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Stroke in the newborn: Classification, manifestations, and diagnosis

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, and diagnosis of perinatal stroke are reviewed here. Management and prognosis are reviewed elsewhere. (See "Stroke in the newborn: Management and prognosis".)

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 2017. | This topic last updated: Sep 28, 2017.
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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. Kirton A, Deveber G, Pontigon AM, et al. Presumed perinatal ischemic stroke: vascular classification predicts outcomes. Ann Neurol 2008; 63:436.
  6. Elbers J, Viero S, MacGregor D, et al. Placental pathology in neonatal stroke. Pediatrics 2011; 127:e722.
  7. Lehman LL, Rivkin MJ. Perinatal arterial ischemic stroke: presentation, risk factors, evaluation, and outcome. Pediatr Neurol 2014; 51:760.
  8. Volpe JJ. Hypoxic-ischemic encephalopathy: Clinical aspects. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadelphia 2008. p.400.
  9. 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.
  10. 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.
  11. Ramaswamy V, Miller SP, Barkovich AJ, et al. Perinatal stroke in term infants with neonatal encephalopathy. Neurology 2004; 62:2088.
  12. Miller V. Neonatal cerebral infarction. Semin Pediatr Neurol 2000; 7:278.
  13. Sreenan C, Bhargava R, Robertson CM. Cerebral infarction in the term newborn: clinical presentation and long-term outcome. J Pediatr 2000; 137:351.
  14. Ruff RL, Shaw CM, Beckwith JB, Iozzo RV. Cerebral infarction complicating umbilical vein catheterization. Ann Neurol 1979; 6:85.
  15. Pellicer A, Cabañas F, García-Alix A, et al. Stroke in neonates with cardiac right-to-left shunt. Brain Dev 1992; 14:381.
  16. Volpe JJ, Pasternak JF. Parasagittal cerebral injury in neonatal hypoxic-ischemic encephalopathy: clinical and neuroradiologic features. J Pediatr 1977; 91:472.
  17. 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.
  18. Lee J, Croen LA, Backstrand KH, et al. Maternal and infant characteristics associated with perinatal arterial stroke in the infant. JAMA 2005; 293:723.
  19. 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.
  20. Wu YW, Lynch JK, Nelson KB. Perinatal arterial stroke: understanding mechanisms and outcomes. Semin Neurol 2005; 25:424.
  21. 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.
  22. Cheong JL, Cowan FM. Neonatal arterial ischaemic stroke: obstetric issues. Semin Fetal Neonatal Med 2009; 14:267.
  23. 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.
  24. Darmency-Stamboul V, Chantegret C, Ferdynus C, et al. Antenatal factors associated with perinatal arterial ischemic stroke. Stroke 2012; 43:2307.
  25. Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. J Pediatr 1986; 108:456.
  26. 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.
  27. 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.
  28. Ecury-Goossen GM, Raets MM, Lequin M, et al. Risk factors, clinical presentation, and neuroimaging findings of neonatal perforator stroke. Stroke 2013; 44:2115.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. Curtis C, Mineyko A, Massicotte P, et al. Thrombophilia risk is not increased in children after perinatal stroke. Blood 2017.
  34. Trenor CC 3rd, Michelson AD. Thrombophilia and pediatric stroke. Circulation 2010; 121:1795.
  35. Andrew ME, Monagle P, deVeber G, Chan AK. Thromboembolic disease and antithrombotic therapy in newborns. Hematology Am Soc Hematol Educ Program 2001; :358.
  36. Newton TH, Gooding CA. Compression of superior sagittal sinus by neonatal calvarial molding. Radiology 1975; 115:635.
  37. 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.
  38. deVeber G, Andrew M, Adams C, et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001; 345:417.
  39. Wu YW, Miller SP, Chin K, et al. Multiple risk factors in neonatal sinovenous thrombosis. Neurology 2002; 59:438.
  40. 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.
  41. Cole L, Dewey D, Letourneau N, et al. Clinical Characteristics, Risk Factors, and Outcomes Associated With Neonatal Hemorrhagic Stroke: A Population-Based Case-Control Study. JAMA Pediatr 2017; 171:230.
  42. Volpe JJ. Hypoxic-ischemic encephalopathy: Neuropathology and pathogenesis. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadelphia 2008. p.347.
  43. 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.
  44. 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.
  45. Arrigoni F, Parazzini C, Righini A, et al. Deep medullary vein involvement in neonates with brain damage: an MR imaging study. AJNR Am J Neuroradiol 2011; 32:2030.
  46. Inder TE, Volpe JJ. Mechanisms of perinatal brain injury. Semin Neonatol 2000; 5:3.
  47. Volpe JJ. Germinal matrix-intraventricular hemorrhage of the premature infant. In: Neurology of the Newborn, 5th ed, Saunders Elsevier, Philadelphia 2008. p.517.
  48. Bassan H, Feldman HA, Limperopoulos C, et al. Periventricular hemorrhagic infarction: risk factors and neonatal outcome. Pediatr Neurol 2006; 35:85.
  49. Guzzetta F, Shackelford GD, Volpe S, et al. Periventricular intraparenchymal echodensities in the premature newborn: critical determinant of neurologic outcome. Pediatrics 1986; 78:995.
  50. 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.
  51. 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.
  52. Roze E, Kerstjens JM, Maathuis CG, et al. Risk factors for adverse outcome in preterm infants with periventricular hemorrhagic infarction. Pediatrics 2008; 122:e46.
  53. Takashima S, Tanaka K. Development of cerebrovascular architecture and its relationship to periventricular leukomalacia. Arch Neurol 1978; 35:11.
  54. Benders MJ, Kersbergen KJ, de Vries LS. Neuroimaging of white matter injury, intraventricular and cerebellar hemorrhage. Clin Perinatol 2014; 41:69.
  55. Agrawal N, Johnston SC, Wu YW, et al. Imaging data reveal a higher pediatric stroke incidence than prior US estimates. Stroke 2009; 40:3415.
  56. Grunt S, Mazenauer L, Buerki SE, et al. Incidence and outcomes of symptomatic neonatal arterial ischemic stroke. Pediatrics 2015; 135:e1220.
  57. Golomb MR, MacGregor DL, Domi T, et al. Presumed pre- or perinatal arterial ischemic stroke: risk factors and outcomes. Ann Neurol 2001; 50:163.
  58. Ilves P, Laugesaar R, Loorits D, et al. Presumed Perinatal Stroke: Risk Factors, Clinical and Radiological Findings. J Child Neurol 2016; 31:621.
  59. 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.
  60. deVeber GA, Kirton A, Booth FA, et al. Epidemiology and Outcomes of Arterial Ischemic Stroke in Children: The Canadian Pediatric Ischemic Stroke Registry. Pediatr Neurol 2017; 69:58.
  61. 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.
  62. 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.
  63. 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.
  64. Berfelo FJ, Kersbergen KJ, van Ommen CH, et al. Neonatal cerebral sinovenous thrombosis from symptom to outcome. Stroke 2010; 41:1382.
  65. Takanashi J, Barkovich AJ, Ferriero DM, et al. Widening spectrum of congenital hemiplegia: Periventricular venous infarction in term neonates. Neurology 2003; 61:531.
  66. Wu YW, Hamrick SE, Miller SP, et al. Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis. Ann Neurol 2003; 54:123.
  67. 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.
  68. Bruno CJ, Beslow LA, Witmer CM, et al. Haemorrhagic stroke in term and late preterm neonates. Arch Dis Child Fetal Neonatal Ed 2014; 99:F48.
  69. 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.
  70. Grode ML, Saunders M, Carton CA. Subarachnoid hemorrhage secondary to ruptured aneurysms in infants. Report of two cases. J Neurosurg 1978; 49:898.
  71. Lee S, Mirsky DM, Beslow LA, et al. Pathways for Neuroimaging of Neonatal Stroke. Pediatr Neurol 2017; 69:37.
  72. 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.
  73. 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.
  74. 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.
  75. McKinstry RC, Miller JH, Snyder AZ, et al. A prospective, longitudinal diffusion tensor imaging study of brain injury in newborns. Neurology 2002; 59:824.
  76. 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.
  77. 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.
  78. Kirton A, Armstrong-Wells J, Chang T, et al. Symptomatic neonatal arterial ischemic stroke: the International Pediatric Stroke Study. Pediatrics 2011; 128:e1402.
  79. Messer J, Haddad J, Casanova R. Transcranial Doppler evaluation of cerebral infarction in the neonate. Neuropediatrics 1991; 22:147.
  80. Nishimaki S, Seki K, Yokota S. Cerebral blood flow velocity in two patients with neonatal cerebral infarction. Pediatr Neurol 2001; 24:320.
  81. 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.
  82. 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.
  83. 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.