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Stroke in the newborn

Rebecca Ichord, MD
Section Editors
Douglas R Nordli, Jr, MD
Joseph A Garcia-Prats, MD
Deputy Editor
John F Dashe, MD, PhD


Perinatal stroke may be defined as an acute neurologic syndrome with chronic sequelae due to cerebral injury of vascular origin occurring between 20 weeks gestation and 28 days postnatal life. These disorders include focal cerebral injury due to arterial ischemic stroke, cerebral venous thrombosis, and primary intracerebral hemorrhage. Perinatal stroke is a common cause of acute neonatal encephalopathy, and may manifest as seizures, altered mental status, and sensorimotor deficits. It is an important cause of chronic neurologic disability.

The epidemiology, pathogenesis, clinical features, diagnosis, prognosis, and management of perinatal stroke are reviewed here.

Neonatal encephalopathies that resemble perinatal stroke can be seen in association with periventricular and intraventricular hemorrhage, diffuse cerebral injury following global cerebral hypoxic-ischemic insults, and periventricular leukomalacia that typically occurs in preterm infants. These disorders are reviewed briefly here and discussed in more detail separately. (See "Etiology and pathogenesis of neonatal encephalopathy" and "Clinical manifestations and diagnosis of intraventricular hemorrhage in the newborn" and "Management and complications of intraventricular hemorrhage in the newborn" and "Periventricular leukomalacia".)


Perinatal stroke encompasses cerebrovascular events that occur between 20 weeks of fetal life and 28 postnatal days [1]. Modern definitions of perinatal stroke incorporate the timing of the condition and major clinical-anatomic stroke subtypes.

Temporal classification is based on neuroimaging and clinical features, and distinguishes three groups [1-4]:


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Literature review current through: Sep 2016. | This topic last updated: Jun 14, 2016.
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  1. Raju TN, Nelson KB, Ferriero D, et al. Ischemic perinatal stroke: summary of a workshop sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Pediatrics 2007; 120:609.
  2. Govaert P, Ramenghi L, Taal R, et al. Diagnosis of perinatal stroke I: definitions, differential diagnosis and registration. Acta Paediatr 2009; 98:1556.
  3. Nelson KB, Lynch JK. Stroke in newborn infants. Lancet Neurol 2004; 3:150.
  4. Govaert P, Ramenghi L, Taal R, et al. Diagnosis of perinatal stroke II: mechanisms and clinical phenotypes. Acta Paediatr 2009; 98:1720.
  5. Armstrong-Wells J, Johnston SC, Wu YW, et al. Prevalence and predictors of perinatal hemorrhagic stroke: results from the kaiser pediatric stroke study. Pediatrics 2009; 123:823.
  6. Kirton A, Deveber G, Pontigon AM, et al. Presumed perinatal ischemic stroke: vascular classification predicts outcomes. Ann Neurol 2008; 63:436.
  7. Golomb MR, MacGregor DL, Domi T, et al. Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes. Ann Neurol 2001; 50:163.
  8. Ilves P, Laugesaar R, Loorits D, et al. Presumed Perinatal Stroke: Risk Factors, Clinical and Radiological Findings. J Child Neurol 2016; 31:621.
  9. Agrawal N, Johnston SC, Wu YW, et al. Imaging data reveal a higher pediatric stroke incidence than prior US estimates. Stroke 2009; 40:3415.
  10. Grunt S, Mazenauer L, Buerki SE, et al. Incidence and outcomes of symptomatic neonatal arterial ischemic stroke. Pediatrics 2015; 135:e1220.
  11. Elbers J, Viero S, MacGregor D, et al. Placental pathology in neonatal stroke. Pediatrics 2011; 127:e722.
  12. Lehman LL, Rivkin MJ. Perinatal arterial ischemic stroke: presentation, risk factors, evaluation, and outcome. Pediatr Neurol 2014; 51:760.
  13. Volpe JJ. Hypoxic-ischemic encephalopathy: Clinical aspects. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadelphia 2008. p.400.
  14. Allan WC, Riviello JJ Jr. Perinatal cerebrovascular disease in the neonate. Parenchymal ischemic lesions in term and preterm infants. Pediatr Clin North Am 1992; 39:621.
  15. de Vries LS, Groenendaal F, Eken P, et al. Infarcts in the vascular distribution of the middle cerebral artery in preterm and fullterm infants. Neuropediatrics 1997; 28:88.
  16. Ramaswamy V, Miller SP, Barkovich AJ, et al. Perinatal stroke in term infants with neonatal encephalopathy. Neurology 2004; 62:2088.
  17. Miller V. Neonatal cerebral infarction. Semin Pediatr Neurol 2000; 7:278.
  18. Sreenan C, Bhargava R, Robertson CM. Cerebral infarction in the term newborn: clinical presentation and long-term outcome. J Pediatr 2000; 137:351.
  19. Ruff RL, Shaw CM, Beckwith JB, Iozzo RV. Cerebral infarction complicating umbilical vein catheterization. Ann Neurol 1979; 6:85.
  20. Pellicer A, Cabañas F, García-Alix A, et al. Stroke in neonates with cardiac right-to-left shunt. Brain Dev 1992; 14:381.
  21. Andrew ME, Monagle P, deVeber G, Chan AK. Thromboembolic disease and antithrombotic therapy in newborns. Hematology Am Soc Hematol Educ Program 2001; :358.
  22. Günther G, Junker R, Sträter R, et al. Symptomatic ischemic stroke in full-term neonates : role of acquired and genetic prothrombotic risk factors. Stroke 2000; 31:2437.
  23. Simchen MJ, Goldstein G, Lubetsky A, et al. Factor v Leiden and antiphospholipid antibodies in either mothers or infants increase the risk for perinatal arterial ischemic stroke. Stroke 2009; 40:65.
  24. Kenet G, Lütkhoff LK, Albisetti M, 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 2010; 121:1838.
  25. Chalmers EA. Perinatal stroke--risk factors and management. Br J Haematol 2005; 130:333.
  26. Trenor CC 3rd, Michelson AD. Thrombophilia and pediatric stroke. Circulation 2010; 121:1795.
  27. Mercuri E, Cowan F, Gupte G, et al. Prothrombotic disorders and abnormal neurodevelopmental outcome in infants with neonatal cerebral infarction. Pediatrics 2001; 107:1400.
  28. Lynch JK, Hirtz DG, DeVeber G, Nelson KB. Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics 2002; 109:116.
  29. Berkun Y, Simchen MJ, Strauss T, et al. Antiphospholipid antibodies in neonates with stroke--a unique entity or variant of antiphospholipid syndrome? Lupus 2014; 23:986.
  30. Volpe JJ, Pasternak JF. Parasagittal cerebral injury in neonatal hypoxic-ischemic encephalopathy: clinical and neuroradiologic features. J Pediatr 1977; 91:472.
  31. Akanli LF, Trasi SS, Thuraisamy K, et al. Neonatal middle cerebral artery infarction: association with elevated maternal anticardiolipin antibodies. Am J Perinatol 1998; 15:399.
  32. Lee J, Croen LA, Backstrand KH, et al. Maternal and infant characteristics associated with perinatal arterial stroke in the infant. JAMA 2005; 293:723.
  33. Wu YW, Lynch JK, Nelson KB. Perinatal arterial stroke: understanding mechanisms and outcomes. Semin Neurol 2005; 25:424.
  34. Martinez-Biarge M, Cheong JL, Diez-Sebastian J, et al. Risk Factors for Neonatal Arterial Ischemic Stroke: The Importance of the Intrapartum Period. J Pediatr 2016; 173:62.
  35. Cheong JL, Cowan FM. Neonatal arterial ischaemic stroke: obstetric issues. Semin Fetal Neonatal Med 2009; 14:267.
  36. Harteman JC, Groenendaal F, Kwee A, et al. Risk factors for perinatal arterial ischaemic stroke in full-term infants: a case-control study. Arch Dis Child Fetal Neonatal Ed 2012; 97:F411.
  37. Darmency-Stamboul V, Chantegret C, Ferdynus C, et al. Antenatal factors associated with perinatal arterial ischemic stroke. Stroke 2012; 43:2307.
  38. Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. J Pediatr 1986; 108:456.
  39. Dominguez R, Aguirre Vila-Coro A, Slopis JM, Bohan TP. Brain and ocular abnormalities in infants with in utero exposure to cocaine and other street drugs. Am J Dis Child 1991; 145:688.
  40. Heier LA, Carpanzano CR, Mast J, et al. Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS. AJNR Am J Neuroradiol 1991; 12:951.
  41. Ecury-Goossen GM, Raets MM, Lequin M, et al. Risk factors, clinical presentation, and neuroimaging findings of neonatal perforator stroke. Stroke 2013; 44:2115.
  42. van der Aa NE, Dudink J, Benders MJ, et al. Neonatal posterior cerebral artery stroke: clinical presentation, MRI findings, and outcome. Dev Med Child Neurol 2013; 55:283.
  43. Rafay MF, Cortez MA, de Veber GA, et al. Predictive value of clinical and EEG features in the diagnosis of stroke and hypoxic ischemic encephalopathy in neonates with seizures. Stroke 2009; 40:2402.
  44. Bouza H, Rutherford M, Acolet D, et al. Evolution of early hemiplegic signs in full-term infants with unilateral brain lesions in the neonatal period: a prospective study. Neuropediatrics 1994; 25:201.
  45. Cowan FM, Pennock JM, Hanrahan JD, et al. Early detection of cerebral infarction and hypoxic ischemic encephalopathy in neonates using diffusion-weighted magnetic resonance imaging. Neuropediatrics 1994; 25:172.
  46. Robertson RL, Ben-Sira L, Barnes PD, et al. MR line-scan diffusion-weighted imaging of term neonates with perinatal brain ischemia. AJNR Am J Neuroradiol 1999; 20:1658.
  47. Krishnamoorthy KS, Soman TB, Takeoka M, Schaefer PW. Diffusion-weighted imaging in neonatal cerebral infarction: clinical utility and follow-up. J Child Neurol 2000; 15:592.
  48. McKinstry RC, Miller JH, Snyder AZ, et al. A prospective, longitudinal diffusion tensor imaging study of brain injury in newborns. Neurology 2002; 59:824.
  49. Kirton A, Armstrong-Wells J, Chang T, et al. Symptomatic neonatal arterial ischemic stroke: the International Pediatric Stroke Study. Pediatrics 2011; 128:e1402.
  50. Hess CP, Fullerton HJ, Metry DW, et al. Cervical and intracranial arterial anomalies in 70 patients with PHACE syndrome. AJNR Am J Neuroradiol 2010; 31:1980.
  51. Siegel DH, Tefft KA, Kelly T, et al. Stroke in children with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome: a systematic review of the literature. Stroke 2012; 43:1672.
  52. Messer J, Haddad J, Casanova R. Transcranial Doppler evaluation of cerebral infarction in the neonate. Neuropediatrics 1991; 22:147.
  53. Nishimaki S, Seki K, Yokota S. Cerebral blood flow velocity in two patients with neonatal cerebral infarction. Pediatr Neurol 2001; 24:320.
  54. Mercuri E, Rutherford M, Cowan F, et al. Early prognostic indicators of outcome in infants with neonatal cerebral infarction: a clinical, electroencephalogram, and magnetic resonance imaging study. Pediatrics 1999; 103:39.
  55. Randò T, Ricci D, Mercuri E, et al. Periodic lateralized epileptiform discharges (PLEDs) as early indicator of stroke in full-term newborns. Neuropediatrics 2000; 31:202.
  56. Zuasnabar A, Bejar R, Sherman F, Mannino F. An interesting case presentation: ultrasound diagnosis of primary atrial thrombosis associated with brain infarctions. J Perinatol 1991; 11:73.
  57. deVeber GA, MacGregor D, Curtis R, Mayank S. Neurologic outcome in survivors of childhood arterial ischemic stroke and sinovenous thrombosis. J Child Neurol 2000; 15:316.
  58. Lee J, Croen LA, Lindan C, et al. Predictors of outcome in perinatal arterial stroke: a population-based study. Ann Neurol 2005; 58:303.
  59. Chabrier S, Peyric E, Drutel L, et al. Multimodal Outcome at 7 Years of Age after Neonatal Arterial Ischemic Stroke. J Pediatr 2016; 172:156.
  60. Rutherford MA, Pennock JM, Cowan FM, et al. Does the brain regenerate after perinatal infarction? Eur J Paediatr Neurol 1997; 1:13.
  61. Mercuri E, Barnett A, Rutherford M, et al. Neonatal cerebral infarction and neuromotor outcome at school age. Pediatrics 2004; 113:95.
  62. Husson B, Hertz-Pannier L, Renaud C, et al. Motor outcomes after neonatal arterial ischemic stroke related to early MRI data in a prospective study. Pediatrics 2010; 126:912.
  63. Kirton A, Shroff M, Visvanathan T, deVeber G. Quantified corticospinal tract diffusion restriction predicts neonatal stroke outcome. Stroke 2007; 38:974.
  64. van der Aa NE, Leemans A, Northington FJ, et al. Does diffusion tensor imaging-based tractography at 3 months of age contribute to the prediction of motor outcome after perinatal arterial ischemic stroke? Stroke 2011; 42:3410.
  65. van Buuren LM, van der Aa NE, Dekker HC, et al. Cognitive outcome in childhood after unilateral perinatal brain injury. Dev Med Child Neurol 2013; 55:934.
  66. Westmacott R, MacGregor D, Askalan R, deVeber G. Late emergence of cognitive deficits after unilateral neonatal stroke. Stroke 2009; 40:2012.
  67. Golomb MR, Garg BP, Carvalho KS, et al. Perinatal stroke and the risk of developing childhood epilepsy. J Pediatr 2007; 151:409.
  68. Wusthoff CJ, Kessler SK, Vossough A, et al. Risk of later seizure after perinatal arterial ischemic stroke: a prospective cohort study. Pediatrics 2011; 127:e1550.
  69. Trauner DA, Nass R, Ballantyne A. Behavioural profiles of children and adolescents after pre- or perinatal unilateral brain damage. Brain 2001; 124:995.
  70. Wu YW, Lindan CE, Henning LH, et al. Neuroimaging abnormalities in infants with congenital hemiparesis. Pediatr Neurol 2006; 35:191.
  71. 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.
  72. Fullerton HJ, Wu YW, Sidney S, Johnston SC. Risk of recurrent childhood arterial ischemic stroke in a population-based cohort: the importance of cerebrovascular imaging. Pediatrics 2007; 119:495.
  73. Newton TH, Gooding CA. Compression of superior sagittal sinus by neonatal calvarial molding. Radiology 1975; 115:635.
  74. Cowan F, Thoresen M. Changes in superior sagittal sinus blood velocities due to postural alterations and pressure on the head of the newborn infant. Pediatrics 1985; 75:1038.
  75. deVeber G, Andrew M, Adams C, et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001; 345:417.
  76. Wu YW, Miller SP, Chin K, et al. Multiple risk factors in neonatal sinovenous thrombosis. Neurology 2002; 59:438.
  77. Jordan LC, Rafay MF, Smith SE, et al. Antithrombotic treatment in neonatal cerebral sinovenous thrombosis: results of the International Pediatric Stroke Study. J Pediatr 2010; 156:704.
  78. Berfelo FJ, Kersbergen KJ, van Ommen CH, et al. Neonatal cerebral sinovenous thrombosis from symptom to outcome. Stroke 2010; 41:1382.
  79. Takanashi J, Barkovich AJ, Ferriero DM, et al. Widening spectrum of congenital hemiplegia: Periventricular venous infarction in term neonates. Neurology 2003; 61:531.
  80. Wu YW, Hamrick SE, Miller SP, et al. Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis. Ann Neurol 2003; 54:123.
  81. Kersbergen KJ, Groenendaal F, Benders MJ, et al. The spectrum of associated brain lesions in cerebral sinovenous thrombosis: relation to gestational age and outcome. Arch Dis Child Fetal Neonatal Ed 2011; 96:F404.
  82. Bezinque SL, Slovis TL, Touchette AS, et al. Characterization of superior sagittal sinus blood flow velocity using color flow Doppler in neonates and infants. Pediatr Radiol 1995; 25:175.
  83. Fitzgerald KC, Williams LS, Garg BP, et al. Cerebral sinovenous thrombosis in the neonate. Arch Neurol 2006; 63:405.
  84. Volpe JJ. Hypoxic-ischemic encephalopathy: Neuropathology and pathogenesis. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadelphia 2008. p.347.
  85. Volpe JJ. Intracranial hemorrhage: Subdural, primary subarachnoid, intracerebellar, intraventricular (term infant) and miscellaneous. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadelphia 2008. p.483.
  86. Schulte R, Jordan LC, Morad A, et al. Rise in late onset vitamin K deficiency bleeding in young infants because of omission or refusal of prophylaxis at birth. Pediatr Neurol 2014; 50:564.
  87. Inder TE, Volpe JJ. Mechanisms of perinatal brain injury. Semin Neonatol 2000; 5:3.
  88. Volpe JJ. Germinal matrix-intraventricular hemorrhage of the premature infant. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadelphia 2008. p.517.
  89. Bassan H, Feldman HA, Limperopoulos C, et al. Periventricular hemorrhagic infarction: risk factors and neonatal outcome. Pediatr Neurol 2006; 35:85.
  90. Guzzetta F, Shackelford GD, Volpe S, et al. Periventricular intraparenchymal echodensities in the premature newborn: critical determinant of neurologic outcome. Pediatrics 1986; 78:995.
  91. Perlman JM, Rollins N, Burns D, Risser R. Relationship between periventricular intraparenchymal echodensities and germinal matrix-intraventricular hemorrhage in the very low birth weight neonate. Pediatrics 1993; 91:474.
  92. de Vries LS, Roelants-van Rijn AM, Rademaker KJ, et al. Unilateral parenchymal haemorrhagic infarction in the preterm infant. Eur J Paediatr Neurol 2001; 5:139.
  93. Roze E, Kerstjens JM, Maathuis CG, et al. Risk factors for adverse outcome in preterm infants with periventricular hemorrhagic infarction. Pediatrics 2008; 122:e46.
  94. Grode ML, Saunders M, Carton CA. Subarachnoid hemorrhage secondary to ruptured aneurysms in infants. Report of two cases. J Neurosurg 1978; 49:898.
  95. Volpe JJ. Intracranial mass lesions: Brain tumors and vein of Galen malformations. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadelphia 2008. p.989.
  96. Takashima S, Tanaka K. Development of cerebrovascular architecture and its relationship to periventricular leukomalacia. Arch Neurol 1978; 35:11.
  97. Roach ES, Golomb MR, Adams R, 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 2008; 39:2644.
  98. Monagle P, Chan AK, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e737S.
  99. Moharir MD, Shroff M, Stephens D, et al. Anticoagulants in pediatric cerebral sinovenous thrombosis: a safety and outcome study. Ann Neurol 2010; 67:590.
  100. Kersbergen KJ, de Vries LS, van Straaten HL, et al. Anticoagulation therapy and imaging in neonates with a unilateral thalamic hemorrhage due to cerebral sinovenous thrombosis. Stroke 2009; 40:2754.