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DOI: 10.1160/TH04-04-0209
Arterial ischaemic stroke in children
Review of the literature and strategies for future stroke studies Grant support: This work was supported by grants from the “Karl-Bröcker-Stiftung” and the “Stiftung Deutsche Schlaganfall-Hilfe”.Publikationsverlauf
Received
02. April 2004
Accepted after revision
15. Juli 2004
Publikationsdatum:
06. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200404/lookinside/thumbnails/10-1160-th04-04-0209-1.jpg)
Summary
Conditions associated with arterial ischaemic stroke in children include a great variety of diseases and triggers such as congenital heart malformations, sickle cell disease, infections and vasculopathies, although up to 50% are cryptogenic. An abnormal vascular status can be demonstrated by vascular imaging in up to 80% of children with ischaemic stroke, and case control studies demonstrate an association between ischaemic stroke in children and hereditary prothrombotic risk factors and infections such as Varicella. Conventional risk factors such as hypertension and dyslipidaemia may also play a role, and most children have several potential triggers rather than one single cause. This review focuses on clinical presentations, imaging methods, stroke subtypes, underlying conditions including prothrombotic risk factors, outcome and recurrence. Although data from randomised controlled trials, on which clinical practice might be based, are sparse, therapeutic approaches and future research directions are discussed.
* All authors contributed equally
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References
- 1 Williams LS, Garg BP, Cohen M. et al. Subtypes of ischaemic stroke in children and young adults. Neurology 1997; 49: 1541-4.
- 2 Early CJ, Kittner SJ, Feeser BR. et al. Stroke in children and sickle-cell disease. Baltimore- Washington co-operative young stroke study. Neurology 1998; 51: 169-76.
- 3 Eeg-Olofsson O, Ringheim Y. Stroke in children. Clinical characteristics and prognosis. Acta Paediatr Scand 1983; 72: 391-5.
- 4 Giroud M. et al. Cerebrovascular disease in children under 16 years of age in the city of Dijon, France: a study of incidence and clinical features from 1985 to 1993. J Clin Epidemiol 1995; 48: 1343-8.
- 5 Roach ES, de Veber G, Kirkham F. Knowledge of consensus: understanding stroke in children. J Child Neurol 2000; 15: 277-8.
- 6 Schoenberg B, Mellinger J, Schoenberg D. Cerebrovascular disease in infants and children: a study of incidence, clinical features, and survival. Neurology 1978; 28: 763-8.
- 7 Takeoka M, Takahashi T. Infectious and inflammatory disorders of the circulatory system and stroke in children. Curr Opin Neurol 2002; 15: 159-64.
- 8 DeVeber G. Stroke and the child’s brain: an overview of epidemiology, syndromes and risk factors. Curr Opin Neurol 2002; 15: 133-8.
- 9 Kirkham FJ. Stroke in childhood. Arch Dis Child 1999; 81: 85-9.
- 10 Kirkham FJ, Prengler M, Hewes KM. et al. Risk factors for arterial ischaemic stroke in children. J Child Neurol 2000; 15: 299-307.
- 11 Nicolaides P, Appelton RE. Stroke in children. Dev Med Clin Neurol 1996; 38: 173-80.
- 12 Prengler M, Pavlakis SG, Prohovnik I. et al. Sickle cell disease: the neurological complications. Ann Neurol 2002; 51: 543-52.
- 13 DeVeber G. Arterial ischemic stroke in infants and children: An overview of current approaches. Semin Thromb Hemost 2003; 29: 567-73.
- 14 Chabrier S, Husson B, Lasjaunias P. et al. Stroke in childhood: Outcome and recurrence risk by mechanism in 59 patients. J Child Neurol 2000; 15: 290-4.
- 15 Ganesan V, Savvy L, Chong WK. et al. Conventional cerebral angiography in children with ischaemic stroke. Pediatr Neurol 1999; 20: 38-42.
- 16 Ganesan V. et al. Investigation of risk factors in children with arterial ischaemic stroke. Ann Neurol 2003; 53: 167-73.
- 17 Shirane R, Sato S, Yoshimoto T. Angiographic findings of ischaemic stroke in children. Childs Nerv Syst 1992; 08: 432-6.
- 18 Velkey I, Lombay B, Panczel G. Obstruction of the cerebral arteries in childhood stroke. Pediatr Radiol 1992; 22: 386-7.
- 19 Akar N, Akar E, Özel D. et al. Common mutations at the homocysteine metabolism pathway and paediatric stroke. Thromb Res 2001; 102: 115-20.
- 20 Becker S, Heller C, Gropp F. et al. Thrombophilic disorders in children with cerebral infarction. Lancet 1998; 352: 1756-8.
- 21 Bonduel M. et al. Prothrombotic disorders in children with moyamoya syndrome. Stroke 2001; 32: 1786-92.
- 22 Bonduel M, Sciuccati G, Hepner M. et al. Prethrombotic disorder in children with arterial ischaemic stroke and sinovenous thrombosis. Arch Neurol 1999; 56: 967-71.
- 23 Cardo E, Monros E, Colome C. et al. Children with stroke: polymorphism of the MTHFR gene, mild hyperhomocysteinemia, and vitamin status. J Child Neurol 2000; 15: 295-8.
- 24 Debus O, Koch HG, Kurlemann G. et al. Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly. Arch Dis Child Fetal Neonatal Ed 1998; 78: F121-F4.
- 25 Devilat M, Toso M, Morales M. Childhood stroke associated with protein C or S deficiency and primary antiphospholipid syndrome. Ped Neurol 1993; 09: 67-70.
- 26 Ganesan V, Kelsey H, Cookson J. et al. Activated protein C resistance in childhood stroke. Lancet 1996; 347: 260.
- 27 Ganesan V, McShane MA, Liesner R. et al. Inherited prothrombotic states and ischaemic stroke in childhood. J Neurol Neurosurg Psychiatry 1998; 65: 508-11.
- 28 Günther G, Junker R, Sträter R. et al. Symptomatic ischaemic stroke in full-term neonates: Role of acquired and genetic prothrombotic risk factors. Stroke 2000; 31: 2437-41.
- 29 Heller C, Becker S, Scharrer I, Kreuz W. Prothrombotic risk factors in childhood stroke and venous thrombosis. Eur J Pediatr 1999; 158 (Suppl): S117-S21.
- 30 Kenet G, Sadetzki S, Murad H. et al. Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischaemic stroke in children. Stroke 2000; 31: 1283-8.
- 31 Lanthier S, Carmant L, David M. et al. Stroke in children. The coexistence of multiple risk factors predicts poor outcome. Neurology 2000; 54: 371-8.
- 32 Manco-Johnson MJ, Nuss R, Key N. et al. Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis. J Pediatr 1996; 128: 319-23.
- 33 McColl MD, Chalmers EA, Thomas A. et al. Factor V Leiden, prothrombin 20210GA and the MTHFR C677T mutations in childhood stroke. Thromb Haemost 1999; 81: 690-4.
- 34 Miller V. Neonatal cerebral infarction. Semin Pediatr Neurol 2000; 07: 278-88.
- 35 Nguyen P. et al. Varicella and thrombotic complications associated with transient protein C and protein S deficiencies in children. Eur J Pediatr 1994; 153: 646-9.
- 36 Nowak-Göttl U. et al. Ischaemic stroke in infancy and childhood: role of the Arg506 to Gln mutation in the factor V gene. Blood Coagul Fibrinolysis 1996; 07: 684-8.
- 37 Nowak-Göttl U, Sträter R, Heinecke A. et al. Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin and methylenetetrahydrofolate reductase are risk factors of ischaemic stroke in childhood. Blood 1999; 94: 3678-82.
- 38 Prengler M. et al. Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: A potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood. Develop Med Child Neurol 2001; 43: 220-5.
- 39 Sträter R, Vielhaber H, Kassenböhmer R. et al. Genetic risk factors of thrombophilia in ischaemic childhood stroke of cardiac origin. A prospective ESPED survey. Eur J Pediatr 1999; 158 (Suppl): S122-S5.
- 40 Sträter R, Becker S, von Eckardstein A. et al. Prospective assessment of risk factors for recurrent stroke during childhood – a 5-year follow-up study. Lancet 2002; 360: 1540-5.
- 41 Van Beynum IM, Smeitink JA, den Heijer M. et al. Hyperhomocysteinemia: a risk for ischaemic stroke in children. Circulation 1999; 99: 2070-2.
- 42 Zenz W, Bodo Z, Plotho J. et al. Factor V Leiden and prothrombin gene G20210A variant in children with stroke. Thromb Haemost 1998; 80: 763-6.
- 43 Lynch JK, Hirtz DG, deVeber G. et al. Report on the National Institute of Neurological Disorders and Stroke Workshop on Perinatal and Childhood Stroke. Paediatrics 2002; 109: 116-23.
- 44 DeVeber G, Roach ES, Riela AR. et al. Stroke in children: recognition, treatment, and future directions. Semin Pediatr Neurol 2000; 07: 309-17.
- 45 Roelants-van Rijn AM, Nikkels PG, Groenendaal F. et al. Neonatal diffusionweighted MR imaging: relation with histopathology or follow-up examination. Neuropaediatrics 2001; 32: 286-94.
- 46 Dusser A, Goutiers F, Aicardi J. Ischaemic strokes in children. J Clin Neurol 1986; 01: 131-6.
- 47 Lanska MJ. et al. Presentation, clinical course, and outcome of childhood stroke. Pediatr Neurol 1991; 07: 333-41.
- 48 Nelson KB, Lynch JK. Stroke in the newborn infants. Lancet Neurol 2004; 03: 150-8.
- 49 Scher MS, Wiznitzer M, Bangert BA. Cerebral infarctions in the fetus and neonate: maternal-placental-fetal considerations. Clin Perinatol 2002; 29: 693-724.
- 50 Vern TZ, Alles AJ, Kowal-Vern A. et al. Frequency of factor V (Leiden) and prothrombin G20210A in placentas and their relationship with placental lesions. Hum Pathol 2000; 31: 1036-43.
- 51 Mercuri E. et al. Neonatal cerebral infarction and neuromotor outcome at school age. Paediatrics 2004; 113: 95-100.
- 52 Sreeman C, Bhargava R, Robertson CMT. Cerebral infarction in the term newborn: Clinical presentation and long-term outcome. J Pediatr 2000; 137: 351-5.
- 53 Kurnik K, Kosch A, Sträter R. et al. Recurrent thromboembolism in infants and children suffering from symptomatic neonatal arterial stroke. A prospective follow-up study. Stroke 2003; 34: 2887-93.
- 54 Delsing BJP, Catsman-Berrevoets CE, Appel IM. Early prognostic indicators of outcome in ischaemic childhood stroke. Paediatric Neurol 2001; 24: 283-9.
- 55 Ganesan V, Chong WK, Cox T. et al. Posterior circulation stroke in childhood. Neurology 2002; 59: 1552-6.
- 56 Kieslich M, Fiedler A, Heller C. et al. Minor head injury as cause and co-factor in the aetiology of stroke in childhood. A report of eight cases. J Neurol Neurosurg Psychiatry 2002; 73: 13-6.
- 57 Pavlakis SG, Kingsley PB, Bialer MG. Stroke in children: Genetic and metabolic issues. J Child Neurol 2000; 15: 308-15.
- 58 Roach ES. Stroke in children. Curr Treat Opt Neurol 2000; 02: 295-303.
- 59 Hoggard N, Wilkinson ID, Grffiths PD. The imaging of ischaemic stroke. Clin Radiol 2001; 56: 171-83.
- 60 Oelerich M, Stögbauer F, Kurlemann G. et al. Craniocervical artery dissection: MR imaging and MR angiographic findings. Eur Radiol 1999; 09: 1385-91.
- 61 Gadian DG, Calamante F, Kirkham F. et al. Diffusion and perfusion magnetic resonance imaging in childhood stroke. J Child Neurol 2000; 15: 279-83.
- 62 Hunter JV. New radiographic techniques to evaluate cerebrovascular disorders in children. Sem Ped Neurol 2000; 07: 261-77.
- 63 Hunter JV. Magnetic resonance imaging in paediatric stroke. Top Magn Reson Imaging 2002; 13: 23-38.
- 64 Husson B, Rodesch G, Lasjaunias P. et al. Magnetic resonance angiography in childhood arterial brain infarcts : a comparative study with contrast angiography. Stroke 2002; 33: 1280-5.
- 65 Husson B, Lasjaunias P. Radiological approach to disorders of arterial vessels associated with childhood arterial stroke – a comparison between MRA and contrast angiography. Pediatr Radiol 2004; 34: 10-5.
- 66 Bydder GM, Rutherford MA. Diffusionweighted imaging of the brain in neonates and infants. Magn Reson Imaging Clin N Am 2001; 09: 83-98.
- 67 Connelly A, Chong WK, Johnson CL. et al. Diffusion weighted magnetic resonance imaging of compromised tissue in stroke. Arch Dis Child 1997; 77: 38-41.
- 68 Kirkham FJ, Calamante F, Bynevelt M. et al. Perfusion MR abnormalities in patients with Sickle cell Disease: relation to symptoms, infarction and cerebrovascular disease. Ann Neurol 2001; 49: 477-85.
- 69 Ganesan V, Kirkham FJ. Mechanisms of ischaemic stroke after chickenpox. Arch Dis Childh 1997; 76: 522-5.
- 70 Chabrier S, Rodesch G, Lasjaunias P. et al. Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with strokes. J Child Neurol 1998; 13: 27-32.
- 71 Manceau E, Giroud M, Dumas R. Moyamoya disease in children. A review of the clinical and radiological features and current treatment. Child’s Nerv Syst 1997; 13: 595-600.
- 72 Singhal AB, Singhal BS, Ursekar MA. et al. Serial MR angiography and constrastenhanced MRI in chickenpox-associated stroke. Neurology 2001; 56: 815-7.
- 73 Fullerton HJ, Johnston SC, Smith WS. Arterial dissection and stroke children. Neurology 2001; 57: 1155-60.
- 74 Silverboard G, Tart R. Cerebrovascular arterial dissection in children and young adults. Semin Pediatr Neurol 2000; 07: 289-300.
- 75 Hasan I, Wapnick S, Tenner M. et al. Vertebral artery dissection in children: A comprehensive review. Pediatr Neurosurg 2002; 37: 168-77.
- 76 Sebire G, Meyer L, Chabrier S. Varicella as a risk factor for cerebral infarction in childhood: A case-control study. Ann Neurol 1999; 45: 679-80.
- 77 Askalan R. et al. Chickenpox and stroke in childhood. A study of frequency and causation. Stroke 2001; 32: 1257-62.
- 78 Diez-Tejedor E, Munoz C, Frank A. Cerebellar infarction in children and young adults related to fibromuscular dysplasia and dissection of the vertebral artery. Stroke 1993; 24: 1096.
- 79 Emparanza JI. et al. Ischaemic stroke due to fibromuscular dysplasia. Neuropaediatrics 1989; 20: 181-2.
- 80 Shields WD. et al. Fibromuscular dysplasia as a cause of stroke in infancy and childhood. Paediatrics 1977; 59: 899-901.
- 81 Moriuchi H, Rodriguez W. Role of Varicellazoster virus in stroke syndromes. Pediatr Infect Dis J 2000; 19: 648-53.
- 82 Chun DS. et al. Incidence, outcome, and risk for stroke after the Fontan procedure. Am J Cardiol 2004; 93: 117-9.
- 83 Schuchlenz HW, Weihs W, Beitzke A. et al. Transesophageal echocardiography for quantifying size of patent foramen ovale in patients with cryptogenic cerebrovascular events. Stroke 2002; 33: 293-6.
- 84 Steiner MM, Di Tullio MR, Rundek T. et al. Patent foramen ovale size and embolic brain imaging findings among patients with ischaemic stroke. Stroke 1998; 29: 944-8.
- 85 Zanette EM, Mancini G, De Castro S. et al. Patent foramen ovale and transcranial doppler. Comparison of different procedures. Stroke 1996; 27: 2251-5.
- 86 Kirkham FJ. et al. Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease. Lancet 2001; 357: 1656-9.
- 87 Andrew M, Paes B, Johnston M. Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hematol Oncol 1990; 12: 95-104.
- 88 Fullerton HJ, Chetkovich DM, Wu YW. et al. Death from stroke in US children. Neurology 2002; 09: 34-9.
- 89 DeSchryver EL, Kapelle LJ, Jennekens-Schinkel A. et al. Prognosis of ischaemic stroke in childhood: a long-term follow-up study. Dev Med Child Neurol 2000; 42: 313-8.
- 90 Ganesan V, Hogan A, Jones A. et al. Parentreported outcome in ischaemic stroke. Dev Med Child Neurol 2000; 42: 455-61.
- 91 Gordon A, Ganesan V, Towell A. et al. Activity limitation following stroke in children. J Child Neurol 2002; 17: 429-34.
- 92 Screenan C, Bhargava R, Robertson CMT. Cerebral infarction in the term newborn: Clinical presentation and long-term outcome. J Pediatr 2000; 137: 351-5.
- 93 Dobson SR, Holden KR, Nietert PJ. et al. Moyamoya syndrome in childhood sickle cell disease: a predictive factor for recurrent cerebrovascular events. Blood 2002; 99: 3144-50.
- 94 Brankovic-Sreckovic V. et al. The recurrence risk of ischaemic stroke in childhood. Med Princ Pract 2004; 13: 153-8.
- 95 Nowak-Göttl U. et al. Antithrombotic drug treatment of pediatric patients with ischemic stroke. Pediatr Drugs 2003; 05: 167-75.
- 96 Albers GW. et al. Antithrombotic and thrombolytic therapy for ischaemic stroke. Chest 1998; 114: S683-S98.
- 97 Kaste M, Thomassen L, Grond M. et al. Thrombolysis for acute ischaemic stroke. A consensus statement of the 3rd Karolinska Stroke Update, October 30-31, 2000. Stroke 2001; 32: 2717-8.
- 98 The ATLANTIS, ECASS, and NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004; 363: 763-74.
- 99 Wardlaw JM. et al. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2003; 03: CD000213
- 100 Gabis LV, Yangala R, Lenn NJ. Time lag to diagnosis of stroke in children. Pediatrics 2002; 110: 924-8.
- 101 Thirumalai SS, Shubin RA. Successful treatment for stroke in a child using recombinant tissue plasminogen activator. J Child Neurol 2000; 15: 558.
- 102 Gruber A, Nasel C, Lang W. et al. Intraarterial thrombolysis for the treatment of perioperative childhood cardioembolic stroke. Neurology 2000; 54: 1684-6.
- 103 Kirton A, Wong JH, Mah J. et al. Successful endovascular therapy for acute basilar thrombosis in an adolescent. Paediatrics 2003; 112: e248-e51.
- 104 Sungarian A, Duncan JA. Vertebrobasilar thrombosis in children: Report of two cases and recommendations for treatment. Pediatr Neurosurg 2003; 38: 16-20.
- 105 Gupta AA, Leaker M, Andrew M. et al. Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children. J Pediatr 2001; 139: 682-8.
- 106 Millman G, Thompson D, Kirkham FJ. Surgical decompression for malignant middle cerebral artery territory infarction in childhood. Dev Med Child Neurol 1998; 40 (Suppl. 79) 24.
- 107 Ikezaki K. Rational approach to treatment of moyamoya disease in childhood. J Child Neurol 2000; 15: 350-6.
- 108 George BD, Neville BGR, Lumley JSP. Transcranial revascularisation in childhood and adolescence. Dev Med Child Neurol 1993; 35: 675-82.
- 109 Satoh S, Shirane R, Yoshimoto T. Clinical survey of ischaemic cerebrovascular disease in children in a district of Japan. Stroke 1991; 22: 586-9.
- 110 Scott RM. Surgery for moyamoya syndrome? Yes. Arch Neurol 2001; 58: 128-9.
- 111 Yilmaz EY, Pritz MB, Bruno A. et al. Moyamoya: Indiana University Medical Center experience. Arch Neurol 2001; 58: 1274-8.
- 112 Roach ES. Immediate surgery for moyamoya syndrome? Not necessarily. Arch Neurol 2001; 58: 130-1.
- 113 Scott RM, Smith JL, Robertson RL. et al. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg 2004; 100 (Suppl. 02) 142-9.
- 114 Goda M. et al. Long-term effects of indirect bypass surgery on collateral vessel formation in pediatric moyamoya disease. J Neurosurg 2004; 100 (Suppl. 02) 156-62.
- 115 Kuroda S, Houkin K, Ishikawa T. et al. Determinants of intellectual outcome after surgical revascularization in paediatric moyamoya disease: a multivariate analysis. Child´s Nerv Syst 2004; 20: 302-8.
- 116 Hogan A, Watkins K, Kirkham F. et al. The importance of longitudinal cognitive evaluation in the clinical management of children with moyamoya disease. Dev Med Child Neurol 1998; 40 (Suppl. 79) 8.
- 117 Klijn CJ, Hankey GJ. American Stroke Association and European Stroke Initiative. Management of acute ischaemic stroke: new guidelines from the American Stroke Association and European Stroke Initiative. Lancet Neurol 2003; 02: 698-701.
- 118 Albisetti M, Andrew M. Low molecular weight heparin in children. Eur J Pediatr 2002; 161: 71-7.
- 119 Andrew M, Michelson AD, Bovill E. et al. Guidelines for antithrombotic therapy in ped-iatric patients. J Pediatr 1998; 132: 575-88.
- 120 Revel-Vilk S, Chan AKC. Anticoagulation therapy in children. Semin Thromb Hemost 2003; 29: 425-32.
- 121 Burak CR, Bowen MD, Barron TF. The use of enoxaparin in children with acute, nonhemorrhagic ischaemic stroke. Pediatr Neurol 2003; 29: 295-8.
- 122 Dix D, Andrew M, Marzinotto V, Charpentier K. et al. The use of low molecular weight heparin in paediatric patients: a prospective cohort study. J Pediatr 2000; 136: 439-45.
- 123 Sträter R, Kurnik K, Heller C. et al. Aspirin versus low-dose low-molecular-weight heparin: Antithrombotic therapy in paediatric stroke patients. A prospective follow-up study. Stroke 2001; 32: 2554-8.
- 124 Lanthier S, Kirkham FJ, Mitchell LG. et al. Increased anticardiolipin antibody IgG titers do not predict recurrent stroke or TIA in children. Neurology 2004; 62: 194-200.