direct current stimulation in stroke recovery. Arch. Neurol. 65, 1571–1576 (2008).

  88. 88

    Baker, J. M., Rorden, C. & Fridriksson, J. Using transcranial direct-current stimulation to treat stroke patients with aphasia. Stroke 41, 1229–1236 (2010).

  89. 89

    Ichord, R N. et al. Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke 42, 613–617 (2011).

  90. 90

    Kitchen, L. et al. A validation study of the paediatric stroke outcome measure [abstract P331]. Stroke 34, 316 (2003).

  91. 91

    Quinn, T. J., Dawson, J., Walters, M. R. & Lees, K. R. Reliability of the modified Rankin Scale: a systematic review. Stroke 40, 3393–3395 (2009).

  92. 92

    Saver, J. L. et al. Improving the reliability of stroke disability grading in clinical trials and clinical practice: the Rankin Focused Assessment (RFA). Stroke 41, 992–995 (2010).

  93. 93

    Perkins, E., Stephens, J., Xiang, H. & Lo, W. The cost of pediatric stroke acute care in the United States. Stroke 40, 2820–2827 (2009).

  94. 94

    Gardner, M. A., Hills, N. K., Sidney, S., Johnston, S. C. & Fullerton, H. J. The 5-year direct medical cost of neonatal and childhood stroke in a population-based cohort. Neurology 74, 372–378 (2010).

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L. C. Jordan (grant K23NS062110) and A. E. Hillis (grants RO1 NS047691 and RO1 DC05375) receive funding from the NIH.

L. Barclay, freelance writer and reviewer, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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L. C. Jordan researched the data for the article, provided a substantial contribution to discussions of the content, wrote the article and contributed to review and editing of the manuscript before submission. A. E. Hillis provided a substantial contribution to discussions of the content and contributed to review and editing of the manuscript before submission.

Correspondence to Lori C. Jordan.

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L. C. Jordan has acted as a consultant for Berlin Heart. A. E. Hillis declares no competing interests.

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